# publications

title: Psilocybin alters visual contextual computations
authors: Aqil M, de Hollander G, Vreugdenhil N, Knapen T, Dumoulin SO.
journal: bioRxiv
publication_date: 2025-02-07
doi: 10.1101/2025.02.06.636848
source_url: https://doi.org/10.1101/2025.02.06.636848
substance_tags: psilocybin
topic_tags: Aging
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
abstract:
Psilocybin alters perception and brain dynamics. Contextual computations are ubiquitous in the brain. Here, we investigate the effects of psilocybin using psychophysics, ultra-high field functional MRI, and computational modeling. We find that 1) psilocybin alters contextual perception in the Ebbinghaus illusion, 2) psilocybin alters contextual modulation in cortical responses to visual stimuli, and 3) we propose a computational model capable of capturing and linking these changes. Leveraging vision as a beachhead, our findings highlight the alteration of contextual computations as a potential general mechanism underlying psychedelic action. Teaser Psilocybin alters visual-contextual computations, a potential general computational mechanism for psychedelic effects in the human brain.

raw_json:
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journal: bioRxiv
publication_date: 2023-05-17
doi: 10.1101/2023.05.16.540994
source_url: https://doi.org/10.1101/2023.05.16.540994
substance_tags: psilocybin,psilocin
study_type: Clinical Trial
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
title:
Novel psilocin prodrugs with altered pharmacological properties as candidate therapies for treatment-resistant anxiety disorders

authors:
Raithatha SA, Hagel JM, Matinkhoo K, Yu L, Press D, Cook SG, Sharma G, D D, Jensen G, Lee JB, Cai C, Gallant J, Bains JS, Tucker JE, Facchini PJ.

abstract:
The psychedelic compound psilocybin has shown therapeutic benefit in the treatment of numerous psychiatric diseases. A recent randomized clinical trial conducted at Johns Hopkins Bayview Medical Center demonstrated the efficacy of psilocybin-assisted therapy in the treatment of Major Depressive Disorder (MDD). Similarly, a phase IIb study evaluating psilocybin-assisted therapy for treatment-resistant depression (TRD) presented statistically meaningful and long-term reduction in depressive symptoms. Also, many studies have reported the successful treatment of severe anxiety after a single oral dose of psilocybin, especially in patients struggling with cancer-related distress (CRD). Despite these compelling clinical results, concerns regarding the duration of the psychedelic experience produced by psilocybin pose a significant barrier to its widespread therapeutic application. Psilocybin, derived from magic mushrooms is the naturally occurring prodrug of the neuroactive compound psilocin. When orally administered, exposure to the acidic gastrointestinal (GI) environment together with enzymatic processing by intestinal and hepatic alkaline phosphatase lead to the dephosphorylation of psilocybin producing elevated levels of systemic psilocin. These plasma levels are detectable up to 24 h and produce a psychoactive episode lasting as long as 6 h post-ingestion. In order to positively modify the kinetics of the acute psychedelic response, we have engineered a library of novel prodrug derivatives (NPDs) of psilocin, introducing a diversity of alternative metabolically cleavable moieties modified at the 4-carbon position of the core indole ring. This library consists of twenty-eight unique compounds represented by nine distinct prodrug classes. Each molecule was screened in vitro for metabolic stability using isolated human serum, and human cellular fractions derived from liver and intestinal tissues. This screen revealed fifteen prodrugs that produced measurable levels of psilocin in vitro, with ester and thiocarbonate-based prodrug derivatives significantly represented. These fifteen NPDs were further evaluated for pharmacokinetic (PK) profiles in mice, assessing plasma levels of both residual prodrug and resultant psilocin. PK results confirmed the efficiency of ester and thiocarbonate-based prodrug metabolism upon oral and intravenous administration, achieving levels reduced, albeit comparable to levels of psilocybin-derived psilocin. Of note, almost all NPDs tested maintained reduced overall exposure of psilocin relative to psilocybin, with no measurable levels detected at 24 h post-dose. Finally, all NPDs were screened for CNS bioavailability in healthy mice using the Head Twitch Response (HTR), a behavioural biomarker of 5-HT2A receptor stimulation and an established proxy for psychoactive potential. Interestingly, five NPDs produced peak HTR that approached or exceeded levels induced by an equivalent dose of psilocybin. Among these bioactive prodrugs, an ester-based and thiocarbonate-based molecule produced long-term anxiolytic benefit in chronically stressed mice evaluated in the marble burying psychiatric model. Overall, this screening campaign identified novel candidate prodrugs of psilocin with altered metabolic profiles and reduced pharmacological exposure, potentially attenuating the duration of the psychedelic response. These molecules still maintained the long-term psychiatric and physiological benefits characteristic of psilocybin therapy. Additionally, these modified parameters also offer the opportunity for altered routes of administration bypassing conventional oral dosing.

topic_tags:
Depression,Anxiety,Pharmacology,Receptor Pharmacology,Biomarkers,Clinical Trial,Animal Study,In Vitro Study,Cancer Patients,Treatment-Resistant Depression

raw_json:
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journal: Research Square
publication_date: 2025-09-24
doi: 10.21203/rs.3.rs-7544401/v1
source_url: https://doi.org/10.21203/rs.3.rs-7544401/v1
substance_tags: psilocybin
topic_tags: Anxiety,Brain Imaging,Consciousness,Biomarkers,Aging,Emotional Processing,Healthy Volunteers
study_type: Other
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
title:
Regional Specificity of the Cingulate Cortex Thickness Association with the Intensity of Psilocybin Experience: A Replication Study

authors:
Greguš D, Hlinka J, Tylš F, Viktorin V, Viktorinová M, Bravermanová A, Androvičová R, Andrashko V, Korčák J, Nikolič M, Adámek P, Beneš M, Páleníček T, Horáček J.

abstract:
Abstract Rationale: Individual variability in psilocybin response is a major challenge for psychedelic-assisted therapy, with structural brain features potentially serving as predictive biomarkers. Lewis et al. (2020) reported that rostral anterior cingulate cortex thickness predicted emotional experiences under psilocybin, suggesting cortical morphometry as a marker of psychedelic responsivity. Objectives: This study sought to replicate and extend these findings by examining associations between cingulate thickness and psilocybin-induced altered states of consciousness using comprehensive assessment and rigorous statistical control. Methods: Twenty-five healthy participants underwent a double-blind, placebo-controlled crossover design with psilocybin (0.26 mg/kg) and placebo. High-resolution T1-weighted magnetic resonance imaging (MRI) measured cortical thickness across cingulate subregions. Subjective effects were assessed with the Altered States of Consciousness (ASC) questionnaire. Analyses applied false discovery rate (FDR) correction for multiple comparisons. Results: The primary Lewis et al. finding-that rostral anterior cingulate cortex thickness predicts emotional psilocybin responses-was not replicated. Instead, we identified a robust anterior-posterior gradient in cingulate thickness that significantly predicted global psychedelic intensity (r = 0.549, FDR p = 0.013). Moreover, general cingulate thickness was associated with the balance between anxiety-dominated and visionary states (r = 0.495, FDR p = 0.016). Conclusions: Findings indicate that structural organization of the cingulate cortex provides a neuroanatomical marker of variability in psychedelic response, with implications for personalized dosing and anticipatory management in psychedelic-assisted therapy. Results highlight the importance of broad cortical organizational patterns, rather than focal regional measures, when predicting psychedelic effects.

raw_json:
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authors: Domzalska M, Kwiatkowska J, Cichon I, Sokolowska E.
journal: Research Square
publication_date: 2025-10-06
doi: 10.21203/rs.3.rs-7269356/v1
source_url: https://doi.org/10.21203/rs.3.rs-7269356/v1
substance_tags: psilocybin
topic_tags: Depression,Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
title:
Towards Novel Antidepressant Strategies: A Comparative Study of Ketamine, Psilocybin, and Fluoxetine in a Chronic Stress Model

abstract:
Abstract Depression is a debilitating mental disorder affecting millions worldwide, yet current pharmacological treatments, such as selective serotonin reuptake inhibitors (SSRIs), often exhibit delayed onset and limited efficacy. The chronic social defeat (CSD) stress model in mice is a well-established preclinical paradigm for inducing depression-like behaviors and evaluating antidepressants effectiveness. This study compared the efficacy of both acute and chronic fluoxetine with acute ketamine and psilocybin treatment in male C57BL/6J mice subjected to CSD. Fluoxetine showed no significant effects 24 hours after a single dose or following 7 days of repeated administration; antidepressant-like effects only appeared after 14 days of continuous treatment. In contrast, a single dose of either ketamine or psilocybin significantly reversed social avoidance behavior at 24 hours, with sustained effects observed at 7- and 14-days post-treatment. These findings suggest that ketamine and psilocybin elicit rapid and durable, antidepressant-like responses in this preclinical model, in contrast to traditional SSRIs, like fluoxetine, which requires extended treatment duration, mirroring clinical efficacy patterns. The results support the utility of the CSD model in evaluating antidepressant efficacy and highlight the therapeutic potential of fast-acting agents such as ketamine and psilocybin as alternatives to conventional treatments for major depressive disorder.

raw_json:
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title: Behavioural Investigations of Psilocybin in Animals 1962-2021: A Scoping Review
journal: bioRxiv
publication_date: 2024-01-04
doi: 10.1101/2024.01.04.574146
source_url: https://doi.org/10.1101/2024.01.04.574146
substance_tags: psilocybin,psilocin
topic_tags: Mechanism of Action,Review Article,Safety,Adverse Events,Toxicity
study_type: Review Article
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
authors:
Shore R, Dobson K, Thomson N, Barnim N, Bergman H, Rideout K, McKeown S, Olmstead MC, Goldie C, Dumont E.

abstract:
Background and Aims Psilocybin is a psychedelic drug that may hold promise for a wide range of human health conditions, yet the identification of therapeutic processes and mechanisms of action remains exploratory. We conducted a scoping review on pre-clinical behavioural investigations of psilocybin in non-human animals to help determine the behavioural effects of psilocybin in non-human animals, to identify studies completed, behavioural tests employed, and what dosing modalities had been studied. Methods A librarian-conducted literature search was performed using predefined key terms and search criteria and additional searching was conducted by reviewers, using electronic databases, grey literature sources, and reference lists of relevant articles or reviews. The final search updated occurred in October, 2021. Studies were reviewed, screened and selected against an a priori protocol using Covidence software by multiple reviewers with results plotted across the Research Domains Criteria construct. Results From 4124 records identified by database searching, 260 publications were subjected to full-text review with 77 studies included in this scoping review, published between 1962-2021. The preponderance of studies (n=64) investigated behavioural outcomes in rodents. Only 43 studies (55.8%) reported on housing conditions, and seventeen studies (22.1%) failed to report sample size. All studies reported behavioural outcomes following drug administration, with fifty-one studies (66.2%) using psilocybin, thirty studies (42.9%) psilocin, four studies (5.2%) administering whole mushroom extracts (WME), and a further eight studies investigating both psilocybin and psilocin and one study reporting the effects of both psilocin and WME. One hundred and thirty distinct behavioural investigations using fifty different behavioral paradigms were identified. Few adverse events were reported, and even exceedingly high doses were apparently well tolerated. Conclusion With seventy-seven publications spanning close to sixty years, there is huge variation in study design and quality. Overall psilocybin presents a unique and strong safety profile with no evidence of biological toxicity, is characterized by unique time and dose-dependent effects, and its pattern of drug action is significantly context and training-sensitive. Data suggest putative effects of psilocybin include acute arousal, dose-dependent sedation, reductions in fear conditioning at low doses, reduced aggression, improved valence, acute disruption of working memory, the rescuing of deficits from chronic stress, and improved learning when combined with repeated environmental exposure after resolution of drug effect.

raw_json:
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authors: Mennenga S, Hanson T, Semple M, Lifshitz D, Flores B, Balducci J, Harker S, Ford A, Lewis C.
journal: Research Square
publication_date: 2025-11-04
doi: 10.21203/rs.3.rs-7890051/v1
source_url: https://doi.org/10.21203/rs.3.rs-7890051/v1
substance_tags: psilocybin
study_type: Animal Study
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
title:
Psilocybin reduces depressive-like behavior and improves cognition in healthy aging mice via epigenetic regulation of plasticity- and immune-related genes

abstract:
Abstract For many, cognitive and affective health declines through typical aging. Although cognitive and affective symptoms are often studied in isolation, they share substantial overlap, and arise, in part, from common biological processes. Aging is accompanied by diminished neural plasticity, heightened neuroinflammation, and widespread alterations in the epigenome. These molecular changes mirror behavioral decline, linking the erosion of cellular adaptability to the decline of cognitive function and emotional well-being in aging. Here, we show that psilocybin reverses age-related behavioral and epigenetic alterations in aged mice. Male and female C57BL/6 mice (11 months old) received two intraperitoneal doses of psilocybin (1mg/kg) or saline one week apart and were evaluated for memory and affective behaviors. Psilocybin improved learning and memory in females and reduced depressive-like behavior across sexes. Genome-wide DNA methylation profiling in the prefrontal cortex and bilateral hippocampus revealed widespread, sex- and region-specific effects, with the right hippocampus of females showing the most extensive gene-level changes. Differentially methylated loci were enriched for pathways related to synaptic organization, axon guidance, and neuroimmune signaling. Notably, psilocybin reversed age-associated methylation at CpG sites linked to typical aging, including within the Tbr1 promoter, a transcription factor essential for excitatory neuron development and synapse formation. Moreover, methylation at Tbr1 mediated psilocybin’s pro-cognitive effects on Y-Maze performance in females. Together, these findings demonstrate that psilocybin induces coordinated behavioral and epigenetic remodeling in the aging brain, with lateralized and sex-dependent signatures implicating neuroimmune and neuroplasticity transcriptional networks. Psilocybin thus emerges as a candidate compound for promoting aging resilience.

topic_tags:
Depression,Neuroplasticity,Mechanism of Action,Aging,Epigenetics,Wellbeing,Resilience,Emotional Processing,Animal Study,Genomics,Inflammation,Immune Function

raw_json:
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authors: Slot J, Bradshaw A, Dentinger B, Borovička J, Konkel Z, Rockefeller A, Bollinger I.
journal: bioRxiv
publication_date: 2026-01-01
doi: 10.64898/2025.12.30.697041
source_url: https://doi.org/10.64898/2025.12.30.697041
substance_tags: psilocybin
topic_tags: Mechanism of Action,Genomics
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
title:
The one that abstained: Psilocybe fuscofulva genome suggests two recent origins of the psilocybin gene cluster in Psilocybe

abstract:
Production of the psychoactive compound psilocybin is a defining feature of the genus Psilocybe, commonly referred to as “psychedelic mushrooms”. However, Psilocybe fuscofulva is a striking exception within Psilocybe sensu stricto as it lacks the stereotypical blue bruising characteristic of the genus, and psilocybin has not been detected in the species.To investigate the evolutionary events leading to differential psilocybin production among Psilocybe species, we produced genome assemblies two P. fuscofulva strains, one Psilocybe polytrichoides strain, and one Psilocybe tampanensis strain, complemented by reannotated public genomes and metagenome-derived assemblies from fungarium specimens. This sample represents both major Psilocybe clades (Clade I and Clade II) and the most closely related genera. Phylogenomic analysis based on 100 single-copy orthologs curated for high branch support strongly placed P. fuscofulva as the earliest-diverging lineage in Psilocybe Clade I. No psilocybin gene cluster (PGC) homologs, whether clustered or dispersed, were identified in P. fuscofulva, whereas a single intact PGC was present in all other examined Psilocybe genomes. The PGC resides in two distinct, clade-specific genomic loci: one conserved in Clade I and another in Clade II, each displaying characteristic gene orders and orientations consistent with rearrangement through circular intermediates. Time-calibrated phylogenies estimated the Psilocybe crown group at approximately 28 million years ago, with major clade divergences occurring in the Miocene. The absence of the PGC in P. fuscofulva, together with clade-specific structural conservation and the lack of remnant sequences at alternate loci, supports two independent origins of the PGC within Psilocybe: one in the ancestor of Clade II and a subsequent origin in Clade I following divergence from P. fuscofulva, most likely via horizontal gene transfer (HGT). Gene phylogenies provide weak support for transfer from Clade I to Clade II, although broader sampling is required for confirmation. These results constrain the timeframe of PGC emergence and dispersal to the Miocene, implying rapid HGT events possibly driven by ecological pressures in expanding grassland ecosystems. This study challenges the assumption of an ancestral psilocybin pathway in Psilocybe and its close relatives and underscores multiple recent acquisitions of the PGC that suggest it is an ecologically important metabolic trait in psychoactive fungi.

raw_json:
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journal: medRxiv
publication_date: 2025-05-28
doi: 10.1101/2025.05.28.25328532
source_url: https://doi.org/10.1101/2025.05.28.25328532
substance_tags: psilocybin
topic_tags: Personality Change,Mystical Experience,Clinical Trial,Adverse Events
study_type: Clinical Trial
source_name: medRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
title:
Understanding the Psychological Effects of Psilocybin and 3,4-Methylenedioxymethamphetamine in a Non-Clinical Population

authors:
Fitzgerald PB, Webb SL, Denning NC, Dowie T, Schweickle MM, Modak A, Chan G, Knight J, Waldron M, Gainsford K, Hawkes H, Zammit S, Sutanto NC, Fitzgibbon BM, Bailey NW.

abstract:
Objective Despite many decades of experimental studies and clinical trials involving a variety of psychedelic agents, we still lack a comprehensive understanding of the effects of these substances on psychological experiences. As such, we designed and conducted a study to comprehensively characterise the effects of both psilocybin and 3,4-Methylenedioxymethamphetamine (MDMA) on a range of psychological outcomes in a substantive non-clinical population. Methods This study involved a single dose administration of psilocybin or MDMA in healthy individuals in a group setting (2-4 people per session). All participants underwent a single preparation session, a drug exposure session, and an integration session within 72 hours of dosing. Outcome assessments were conducted at a pre-dosing baseline, 1-3 days post dose (side effects only), one week post dose and at 3 month follow up (the later time point data is not included here). Results Of 48 participants, 25 initially received MDMA and 23 psilocybin. Ten cross-over participants received MDMA and then psilocybin and six participants received both in the reverse order: making a total of 31 MDMA and 33 psilocybin dosing sessions. In the week after dosing, we found significant changes in personality (a reduction in neuroticism and increase in extraversion), mindfulness, and connectedness following the administration of psilocybin but not MDMA. Psilocybin also produced significantly stronger mystical experiences compared to MDMA, and there was a significant correlation between the magnitude of these mystical experiences and changes in connectedness and mindfulness (but not changes in personality). Of note, participants seemed more comfortable with, and preferred, larger group sizes when being administered MDMA than psilocybin. Discussion Our results identified a range of short-term psychological effects in non-clinical participants following a single dose of psilocybin, that were not reported following a single dose of MDMA. Notably, our results indicate that these effects following psilocybin may be moderated through its induction of mystical experiences, as has been previously hypothesised. Although preliminary, our results also suggest that larger group dosing sessions seem more feasible with MDMA than psilocybin.

raw_json:
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journal: medRxiv
publication_date: 2025-08-15
doi: 10.1101/2025.08.13.25333530
source_url: https://doi.org/10.1101/2025.08.13.25333530
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: medRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
title:
Psilocybin treatment for symptoms of depression: a living systematic review, meta-analysis, and data resource

authors:
Singleton SP, Sevchik BL, Lahey A, Cuijpers P, Harrer M, Jones MT, Nayak SM, Strain EC, Vandekar SN, Dworkin RH, Scott JC, Satterthwaite TD.

abstract:
Importance Depression is a major cause of disability worldwide, motivating substantial interest in psilocybin as a potential treatment. Objective To conduct a systematic review and meta-analysis of psilocybin’s impact on depressive symptoms and provide a living open data resource. Data Sources PubMed, Embase, Scopus, Web of Science, and PsycINFO retrieved by a systematic search up to July 1, 2025. Study Selection We included randomized controlled trials of psilocybin or psilocybin-assisted therapy compared against a placebo or waitlist condition. Data Extraction and Synthesis Data extraction was completed independently by two extractors. A random-effects meta-analysis was used to synthesize data. Risk of bias was assessed with Cochrane’s RoB 2.0 tool. Main Outcomes and Measures The main outcome was the standardized mean difference (Hedges’ g ) in depression scores at the primary study endpoint. Results Twelve studies comprising 711 participants were included in the database, with nine of those studies (n = 529) included in our primary model. Of the nine studies included in the primary model, two had a high risk of bias, four had some concerns, while three had a low risk of bias. Compared to control conditions, psilocybin showed a greater reduction in depression scores, with a pooled Hedges’ g = -0.91 (95% CI, [-1.35; -0.48]; k = 9; p = 0.0013, I2 = 58.1%, tau 2 = 0.13, n = 501). Sensitivity analyses revealed robust effects consistent with the primary model across a variety of design parameters and analysis choices, while also suggesting that waitlist control and crossover design studies contribute a large amount of heterogeneity to the primary model. Meta-regression revealed that psilocybin’s effects were rapid and consistent over several weeks (intercept = -0.92 [-1.26; -0.58], p < 0.0001; slope = 0.0009 [-0.0023; 0.0041], p = 0.57). Conclusions and Relevance This systematic review and meta-analysis suggests that psilocybin-assisted therapy results in substantial decreases in depressive symptoms across studies to date. However, many studies have small sample sizes or risk of bias. This living systematic review, meta-analysis, database, and online dashboard will continue to be updated as evidence emerges, providing a valuable resource for researchers in a rapidly evolving field. Key Points Question What is the efficacy of psilocybin or psilocybin-assisted therapy for depressive symptoms? Findings In this living systematic review and meta-analysis, the initial evidence suggests that psilocybin is more effective in reducing depression symptoms compared to control conditions. Our publicly released database and interactive dashboard contains over 200 effect sizes from 12 randomized clinical trials testing psilocybin’s impacts on depression and will be updated regularly to keep pace with this rapidly moving field. Meaning The current evidence suggests promise for psilocybin therapy for depression, though more studies are needed.

topic_tags:
Depression,Clinical Trial,Randomized Controlled Trial,Meta-Analysis,Systematic Review,Review Article,Safety

raw_json:
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title: Epigenome-wide Association Study of Psilocybin-Induced Methylome Changes in Alcohol Use Disorder
authors: Urban MM, Zillich L, Rieser NM, Herdener M, Vollenweider FX, Spanagel R, Preller KH, Meinhardt MW.
journal: bioRxiv
publication_date: 2025-07-17
doi: 10.1101/2025.07.18.664368
source_url: https://doi.org/10.1101/2025.07.18.664368
substance_tags: psilocybin
study_type: Observational Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
abstract:
The serotonergic hallucinogen psilocybin has shown potential as a treatment for psychiatric conditions like alcohol use disorder (AUD) and depression in clinical studies. Epigenetic mechanisms, including DNA methylation, are hypothesized to contribute to its lasting therapeutic benefits. In this exploratory study, we present the first methylome-wide analysis of psilocybin-induced changes in a cohort of detoxified patients with AUD. The longitudinal study design included three assessment days in 40 patients with blood sampling and acquisition of psychometrics - at baseline, 24 hours after administration of psilocybin (25 mg) or placebo (mannitol), and one month after treatment. Our epigenome-wide association study (EWAS) identified one CpG site in TLE4 ( p = 1.1e-7) associated with psilocybin treatment. Screening for differentially methylated regions, we observed altered methylation in the gene RASGRP4 ( pFDR = 3.2e-4). Network analysis revealed co-methylation modules related to psilocybin treatment, as well as modules associated with the reduction of depressive symptoms and drinking behavior. Gene ontology analysis indicated involvement of these modules in neuroplasticity and immune functions, suggesting that they may reflect abstinence-related recovery processes. Investigating candidate genes at nominal significance ( p < 0.05) uncovered promoter-associated methylation changes in HTR2A and TNF. Furthermore, at p < 0.05, we found baseline differences between treatment responders (< 1 standard unit alcohol in 4-week follow-up) and non-responders in genes related to synaptic plasticity and different neurotransmitter systems. While these findings are limited by the modest sample size, they align well with previous literature and might provide starting points for further, large-scale investigations or hypothesis-driven experiments.

topic_tags:
Depression,Addiction,Neuroplasticity,Mechanism of Action,Epigenetics,Observational Study,Genomics,Immune Function

raw_json:
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title: An open-label, dose-escalation trial of psilocybin-assisted therapy for bipolar 2 depression
journal: PsyArXiv
publication_date: 2025-07-06
source_url: https://osf.io/preprints/psyarxiv/97cqx_v1
keywords: bipolar, depression, psilocybin, psychedelics, Psychiatry
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Headache / Migraine,Safety,Adverse Events
study_type: Other
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"97cqx_v1","version":1,"reviews_state":"pending"}
abstract:
Background: Individuals with bipolar II disorder (BD-II) and depression face limited treatment options and are often excluded from psilocybin therapy trials due to theoretical concerns of precipitating mania or psychosis. Although psilocybin has demonstrated antidepressant effects when combined with psychotherapy, adverse event reporting is inconsistent, and restrictive eligibility criteria limit generalizability. Aims: To evaluate the safety, tolerability, and preliminary efficacy of psilocybin therapy in individuals with BD-II experiencing moderate-to-severe depression. Method: In this open-label, single-arm pilot trial, 14 participants received 10 mg of psilocybin, followed by 25 mg if depressive symptoms persisted. Participants underwent psychotherapy before, during, and after psilocybin administration sessions and were proactively monitored for adverse events. Depression and quality of life were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) and Quality of Life in Bipolar Disorder Questionnaire (QoL BD), along with exploratory measures. Results: Psilocybin was well tolerated, with transient increases in heart rate and blood pressure and no serious adverse events. Common adverse events included mild-to-moderate anxiety, nausea, and headache. Three participants experienced notable psychiatric adverse events (suicidal ideation and hypomania) which resolved with support. The frequency and nature of both serious and non-serious adverse events were broadly comparable to those reported in psilocybin studies for other conditions. MADRS scores improved at all timepoints: 21 days after 10 mg (-12.7 [2.7], p


authors: Wolff M, Kangaslampi S, Zeifman R, Spangemacher M.
journal: PsyArXiv
publication_date: 2026-05-14
doi: 10.31234/osf.io/8s7xk_v2
source_url: https://doi.org/10.31234/osf.io/8s7xk_v2
substance_tags: psilocybin
topic_tags: Depression,Treatment-Resistant Depression
study_type: Other
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
title:
Strong alliance, weak conclusions: Comment on Goodwin et al. (2026) “The role of therapeutic alliance in psilocybin treatment for treatment-resistant depression”

abstract:
This commentary critically examines the interpretation and analytic choices in Goodwin and colleagues’ recent analysis of therapeutic alliance in psilocybin treatment for treatment-resistant depression. While the authors conclude that alliance did not meaningfully contribute to treatment efficacy, we argue that this interpretation is not supported by the reported results, which are, in addition, shaped by methodological decisions that obscure relevant effects. By contextualizing the observed associations, clarifying the logic of mediation analysis, and pointing out methodological weaknesses, we show that the available evidence is more consistent with a meaningful role of therapeutic alliance in shaping both the psychedelic experience and clinical outcomes. Furthermore, we highlight unexplained deviations from the study protocol that warrant scrutiny. These concerns underscore the importance of accurately characterizing psychological and contextual factors in psychedelic treatment research and calls for more comprehensive and transparent analyses of psychotherapeutic processes.

raw_json:
{"europe_pmc_id":"PPR1208581","source":"PPR","pub_type":null,"publisher":"PsyArXiv","importer":"Europe PMC"}


title: Psilocybin-Assisted Therapy Increases Self-Compassion in Patients with Alcohol Use Disorder
journal: PsyArXiv
publication_date: 2025-06-09
source_url: https://osf.io/preprints/psyarxiv/f27jm_v1
keywords: Psychiatry
substance_tags: psilocybin
topic_tags: Addiction,Safety
study_type: Clinical Trial
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"f27jm_v1","version":1,"reviews_state":"accepted"}
abstract:
A recent randomized, double-blind, placebo-controlled, parallel-group trial (NCT02061293) found that psilocybin-assisted therapy significantly improved drinking outcomes compared to an active placebo in adults with alcohol use disorder (AUD). In this secondary analysis, we assessed whether psilocybin-assisted therapy improved self-compassion and whether these changes predicted drinking outcomes. Of the 95 participants enrolled, 86 had self-compassion and drinking outcome data. Forty-four participants were randomized to 2 medication sessions with psilocybin and forty-two to active-placebo control (diphenhydramine); all participants received 12 sessions of manualized psychotherapy. Psilocybin-assisted therapy robustly increased compassionate self-responding (CS) and decreased uncompassionate self-responding (UCS), with the largest effect sizes observed in reducing UCS components (Self-Judgment, Isolation, Over-Identification). Across the full sample, small but significant correlations emerged between improvements in self-compassion and reductions in drinking. However, group-specific analyses revealed that participants in the control group exhibited moderate associations between gains in self-compassion and decreased drinking, whereas no significant association was observed in the psilocybin group. In both groups, these associations were stronger among participants who maintained moderate-to-high-risk drinking during the first four weeks of therapy prior to medication administration. Although the control group consistently exhibited significant correlations and the psilocybin group did not, the between-group differences in correlation strength were not statistically significant. These findings underscore the clinical relevance of self-compassion in AUD treatment but suggest that self-compassion may not mediate outcomes when psilocybin is administered as part of therapy. Larger studies with additional mechanistic analyses are needed to further clarify how self-compassion interacts with psychological processes and pharmacological interventions in shaping treatment response, ultimately informing improvements to psilocybin-assisted therapy for AUD.


journal: Research Square
publication_date: 2024-08-22
doi: 10.21203/rs.3.rs-4947184/v1
source_url: https://doi.org/10.21203/rs.3.rs-4947184/v1
substance_tags: psilocybin,psilocin
topic_tags: Addiction,Pharmacology,Receptor Pharmacology,Clinical Trial,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
title:
­­­­Single-Dose Psilocybin Therapy for Alcohol Use Disorder: Pharmacokinetics, Feasibility, Safety, and Efficacy in an Open-Label Study

authors:
Jensen ME, Stenbæk DS, Messell CD, Poulsen ED, Varga TV, Fisher PM, Nielsen MKK, Johansen SS, Volkow ND, Knudsen GM, Fink-Jensen A.

abstract:
Abstract Background Psilocybin, a serotonin 2A receptor agonist with psychedelic properties, shows promise as a novel treatment for alcohol use disorder (AUD). While current studies involve two dosing sessions, the effects a single dose have not been investigated. Aims To investigate the pharmacokinetics, feasibility, safety, and efficacy of single-dose psilocybin therapy in AUD. Methods This open-label, single-group study investigated single-dose psilocybin therapy in ten treatment-seeking adults (eight men and two women; median age 44 years) with severe AUD. The treatment involved two preparation sessions, a high-dose psilocybin session (25 mg), and two integration sessions. Pharmacokinetics were determined by noncompartmental analysis, and changes in alcohol consumption, craving and self-efficacy, were assessed with a linear mixed model. Results Notable between-participant pharmacokinetic variations were observed, with peak plasma psilocin concentrations ranging from 14-59 µg/L. Alcohol consumption significantly decreased over the 12 weeks following psilocybin administration. Heavy drinking days were reduced by 37.5 percentage points (95% CI, -61.1, -13.9, p = 0.005), and drinks per day decreased by 3.4 units (95% CI: -6.5, -0.3), p = 0.035). This was corroborated by reports of rapid and sustained reductions in craving and increases in self-efficacy. Conclusions Despite pharmacokinetic variations, a single 25 mg psilocybin dose was safe and effective in reducing alcohol consumption in AUD patients. Larger randomised, placebo-controlled, single-dose AUD trials are warranted. Funding This work was supported by The Novo Nordisk Foundation (NNF19OC0058412), The Lundbeck Foundation (R-355-2020-945), The Health Foundation(21-B-0358) and The Ivan Nielsen Foundation. Clinical trial registration: NCT05347849

raw_json:
{"europe_pmc_id":"PPR899973","source":"PPR","pub_type":null,"publisher":"Research Square","importer":"Europe PMC"}


authors: Huang Z, Wei X, Wang Y, Tian J, Dong J, Liang B, Lu L, Zhang W.
journal: bioRxiv
publication_date: 2024-01-06
doi: 10.1101/2024.01.07.573163
source_url: https://doi.org/10.1101/2024.01.07.573163
substance_tags: psilocybin,psilocin
topic_tags: Depression,Addiction,OCD,Mechanism of Action,Receptor Pharmacology
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
title:
Psilocybin Promotes Cell-Type-Specific Changes in the Orbitofrontal Cortex Revealed by Single-Nucleus RNA-seq

abstract:
Recent clinical breakthroughs hold great promise for the application of psilocybin in the treatments of psychological disorders, such as depression, addiction, and obsessive-compulsive disorder. Psilocybin is a psychedelic whose metabolite, psilocin, is a 5-HT2A receptor agonist. Nevertheless, the underlying mechanisms for the effects of psilocybin on the brain are not fully illustrated, and cell type-specific and circuit effects of psilocybin are not fully understood. Here, we combined single-nucleus RNA-seq with functional assays to study the long-term effects of psilocybin on the orbitofrontal cortex (OFC), a brain region vulnerable to psychological disorders such as depression. We showed that a single dose of psilocybin induced long-term genetic and functional changes in neurons of the OFC, and excitatory and inhibitory neurons collectively reduced circuit activity of the brain region. Knockdown of 5-HT2A receptor in deep layer excitatory neurons abated psilocybin-induced functional changes and the anti-depressant effect. Together, these results showed the cell type-specific mechanisms of psilocybin and shed light on the brain region difference in the effect of psychedelics.

raw_json:
{"europe_pmc_id":"PPR783465","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


authors: Hitchins K, Reynolds J.
journal: PsyArXiv
publication_date: 2025-02-24
doi: 10.31234/osf.io/48yg7_v2
source_url: https://doi.org/10.31234/osf.io/48yg7_v2
substance_tags: psilocybin
topic_tags: Longevity,Observational Study,Safety
study_type: Observational Study
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
title:
The Impact of Communicating the Benefits and Safety of Psilocybin on Policy Support: A Survey Based Experiment.

abstract:
Background: Preliminary evidence suggests psilocybin may have therapeutic value for various mental health conditions; despite this, it is currently illegal in the UK. Less is known about how people form their attitudes towards psilocybin policies. Objectives: To explore whether beliefs about the benefits and safety of psilocybin influence support for psilocybin policies. Methods: In an online survey experiment, 804 participants were randomised to receive one of four interventions in a 2 (no information vs evidence for psilocybin benefits) x 2 (no information vs evidence for psilocybin safety) design. Public support for four psilocybin policies and beliefs about the benefits and safety of psilocybin were measured before and after participants were randomised to a group. Results: In a two-way ANCOVA, the Benefits Intervention significantly increased policy support overall and for two of four psilocybin policies when analysed separately. Furthermore, the Benefits Intervention significantly strengthened beliefs that psilocybin is beneficial and safe. The Safety Intervention increased psilocybin policy support overall (d =.10, p =.003); and for three of four psilocybin policies when analysed separately. The Safety Intervention also strengthened beliefs that psilocybin is safe but not that it is beneficial. Conclusions: Communicating the benefits and safety of psilocybin can increase psilocybin policy support and strengthen beliefs about psilocybin, however further research is needed to explore the longevity of these results.

raw_json:
{"europe_pmc_id":"PPR982614","source":"PPR","pub_type":null,"publisher":"PsyArXiv","importer":"Europe PMC"}


title: Psilocybin Modulates TPJ Effective Connectivity during Out-of-Body Experiences
authors: Stoliker D, Bernasconi F, Blanke O, Razi A.
journal: medRxiv
publication_date: 2025-06-24
doi: 10.1101/2025.06.24.25330245
source_url: https://doi.org/10.1101/2025.06.24.25330245
substance_tags: psilocybin
topic_tags: Consciousness
study_type: Other
source_name: medRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
abstract:
Serotonergic psychedelics alter self-boundaries and can induce out-of-body experiences (OBEs)-the sense of being located outside one’s physical body. While OBEs also occur in clinical conditions and can be experimentally induced, their neural basis under psychedelics remains underexplored. In an open-label, baseline-controlled MRI study of 62 healthy adults administered psilocybin, we examined effective connectivity changes in regions implicated in clinical and induced OBEs. Spectral dynamic causal modelling (spDCM) was applied to resting-state and music-listening scans to estimate connectivity changes from baseline and assess their consistency across contexts. Participants were grouped by self-reported OBE symptom intensity at the end of the dosing day. In those reporting high-intensity OBEs, psilocybin reduced effective connectivity from the right to left anterior insula and between the right anterior insula and right temporoparietal junction (TPJ), inhibiting these connections across both scan types. These changes parallel known disruptions in TPJ-insula circuits linked to OBEs in clinical and experimental settings, particularly in the right hemisphere. Our findings highlight how psilocybin-induced disembodiment corresponds to altered effective connectivity and demonstrate the utility of spDCM for mapping causal neural dynamics underlying bodily self-consciousness.

raw_json:
{"europe_pmc_id":"PPR1041878","source":"PPR","pub_type":null,"publisher":"medRxiv","importer":"Europe PMC"}


title: Context-dependent structurally informed effective connectivity under psilocybin
authors: Greaves MD, Barta T, Novelli L, Stoliker D, Razi A.
journal: bioRxiv
publication_date: 2025-08-21
doi: 10.1101/2025.08.18.671000
source_url: https://doi.org/10.1101/2025.08.18.671000
substance_tags: psilocybin
topic_tags: Brain Imaging,Mechanism of Action,Mystical Experience,Drug Interactions
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
abstract:
The extent to which anatomical connectivity constrains pharmacologically altered brain dynamics remains poorly understood. Here, we combined psilocybin administration with a structurally informed effective-connectivity model to examine how structural connectivity shapes directed inter-regional influences across experiential contexts. Using dynamic causal modeling embedded in a hierarchical empirical Bayes framework, we analyzed fMRI data acquired from a hippocampo-thalamo-cortical network during rest, guided meditation, music listening and movie viewing. Across contexts, psilocybin reorganized directed interactions while preserving structure-based scaling. Effects converged on efferents (outgoing influences) from the left hippocampus-a hub interfacing mnemonic and associative systems with the default-mode network and thalamus. Notably, the left-hippocampus-to-thalamus pathway showed a sign-reversed association with mystical-experience scores (downregulation during guided meditation and upregulation during music listening). In model-based leave-one-out cross-validation, left-hippocampal efferents predicted individual differences in mystical-experience intensity. A minimal model-free benchmark (hippocampal signal variability) also showed modest associations with mystical experience. Together, these findings link context-specific, structurally informed effective connectivity to individual differences in the acute psychedelic experience, providing a mechanistic bridge between anatomy, neurodynamics, and phenomenology.

raw_json:
{"europe_pmc_id":"PPR1071263","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


authors: Hitchins K, Reynolds J.
journal: PsyArXiv
publication_date: 2025-02-23
doi: 10.31234/osf.io/48yg7_v1
source_url: https://doi.org/10.31234/osf.io/48yg7_v1
substance_tags: psilocybin
topic_tags: Longevity,Observational Study,Safety
study_type: Observational Study
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
title:
The Impact of Communicating the Benefits and Safety of Psilocybin on Policy Support: A Survey Based Experiment.

abstract:
Background: Preliminary evidence suggests psilocybin may have therapeutic value for various mental health conditions; despite this, it is currently illegal in the UK. Less is known about how people form their attitudes towards psilocybin policies. Objectives: To explore whether beliefs about the benefits and safety of psilocybin influence support for psilocybin policies. Methods: In an online survey experiment, 804 participants were randomised to receive one of four interventions in a 2 (no information vs evidence for psilocybin benefits) x 2 (no information vs evidence for psilocybin safety) design. Public support for four psilocybin policies and beliefs about the benefits and safety of psilocybin were measured before and after participants were randomised to a group. Results: In a two-way ANCOVA, the Benefits Intervention significantly increased policy support overall (d =.11, p<.001); and for two of four psilocybin policies when analysed separately. Furthermore, the Benefits Intervention significantly strengthened beliefs that psilocybin is beneficial (d =.44, p<.001) and safe (d =.26, p<.001). The Safety Intervention increased psilocybin policy support overall (d =.10, p =.003); and for three of four psilocybin policies when analysed separately. The Safety Intervention also strengthened beliefs that psilocybin is safe (d =.28, p <.001) but not that it is beneficial. Conclusions: Communicating the benefits and safety of psilocybin can increase psilocybin policy support and strengthen beliefs about psilocybin, however further research is needed to explore the longevity of these results.

raw_json:
{"europe_pmc_id":"PPR982270","source":"PPR","pub_type":null,"publisher":"PsyArXiv","importer":"Europe PMC"}


authors: Joseph K, Collins J, Genovese T, Maxwell M, Lieberman JA, Osten P.
journal: bioRxiv
publication_date: 2025-05-29
doi: 10.1101/2025.05.26.655791
source_url: https://doi.org/10.1101/2025.05.26.655791
substance_tags: psilocybin
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
title:
Converging pathways: shared brain circuitry engaged by monoaminergic antidepressants, ketamine and psilocybin

abstract:
Ketamine has transformed depression treatment by providing therapeutic relief within a single day, unlike monoaminergic antidepressants that require weeks to take effect. Here, we conducted whole-brain screening in mice to compare drug-evoked c-fos expression-acting as a marker of brain activity leading to protein synthesis-dependent forms of plasticity-following treatment with monoaminergic antidepressants, ketamine and psilocybin. Our findings reveal a shared limbic brain circuit comprising subcortical and frontal cortical regions, with a key distinction: c-fos-based activity in the prelimbic and infralimbic frontal cortex-areas strongly implicated in depression-was acutely induced by ketamine and high-dose psilocybin, but emerged only after chronic dosing with the selective serotonin reuptake inhibitor fluoxetine or psilocybin microdosing. These results suggest the existence of a core limbic subcortico-cortical circuit underlying antidepressant efficacy, provide mechanistic insight into the delayed therapeutic effects of monoaminergic antidepressants, and reveal a close similarity in brain activity evoked by monoaminergic antidepressants and psilocybin microdosing.

topic_tags:
Depression,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Biomarkers,Microdosing,Animal Study

raw_json:
{"europe_pmc_id":"PPR1028717","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: PsiConnect: A Multimodal Neuroimaging Study of Psilocybin-Induced Changes in Brain and Behaviour
authors: Novelli L, Stoliker D, Barta T, Greaves MD, Chopra S, Jackson J, Kwee J, Williams ML, Razi A.
journal: bioRxiv
publication_date: 2025-04-13
doi: 10.1101/2025.04.11.643415
source_url: https://doi.org/10.1101/2025.04.11.643415
substance_tags: psilocybin
topic_tags: Brain Imaging,Aging,Observational Study,Drug Interactions
study_type: Observational Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
abstract:
ABSTRACT PsiConnect is a large-scale neuroimaging study designed to investigate the neural and subjective effects of psilocybin using multimodal neuroimaging. It combines functional, structural, and diffusion-weighted MRI with EEG to examine brain activity in 62 participants before and after a 19 mg dose of psilocybin. The design includes resting-state scans and three naturalistic conditions: guided meditation, music listening, and movie watching. Half of the cohort underwent an 8-week meditation training program, enabling the exploration of interactions among meditation, psilocybin, and brain function. The fMRI data was obtained through multi-echo fMRI, which enhances the signal-to-noise ratio and reduces susceptibility artifacts, thereby improving the reliability of the analyses. A comprehensive battery of behavioural and self-report measures captured both acute and longitudinal cognitive and subjective effects, with follow-ups extending to one year post-administration. The large sample size, multimodal neuroimaging, diversity of contexts, and longitudinal behavioural follow-ups enable the study of psilocybin-induced changes in brain and behaviour with an unprecedented level of detail and reliability. Furthermore, the data is curated according to open science principles to ensure accessibility and interoperability with established neuroimaging processing pipelines. These factors make PsiConnect a valuable and highly reusable resource for researchers in cognitive and computational neuroscience.

raw_json:
{"europe_pmc_id":"PPR1003820","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: Psilocybin-induced modulation of visual salience processing
authors: Muller S, Cavanna F, de la Fuente LA, Bruno N, D’Amelio TA, Pallavicini C, Tagliazucchi E.
journal: bioRxiv
publication_date: 2025-05-11
doi: 10.1101/2025.05.10.652897
source_url: https://doi.org/10.1101/2025.05.10.652897
substance_tags: psilocybin
topic_tags: Brain Imaging
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
abstract:
Psychedelic compounds significantly reshape conscious perception, yet the implications of these alterations for complex visual-guided behaviors remain poorly understood. We investigated how psilocybin modulates visual salience processing during natural scene perception. Twenty-three participants completed eye-tracking tasks under self-blinded low and high doses of psilocybin, in a naturalistic design with experimental conditions unknown to participants and researchers. Subjects viewed natural scenes while their gaze patterns were recorded and analyzed in relation to normative computational saliency maps generated using a deep learning model of visual attention. Results revealed increased fixation on salient image regions and reduced inter-fixation distance under the high-dose condition, suggesting heightened sensitivity to visual salience and more localized gaze behavior. The Shannon entropy of fixations on high-saliency regions indicated a more exploratory and less predictable visual scanning of the images. Complementary EEG recordings showed broadband spectral power reductions and increased Lempel-Ziv complexity, with delta power negatively correlating with salience metrics. These findings suggest psilocybin enhances bottom-up attentional control while weakening top-down modulation, consistent with theoretical models positing facilitated bottom-up information flow under the acute effect of psychedelics.

raw_json:
{"europe_pmc_id":"PPR1018727","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: Psilocybin mushrooms (“Magic Mushrooms”)
journal: Organization of Teratology Information Specialists (OTIS), Brentwood (TN)
publication_date: 2025-03-31
pubmed_id: 35952083
source_url: https://europepmc.org/article/MED/35952083
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
abstract:
This sheet is about exposure to psilocybin mushrooms (“Magic Mushrooms”) in pregnancy and while breastfeeding. This information is based on published research studies. It should not take the place of medical care and advice from your healthcare provider.

raw_json:
{"europe_pmc_id":"35952083","source":"MED","pub_type":null,"publisher":"Organization of Teratology Information Specialists (OTIS), Brentwood (TN)","importer":"Europe PMC"}


authors: Wolff M, Kangaslampi S, Zeifman R, Spangemacher M.
journal: PsyArXiv
publication_date: 2026-03-29
doi: 10.31234/osf.io/8s7xk_v1
source_url: https://doi.org/10.31234/osf.io/8s7xk_v1
substance_tags: psilocybin
topic_tags: Depression,Treatment-Resistant Depression
study_type: Other
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
title:
Strong alliance, weak conclusions: Comment on Goodwin et al. (2026) “The role of therapeutic alliance in psilocybin treatment for treatment-resistant depression”

abstract:
This commentary critically examines the interpretation and analytic choices in Goodwin et al.’s (2026) analysis of therapeutic alliance in psilocybin treatment for treatment-resistant depression. While the authors conclude that alliance did not meaningfully contribute to treatment efficacy, we argue that this interpretation is not supported by the reported results, which are, in addition, shaped by methodological decisions that obscure relevant effects. By contextualizing the observed associations, clarifying the logic of mediation analysis, and pointing out methodological weaknesses, we show that the available evidence is more consistent with a meaningful role of therapeutic alliance in shaping both the psychedelic experience and clinical outcomes. Furthermore, we highlight unexplained deviations from the study protocol that warrant scrutiny. The commentary underscores the importance of accurately characterizing psychological and contextual factors in psychedelic treatment research and calls for more comprehensive and transparent analyses of psychotherapeutic processes.

raw_json:
{"europe_pmc_id":"PPR1171795","source":"PPR","pub_type":null,"publisher":"PsyArXiv","importer":"Europe PMC"}


title: Age- and estrous-dependent effects of psilocybin in rats
journal: bioRxiv
publication_date: 2025-01-13
doi: 10.1101/2025.01.10.632408
source_url: https://doi.org/10.1101/2025.01.10.632408
substance_tags: psilocybin
topic_tags: Anxiety,Receptor Pharmacology,Animal Study,Adolescents,Safety
study_type: Clinical Trial
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
authors:
Zylko A, Rakoczy R, Roberts B, Wilson M, Powell A, Page A, Heitkamp M, Fiest D, Jones J, McMurray M.

abstract:
Psilocybin, a psychedelic compound in “magic” mushrooms, has promise as a novel treatment for psychiatric disorders, many of which are more prevalent in females and have onsets during adolescence. However, there is a lack of research about how factors such as sex and age affect responses to psilocybin, as well as potential safety concerns with developmental exposure. The primary objectives of this preclinical study were to determine if psilocybin-induced head twitch responses differ between adolescent and adult rats, and if estrous phase contributes to variation in female head twitch responses. Secondarily, this study sought to determine if treatment with psilocybin during adolescence has long-term effects on anxiety-associated behaviors and behavioral flexibility. Results showed that 1 mg/kg intraoral psilocybin failed to elicit head twitch responses in adolescents (P35 and P45) but elicited robust responses in adult rats. Further, adolescent psilocybin exposure did not cause long-term differences in performance on the elevated zero maze or probabilistic reversal learning tasks. Lastly, adult females in diestrus showed increased head twitch responses after 1 mg/kg psilocybin compared to females in proestrus. Head twitch responses are thought to be mediated by 5-HT2A receptors, but no age-or estrous-related differences in 5-HT2A receptor expression were observed in the medial prefrontal cortex. Collectively, these results highlight the existence of age-and sex-dependent differences in the effects of psychedelics, while finding no long-term effects on selected behaviors after adolescent exposure. These findings have implications on psychedelic study design, emphasizing the need for inclusive research considering age, sex, and hormonal status.

raw_json:
{"europe_pmc_id":"PPR966388","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


journal: medRxiv
publication_date: 2021-12-16
doi: 10.1101/2021.12.17.21267992
source_url: https://doi.org/10.1101/2021.12.17.21267992
substance_tags: psilocybin,psilocin
topic_tags: Brain Imaging,Consciousness,Aging,Personality Change
study_type: Other
source_name: medRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
title:
Psilocybin modulation of dynamic functional connectivity is associated with plasma psilocin and subjective effects

authors:
Olsen AS, Lykkebo-Valløe A, Ozenne B, Madsen MK, Stenbæk DS, Armand S, Mørup M, Ganz M, Knudsen GM, Fisher PM.

abstract:
Background Psilocin, the neuroactive metabolite of psilocybin, is a serotonergic psychedelic that induces an acute altered state of consciousness, evokes lasting changes in mood and personality in healthy individuals, and has potential as an antidepressant treatment. Examining the acute effects of psilocin on resting-state dynamic functional connectivity implicates network-level connectivity motifs that may underlie acute and lasting behavioral and clinical effects. Aim Evaluate the association between resting-state dynamic functional connectivity (dFC) characteristics and plasma psilocin level (PPL) and subjective drug intensity (SDI) before and right after intake of a psychedelic dose of psilocybin in healthy humans. Methods Fifteen healthy individuals completed the study. Before and at multiple time points after psilocybin intake, we acquired 10-minute resting-state blood-oxygen-level-dependent functional magnetic resonance imaging scans. Leading Eigenvector Dynamics Analysis (LEiDA) and diametrical clustering were applied to estimate discrete, sequentially active brain states. We evaluated associations between the fractional occurrence of brain states during a scan session and PPL and SDI using linear mixed-effects models. We examined associations between brain state dwell time and PPL and SDI using frailty Cox proportional hazards survival analysis. Results Fractional occurrences for two brain states characterized by lateral frontoparietal and medial fronto-parietal-cingulate coherence were statistically significantly negatively associated with PPL and SDI. Dwell time for these brain states was negatively associated with SDI and, to a lesser extent, PPL. Conversely, fractional occurrence and dwell time of a fully connected brain state was positively associated with PPL and SDI. Conclusion Our findings suggest that the acute perceptual psychedelic effects induced by psilocybin may stem from drug-level associated decreases in the occurrence and duration of lateral and medial frontoparietal connectivity motifs in exchange for increases in a uniform connectivity structure. We apply and argue for a modified approach to modeling eigenvectors produced by LEiDA that more fully acknowledges their underlying structure. Together these findings contribute to a more comprehensive neurobiological framework underlying acute effects of serotonergic psychedelics. Highlights We examined psilocybin effects on resting-state fMRI dynamic functional connectivity Diametrical clustering described as improved strategy for LEiDA-defined brain states Individual brain state dynamics defined by fractional occurrence and dwell time Two frontoparietal states and a fully connected brain state affected by psilocybin Brain state dynamics associated with psilocin level and subjective experience

raw_json:
{"europe_pmc_id":"PPR433963","source":"PPR","pub_type":null,"publisher":"medRxiv","importer":"Europe PMC"}


authors: Wang Z, Robbins B, Zhuang R, Bruggen Rv, Sandini T, Li X, Zhang Y.
journal: Research Square
publication_date: 2025-05-05
doi: 10.21203/rs.3.rs-5493661/v1
source_url: https://doi.org/10.21203/rs.3.rs-5493661/v1
substance_tags: psilocybin
study_type: Other
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
title:
Psilocybin Mitigates Behavioral Despair and Cognitive Impairment in Treatment-resistant Depression Model using Wistar Kyoto Rats

abstract:
Abstract Major depressive disorder (MDD) is a leading cause of disability that affects over 300 million people globally. Despite multiple antidepressant trials, approximately one-third of MDD patients remain symptomatic, progressing to treatment-resistant depression (TRD). This persistence possibly is due to the multifaceted etiology of TRD, encompassing biological, psychological, and environmental factors. Chronic stress, prevalent in modern life, significantly contributes to mental health disorders and complicates TRD treatment. This study investigated psilocybin as a potential TRD treatment using a diathesis-stress animal model. Twenty-two male Wistar-Kyoto (WKY) rats were divided into control and stress groups, with the stress group further subdivided to receive either sham treatment or psilocybin as early intervention. Behavioral assessments demonstrated a significant and sustained beneficial effect of psilocybin on behavioral despair and cognitive impairment. Biochemical analyses revealed psilocybin-induced increases in thyroid-stimulating hormone (TSH) levels without significant changes in the hypothalamic-pituitary-adrenal (HPA) axis. The ability of psilocybin to counter stress-induced TSH reductions suggested that TSH may serve as a proxy marker of therapeutic response, although its causal role in mood regulation remains unclear. Additionally, following psilocybin administration, changes in cannabinoid receptor type I (CB1R) suggest a potential modulation of psilocybin intervention on the component of the endocannabinoid system (ECS), though causal links remain unconfirmed without antagonist studies. These findings highlight the potential of psilocybin to treat TRD through the targeting of previously unexplored biological pathways.

topic_tags:
Depression,Mechanism of Action,Receptor Pharmacology,Biomarkers,Animal Study,Treatment-Resistant Depression

raw_json:
{"europe_pmc_id":"PPR1015165","source":"PPR","pub_type":null,"publisher":"Research Square","importer":"Europe PMC"}


authors: Chwyl C, Spata A, Lucas W, Luoma JB.
journal: Research Square
publication_date: 2025-09-11
doi: 10.21203/rs.3.rs-7266162/v1
source_url: https://doi.org/10.21203/rs.3.rs-7266162/v1
substance_tags: psilocybin
topic_tags: Mechanism of Action,Personality Change,Emotional Processing,Spirituality,Mystical Experience
study_type: Clinical Trial
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
title:
Mindset Over Molecule: Comparing Self-Transcendent and Mystical Experiences Across Recreational Psilocybin, MDMA, and Cannabis Use

abstract:
Abstract Background Self-transcendent and mystical experiences may be key mechanisms underlying psychedelics’ therapeutic effects, yet how these experiences differ across substances remains unclear. This study compared mystical and self-transcendent experiences across psilocybin, 3,4-Methylenedioxymethamphetamine (MDMA), and cannabis in a diverse, community-based sample, while accounting for covariates. Additionally, we examined the relative contributions of pharmacological versus psychological factors in shaping self-transcendent and mystical experiences. Methods Adults aged 18 years and older ( N = 397) were recruited with general, non-psychedelic-targeted advertisements on a crowdsourcing platform, and randomized to report on their most intense use experience with either cannabis, psilocybin or MDMA in the past five years. Participants completed measures of self-transcendent and mystical experiences, emotions, and variables previously found to predict mystical experiences (e.g., personality traits, motivations for use, intentions/expectations for the experience). Hierarchical multiple linear regressions examined the effects of substance type (cannabis/psilocybin/MDMA) on outcomes, both alone and while adjusting for contextual (set/setting) variables. Results Most of the sample reported recreational reasons for use (83%) and concurrently used other substances (75%). Psilocybin and MDMA corresponded to greater self-transcendent and mystical experiences than cannabis, even after controlling for contextual factors. However, effect sizes were generally small (standardized regression coefficients β =.14-34, p s.33). Notably, mindset-particularly surrendering to the experience and having spiritual/prosocial motivations-emerged as the strongest predictors, with models including these variables accounting for up to 58% of variance (compared to ≤ 10% for substance alone). Conclusions Findings indicate a “mindset-over-molecule” pattern wherein psychological context (“set”) is more strongly associated with psychedelic outcomes than substance type alone.

raw_json:
{"europe_pmc_id":"PPR1084679","source":"PPR","pub_type":null,"publisher":"Research Square","importer":"Europe PMC"}


title: Age and cannabis co-use moderate experience and perceived benefits of psilocybin
journal: PsyArXiv
publication_date: 2025-05-21
source_url: https://osf.io/preprints/psyarxiv/dczw2_v1
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Addiction,Mechanism of Action,Aging,Mystical Experience,Older Adults
study_type: Other
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"dczw2_v1","version":1,"reviews_state":"accepted"}
abstract:
As psychedelic use increases, understanding how demographic and behavioral factors influence the effects of psychedelics is essential for both research and public health. This cross-sectional study examined 365 current psilocybin users, analyzing differences in acute experiences, psychological outcomes, and substance co-use patterns. Participants were categorized into young (18-25), middle-aged (26-54), and older (55-77) adults. Results showed that younger participants reported significantly more adverse experiences while older adults had milder subjective effects. Despite differences in adverse experiences, age did not significantly impact mystical experiences, psychological insight, or psychological outcomes. Polysubstance use patterns also varied by age, as younger adults were more likely to co-use nicotine with psilocybin. Cannabis co-use specifically was associated with greater improvements in quality of life, anxiety, depression, and alcohol abuse, suggesting potential synergies between psilocybin and THC. These findings emphasize that age and cannabis co-use may modulate aspects of psilocybin’s acute effects and therapeutic outcomes. Given the increasing legalization and accessibility of psychedelics, future research should further investigate mechanisms underlying individual differences and assess the impact of polysubstance use with psychedelics.

keywords:
age, cannabis, harms, psilocybin, psychedelic, public health, well being, Social and Behavioral Sciences, Health Psychology


authors: Turizo Smith AD, Botero Jsramillo N, Berrio Cuartas DM.
journal: Preprints.org
publication_date: 2025-04-09
doi: 10.20944/preprints202504.0888.v1
source_url: https://doi.org/10.20944/preprints202504.0888.v1
substance_tags: psilocybin
topic_tags: End-of-Life Distress,Pharmacology,Wellbeing,Emotional Processing,Spirituality,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
title:
Psilocybin as a Tool in the Management of Palliative Care: An Historical, Pharmacological, and Clinical Approach

abstract:
Psilocybin, a psychedelic compound in certain mushrooms, has been used for centuries in spiritual ceremonies and neuropsychiatric therapy. Despite its stigmatization as a Schedule I substance in 1970, research into psilocybin has resurged since the early 2000s, particularly in psychiatry and palliative care. This review examines psilocybin's potential to improve the quality of life in palliative care by reducing psychological distress and enhancing emotional well-being. The discussion includes its historical context, pharmacokinetics, pharmacodynamics, legal status, and future perspectives in palliative care.

raw_json:
{"europe_pmc_id":"PPR1003557","source":"PPR","pub_type":null,"publisher":"Preprints.org","importer":"Europe PMC"}


title: Effects of a single dose of psilocybin on diet-induced weight loss in obese mice
journal: Research Square
publication_date: 2025-03-30
doi: 10.21203/rs.3.rs-6225000/v1
source_url: https://doi.org/10.21203/rs.3.rs-6225000/v1
substance_tags: psilocybin
topic_tags: Neuroplasticity,Mechanism of Action,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
authors:
Keenan R, Haque R, Jin X, Mustafa T, Homman-Ludiye J, Elysee K, Wee ZS, Simonds S, Foldi C, Cowley M.

abstract:
Abstract Prolonged obesity induces enduring structural changes within neural circuits that contribute to maintaining the body at an elevated/obese body weight. These circuits regulate various mechanisms which can inhibit extreme or persistent weight loss. Therefore, a potential therapeutic strategy to facilitate weight loss is to promote structural plasticity within the brain. Psychedelic compounds, such as psilocybin, promote neural plasticity caused by a rapid and persistent growth of dendritic spines, which can facilitate the remodelling of neural circuits. Preclinical and clinical studies using psychedelic compounds have demonstrated efficacy for various neuropsychiatric disorders, which are often comorbid with obesity, and share underlying neural mechanisms. Here, we evaluate the effects of a single dose of psilocybin on body weight, food intake and energy expenditure in diet-induced obese (DIO) mice switched onto a low-fat chow. Psilocybin exacerbated diet-induced weight loss over a four-week period in DIO mice and increased the susceptibility for mice to exhibit more profound weight loss. Psilocybin appears to exert these effects predominantly through modulating food intake, with no influence on energy expenditure. No differences were observed in body weight or food intake in DIO mice maintained on a high-fat diet, indicating psilocybin does not necessarily directly promote weight loss or reduce food intake. Rather, it may help facilitate weight loss, provided it is administered in combination with other weight loss promoting interventions. Additional experimentation is required to examine the precise mechanisms involved; however, this data supports further investigation into the use of psychedelic compounds as an adjunct therapy for obesity.

raw_json:
{"europe_pmc_id":"PPR996923","source":"PPR","pub_type":null,"publisher":"Research Square","importer":"Europe PMC"}


authors: Koning E, Gamberg S, Keshen A.
journal: Preprints.org
publication_date: 2025-12-18
doi: 10.20944/preprints202512.1705.v1
source_url: https://doi.org/10.20944/preprints202512.1705.v1
substance_tags: psilocybin
topic_tags: Eating Disorders,Neuroplasticity,Emotional Processing,Safety
study_type: Other
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
title:
Psilocybin Treatment as an Adjunct to Cognitive Behavioral Therapy for Eating Disorders: Therapeutic Rationale & Considerations for Protocol Development

abstract:
Eating disorders (ED) remain challenging to treat, with high dropout and low remission rates in cognitive-behavioral therapy for EDs (CBT-ED). Psilocybin treatment (PT) demonstrates therapeutic potential to enhance CBT-ED by exerting several neurobiological, psychological, and experiential effects (e.g., antidepressant, neuroplasticity, emotional openness) that are hypothesized to increase psychotherapeutic engagement, reduce dropout, and improve clinical outcomes. This article provides the first consolidation of existing theoretical evidence for PT/CBT-ED, proposes considerations for a con-current intervention protocol, and presents clinical and research considerations to empirically test its feasibility, safety, and efficacy. This line of inquiry is expected to advance the development of approaches that improve ED treatment outcomes and, more broadly, advance the study of psychedelics as tools to enhance evidence-based psychotherapy models.

raw_json:
{"europe_pmc_id":"PPR1136419","source":"PPR","pub_type":null,"publisher":"Preprints.org","importer":"Europe PMC"}


title: Pharmacological and behavioral effects of tryptamines present in psilocybin-containing mushrooms
journal: bioRxiv
publication_date: 2023-10-22
doi: 10.1101/2023.10.19.563138
source_url: https://doi.org/10.1101/2023.10.19.563138
substance_tags: psilocybin,psilocin
topic_tags: Pharmacology,Receptor Pharmacology,Biomarkers,Animal Study,In Vitro Study,Safety
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
authors:
Rakoczy RJ, Runge GN, Sen AK, Sandoval O, Nguyen Q, Roberts BR, Sciortino JH, Gibbons WJ, Friedberg LM, Andrew Jones J, McMurray MS.

abstract:
ABSTRACT Demand for more efficacious antidepressants, particularly those with a rapid onset of action, has resulted in a reevaluation of psychedelic drugs for their therapeutic potential. Several tryptamines found in psilocybin-containing ‘magic’ mushrooms share chemical similarities with psilocybin, and early work suggests they may also share receptor targets. However, few studies have explored their pharmacological and behavioral effects. To accomplish this, we compared baeocystin, norbaeocystin, and aeruginascin with psilocybin to determine if they are metabolized by the same enzymes, penetrate the blood brain barrier, serve as ligands for similar centrally located receptors, and modulate behavior in rodents similarly. We first assessed the stability and optimal storage and handling conditions for each compound. In vitro enzyme kinetics assays then found that all compounds shared nearly identical rates of dephosphorylation via alkaline phosphatase and metabolism by monoamine oxidase. Further, we found that only the dephosphorylated products of baeocystin and norbaeocystin could cross a blood brain barrier mimetic to a similar degree as the dephosphorylated form of psilocybin, psilocin. Behaviorally, only psilocybin was found to induce head twitch responses in rats, a marker of 5HT2A agonism and indicator of the compound’s hallucinogenic potential. However, like psilocybin, norbaeocystin was also found to improve outcomes in the forced swim test. All compounds were found to cause minimal changes to metrics of renal and hepatic health, suggesting innocuous safety profiles. Collectively, this work suggests that other naturally-occurring tryptamines, especially norbaeocystin, may share the same therapeutic potential as psilocybin, but without causing hallucinations. HIGHLIGHTS Baeocystin, norbaeocystin, and aeruginascin may have similar therapeutic value to psilocybin, but are understudied Compound stability varied widely, with dephosphorylated forms showing lowest stability Rates of metabolism by alkaline phosphatase and monoamine oxidase were similar across compounds Blood brain barrier penetration was limited to dephosphorylated forms of psilocybin, baeocystin, and norbaeocystin Rat behavioral testing suggested norbaeocystin may have therapeutic utility similar to psilocybin, without causing hallucinations

raw_json:
{"europe_pmc_id":"PPR746275","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: Patient perceptions towards psychedelics for musculoskeletal pain: A cross-sectional survey
journal: medRxiv
publication_date: 2026-05-31
doi: 10.64898/2026.05.29.26354422
source_url: https://doi.org/10.64898/2026.05.29.26354422
substance_tags: psilocybin
topic_tags: Addiction,Chronic Pain,Microdosing,Observational Study,Safety
study_type: Observational Study
source_name: medRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
authors:
Li EJ, Mosharraf B, Ali H, Noyes M, Doshi P, Wallace C, Petranker R, Adili A, Khan M, Busse JW, MacKillop J, Madden K.

abstract:
Background: Psychedelics are emerging as potential management options for chronic musculoskeletal pain due to preliminary evidence of effectiveness and low addictive potential, but patients’ perceptions remain unknown. This study assessed patient perceptions regarding psilocybin for musculoskeletal pain. Methods: We conducted a cross-sectional survey of adults (≥19) with musculoskeletal pain attending a hospital-based orthopaedic clinic. Participants reported demographics, perceptions of psychedelics for pain management, and willingness to participate in psychedelic research. Multivariable regression explored factors associated with perceived analgesic potential, and willingness to try a full therapeutic dose of psilocybin or a microdose. Results: Among 295 participants, 73% reported moderate-to-severe pain; 75% used analgesics; of these, 41% used opioids (86/209). While 24% reported prior psychedelic use, only 3% had discussed psychedelics with a healthcare provider. Most perceived that psilocybin had moderate-to-high effectiveness for pain (76%). Most respondents endorsed a moderate-to-high willingness to try microdoses (58%) and macrodoses (53%) of psilocybin for pain. Prior non-therapeutic psychedelic use predicted a 1.05-unit increase in perceived analgesic potential on the 10-point scale (p=.013). Willingness to try a macrodose of psilocybin was most strongly associated with prior non-therapeutic (B=3.16) and therapeutic (B=2.42) psychedelic use; in contrast, pain severity had a significant but modest association, with a 0.21-point increase in willingness for every 1-unit increase in pain severity (p=.017). Similarly, willingness to try a microdose of psilocybin was predicted by non-therapeutic (B=2.82) and therapeutic (B=2.48) use, whereas the effects of pain severity (B=0.20) and younger age (B=−0.30) were significant but small. Most respondents (52%) reported moderate-to-high willingness to participate in a trial of psilocybin for pain relief, and health risks were the primary concern (33%). Conclusions: Study findings suggest a majority hold neutral-to-positive perceptions of psilocybin for pain. Addressing perceived barriers, including health effects and gaps in patient knowledge, should be considered when designing future trials.

raw_json:
{"europe_pmc_id":"PPR1243498","source":"PPR","pub_type":null,"publisher":"medRxiv","importer":"Europe PMC"}


title: The Emerging Use of Psilocybin in Adult Populations with Alcohol Use Disorder: A Scoping Review
authors: Daroui D, Mastrostefano A, Davini F, Giuseppe G, Terracina S.
journal: Preprints.org
publication_date: 2025-06-18
doi: 10.20944/preprints202506.1536.v1
source_url: https://doi.org/10.20944/preprints202506.1536.v1
substance_tags: psilocybin
topic_tags: Addiction,Mechanism of Action,Randomized Controlled Trial,Review Article,Case Report,Safety
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
abstract:
Background: Alcohol Use Disorder (AUD) is a chronic pathological condition with significant burdens throughout the world. Despite the effectiveness of the current pharmacological treatments, the ongoing issues with AUD and the high relapse rates necessitate the exploration of innovative therapies, including the use of psychedelic drugs, which have shown promising initial results. The purpose of the current study is to map the evidence on potential uses of psilocybin and its neurobiological pathways, highlighting gaps in knowledge and suggesting research opportunities. Methods: A scoping review of the literature was performed according to the population, concept, and context (PCC) framework. Data were synthesized in tabular form to summarize key study characteristics. Results and discussion: After screening 757 records, we included 12 studies published between 1968 and 2025: 7 RCTs, 4 open-label studies, and 1 case report. Early Polish studies suggested long-term remission of alcohol cravings, while recent U.S.-based RCTs showed that psilocybin, when paired with psychotherapy, reduced heavy drinking days and alcohol-related and mental problems. Limitations have been identified in small sample sizes and short follow-up periods in patient safety data, particularly in those with comorbidities. Most of the studies have been carried out in a hospital and university psychiatry department setting involving physicians and psychologists. Conclusion: Psilocybin has emerged as a promising and innovative compound for the treatment of AUD in an experimental phase. Future research should be conducted to assess pharmacological effects, efficacy, and patient safety through rigorous RCTs across diverse populations. To achieve better outcomes, it is essential to address drug development and pharmaceutical legislation regarding safe therapeutic algorithms.

raw_json:
{"europe_pmc_id":"PPR1039854","source":"PPR","pub_type":null,"publisher":"Preprints.org","importer":"Europe PMC"}


publication_date: 2025-07-14
doi: 10.1007/s00284-025-04379-8
pubmed_id: 40663181
source_url: https://doi.org/10.1007/s00284-025-04379-8
keywords: Animals, Humans, Agaricales, Hallucinogens, Psilocybe, Psilocybin
substance_tags: psilocybin,psilocin
topic_tags: Depression,Anxiety,PTSD,Addiction,Headache / Migraine,Mechanism of Action,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
title:
Biochemical Insights into Diverse Psilocybe Mushrooms and Their Metabolites as Sources of Neuroactive Agents: A Review.

authors:
Sudhakaran G, Chakraborty S, Kumar A, Bharti SAK, Csaba V, Valan Arasu M, Namasivayam SKR, Arockiaraj J.

abstract:
Psilocybe species, commonly known as "magic mushrooms", are a group of hallucinogenic fungi known for their psychoactive compounds such as psilocybin, psilocin, baeocystin, and norbaeocystin. These species have been the focus of scientific study due to their potential therapeutic applications, despite their classification as controlled substances in many jurisdictions. This review aims to provide a comprehensive overview of various Psilocybe mushrooms, highlighting their chemical compositions, genetic diversity, and therapeutic potential, particularly in the treatment of mental health conditions such as depression, anxiety, PTSD, addiction, and cluster headaches. By reviewing existing scientific literature, this review examines the pharmacological effects and therapeutic applications of Psilocybe mushrooms. The review includes novel contributions such as the identification of alternative pathways for psilocybin synthesis and taxonomic consolidations among Psilocybe species. It also explores the cultural context and traditional uses of these mushrooms. The findings indicate that Psilocybe mushrooms exhibit significant potential for therapeutic use in mental health treatment. The review also underscores the importance of ongoing research into the pharmacological properties of these mushrooms to better understand their effects and potential benefits. Despite their current legal status, Psilocybe mushrooms hold considerable promise for future therapeutic applications. There is a need for further investigation to fully explore their potential in medical and cultural contexts. This review sets a foundation for future research and drug development endeavors, advocating for a more nuanced understanding of these complex biological entities.

raw_json:
{"europe_pmc_id":"40663181","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The serotonin 1B receptor is required for some of the behavioral effects of psilocybin in mice
authors: Fleury S, Nautiyal KM.
journal: bioRxiv
publication_date: 2024-10-20
doi: 10.1101/2024.10.18.618582
source_url: https://doi.org/10.1101/2024.10.18.618582
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Neuroplasticity,Receptor Pharmacology,Emotional Processing,Animal Study
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
abstract:
Recent studies highlight the promising use of psychedelic therapies for psychiatric disorders, including depression. The persisting clinical effects of psychedelics such as psilocybin are commonly attributed to activation of the serotonin 2A receptor (5-HT2AR) based on its role in the acute hallucinatory effects. However, the active metabolite of psilocybin binds to many serotonin receptor subtypes, including the serotonin 1B receptor (5-HT1BR). Given the known role of 5-HT1BR in mediating depressive phenotypes and promoting neural plasticity, we hypothesized that it mediates the effects of psilocybin on neural activity and behavior. We first examined the acute neural response to psilocybin in mice lacking 5-HT1BR. We found that 5-HT1BR expression influenced brain-wide activity following psilocybin administration, measured by differences in the patterns of the immediate early gene c-Fos, across regions involved in emotional processing and cognitive function, including the amygdala and prefrontal cortex. Functionally, we demonstrated that 5-HT1BR mediates some of the acute and persisting behavioral effects of psilocybin. Although there was no effect of 5-HT1BR expression on the acute head twitch response, mice lacking 5-HT1BRs had attenuated hypolocomotion to psilocybin. We also measured the persisting effects of psilocybin on anhedonia and anxiety-like behavior using transgenic and pharmacological 5-HT1BR loss-of-function models and found that 5-HT1B is involved in mediating the decreased anhedonia and reduced anxiety-like behavior. Finally, using a network analysis, we identified neural circuits through which 5-H1BR may modulate the response to psilocybin. Overall, our research implicates the 5-HT1BR, a non-hallucinogenic serotonin receptor, as a mediator of the behavioral and neural effects of psilocybin in mice.

raw_json:
{"europe_pmc_id":"PPR928116","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: Ketamine and Psilocybin Differentially Impact Sensory Learning During the Mismatch Negativity
journal: Research Square
publication_date: 2024-09-25
doi: 10.21203/rs.3.rs-4492873/v1
source_url: https://doi.org/10.21203/rs.3.rs-4492873/v1
substance_tags: psilocybin
topic_tags: Depression,Brain Imaging,Mechanism of Action
study_type: Other
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
authors:
Allohverdi S, Soltanzadeh M, Schmidt A, Charlton C, Hauke D, Karvelis P, Vollenweider F, Diaconescu A.

abstract:
Abstract Ketamine and psilocybin show potential as therapies for various mental illnesses, including major depressive disorder. However, further investigation into their neural mechanisms is required to understand their effects on the brain. By combining computational modelling with electroencephalography (EEG), we examine the effects of ketamine and psilocybin on hierarchical sensory precision-weighted prediction error (pwPE) learning in the context of the auditory mismatch negativity, an event-related potential consistently shown to be reduced under psychotomimetic interventions. We employed a Bayesian framework and re-analyzed a previously acquired EEG dataset (Schmidt et al., 2012) by modelling single-trial EEG data using the Hierarchical Gaussian Filter. Using a placebo-controlled within-subject crossover design, healthy subjects were administered either S-ketamine or psilocybin during an auditory roving paradigm of pure sinusoidal tones. Our findings elucidate distinct neural impacts of ketamine and psilocybin on sensory learning: ketamine led to a larger reduction in the effect of sensory precision compared to placebo from 207 to 316 ms peaking at 277 ms in the frontal central channels, while psilocybin showed no significant effect. Both drugs reduced the expression of belief precision between 160 to 184 ms, peaking at 172 ms. For higher-level volatility pwPEs, ketamine reduced the expression while psilocybin had null effect at 312 ms. For perception of elementary imagery, ketamine had a greater effect than psilocybin on sensory and volatility precision, while psilocybin had a greater effect on volatility pwPEs. Our findings suggest hallucinogens have distinct effects on sensory learning that could inform tailored therapies for major depression.

raw_json:
{"europe_pmc_id":"PPR916682","source":"PPR","pub_type":null,"publisher":"Research Square","importer":"Europe PMC"}


title: Psilocybin Reduces Grooming in the SAPAP3 Knockout Mouse Model of Compulsive Behaviour
authors: Gattuso JJ, Wilson C, Hannan AJ, Renoir T.
journal: bioRxiv
publication_date: 2024-10-23
doi: 10.1101/2024.10.23.619763
source_url: https://doi.org/10.1101/2024.10.23.619763
substance_tags: psilocybin
topic_tags: Anxiety,Receptor Pharmacology,Animal Study,Adverse Events
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
abstract:
Psilocybin is a serotonergic psychedelic compound which shows promise for treating compulsive behaviours. This is particularly pertinent as compulsive disorders require research into new pharmacological treatment options as the current frontline treatments such as selective serotonin reuptake inhibitors, require chronic administration, have significant side effects, and leave almost half of the clinical population refractory to treatment. In this study, we investigated psilocybin administration in male and female SAPAP3 knockout (KO) mice, a well-validated mouse model of obsessive compulsive and related disorders. We assessed the effects of acute psilocybin (1 mg/kg, intraperitoneal) administration on head twitch and locomotor behaviour as well as anxiety- and compulsive-like behaviours at multiple time-points (1-, 3- and 8-days post-injection). While psilocybin did not have any effect on anxiety-like behaviours, we revealed for the first time that acute psilocybin administration led to enduring reductions in compulsive behaviour in male SAPAP3 KO mice and reduced grooming behaviour in female WT and SAPAP3 KO mice. We also found that psilocybin increased locomotion in wild-type littermates but not in SAPAP3 KO mice, suggesting in vivo serotonergic dysfunctions in KO animals. On the other hand, the typical head-twitch response following acute psilocybin (confirming its hallucinogenic-like effect at this dose) was observed in both genotypes. Our novel findings suggest that acute psilocybin may have potential to reduce compulsive-like behaviours (up to 1 week after a single injection). Our study can inform future research directions as well as supporting the utility of psilocybin as a novel treatment option for compulsive disorders.

raw_json:
{"europe_pmc_id":"PPR930010","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: Psilocybin causes sex, time, and dose dependent alterations in brain signaling pathways
authors: Barnett JH, Todd KT, Benetatos J, Rabichow BE, Gibson KA, Olney KC, Fryer JD.
journal: bioRxiv
publication_date: 2024-12-16
doi: 10.1101/2024.12.16.628764
source_url: https://doi.org/10.1101/2024.12.16.628764
substance_tags: psilocybin
study_type: Clinical Trial
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
abstract:
Psilocybin is a psychedelic tryptamine that has emerged as a potential candidate for the treatment of a variety of conditions, including treatment resistant depression and post-traumatic stress disorder. Clinical trials which have assessed the efficacy of psilocybin for these conditions report a rapid and sustained improvement in patient- and clinician-rated depression scores. The established mechanism of action for psychedelics such as psilocybin is agonism of the serotonin 2A receptor (5HT 2A R), however, the downstream events that mediate their therapeutic effects remain uncertain. As high doses of psychedelics are known to induce strong perceptual alterations, an additional outstanding question is whether subperceptual doses induce similar molecular effects as psychoactive dosages. Here, we report the first analysis of dose- and sex-dependent transcriptional changes in forebrains of female and male mice at 3 timepoints (8 hours, 24 hours, and 7 days) following a single administration of psilocybin at low (0.25 mg/kg) or high (1 mg/kg) doses. Grouped analysis of both sexes reveals dose- and time-dependent transcriptomic alterations. We report more rapid transcriptional changes and attenuation of such changes in females following a single low-dose relative to males treated identically. Females also responded more robustly to high-dose administration relative to males at 8 and 24 hours, with signal attenuation in both sexes by 7 days. A notable observation was the persistent transcriptional effect of low-dose psilocybin at 7 days, which outlasted high-dose changes, and which suggests that low doses may have prolonged biological effects. A myriad of pathways were altered depending on sex and timepoint, but common features included functions related to neuronal differentiation, neurogenesis, and changes in receptor signaling. These data reveal dose- and sex-dependent molecular effects of psilocybin and support previous studies demonstrating its effect on dendritogenesis. Given ongoing clinical interest in psilocybin for treating mental health disorders, our results suggest that these sexually divergent changes should be considered when weighing treatment strategies. Additional consideration should be given to temporal effects of low vs high dosages on gene transcription, especially when timing psilocybin with adjuvant cognitive behavioral therapy.

topic_tags:
Depression,PTSD,Neurogenesis,Mechanism of Action,Receptor Pharmacology,Clinical Trial,Animal Study,Healthcare Workers,Transcriptomics

raw_json:
{"europe_pmc_id":"PPR961267","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: Psilocybin induces sex- and context-specific recruitment of the stress axis
authors: Cook SG, Lee S, Ference E, Shi Y, Rojas-Carvajal M, Hen R, Bains JS, Füzesi T, Turi GF.
journal: bioRxiv
publication_date: 2025-01-05
doi: 10.1101/2025.01.06.631556
source_url: https://doi.org/10.1101/2025.01.06.631556
substance_tags: psilocybin
topic_tags: Animal Study
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
abstract:
ABSTRACT Psychedelics have reemerged as potential treatments for mental health disorders, yet their impact on stress-related brain regions remains poorly understood. Here, we provide the first real-time, in vivo evidence of psilocybin-induced neuronal activation, specifically in hypothalamic corticotropin-releasing hormone neurons. Notably, psilocybin elicited more pronounced responses in female mice and produced context-related alterations in threat assessment. Our findings provide valuable insight into the impact of psychedelics on a key stress center in the brain.

raw_json:
{"europe_pmc_id":"PPR963599","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


authors: McCoy K, Reed F, Conn K, Foldi CJ.
publication_date: 2025-05-19
doi: 10.1016/j.physbeh.2025.114957
pubmed_id: 40403997
source_url: https://doi.org/10.1016/j.physbeh.2025.114957
keywords: Brain, Animals, Humans, Dopamine, Serotonin, Hallucinogens, Reward, Anorexia Nervosa, Psilocybin
substance_tags: psilocybin
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:00
title:
Separate or inseparable? Serotonin and dopamine system interactions may underlie the therapeutic potential of psilocybin for anorexia nervosa.

abstract:
Psilocybin, a serotonergic psychedelic, has emerged as a promising treatment for a range of mental health conditions, including anorexia nervosa. Recent insights from animal models and human imaging studies suggest psilocybin enhances cognitive flexibility and modifies reward processing - two core processes disrupted in anorexia nervosa. Both cognitive flexibility and reward processing are highly dependent on interactions between serotonin (5-HT) and dopamine (DA) systems in key brain regions such as the prefrontal cortex and nucleus accumbens. Psilocybin's influence on neuroplasticity, particularly in promoting structural and functional changes in neural circuits, underpins its therapeutic potential. While its effects are predominantly attributed to activity of the 5-HT2A receptor subtype, recent evidence suggests a broader network of brain receptor interactions, particularly those with dopaminergic pathways, plays a crucial role. Investigations using rodent models reveal that psilocybin induces both rapid and enduring neuroplastic changes, improving cognitive flexibility through these complex neurochemical mechanisms. Advances in real-time in vivo neurochemical recording now allow simultaneous monitoring of 5-HT and DA signalling, which will provide essential insights into their distinct and coordinated actions during cognitive performance. This integrative framework highlights the need for further research into psilocybin's dual modulation of 5-HT and DA systems to optimize its therapeutic applications for anorexia nervosa, a life-threatening condition that is characterized by impairments in cognitive flexibility and reward processing.

topic_tags:
Eating Disorders,End-of-Life Distress,Neuroplasticity,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Aging,Animal Study,Drug Interactions

raw_json:
{"europe_pmc_id":"40403997","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Henry J, Giribaldi B, Nutt DJ, Erritzoe D, Carhart-Harris R, Lyons T.
journal: medRxiv
publication_date: 2025-03-20
doi: 10.1101/2025.03.17.25324123
source_url: https://doi.org/10.1101/2025.03.17.25324123
substance_tags: psilocybin
topic_tags: Depression,Randomized Controlled Trial
study_type: Randomized Controlled Trial
source_name: medRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:01
title:
The effects of psilocybin therapy versus escitalopram on cognitive bias: A secondary analysis of a randomized controlled trial

abstract:
Background Patients with Major Depressive Disorder (MDD) have more dysfunctional attitudes and pessimism than healthy individuals and these biases are correlated with depression severity. Psilocybin has demonstrated sustained remission in MDD. Methods Secondary analysis of a two-arm, randomized controlled trial ( ClinicalTrials.gov Identifier: NCT03429075 ) assessing the effect of psilocybin therapy versus escitalopram on ‘maladaptive’ cognitive biases relevant to the construct of depression. Psilocybin group participants received two 25mg doses and escitalopram group received three weeks of daily 10mg, increased to 20mg for a following three weeks. Primary outcomes in this analysis were post-treatment changes in biases at six weeks compared with baseline, as measured using three validated psychological scales. Findings Fifty-nine MDD patients were randomly allocated to the psilocybin (n=30) or escitalopram (n=29) groups. Self-reported optimism showed a large and significant increase six-weeks after psilocybin treatment ( M diff =6·63 p

raw_json:
{"europe_pmc_id":"PPR993220","source":"PPR","pub_type":null,"publisher":"medRxiv","importer":"Europe PMC"}


journal: bioRxiv
publication_date: 2025-02-05
doi: 10.1101/2025.02.01.636078
source_url: https://doi.org/10.1101/2025.02.01.636078
substance_tags: psilocybin
topic_tags: Brain Imaging,Aging,Animal Study
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:01
title:
Dose-dependent changes in global brain activity and functional connectivity following exposure to psilocybin: a BOLD MRI study in awake rats

authors:
Fuini E, Chang A, Ortiz RJ, Nasseef T, Edwards J, Latta M, Gonzalez E, Woodward TJ, Bradshaw HB, Axe B, Maheswari A, Cavallaro N, Kulkarni PP, Ferris CF.

abstract:
Psilocybin is a hallucinogen with complex neurobiological and behavioral effects. This is the first study to use MRI to follow functional changes in brain activity in response to different doses of psilocybin in fully awake, drug naive rats. Female and male rats were given IP injections of vehicle or psilocybin in doses of 0.03 mg/kg, 0.3 mg/kg, and 3.0 mg/kg while fully awake during the imaging session. Changes in BOLD signal were recorded over a 20 min window. Data for resting state functional connectivity were collected approximately 35 min post injection All data were registered to rat 3D MRI atlas with 173 brain regions providing site-specific changes in global brain activity and changes in functional connectivity. Treatment with psilocybin resulted in a significant dose-dependent increase in positive BOLD signal. The areas most affected by the acute presentation of psilocybin were the somatosensory cortex, basal ganglia and thalamus. Females were significantly more sensitive to the 0.3 mg/kg dose of psilocybin than males. There was a significant dose-dependent global increase in functional connectivity, highlighted by hyperconnectivity to the cerebellum. Brain areas hypothesized to be involved in loss of sensory filtering and organization of sensory motor stimuli such as the claustrum and the cortico-basal ganglia-thalamic-cortical loop were all affected by psilocybin in a dose-dependent manner. Indeed, the general neuroanatomical circuitry associated with the psychedelic experience was affected but the direction of the BOLD signal and pattern of activity between neural networks was inconsistent with the human literature.

raw_json:
{"europe_pmc_id":"PPR976027","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: Human brain changes after first psilocybin use
journal: bioRxiv
publication_date: 2024-10-13
doi: 10.1101/2024.10.11.617955
source_url: https://doi.org/10.1101/2024.10.11.617955
substance_tags: psilocybin
topic_tags: Brain Imaging,Aging,Wellbeing
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:01
authors:
Lyons T, Spriggs M, Kerkelä L, Rosas F, Roseman L, Mediano P, Timmermann C, Oestreich L, Pagni B, Zeifman R, Hampshire A, Trender W, Douglass H, Girn M, Godfrey K, Kettner H, Sharif F, Espasiano L, Gazzaley A, Wall M, Erritzoe D, Nutt D, Carhart-Harris R.

abstract:
ABSTRACT Psychedelics have robust effects on acute brain function and long-term behavior but whether they also cause enduring functional and anatomical brain changes is unknown. In a placebo-controlled, within-subjects, electroencephalography, and magnetic resonance imaging study in 28 healthy, entirely psychedelic-naive participants, anatomical and functional brain changes were detected from one-hour to one-month after a single high-dose (25 mg) of psilocybin. Increases in cognitive flexibility, psychological insight, and well-being were seen at one-month. Diffusion imaging done before and one-month after 25mg psilocybin revealed decreased axial diffusivity bilaterally in prefrontal-subcortical tracts that correlated with decreased brain network modularity over the same time period. Decreased modularity also correlated with improved well-being. Increased cortical signal entropy at 1- and 2-hours post-dosing predicted improved psychological well-being at one-month. Next-day psychological insight mediated the entropy to well-being relationship. All effects were exclusive to 25mg psilocybin; no effects occurred with a 1mg psilocybin ‘placebo’ dose.

raw_json:
{"europe_pmc_id":"PPR924123","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


journal: bioRxiv
publication_date: 2025-01-07
doi: 10.1101/2025.01.08.631940
source_url: https://doi.org/10.1101/2025.01.08.631940
substance_tags: psilocybin
topic_tags: Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:01
title:
Cell-type specific transcriptional modulation by psilocybin induces sustained plasticity in mouse medial prefrontal cortex

authors:
Schuler H, Zhou D, Savignac C, Cvetkovska V, Tse Y, Meccia J, Lopez J, Harutyunyan AS, Ragoussis J, Bzdok D, Bagot RC.

abstract:
Despite enormous interest in psychedelics for psychiatric interventions, potential underlying biological mechanisms remain unclear. Here, we confirm that a single dose of psilocybin increases synaptic transmission in mouse medial prefrontal cortex. Using scRNA-sequencing, we identify cell-type specific mechanisms of sustained neuroplastic effects. We show that, 24h post-psilocybin, expression of plasticity-related genes is increased in excitatory neurons and that transcription in a type of deep layer near projecting neuron, L5/6 NP, is robustly altered. Analyzing receptor expression patterns reveals that this cell-type specificity does not align with 5-HT2A expression but aligns with 5-HT2C expression patterns. Further, multivariate analyses identify psilocybin-induced gene expression patterns in L5/6 NP neurons predict 5-HT2C, but not 5-HT2A, transcript levels. Pharmacologic manipulation with a 5-HT2C antagonist attenuates the post-acute sustained effect of psilocybin on synaptic transmission, highlighting 5-HT2C signaling and L5/6 NP neurons as key mediators of psychedelic drug action’s sustained neuroplastic effects in mPFC.

raw_json:
{"europe_pmc_id":"PPR963790","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


journal: bioRxiv
publication_date: 2024-11-06
doi: 10.1101/2024.11.06.622302
source_url: https://doi.org/10.1101/2024.11.06.622302
substance_tags: psilocybin
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:01
title:
Long-term effects of psilocybin on dynamic and effectivity connectivity of fronto-striatal-thalamic circuits

authors:
Pasquini L, Vohryzek J, Escrichs A, Sanz Perl Y, Ponce-Alvarez A, Idesis S, Girn M, Roseman L, Mitchell JM, Gazzaley A, Kringelbach M, Nutt DJ, Lyons T, Carhart-Harris RL, Deco G.

abstract:
Psilocybin has been shown to induce fast and sustained improvements in mental well-being across various populations, yet its long-term mechanisms of action are not fully understood. Initial evidence suggests that longitudinal functional and structural brain changes implicate fronto-striatal-thalamic (FST) circuitry, a broad system involved in goal-directed behavior and motivational states. Here, we apply empirical methods and computational modeling to resting-state fMRI data from a within-subject longitudinal psilocybin trial in psychedelic-naïve healthy volunteers. We first show increases in FST dynamic activity four weeks after a full dose of psilocybin. We then proceed to mechanistically account for these increased dynamics, by showing that reduced structural constraints underlie increased FST dynamic activity post psilocybin. Further, we show that these reduced structural constraints come along with increased bottom-up and reduced top-down modulation of FST circuits. While cortical reductions in top-down modulation are linked to regional 5-HT2A receptor availability, increased information outflow via subcortical and limbic regions relate to local D2 receptor availability. Together, these findings show that increased FST flexibility weeks after psilocybin administration is linked to serotonergic-mediated decreases in top-down information flow and dopaminergic-mediated increases in bottom-up information flow. This long-term functional re-organization of FST circuits may represent a common mechanism underling the potential clinical efficacy of psilocybin across various neuropsychiatric disorders including substance abuse, major depression, and anorexia. Significance Statement Fronto-striatal-thalamic systems, which underlie motivation and reward, go through profound functional and structural changes following psilocybin administration. We leveraged longitudinal fMRI data from a within-subject psilocybin trial in psychedelic-naïve healthy participants to show that psilocybin increases fronto-striatal-thalamic dynamic activity as well as flexibility four weeks after dosing. Computational modeling revealed that this increased flexibility is mechanistically caused by reduced structural constraints on functional dynamics. Further long-term changes included increased bottom-up and reduced top-down information flow mediated by the serotonergic and dopaminergic systems. This long-term functional re-organization of fronto-striatal-thalamic circuits may reflect a common mechanism underlying clinical symptoms improvements across diagnostic groups, such as increased openness, improved well-being, and reductions in anhedonia, apathy, and substance craving.

topic_tags:
Depression,Eating Disorders,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Wellbeing,Healthy Volunteers

raw_json:
{"europe_pmc_id":"PPR936542","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


journal: PsyArXiv
publication_date: 2025-02-27
source_url: https://osf.io/preprints/psyarxiv/93x5h_v3
keywords: Psychiatry, Neuroscience, Social and Behavioral Sciences
substance_tags: psilocybin
topic_tags: Addiction,Mechanism of Action,Spirituality,Safety
study_type: Other
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"93x5h_v3","version":3,"reviews_state":"accepted"}
title:
Tū Wairua: Development of an Indigenous Rongoā Māori Approach to Healing with Psilocybin Containing Mushrooms

abstract:
Psilocybin, a naturally occurring psychedelic compound found in certain fungi, has long been used by Indigenous cultures worldwide for healing and spiritual purposes. While emerging evidence points to psychedelic agents being novel avenues for the treatment of substance use disorders, the predominantly Western medical models of psychedelic-assisted therapy being developed lack Indigenous wisdom and input, raising concerns about safety, efficacy, ownership, and continuing colonial dynamics. In Aotearoa (New Zealand), the enduring impacts of colonisation on Māori include the suppression of Indigenous wisdom, even as research affirming the knowledge and practice of traditional Māori healing is on the rise. The Tū Wairua project will explore the integration of rongoā Māori (traditional Māori healing practices) with psilocybin-assisted therapy (PAT) for addressing problematic methamphetamine use (PMU) in Māori communities. This Māori-led project is driven by kaupapa Māori methodology and rongoā Māori conceptualisations of health and informed by biomedical psychedelic science. Based at Rangiwaho Marae in Te Tairāwhiti, a community with a high Māori population and a significant burden of PMU, the project aims to develop a culturally-appropriate PAT to explore the efficacy of psilocybin in treating PMU. This research represents a shift toward health interventions that respect and extend Indigenous wisdom, addressing the unique needs of Māori communities. It also seeks to develop a skilled Māori workforce to continue these healing practices, and challenge current legislation that restricts the use of Indigenous psychedelics. In creating sustainable pathways for healing through a community-driven, culturally-resonant PAT, Tū Wairua charts new directions in Indigenous-led psychedelic science.


authors: Hodge A, Forsyth A, Noorani T, Muthukumaraswamy S, Rolleston A, McHugh P.
journal: PsyArXiv
publication_date: 2025-02-27
doi: 10.31234/osf.io/93x5h_v2
source_url: https://doi.org/10.31234/osf.io/93x5h_v2
substance_tags: psilocybin
topic_tags: Addiction,Mechanism of Action,Spirituality,Safety
study_type: Other
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:01
title:
Tū Wairua: Development of an Indigenous Rongoā Māori Approach to Healing with Psilocybin Containing Mushrooms

abstract:
Psilocybin, a naturally occurring psychedelic compound found in certain fungi, has long been used by Indigenous cultures worldwide for healing and spiritual purposes. While emerging evidence points to psychedelic agents being novel avenues for the treatment of substance use disorders, the predominantly Western medical models of psychedelic-assisted therapy being developed lack Indigenous wisdom and input, raising concerns about safety, efficacy, ownership, and continuing colonial dynamics. In Aotearoa (New Zealand), the enduring impacts of colonisation on Māori include the suppression of Indigenous wisdom, even as research affirming the knowledge and practice of traditional Māori healing is on the rise. The Tū Wairua project will explore the integration of rongoā Māori (traditional Māori healing practices) with psilocybin-assisted therapy (PAT) for addressing problematic methamphetamine use (PMU) in Māori communities. This Māori-led project is driven by kaupapa Māori methodology and rongoā Māori conceptualisations of health and informed by biomedical psychedelic science. Based at Rangiwaho Marae in Te Tairāwhiti, a community with a high Māori population and a significant burden of PMU, the project aims to develop a culturally-appropriate PAT to explore the efficacy of psilocybin in treating PMU. This research represents a shift toward health interventions that respect and extend Indigenous wisdom, addressing the unique needs of Māori communities. It also seeks to develop a skilled Māori workforce to continue these healing practices, and challenge current legislation that restricts the use of Indigenous psychedelics. In creating sustainable pathways for healing through a community-driven, culturally-resonant PAT, Tū Wairua charts new directions in Indigenous-led psychedelic science.

raw_json:
{"europe_pmc_id":"PPR984267","source":"PPR","pub_type":null,"publisher":"PsyArXiv","importer":"Europe PMC"}


authors: Purple RJ, Gupta R, Thomas CW, Golden CT, Froudist-Walsh S, Jones MW.
journal: bioRxiv
publication_date: 2024-12-12
doi: 10.1101/2024.12.10.627734
source_url: https://doi.org/10.1101/2024.12.10.627734
substance_tags: psilocybin
topic_tags: Neuroplasticity,Brain Imaging,Biomarkers,Aging,Animal Study
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:01
title:
Short- and long-term reconfiguration of rat prefrontal cortical networks following single doses of psilocybin

abstract:
SUMMARY We quantify cellular- and circuit-resolution neural network dynamics following therapeutically relevant doses of the psychedelic psilocybin. Using chronically implanted Neuropixels probes, we recorded local field potentials (LFP) alongside action potentials from hundreds of neurons spanning infralimbic, prelimbic and cingulate subregions of the medial prefrontal cortex of freely-behaving adult rats. Psilocybin (0.3mg/kg or 1mg/kg i.p.) unmasked 100Hz high frequency oscillations that were most pronounced within the infralimbic cortex, persisted for approximately 1h post-injection and were accompanied by decreased net pyramidal cell firing rates and reduced signal complexity. These acute effects were more prominent during resting behaviour than during a sustained attention task. LFP1-, 2- and 6-days post-psilocybin showed gradually-emerging increases in beta and low-gamma (20-60Hz) power, specific to the infralimbic cortex. These findings reveal features of psychedelic action not readily detectable in human brain imaging, implicating infralimbic network oscillations as potential biomarkers of psychedelic-induced network plasticity over multi-day timescales.

raw_json:
{"europe_pmc_id":"PPR954729","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


journal: bioRxiv
publication_date: 2021-02-04
doi: 10.1101/2021.02.03.429325
source_url: https://doi.org/10.1101/2021.02.03.429325
substance_tags: psilocybin,psilocin
topic_tags: Brain Imaging,Mechanism of Action,Receptor Pharmacology,Default Mode Network,Consciousness,Aging
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:01
title:
Psilocybin-induced changes in brain network integrity and segregation correlate with plasma psilocin level and psychedelic experience

authors:
Madsen MK, Stenbæk DS, Arvidsson A, Armand S, Marstrand-Joergensen MR, Johansen SS, Linnet K, Ozenne B, Knudsen GM, Fisher PM.

abstract:
The emerging novel therapeutic psilocybin produces psychedelic effects via engagement of cerebral serotonergic targets by psilocin (active metabolite). The serotonin 2A receptor critically mediates these effects by altering distributed neural processes that manifest as increased entropy, reduced functional connectivity (FC) within discrete brain networks (i.e., reduced integrity) and increased FC between networks (i.e., reduced segregation). Reduced integrity of the default mode network (DMN) is proposed to play a particularly prominent role in psychedelic phenomenology, including perceived ego-dissolution. Here, we investigate the effects of a psychoactive oral dose of psilocybin (0.2-0.3 mg/kg) on plasma psilocin level (PPL), subjective drug intensity (SDI) and their association in fifteen healthy individuals. We further evaluate associations between these measures and resting-state FC, measured with functional magnetic resonance imaging, acquired over the course of five hours after psilocybin administration. We show that PPL and SDI correlate negatively with measures of network integrity (including DMN) and segregation, both spatially constrained and unconstrained. We also find that the executive control network and dorsal attention network desegregate, increasing connectivity with other networks and throughout the brain as a function of PPL and SDI. These findings provide direct evidence that psilocin critically shapes the time course and magnitude of changes in the cerebral functional architecture and subjective experience following psilocybin administration. Our findings provide novel insight into the neurobiological mechanisms underlying profound perceptual experiences evoked by this emerging transnosological therapeutic and implicate the expression of network integrity and segregation in the psychedelic experience and consciousness.

raw_json:
{"europe_pmc_id":"PPR278731","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


journal: PsyArXiv
publication_date: 2026-02-16
source_url: https://osf.io/preprints/psyarxiv/yrgkf_v1
substance_tags: psilocybin
topic_tags: End-of-Life Distress,Mechanism of Action,Aging,Clinical Trial,Cancer Patients
study_type: Clinical Trial
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"yrgkf_v1","version":1,"reviews_state":"accepted"}
title:
Mindfulness-Based Psilocybin-Assisted Therapy (MB-PAT) for cancer-related demoralization in Canada: the case for a hybrid group-based delivery model

abstract:
Demoralization syndrome (DS) - a distinct clinical entity characterized by helplessness, hopelessness, and a persistent loss of meaning - affects approximately one in five Canadians with advanced cancer and is associated with increased desire for hastened death, negative clinical outcomes, and higher economic burden, yet recognition and treatment of DS remains suboptimal in modern oncology. While current pharmacological treatments fail to address demoralization's existential dimensions, and despite the potential effectiveness of a number of psychosocial interventions, not everyone responds to behavioral therapies and they remain chronically underfunded in mainstream oncology. Mindfulness-Based Psilocybin-Assisted Therapy (MB-PAT) offers enhanced therapeutic potential by synergistically integrating evidence-based mindfulness training with psilocybin's neuroplastic effects; however, the traditional dyadic delivery model limits scalability within healthcare s settings. This viewpoint opines that MB-PAT delivered in a group format represents a potentially optimal solution to this evidence-implementation gap. Our contention is that MB-PAT may harness synergistic biopsychosocial mechanisms that directly counter the isolation of demoralization through an integrative approach. We finish by highlighting the Canadian Network for Psychedelic-Assisted Cancer Therapy (CAN-PACT) as a pioneering initiative poised to generate critical evidence, infrastructure and capacity through its planned multi-phase initiatives and projects. By leveraging existing group-therapy infrastructure and therapist familiarity with mindfulness-based interventions as the basis for multi-site national clinical trials, and developing a scalable, equity-focused delivery model, MB-PAT offers a pragmatic pathway to integrate potentially transformative existential care into publicly funded Canadian oncology practice.

keywords:
Canadian healthcare, cancer, demoralization, existential distress, group therapy, implementation science, mindfulness, mindfulness-based interventions, palliative care, psychedelic-assisted therapy, psychedelic medicine, psychedelics, psychosocial oncology, Psychiatry, Neuroscience, Social and Behavioral Sciences


title: Characterizing psilocybin as an antidepressant for adolescence in male and female rats
authors: García-Cabrerizo R, Beruete-Fresnillo I, García-Fuster MJ.
journal: bioRxiv
publication_date: 2024-12-21
doi: 10.1101/2024.12.20.629571
source_url: https://doi.org/10.1101/2024.12.20.629571
substance_tags: psilocybin
topic_tags: Depression,Adolescents
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:01
abstract:
Adolescent depression is a significant public health concern, yet treatment options remain limited, particularly due to age- and sex-related differences in antidepressant efficacy. This study explored the rapid and long-lasting antidepressant-like potential of psilocybin in adolescent Sprague-Dawley rats, examining acute and repeated oral dosing effects while incorporating sex as a biological variable. An acute administration of psilocybin produced rapid antidepressant-like effects 30 minutes post-treatment in both male and female rats, demonstrated by reduced immobility and increased escape-related behaviour in the forced swim test. However, repeated daily administrations over 7 days revealed notable sex differences. In males, the antidepressant-like effects were sustained, at least, for up to 15 days post-treatment at both tested doses. In contrast, in females, the effects were dose-dependent and less enduring, persisting only up to 8 days at the highest dose tested. To the best of our knowledge, these results are the first ones to underscore psilocybin’s potential as a fast-acting and long-lasting antidepressant during adolescence, a developmental stage marked by high vulnerability to depression and reduced response to conventional treatments, while also emphasizing the importance of tailoring therapeutic approaches to individual biological factors such as sex.

raw_json:
{"europe_pmc_id":"PPR959351","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


authors: Askey T, Allen-Ross D, Lasrado R, Gilmour G, Hunt S, Tamagnini F, Ahmed M, Stephens G, Maiarú M.
journal: Research Square
publication_date: 2024-09-19
doi: 10.21203/rs.3.rs-5026806/v1
source_url: https://doi.org/10.21203/rs.3.rs-5026806/v1
substance_tags: psilocybin
topic_tags: Chronic Pain,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:01
title:
Psilocybin ameliorates neuropathic pain-like behaviour in mice and facilitates the gabapentin-mediated analgesia

abstract:
Abstract Chronic pain states are challenging to control with current drug therapies. Here, we demonstrate that a single dose of psilocybin can produce a sustained anti-nociceptive effect in a mouse model of chronic neuropathic pain. Beyond this, the single dose of psilocybin caused a dramatic increase in the anti-nociceptive potential of gabapentin, a widely used treatment for neuropathic pain, such data are suggestive of establishment of longer lasting changes in network processing.

raw_json:
{"europe_pmc_id":"PPR913343","source":"PPR","pub_type":null,"publisher":"Research Square","importer":"Europe PMC"}


authors: Quah S, Glick C, Roseman L, Pasquini L, Carhart-Harris R, Saggar M.
journal: bioRxiv
publication_date: 2025-03-09
doi: 10.1101/2025.03.05.641592
source_url: https://doi.org/10.1101/2025.03.05.641592
substance_tags: psilocybin
topic_tags: Depression,Brain Imaging,Mechanism of Action,Default Mode Network,Drug Interactions
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:46
last_checked: 2026-07-01 11:22:01
title:
Revealing Changes in Linear and Nonlinear Functional Connectivity After Psilocybin and Escitalopram Treatment in Patients with Depression

abstract:
Major Depressive Disorder (MDD) is typically characterized by altered linear functional connectivity (FC) across large-scale brain networks. Yet, it is unclear whether similar alterations are observed when nonlinear FC is examined. This study investigated how antidepressant treatment (i.e., psilocybin and escitalopram) modulates both linear FC and nonlinear FC in individuals with MDD. Here, we focused specifically on five key canonical brain networks: the Default Mode Network (DMN), Frontoparietal Network (FPN), Salience Network (SAL), Dorsal Attention Network (DAN), and Ventral Attention Network (VAN). Across both treatments, using resting-state fMRI data, we first compared changes in linear and nonlinear FC between responders and non-responders. Responders exhibited increased linear FC within the VAN and greater nonlinear FC within the DMN and VAN than non-responders. We also observed more between-network linear FC for DMN-DAN and nonlinear FC for DMN-VAN in responders than non-responders. Next, we compared treatments and observed that Psilocybin responders showed greater connectivity between FPN-VAN (linear FC), DMN-VAN (nonlinear FC), and SAL-VAN (nonlinear FC) integration than Escitalopram responders, reflecting enhanced coordination and integration between higher-order networks. Conversely, Escitalopram responders exhibited reduced within-network linear FC within the DMN and SAL and between the DMN and VAN, consistent with a dampening of self-referential and salience processing and altered attentional control. These findings highlight potentially distinct mechanisms of action for psilocybin and escitalopram. Incorporating both linear and nonlinear FC analyses provided a novel characterization of these effects, emphasizing the role of these different interactions in antidepressant response. Future studies should investigate the long-term stability of these network changes and their relationship to clinical outcomes.

raw_json:
{"europe_pmc_id":"PPR987622","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: Psilocybin’s Kinematic Effect on Manual Dexterity
authors: Klintefors P, Bhagavan C, Kanaan R, Bryson A, Berlowitz D, Attard Z, Carter O.
journal: Research Square
publication_date: 2026-04-14
doi: 10.21203/rs.3.rs-9291780/v1
source_url: https://doi.org/10.21203/rs.3.rs-9291780/v1
substance_tags: psilocybin
topic_tags: Clinical Trial,Review Article,Healthy Volunteers,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
abstract:
Abstract Rationale Clinical interest in psilocybin-assisted rehabilitation for motor disorders is growing. However, psilocybin’s motor effects are under-researched, and quantifying them is essential for assessing treatment risks and outcomes. Objectives This study aims to clarify whether acute effects of psilocybin disrupts established patterns of manual dexterity and coordination. Specifically, we evaluate the impact of psilocybin on velocity, smoothness and kinematic synergies. Methods In a randomised, blinded trial, healthy participants received three doses of psilo-cybin (5-20 mg) administered one week apart. Manual dexterity was assessed using the Box and Block Test (BBT) at baseline and 1.5, 3, and 4.5 hours post-drug administration. Task performance was analysed using a Bayesian mixed-effects model. For kinematic analysis, 21 hand landmarks were tracked from video recordings obtained at baseline and 1.5 hours post-administration. Principal component analysis (PCA) was the basis for evaluating the stability and dimensionality of kinematic synergies. Results BBT performance showed a modest biphasic dose-response pattern at higher doses (10-20 mg), with slight impairment during peak effects and slight improvement 4.5 hours post-administration relative to baseline. Effect sizes were small compared to inter-individual baseline variability. Kinematic analyses revealed no substantial changes in movement smoothness or velocity. Dimensionality metrics indicated a stable coordination structure, although finger movements showed a subtle increase in complexity. Conclusions Low to moderate doses of psilocybin did not meaningfully disrupt manual dexterity or the latent structure of hand coordination. These findings support the feasibility of combining psilocybin administration with active motor rehabilitation. Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12621000560897 Date registered: 12 May 2021 URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id= 381526&isReview=true

raw_json:
{"europe_pmc_id":"PPR1177862","source":"PPR","pub_type":null,"publisher":"Research Square","importer":"Europe PMC"}


title: Psilocybin increases optimistic engagement over time: computational modelling of behavior in rats
authors: Fisher EL, Smith R, Corcoran AW, Milton LK, Conn K, Hohwy J, Foldi CJ.
journal: bioRxiv
publication_date: 2024-05-16
doi: 10.1101/2024.05.16.594614
source_url: https://doi.org/10.1101/2024.05.16.594614
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Clinical Trial
study_type: Clinical Trial
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
abstract:
Psilocybin has shown promise as a novel pharmacological intervention for treatment of depression, where post-acute effects of psilocybin treatment have been associated with increased positive mood and decreased pessimism. Although psilocybin is proving to be effective in clinical trials for treatment of psychiatric disorders, the information processing mechanisms affected by psilocybin are not well understood. Here, we fit computational models of underlying decision-making mechanisms to behaviour in rats. The model revealed that rats treated with psilocybin achieve more rewards through increased task engagement, mediated by modification of forgetting rates and reduced loss aversion. These findings suggest that psilocybin may afford an optimism bias that arises through altered belief updating, with translational potential for clinical populations characterised by lack of optimism.

raw_json:
{"europe_pmc_id":"PPR853997","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


authors: Viohl N, Zanjani AAH, Khandelia H.
journal: bioRxiv
publication_date: 2024-07-23
doi: 10.1101/2024.07.23.604750
source_url: https://doi.org/10.1101/2024.07.23.604750
substance_tags: psilocin
topic_tags: Receptor Pharmacology,Drug Interactions
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
Molecular insights into the modulation of the 5HT 2A receptor by serotonin, psilocin, and the G protein subunit Gqα

abstract:
SUMMARY The 5HT 2A receptor (5HT 2A R) is a G protein-coupled receptor that drives many neuronal functions and is one of the primary targets for psychedelic drugs, which have recently shown promise in treating mental disorders. Understanding ligand interactions and conformational transitions is essential for developing effective pharmaceuticals, but mechanistic details of 5HT 2A R activation and ligand binding modes remain poorly understood. We conducted all-atom molecular dynamics simulations and free energy calculations of the active and inactive forms of 5HT 2A R with psilocin and serotonin. Both serotonin and psilocin have higher binding affinities for the orthosteric binding pocket than the extended binding pocket. Active state 5HT 2A R collapses to a closed state in the absence of Gqα. We also discover a ‘partially-open’ receptor conformation that is intermediate between the active and inactive states. Our discoveries can inform the design of new pharmaceuticals that target specific receptor conformations, potentially leading to more effective treatments for mental disorders.

raw_json:
{"europe_pmc_id":"PPR886272","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


authors: Nikolic M, Mediano P, Froese T, Reydellet D, Palenicek T.
journal: medRxiv
publication_date: 2024-09-10
doi: 10.1101/2024.09.09.24313316
source_url: https://doi.org/10.1101/2024.09.09.24313316
substance_tags: psilocybin
topic_tags: Brain Imaging,Receptor Pharmacology,Default Mode Network,Aging,Wellbeing,Emotional Processing
study_type: Other
source_name: medRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
Psilocybin alters brain activity related to sensory and cognitive processing in a time-dependent manner

abstract:
Psilocybin is a classic psychedelic and a novel treatment for mood disorders. Psilocybin induces dose-dependent transient (4-6 hours) usually pleasant changes in perception, cognition, and emotion by non-selectively agonizing the 5-HT2A receptors and negatively regulating serotonin reuptake, and long-term positive antidepressant effect on mood and well-being. Long-term effects are ascribed to the psychological quality of the acute experience, increase in synaptodensity and temporary (1-week) down-regulation of 5-HT2A receptors. Electroencephalography, a non-invasive neuroimaging tool, can track the acute effects of psilocybin; these include the suppression of alpha activity, decreased global connectivity, and increased brain entropy (i.e. brain signal diversity) in eyes-closed resting-state. However, few studies investigated how these modalities are affected together through the psychedelic experience. The current research aimed to evaluate the psilocybin intoxication temporal EEG profile. 20 healthy individuals (10 women) underwent oral administration of psilocybin (0.26 mg/kg ) as part of a placebo-controlled cross-over study, resting-state 5-minute eyes closed EEG was obtained at baseline and 1, 1.5, 3, 6, and 24 hours after psilocybin administration. Absolute power, relative power spectral density (PSD), power envelope global functional connectivity (GFC), Lempel-Ziv complexity (LZ), and a Complexity via State-Space Entropy Rate (CSER) were obtained together with measures of subjective intensity of experience. Absolute power decreased in alpha and beta band, but increased in delta and gamma frequencies. 24h later was observed a broadband decrease. The PSD showed a decrease in alpha occipitally between 1 and 3 hours and a decrease in beta frontally at 3 hours, but power spectra distribution stayed the same 24h later. The GFC showed decrease acutely at 1, 1.5, and 3 hours in the alpha band. LZ and showed an increase at 1 and 1.5 hours. Decomposition of CSER into functional bands shows a decrease in alpha band but increase over higher frequencies. Further, complexity over a source space showed opposing changes in the Default Mode Network (DMN) and visual network between conditions, suggesting a relationship between signal complexity, stimulus integration, and perception of self. In an exploratory attempt, we found that a change in gamma GFC in DMN correlates with oceanic boundlessness. Psychological effects of psilocybin may be wrapped in personal interpretations and history unrelated to underlying neurobiological changes, but changes to perception of self may be bound to perceived loss of boundary based on whole brain synchrony with the DMN in higher frequency bands.

raw_json:
{"europe_pmc_id":"PPR909013","source":"PPR","pub_type":null,"publisher":"medRxiv","importer":"Europe PMC"}


journal: PsyArXiv
publication_date: 2024-10-06
source_url: https://osf.io/preprints/psyarxiv/ga9p2_v1
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Microdosing,Review Article
study_type: Review Article
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"ga9p2_v1","version":1,"reviews_state":"accepted"}
title:
Qualitative Research on Psilocybin-Assisted Psychotherapy for the Treatment of Mental Health Disorders: A Scoping Review Protocol

abstract:
Introduction There has been a surge in research into psilocybin-assisted psychotherapy over the past decade, with many studies indicating this may be an effective novel intervention for several mental health disorders. Researchers are increasingly incorporating qualitative analysis into their studies in recognition of the rich, contextual information this provides. This scoping review aims to identify the existing qualitative research on psilocybin-assisted psychotherapy for the treatment of mental health disorders, analyse trends in research questions and methods, and recognise opportunities for future qualitative research. Methods and Analysis The methodological guidelines set out in the JBI Manual for Evidence Synthesis (Aromataris et al., 2024) will be used to conduct the review. The review will include qualitative studies involving psilocybin-assisted psychotherapy, administered in a controlled research setting, for the treatment of any mental health disorder. Microdosing studies will be excluded. PubMed, Scopus, PsycNET, and reference lists of included studies will be searched. Two reviewers will screen papers for inclusion. Data will be extracted into a table and findings will be presented in a narrative form. Relevant qualitative research will be identified, trends in the qualitative research questions and methods will be analysed, and opportunities for future qualitative research will be discussed. Ethics and Dissemination Ethics approval is not required. Findings will be submitted for publication in a peer-reviewed journal. Key Words or Phrases Anxiety, depression, psilocybin, psychedelic, qualitative.

keywords:
anxiety, depression, IPA, novel interventions, psilocybin, psilocybin-assisted psychotherapy, psychedelic, psychedelic-assisted psychotherapy, qualitative, scoping review, thematic analysis, Psychiatry, Neuroscience, Social and Behavioral Sciences


authors: Mageean S, Daniel A, Tai S.
journal: Research Square
publication_date: 2024-09-17
doi: 10.21203/rs.3.rs-4862438/v1
source_url: https://doi.org/10.21203/rs.3.rs-4862438/v1
substance_tags: psilocybin
topic_tags: Cancer Patients,Safety,Drug Interactions
study_type: Other
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
Exploring U.K. cancer doctors’ attitudes toward psilocybin-assisted psychotherapy for cancer-related distress

abstract:
Abstract Background A diagnosis of cancer is often associated with significant psychological distress. Current approaches to cancer-related distress predominantly fall short of meeting the needs of patients. Recent investigations have shown that administering psilocybin in combination with psychotherapy might be effective at reducing distress in cancer patients. Oncologists are often ‘gatekeepers’, who oversee cancer patient care; if this intervention were to become more routinely available, it is important to understand doctors’ attitudes toward psilocybin-assisted psychotherapy. Method Nine oncologists who worked across two National Health Service Trusts in England were interviewed using a semi-structured interview approach. Thematic analysis was used to analyse the interviews and guide the development of overarching themes and subthemes. Results The analysis revealed five overarching themes relating to oncologists’ experiences of cancer-related distress and attitudes towards psilocybin-assisted psychotherapy: current approaches to distress; attitudes towards psychedelics and psilocybin; quality research; service design and delivery; distress and patients from different backgrounds. Limitations: Future research should aim to explore the experiences and attitudes of other professionals, such as specialist cancer nurses, who are more likely to broach the subject of distress with cancer patients. Conclusions Oncologists are open to novel interventions for supporting patients experiencing cancer-related psychological distress. Future research should aim to address their concerns regarding the safety and potential interactions of psilocybin with anticancer treatments and should stratify trials with different patient groups, owing to the idiosyncratic nature of specific types of cancer.

raw_json:
{"europe_pmc_id":"PPR911306","source":"PPR","pub_type":null,"publisher":"Research Square","importer":"Europe PMC"}


authors: Mallaroni P, Singleton P, Mason NL, Satterthwaite TD, Ramaekers JG.
journal: bioRxiv
publication_date: 2024-10-21
doi: 10.1101/2024.10.22.619393
source_url: https://doi.org/10.1101/2024.10.22.619393
substance_tags: psilocybin
topic_tags: Pharmacology,Receptor Pharmacology,Biomarkers,Healthy Volunteers
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
The forgotten psychedelic: Spatiotemporal mapping of brain organisation following the administration of 2C-B and psilocybin

abstract:
As psychedelic-assisted psychotherapy gains momentum, clinical investigation of next-generation psychedelics may lead to novel compounds tailored for specific populations. 2,5-dimethoxy-4-bromophenethylamine (2C-B) is a psychedelic phenethylamine reported to produce less dysphoria and subjective impairment than the psychedelic tryptamine psilocybin. Despite its popularity among recreational users and distinct pharmacodynamics, the neural correlates of 2C-B remain unexplored. Using 7T resting−state functional MRI in 22 healthy volunteers, we mapped out the acute effects of matched doses of 20 mg 2C-B, 15 mg psilocybin and placebo across spatiotemporal benchmarks of functional brain organisation. In a within-subjects, double-blind, placebo-controlled crossover design, we evaluated the neuropharmacological and neurobehavioural correlates of an array of connectivity measures - including static (sFC) and global connectivity (gFC), dynamic connectivity variability (dFC), and spontaneous brain complexity. Compared to placebo, 2C-B and psilocybin selectively reduced intra-network sFC, while broadly increasing between-network and subcortical-cortical connectivity. Compared to psilocybin, 2C-B exhibited less pronounced reductions in between-network FC but elicited elevations in transmodal sFC. Both compounds yielded spatially divergent increases in gFC yet produced similar increases in brain complexity. Using PET density modelling, the spatial distribution of neural effects aligned with documented differences in monoaminergic transporter and serotonergic receptor binding affinity beyond 5-HT2A, highlighting the role of pharmacology in shaping functional dynamics. Lastly, we show behavioural markers of psychedelic effects are non-linearly reflected by the desynchronisation of the transmodal axis of functional brain organisation. Together, our findings highlight 2C-B as a useful new addition to the study of psychedelic neuroscience and may motivate new pharmacotherapy strategies.

raw_json:
{"europe_pmc_id":"PPR929517","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


authors: Lane CP, Tarka VM, Valentin O, Lehmann A, Hamel E, de Villers-Sidani E.
journal: bioRxiv
publication_date: 2024-09-29
doi: 10.1101/2024.09.27.614985
source_url: https://doi.org/10.1101/2024.09.27.614985
substance_tags: psilocybin
topic_tags: Brain Imaging,Aging,Animal Study
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
Psilocybin prevents habituation to familiar stimuli and preserves sensitivity to sound following repeated stimulation in mouse primary auditory cortex

abstract:
Psilocybin, a psychoactive substance derived from fungi, has been utilized historically by diverse cultures for both medicinal and non-medicinal purposes, owing to its ability to elicit profound sensory and cognitive alterations and sustain long-term changes in mood and cognition. Promising results from recent clinical studies have generated a wave of interest in employing psilocybin to treat neuropsychiatric and neuro-degenerative conditions. How psychedelics cause acute perceptual effects, and how these relate to long-lasting alterations is still debated. Whereas it is thought that perceptual disturbances may be caused by disrupted flow of information between sensory and higher order areas, in vivo studies have focused mostly on the latter. In particular, there has been little study of how psilocybin affects sensory representations in primary auditory cortex (A1). We used two-photon microscopy and wide field calcium imaging to examine how psilocybin affects A1 neuron response properties in the mouse. Administration of 1 mg/kg psilocybin prevented habituation of sound-evoked responses to repeated stimuli, maintaining overall responsiveness, bandwidth, and sound-level response thresholds after repeated stimulation. This was in contrast to marked habituation of responses and narrowing of tuning in controls. We observed no effect on overall distribution of best frequencies at the cortical level, suggesting psilocybin in A1 disrupts normal sensory gating, rather than tonotopic organization. This supports models of psychedelic action in which perceptual disturbances are driven by disrupted hierarchical sensory gating. With further research, influences of psychedelics on sensory representations could be harnessed to target maladaptive sensory processing in conditions such as tinnitus. Significance Statement Despite its role in altering auditory sensory perception, the impact of psilocybin on modulating neuronal activity in the auditory cortex remains understudied. This study is the first to identify an inhibition of normal auditory habituation to repeated stimuli with single-neuron resolution. We identify a role for psilocybin in the targeted, context-dependent modulation of auditory sensory neural tuning properties, which may help to explain how disruption of hierarchical control of sensory representations leads to perceptual disturbances. With further work, this influence on sensory representations could be used to target conditions where maladaptive sensory processing leads to deleterious health outcomes.

raw_json:
{"europe_pmc_id":"PPR917832","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: Psilocybin biphasically modulates cortical and behavioral activity in mice
authors: Brockett AT, Francis NA.
journal: bioRxiv
publication_date: 2024-01-19
doi: 10.1101/2024.01.18.576229
source_url: https://doi.org/10.1101/2024.01.18.576229
substance_tags: psilocybin
topic_tags: Brain Imaging,Aging,Animal Study
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
abstract:
SUMMARY Psilocybin is a serotonergic psychedelic believed to have therapeutic potential for neuropsychiatric conditions. Despite well-documented prevalence of perceptual alterations, hallucinations, and synesthesia associated with psychedelic experiences, little is known about how psilocybin affects sensory cortex or alters the activity of neurons in awake animals. To investigate, we conducted 2-photon imaging experiments in auditory cortex of awake mice and video analysis of mouse behavior, both at baseline and during psilocybin treatment. We found biphasic effects of psilocybin on behavioral and cortical activity. A2 mg/kg dose of psilocybin initially increased behavioral activity and neural responses to sound. 30 minutes post-dose, mice became behaviorally hypoactive and cortical responses to sound decreased, while neural response variance and noise correlations increased. In contrast, neuronal selectivity for auditory stimuli remained stable during psilocybin treatment. Our results suggest that psilocybin modulates the role of intrinsic versus stimulus-driven activity in sensory cortex, while preserving fundamental sensory processing. Graphical Abstract. Summary of psilocybin’s effect on auditory cortical responses to sound in mice. 30 minutes after injecting the inert vehicle saline, typical auditory responses occur within a relatively narrow range of possible amplitudes, i.e., each neuron’s response variance is weakly correlated with a neighboring neuron’s response variance. In contrast, 30 minutes after injecting 2 mg/kg of psilocybin, population response variance becomes more correlated between individual neurons, and the range of response amplitudes increases. These findings suggest that psilocybin modulates the role of intrinsic versus stimulus-driven neural activity in sensory perception, which may serve as a basis for auditory hallucination at the level of neuronal micro-circuits.

raw_json:
{"europe_pmc_id":"PPR790246","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: Brain dynamics predictive of response to psilocybin for treatment-resistant depression
journal: Research Square
publication_date: 2022-09-19
doi: 10.21203/rs.3.rs-2060381/v1
source_url: https://doi.org/10.21203/rs.3.rs-2060381/v1
substance_tags: psilocybin,psilocin
topic_tags: Depression,Mechanism of Action,Receptor Pharmacology,Treatment-Resistant Depression
study_type: Other
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
authors:
Vohryzek J, Cabral J, Lord L, Fernandes H, Roseman L, Nutt D, Carhart-Harris R, Deco G, Kringelbach M.

abstract:
Abstract Psilocybin therapy for depression has started to show promise, yet the underlying causal mechanisms are not currently known. Here we leveraged the differential outcome in responders and non-responders to psilocybin (10mg and 25mg, 7 days apart) therapy for depression - to gain new insights into regions and networks implicated in the restoration of healthy brain dynamics. We used whole-brain modelling to fit the spatiotemporal brain dynamics at rest in both responders and non-responders before treatment. Dynamic sensitivity analysis of systematic perturbation of these models enabled us to identify specific brain regions implicated in a transition from a depressive brain state to a heathy one. Binarizing the sample into treatment responders (> 50% reduction in depressive symptoms) versus non-responders enabled us to identify a subset of regions implicated in this change. Interestingly, these regions correlate with in vivo density maps of serotonin receptors 5-HT2A and 5-HT1A, which psilocin, the active metabolite of psilocybin, has an appreciable affinity for, and where it acts as a full-to-partial agonist. Serotonergic transmission has long been associated with depression and our findings provide causal mechanistic evidence for the role of brain regions in the recovery from depression via psilocybin.

raw_json:
{"europe_pmc_id":"PPR548038","source":"PPR","pub_type":null,"publisher":"Research Square","importer":"Europe PMC"}


authors: Hodge A, Forsyth A, Noorani T, Muthukumaraswamy S, Rolleston A, McHugh P.
journal: PsyArXiv
publication_date: 2024-11-06
doi: 10.31234/osf.io/93x5h_v1
source_url: https://doi.org/10.31234/osf.io/93x5h_v1
substance_tags: psilocybin
topic_tags: Addiction,Mechanism of Action,Spirituality,Safety
study_type: Other
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
Tū Wairua: Development of an Indigenous Rongoā Māori Approach to Healing with Psilocybin Containing Mushrooms

abstract:
Psilocybin, a naturally occurring psychedelic compound found in certain fungi, has long been used by Indigenous cultures worldwide for healing and spiritual purposes. While emerging evidence points to psychedelic agents being novel avenues for the treatment of substance use disorders, the predominantly Western medical models of psychedelic-assisted therapy being developed lack Indigenous wisdom and input, raising concerns about safety, efficacy, ownership, and continuing colonial dynamics. In Aotearoa (New Zealand), the enduring impacts of colonisation on Māori include the suppression of Indigenous wisdom, even as research affirming the knowledge and practice of traditional Māori healing is on the rise. The Tū Wairua project will explore the integration of rongoā Māori (traditional Māori healing practices) with psilocybin-assisted therapy (PAT) for addressing problematic methamphetamine use (PMU) in Māori communities. This Māori-led project is driven by kaupapa Māori methodology and rongoā Māori conceptualisations of health and informed by biomedical psychedelic science. Based at Rangiwaho Marae in Te Tairāwhiti, a community with a high Māori population and a significant burden of PMU, the project aims to develop a culturally-appropriate PAT to explore the efficacy of psilocybin in treating PMU. This research represents a shift toward health interventions that respect and extend Indigenous wisdom, addressing the unique needs of Māori communities. It also seeks to develop a skilled Māori workforce to continue these healing practices, and challenge current legislation that restricts the use of Indigenous psychedelics. In creating sustainable pathways for healing through a community-driven, culturally-resonant PAT, Tū Wairua charts new directions in Indigenous-led psychedelic science.

raw_json:
{"europe_pmc_id":"PPR984269","source":"PPR","pub_type":null,"publisher":"PsyArXiv","importer":"Europe PMC"}


authors: Hodge A, Forsyth A, Noorani T, Muthukumaraswamy S, Rolleston A, McHugh P.
journal: PsyArXiv
publication_date: 2024-11-06
doi: 10.31234/osf.io/93x5h
source_url: https://doi.org/10.31234/osf.io/93x5h
substance_tags: psilocybin
topic_tags: Addiction,Mechanism of Action,Spirituality,Safety
study_type: Other
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
raw_json:
{"europe_pmc_id":"PPR937024","source":"PPR","pub_type":null,"publisher":"PsyArXiv","importer":"Europe PMC"}


title: Psilocybin facilitates fear extinction: importance of dose, context, and serotonin receptors
authors: Woodburn SC, Levitt CM, Koester AM, Kwan AC.
journal: bioRxiv
publication_date: 2024-05-05
doi: 10.1101/2024.05.04.592469
source_url: https://doi.org/10.1101/2024.05.04.592469
substance_tags: psilocybin
topic_tags: PTSD,Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
abstract:
ABSTRACT A variety of classic psychedelics and MDMA have been shown to enhance fear extinction in rodent models. This has translational significance because a standard treatment for posttraumatic stress disorder (PTSD) is prolonged exposure therapy. However, few studies have investigated psilocybin’s potential effect in fear learning paradigms. More specifically, the extents to which dose, timing of administration, and serotonin receptors may influence psilocybin’s effect on fear extinction are not understood. In this study, we used an auditory delay fear conditioning paradigm to determine the effects of psilocybin on fear extinction, extinction retention, and fear renewal in male and female mice. Psilocybin robustly enhances fear extinction when given acutely prior to testing for all doses tested. Psilocybin exerts long-term effects to elevate extinction retention and suppress fear renewal in a novel context, though these changes were sensitive to dose. Administration of psilocybin prior to fear learning or immediately after extinction yielded no change in behavior, indicating that concurrent extinction experience is necessary for the drug’s effects. Co-treatment with a 5-HT2A receptor antagonist blocked psilocybin’s effects for extinction, extinction retention and fear renewal, whereas 5-HT1A receptor antagonism attenuated only the effect on fear renewal. Collectively, these results highlight dose, context, and serotonin receptors as crucial factors in psilocybin’s ability to facilitate fear extinction. The study provides preclinical evidence to support investigating psilocybin as a pharmacological adjunct for extinction-based therapy for PTSD.

raw_json:
{"europe_pmc_id":"PPR848036","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


journal: bioRxiv
publication_date: 2024-06-12
doi: 10.1101/2024.06.13.598878
source_url: https://doi.org/10.1101/2024.06.13.598878
substance_tags: psilocybin
topic_tags: Neuroplasticity,Wellbeing,Healthy Volunteers
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
Co-administration of midazolam and psilocybin: Differential effects on subjective quality versus memory of the psychedelic experience

authors:
Nicholas CR, Banks MI, Lennertz RL, Wenthur CJ, Krause BM, Riedner BA, Smith RF, Hutson PR, Sauder CJ, Dunne JD, Roseman L, Raison CL.

abstract:
Aspects of the acute experience induced by the serotonergic psychedelic psilocybin predict symptomatic relief in multiple psychiatric disorders and improved well-being in healthy participants, but whether these therapeutic effects are immediate or are based on memories of the experience is unclear. To examine this, we co-administered psilocybin (25 mg) with the amnestic benzodiazepine midazolam in 8 healthy participants and assayed the subjective quality of, and memory for, the dosing-day experience. We identified a midazolam dose that allowed a conscious psychedelic experience to occur while partially impairing memory for the experience. Furthermore, midazolam dose and memory impairment tended to associate inversely with salience, insight, and well-being induced by psilocybin. These data suggest a role for memory in therapeutically relevant behavioral effects occasioned by psilocybin. Because midazolam blocks memory by blocking cortical neural plasticity, it may also be useful for evaluating the contribution of the pro-neuroplastic properties of psychedelics to their therapeutic activity.

raw_json:
{"europe_pmc_id":"PPR867616","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: Brain dynamics predictive of response to psilocybin for treatment-resistant depression
journal: bioRxiv
publication_date: 2022-07-03
doi: 10.1101/2022.06.30.497950
source_url: https://doi.org/10.1101/2022.06.30.497950
substance_tags: psilocybin,psilocin
topic_tags: Depression,Mechanism of Action,Receptor Pharmacology,Treatment-Resistant Depression
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
authors:
Vohryzek J, Cabral J, Lord L, Fernandes HM, Roseman L, Nutt DJ, Carhart-Harris RL, Deco G, Kringelbach ML.

abstract:
Psilocybin therapy for depression has started to show promise, yet the underlying causal mechanisms are not currently known. Here we leveraged the differential outcome in responders and non-responders to psilocybin (10mg and 25mg, 7 days apart) therapy for depression - to gain new insights into regions and networks implicated in the restoration of healthy brain dynamics. We used whole-brain modelling to fit the spatiotemporal brain dynamics at rest in both responders and non-responders before treatment. Dynamic sensitivity analysis of systematic perturbation of these models enabled us to identify specific brain regions implicated in a transition from a depressive brain state to a heathy one. Binarizing the sample into treatment responders (>50% reduction in depressive symptoms) versus non-responders enabled us to identify a subset of regions implicated in this change. Interestingly, these regions correlate with in vivo density maps of serotonin receptors 5-HT2A and 5-HT1A, which psilocin, the active metabolite of psilocybin, has an appreciable affinity for, and where it acts as a full-to-partial agonist. Serotonergic transmission has long been associated with depression and our findings provide causal mechanistic evidence for the role of brain regions in the recovery from depression via psilocybin.

raw_json:
{"europe_pmc_id":"PPR521801","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


authors: Nogueira M, García-Hernández S, Roberto GS, Marques LZ.
journal: medRxiv
publication_date: 2024-07-11
doi: 10.1101/2024.07.11.24310147
source_url: https://doi.org/10.1101/2024.07.11.24310147
substance_tags: psilocybin
topic_tags: Addiction,Safety,Adverse Events
study_type: Other
source_name: medRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
Psilocybin mushrooms and public health in Brazil: a low-risk adverse event profile calls for evidence-based regulatory discussions

abstract:
Background Current drug policy classifies psilocybin, a substance produced by psychoactive mushrooms, as having a high potential for abuse, neglecting its therapeutic properties. We aimed to investigate if psilocybin mushrooms pose a risk to Brazilian public health compared to other toxic agents and whether evidence-based regulatory discussions are needed. Methods A retrospective cross-sectional study was conducted following STROBE guidelines. Data were obtained from the Sistema de Agravos de Notificação (SINAN) on adverse events reported from 2007 to 2022. Participants were categorized into three groups: drug abuse, psilocybin mushrooms, and unknown mushrooms. Clinical outcomes assessed included non-hospitalization, hospitalization, and death. Associations between variables were analyzed using the Chi-square test. Results A total of 112,451 individuals sought medical attention for drug abuse-related adverse events. Among them, men constituted the majority (n = 79,514; 70.7%), followed by whites (n = 37,565; 33.4%) and those aged 26-35 (n = 29,163; 25.9%) (p < 0.001). Alcohol was the primary toxic agent (n = 71,824; 49.2%) (p < 0.001). The psilocybin mushroom group reported 13 adverse events, and the unknown mushroom group recorded 51 adverse events. Hospitalization rates were 19.5% (n = 21,923) for drug abuse, 46.2% (n = 6) for psilocybin mushrooms (0.02% of all hospitalizations) (99% CI: 10.6% - 81.6%), and 23.5% (n = 12) for unknown mushrooms (0.04% of hospitalizations) (99% CI: 8.3% - 38.7%). The mortality rate was 1.8% (n = 2035) for drug abuse, with no fatalities in the psilocybin or unknown mushroom groups. Most hospitalizations involved alcohol (45.0%), and deaths were mainly associated with cocaine (33.3%). Conclusion Our findings suggest that psilocybin mushrooms have a low-risk profile for adverse events, although underreporting may be a factor. This study highlights the need for evidence-based regulatory discussions to prevent arbitrary arrests and ensure safe access to psilocybin for clinical and ceremonial use.

raw_json:
{"europe_pmc_id":"PPR880121","source":"PPR","pub_type":null,"publisher":"medRxiv","importer":"Europe PMC"}


title: Psychedelic Therapy: A Primer for Primary Care Clinicians - Part IV. Psilocybin
journal: PsyArXiv
publication_date: 2023-12-25
source_url: https://osf.io/preprints/psyarxiv/a8xwk_v1
keywords: Psychiatry
substance_tags: psilocybin
study_type: Clinical Trial
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"a8xwk_v1","version":1,"reviews_state":"accepted"}
abstract:
Background: The primary psychoactive drug in magic mushrooms, psilocybin induces profound alterations in consciousness through its action at the 5-HT2A receptor. This comprehensive review consolidates current research findings to elucidate the pharmacology, safety profile, and clinical applications of psilocybin. Areas of Uncertainty: Despite initial concerns that psilocybin could cause long-lasting mental health problems such as psychosis, contemporary research has demonstrated that psilocybin is psychologically and physiologically safe. Adverse psychiatric outcomes can generally be avoided in controlled settings such as clinical trials. However, considerations regarding optimal dosing, therapeutic protocols, and integration strategies for psychedelic experiences remain imperative for the responsible clinical implementation of psilocybin-assisted therapy. Therapeutic Advances: In clinical trials, psilocybin has shown promise for treating major depressive disorder and treatment-resistant depression. Initial studies indicated that 42-57% of patients underwent remission after psilocybin-assisted therapy, which suggests that psilocybin is more effective than existing antidepressant medications. However, larger Phase II trials with more than 100 participants have shown a much smaller remission rate of 25-29%, though these studies still observed that psilocybin causes a significant reduction in depressive symptoms. Clinical data has also demonstrated that psilocybin can manage substance use disorders and end-of-life anxiety. Conclusion: Psilocybin is the most clinically well-researched psychedelic drug, with trials that have enrolled hundreds of participants and therapeutic applications that span multiple psychiatric conditions. Phase III trials, which have already commenced, will determine whether psilocybin lives up to the promise that it showed in previous clinical trials.

topic_tags:
Depression,Anxiety,Addiction,End-of-Life Distress,Pharmacology,Receptor Pharmacology,Consciousness,Clinical Trial,Review Article,Treatment-Resistant Depression,Healthcare Workers,Safety


journal: PsyArXiv
publication_date: 2024-11-03
doi: 10.31234/osf.io/j8zb5
source_url: https://doi.org/10.31234/osf.io/j8zb5
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
Preliminary safety and effectiveness of psilocybin-assisted therapy in adults with fibromyalgia: An open-label, pilot clinical trial

authors:
Aday JS, McAfee J, Conroy DA, Hosanagar A, Tarnal V, Weston C, Scott K, Horowitz D, Harte SE, Pouyan N, Glynos NG, Baker AK, Guss J, Davis AK, Burgess HJ, Mashour GA, Clauw DJ, Boehnke KF.

abstract:
Fibromyalgia (FM) is the prototypical nociplastic pain condition, characterized by widespread pain and issues with cognition, mood, and sleep. Currently, there are limited treatment options available that effectively treat FM symptoms. Psilocybin-assisted therapy (PAT) is an emerging combined drug-therapy intervention, but no studies to-date have investigated PAT for FM. Here, we report findings from an open-label, proof-of-concept trial of PAT for FM (N=5; NCT05128162). In conjunction with psychotherapy (two preparatory, four integration sessions), participants received two doses of oral psilocybin (15mg and 25mg) delivered two weeks apart. Regarding safety (primary outcome), there were transient elevations of blood pressure or heart rate during dosing which normalized by the end of treatment, with no serious adverse events. Four of five participants reported transient headaches following dosing. Compared to baseline, participants reported clinically meaningful improvements in the following secondary outcomes one month following their second psilocybin dose (reported as Cohen’s d): pain severity (d=-2.1, 95% CI[-3.7 to -0.49]), pain interference (d=-1.8, 95% CI [-3.27 to -0.24]), and sleep disturbance (d=-2.5, 95% CI [-4.21 to -0.75]). Using the Patient Global Impression of Change, one participant reported their symptoms “very much improved,” two reported “much improved,” and two reported “minimally improved.” Compared to baseline, there were improvements in the following exploratory outcomes after the intervention: FM symptoms, anxiety, and fatigue. This small open-label trial preliminarily supports that PAT is well-tolerated by people with FM, establishing a basis for larger randomized controlled trials.

topic_tags:
Anxiety,Chronic Pain,Headache / Migraine,Clinical Trial,Randomized Controlled Trial,Safety,Adverse Events

raw_json:
{"europe_pmc_id":"PPR935081","source":"PPR","pub_type":null,"publisher":"PsyArXiv","importer":"Europe PMC"}


title: Psilocybin decelerates cellular senescence
authors: Hecker L, kato k, Kleinhenz JMK, Shin Y, Papageorgiou J, Zarrabi A.
journal: Research Square
publication_date: 2023-06-26
doi: 10.21203/rs.3.rs-2921423/v1
source_url: https://doi.org/10.21203/rs.3.rs-2921423/v1
substance_tags: psilocybin
study_type: In Vitro Study
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
abstract:
Abstract Psilocybin is the psychoactive substance contained in the psilocybe(hallucinogenic) mushroom, which has received considerable attention among the scientific community in recent years. Human studies have demonstrated that even a single-dose of psilocybin can improve debilitating physical and psychological symptoms with durable long-term effects. >136 clinical studies with psilocybin have been completed or are ongoing for various indications, including psychiatric, neurodegenerative, chronic pain, and more. However, despite considerable clinical evidence for the therapeutic effects, the underlying molecular mechanisms responsible for its beneficial actions remain enigmatic. Studies with psilocybin have overwhelmingly focused on neurological impacts and/or behavioral outcomes; however, few studies have evaluated other mechanisms by which it exerts beneficial effects. It has recently been hypothesized that psilocybin may exert beneficial effects on aging; however, no studies have experimentally investigated the impact of psilocybin on senescence/aging. Using a previously validated human cell model of replicative senescence in vitro, cells were treated with psilocybin continuously throughout their replicative cellular lifecycle. Psilocybin treatment led to a dose-dependent decrease in cell-cycle arrest markers, increased markers of DNA replication and proliferation, reduced senescence-associated secretory phenotype (SASP), and reduced oxidative stress levels. Further, psilocybin did not demonstrate senolytic activity. Overall, these data are the first experimental evidence suggesting that psilocybin may decelerate the process of cellular senescence. Given that senescence and inflammation contribute to the pathogenesis of numerous age-related diseases, these studies could lay the foundation for the use of psilocybin as a therapeutic strategy for many age-related disease indications and/or as a geroprotective agent.

topic_tags:
Chronic Pain,Mechanism of Action,Biomarkers,Aging,Cellular Senescence,Oxidative Stress,In Vitro Study,Inflammation

raw_json:
{"europe_pmc_id":"PPR682607","source":"PPR","pub_type":null,"publisher":"Research Square","importer":"Europe PMC"}


authors: Luoma JB, Wilson-Poe A, Pertl K, Hoffman K, Bazinet A, Stauffer C, McCarty D, Korthuis P.
journal: PsyArXiv
publication_date: 2024-10-30
doi: 10.31234/osf.io/dwhcu_v1
source_url: https://doi.org/10.31234/osf.io/dwhcu_v1
substance_tags: psilocybin
topic_tags: Wellbeing,Clinical Trial,Safety
study_type: Clinical Trial
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
Personal Psychedelic Experience as a Training Qualification for Facilitators: A Thematic Analysis of Qualitative Interviews with Psilocybin Experts

abstract:
Emerging legal frameworks in Oregon and Colorado license facilitators to support adults receiving psychedelic services. The current legal frameworks are silent regarding facilitators’ personal experience with psychedelics. An eDelphi process recruited 36 experts with at least 5 years’ experience facilitating psilocybin experiences in ceremonial settings, indigenous practices, or clinical trials. Respondents completed in-depth, semi-structured qualitative interviews via secure web links. Interviews were recorded, transcribed, and analyzed using Thematic Analysis. Experts with a mean of 15.2 (SD13.1) years’ experience providing psilocybin services expressed the importance of first-hand experience with psychedelics as a qualification for the emerging workforce. One participant questioned the necessity of personal psychedelic experience. Experts suggested that personal experience may indirectly support high-quality care because it enhances facilitators’ personal wellbeing, and may help facilitators understand the complexity and nature of their clients’ psychedelic experiences. Novel statelegal psychedelic paradigms create a real-world opportunity to assess associations between facilitators’ personal psychedelic experience and the safety and outcomes of psychedelic services.

raw_json:
{"europe_pmc_id":"PPR1055707","source":"PPR","pub_type":null,"publisher":"PsyArXiv","importer":"Europe PMC"}


authors: Hinchcliffe JK, Bartlett J, Thomas CW, Golden CT, Gilmour G, Bortolotto ZA, Robinson ES.
journal: bioRxiv
publication_date: 2026-04-21
doi: 10.64898/2026.04.20.719483
source_url: https://doi.org/10.64898/2026.04.20.719483
substance_tags: psilocybin
topic_tags: Pharmacology,Mechanism of Action,Receptor Pharmacology,Emotional Processing,Animal Study
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
Distinct Modulatory Effects on Affective Biases by Different Serotonergic Psychedelics and MDMA in Male Rats: Possible Implications for Antidepressant Effects

abstract:
Affective biases are important neuropsychological mechanisms by which emotions modulate cognition, behaviour and the subjective experience of mood. Previous studies have shown that the rapid-acting antidepressant, ketamine, and serotonergic psychedelic, psilocybin, modulate affective biases in a translational rat model. Both treatments differ from conventional, delayed onset antidepressants in being able to attenuate negatively biased memories and facilitate re-learning with a more positive affective valence. Psilocybin, but not ketamine, also positively biased new experiences, an effect similar to conventional antidepressants. This study used the different affective bias test protocols, in adult male rats, to investigate the effects of acute treatment with the serotonergic psychedelics N,N-DMT, LSD and 5-MeO-DMT, and MDMA. These drugs have different pharmacology in relation to their effects on serotonin receptor subtypes and we hypothesised this may influence their modulation of affective biases. When comparing the ability to attenuate a negatively biased memory, only MDMA had specific effects although for all drugs tested, retrieval of the FG7142-induced negative affective bias was more variable and less robust statistically. LSD attenuated the negative bias at higher doses but had non-specific effects on memory retrieval. At 24hrs post treatment only N,N-DMT had a sustained effect and none of the treatments facilitated re-learning with a more positive affective valence. However, like psilocybin and conventional antidepressants, N,N-DMT positively biased new experiences. These findings suggest there are divergent affective bias modulating effects associated with different psychedelics which may be relevant to their antidepressant effects.

raw_json:
{"europe_pmc_id":"PPR1213772","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: A whole genome atlas of 81 Psilocybe genomes as a resource for psilocybin production.
authors: McKernan K, Kane L, Helbert Y, Zhang L, Houde N, McLaughlin S.
journal: F1000Res
publication_date: 2021-12-16
doi: 10.12688/f1000research.55301.2
source_url: https://doi.org/10.12688/f1000research.55301.2
substance_tags: psilocybin,psilocin
topic_tags: Mechanism of Action,Genomics
study_type: Other
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
abstract:
The Psilocybe genus is well known for the synthesis of valuable psychoactive compounds such as Psilocybin, Psilocin, Baeocystin and Aeruginascin. The ubiquity of Psilocybin synthesis in Psilocybe has been attributed to a horizontal gene transfer mechanism of a ~20Kb gene cluster. A recently published highly contiguous reference genome derived from long read single molecule sequencing has underscored interesting variation in this Psilocybin synthesis gene cluster. This reference genome has also enabled the shotgun sequencing of spores from many Psilocybe strains to better catalog the genomic diversity in the Psilocybin synthesis pathway. Here we present the de novo assembly of 81 Psilocybe genomes compared to the P.envy reference genome. Surprisingly, the genomes of Psilocybe galindoi, Psilocybe tampanensis and Psilocybe azurescens lack sequence coverage over the previously described Psilocybin synthesis pathway but do demonstrate amino acid sequence homology to a less contiguous gene cluster and may illuminate the previously proposed evolution of psilocybin synthesis.

raw_json:
{"europe_pmc_id":"PPR433636","source":"PPR","pub_type":null,"publisher":"F1000Res","importer":"Europe PMC"}


title: Enhanced visual contrast suppression during peak psilocybin effects: A psychophysical study
journal: PsyArXiv
publication_date: 2024-01-10
source_url: https://osf.io/preprints/psyarxiv/5rm62_v1
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action
study_type: Other
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"5rm62_v1","version":1,"reviews_state":"accepted"}
abstract:
In visual perception, an effect known as surround suppression occurs wherein the apparent contrast of a center stimulus is reduced when it is presented within a higher-contrast surrounding stimulus. Many key aspects of visual perception involve surround suppression, yet the neuromodulatory processes involved remain unclear. Psilocybin is a serotonergic psychedelic compound known for its robust effects on visual perception, particularly texture, color, object, and motion perception. We asked whether surround suppression is altered under peak effects of psilocybin. Using a contrast-matching task with different center-surround stimulus configurations, we measured surround suppression after 25 mg of psilocybin compared with placebo (100 mg niacin). After taking psilocybin, participants (n = 6) reported stronger surround suppression of perceived contrast compared to placebo. Furthermore, we found that the intensity of subjective ‘psychedelic visuals’ induced by psilocybin correlated positively with the magnitude of surround suppression. We note the potential impact of our findings for the field of psychiatry, given that recent studies have demonstrated weakened visual surround suppression in patients with major depressive disorder, for which psilocybin has recently been identified as a breakthrough therapy. Our finding is thus relevant to understanding the visual effects of psilocybin, and the potential mechanisms of psychedelic therapies for mental health disorders.

keywords:
context effects, hallucinogenic, illusion, perception, psilocybin, psychedelic, surround suppression, visual, Neuroscience, Cognitive Neuroscience


authors: Ivan V, Tomas-Cuesta D, Esteves I, Luczak A, Mohajerani M, McNaughton B, Gruber A.
journal: Authorea Preprints
publication_date: 2024-04-21
doi: 10.22541/au.171378690.00112411/v1
source_url: https://doi.org/10.22541/au.171378690.00112411/v1
substance_tags: psilocybin
topic_tags: Mechanism of Action,Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
Psilocybin reduces functional connectivity and the encoding of spatial information by neurons in mouse retrosplenial cortex

abstract:
Psychedelic drugs have profound effects on perception, cognition, and mood. How psychedelics affect neural signaling to produce these effects remains poorly understood. We investigated the effect of the classic psychedelic psilocybin on neural activity patterns and spatial encoding in the retrosplenial cortex of head-fixed mice navigating on a treadmill. The place specificity of neurons to distinct locations along the belt was reduced by psilocybin. Moreover, the stability of place-related activity across trials decreased. Psilocybin also reduced the functional connectivity among simultaneously recorded neurons. The 5-HT2AR (serotonin 2A receptor) antagonist ketanserin blocked the majority of these effects. These data are consistent with proposals that psychedelics increase the entropy of neural signaling, and provide a potential neural mechanism contributing to disorientation frequently reported by humans after taking psychedelics.

raw_json:
{"europe_pmc_id":"PPR841741","source":"PPR","pub_type":null,"publisher":"Authorea Preprints","importer":"Europe PMC"}


journal: medRxiv
publication_date: 2024-08-25
doi: 10.1101/2024.08.26.24311611
source_url: https://doi.org/10.1101/2024.08.26.24311611
substance_tags: psilocybin,psilocin
topic_tags: Anxiety,Brain Imaging,Consciousness,Emotional Processing,Clinical Trial,Healthy Volunteers,Safety
study_type: Clinical Trial
source_name: medRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
The phenomenology of psilocybin’s experience mediates subsequent persistent psychological effects independently of sex, previous experience or setting

authors:
Klučková T, Nikolič M, Tylš F, Viktorin V, Vejmola Č, Viktorinová M, Bravermanová A, Androvičová R, Andrashko V, Korčák J, Zach P, Hájková K, Kuchař M, Balíková M, Brunovský M, Horáček J, Páleníček T.

abstract:
Background Recent studies have intensively explored the potential antidepressant effects of psilocybin. However, important variables such as previous experience, repeated administration, setting and sex remain underexplored. This study describes the acute psilocybin experience and long-term effects in a small sample of healthy individuals. Methods In a double-blind, placebo-controlled, cross-over study, 40 healthy participants (20 females, mean age 38, sd 8) received two doses of psilocybin 0.26 mg/kg per os at least 56 days apart (mean 354 days) in two study arms (EEG and fMRI). Near half of participants had experience with psychedelics. The Altered State of Consciousness Scale (ASC) and a visual analogue scale (VAS) on emotional valence of the phenomenology assessed acute phenomenology. The Persisting Effects Questionnaire (PEQ) assessed long- term effects. Venous blood samples were taken to measure serum psilocin levels. Results All results were independent of previous experience, sex, EEG or fMRI arm/setting. Acute psychedelic effects were of moderate intensity on ASC. The VAS showed mostly pleasant and fluctuating, and only one unpleasant only experience. All experiences resolved in a positive or neutral state at the end of the session. Psilocybin induced sustained positive effects on all domains of the PEQ, with negligible negative effects. Oceanic Boundlessness and Visual Restructuralization were associated with positive effects on PEQ. Contrary to expectations, Dread of Ego Dissolution, typically associated with fearful experiences, was not associated with PEQ negative outcomes. The type of experience (pleasant or mixed) did not correlate with the intensity or direction of the lasting effect; however, peak experiences culminating in a positive mood were associated with positive long- term effects. Conclusion In our sample repeated administration of psilocybin to healthy volunteers, induces positive, lasting effects. This underscores the psychological safety of psilocybin in a laboratory setting and supports its repeated use in clinical trials. In particular, challenging or anxiety-provoking experiences in controlled environments did not lead to adverse long-term outcomes. Clinical trial registration: EudraCT 2012-004579-37, https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-004579-37/CZ.

raw_json:
{"europe_pmc_id":"PPR902135","source":"PPR","pub_type":null,"publisher":"medRxiv","importer":"Europe PMC"}


title: Psilocybin as an antidepressant strategy - a review of safety aspects
authors: Zeiss R.
publication_date: 2023-07-18
source_url: https://europepmc.org/article/PMC/PMC10405689
substance_tags: psilocybin
topic_tags: Headache / Migraine,Review Article,Safety,Adverse Events
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
abstract:
Introduction Psilocybin is considered a classical psychedelic and is increasingly attracting scientific and media attention as an alternative approach to the treatment of various mental disorders. Apart from its efficacy, an important question is the tolerability and safety of psilocybin in general and in a controlled environment. Accurate knowledge of drug safety aspects might be essential for applicability in clinical practice and for drug adherence. Objectives This paper aims to provide an overview of drug safety aspects of psilocybin. Methods A narrative review was conducted. The literature search was conducted using the bibliographic database MEDLINE. Results The literature search of papers published in recent years showed no serious side effects under psilocybin in controlled study conditions. Common reported ADRs were headache, gastrointestinal complaints such as nausea, diarrhoea and vomiting, tachycardia and arterial hypertension. The lethal dose of psilocybin is many times higher than the therapeutic dose and overdose deaths have not been identified. An often mentioned problem is the occurrence of hallucinogenic persisting perception disorder (HPPD) which, however, did not occur in the studies examined and is most likely to be a problem in the context of recreational use. The results on the safety of psilocybin must be regarded as preliminary; in the studies conducted, risk populations were predominantly excluded, which is, however, relevant for everyday clinical practice. The risk of delusional experiences and so-called “bad trips” is also a relevant safety risk, as it can be associated with risky behaviours. However, these would also be observed more in the area of recreational use. Conclusions The use of psilocybin in rigorously controlled study designs appears to be predominantly safe and without serious side effects. At the same time, it should be noted that the results must be considered preliminary and many questions remain open. Many of the risks are more likely to occur in uncontrolled recreational use of psilocybin. At the same time, we see a certain risk in the use of a substance associated with high expectations and a certain “fame” that, without appropriate regulations, the boundaries between sensible therapeutic use and abusive use could become blurred and permeable. Disclosure of Interest None Declared

raw_json:
{"europe_pmc_id":"PMC10405689","source":"PMC","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Lazar M, Brownstien M, Botvinnik A, Shevakh C, Shahar O, Lifschytz T, Lerer B.
journal: bioRxiv
publication_date: 2024-09-22
doi: 10.1101/2024.09.22.614317
source_url: https://doi.org/10.1101/2024.09.22.614317
substance_tags: psilocybin
topic_tags: Anxiety,OCD,Neuroplasticity,Emotional Processing,Animal Study,Drug Interactions
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
Premorbid Characteristics of the SAPAP3-Mouse Model of Obsessive-Compulsive Disorder: Behavior, Neuroplasticity, and Psilocybin Treatment

abstract:
Background SAPAP3-knockout (KO) mice develop excessive self-grooming behavior at 4-6 months of age, serving as a model for obsessive-compulsive disorder (OCD). Given that anxiety often precedes OCD diagnosis in humans, this study investigated whether juvenile SAPAP3-KO mice exhibit anxiety-like behaviors before developing the self-grooming phenotype, and whether such behaviors respond to psilocybin treatment. The study also examined four key neuroplasticity-related synaptic proteins-GAP43, PSD95, synaptophysin, and SV2A - as SAPAP3 is a postsynaptic scaffold protein that interacts with PSD95 and may affect synaptic function. Methods Two studies were conducted using male and female juvenile (10-13 weeks) SAPAP3- KO mice. Study 1 compared behavioral phenotypes between homozygous (HOM), heterozygous (HET), and wild-type (WT) mice. Study 2 evaluated a different sample of HOM and WT mice and assessed the effect of psilocybin (4.4 mg/kg) on identified behavioral differences. Both studies included comprehensive behavioral testing focused on anxiety, social interaction, and cognitive function. Additionally, levels of four synaptic proteins were measured by western blots in the frontal cortex, hippocampus, amygdala, and striatum of juvenile and adult SAPAP3-KO mice. Results In both studies, juvenile HOM SAPAP3-KO mice showed significant anxiety-like behaviors compared to WT mice, spending less time in open field center, and elevated plus maze open arms. They also buried fewer marbles and found fewer buried Oreos than WT mice. Psilocybin treatment did not improve these behavioral manifestations. Analysis of synaptic proteins revealed significant increases in GAP43, synaptophysin, and SV2A across multiple brain regions in adult male HOM mice and of SV2A in the frontal cortex of HOM females compared to WT, but not in juvenile mice of either sex. Conclusions Juvenile SAPAP3-KO mice exhibit anxiety-like behaviors before developing the characteristic excessive self-grooming phenotype, paralleling the prodromal anxiety often seen in human OCD. Unlike in adult SAPAP3-KO mice, these early manifestations were not responsive to psilocybin treatment. The age-dependent increases in synaptic proteins observed in adult but not juvenile male SAPAP3-KO mice and to a lesser extent in females, may represent compensatory plasticity changes in response to the phenotype. These results provide insights into the developmental trajectory of OCD-like behaviors and associated neuroplastic adaptations. Significance Statement Obsessive-compulsive disorder (OCD) frequently emerges during adolescence, with anxiety as a common prodromal symptom. This study investigated behavioral and molecular characteristics of juvenile SAPAP3 knockout (KO) mice, an established preclinical model of OCD, prior to manifestation of their characteristic excessive grooming phenotype. Juvenile SAPAP3 KO mice exhibited significant anxiety-like behaviors on multiple behavioral measures. While psilocybin treatment reduces OCD-like behaviors in adult SAPAP3 knockout mice, it did not ameliorate anxiety-like behaviors in juvenile mice, indicating age-dependent therapeutic effects. Notably, adult male SAPAP3 KO mice showed elevated levels of synaptic plasticity-related proteins in emotion-regulatory brain regions, whereas juvenile KO showed no such alterations. These findings demonstrate that anxiety precedes compulsive behaviors in this model and reveal age- dependent neuroplasticity changes. This developmental trajectory parallels clinical observations in OCD and provides a framework for investigating early intervention strategies.

raw_json:
{"europe_pmc_id":"PPR914309","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


authors: Kaadt E, Søkilde R, Hansen H, Raval N, Lundgaard L, Just J, Knudsen G, Elfving B.
journal: Research Square
publication_date: 2024-01-11
doi: 10.21203/rs.3.rs-3787179/v1
source_url: https://doi.org/10.21203/rs.3.rs-3787179/v1
substance_tags: psilocybin
topic_tags: Depression,Personality Change,Inflammation
study_type: Other
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
MicroRNAs underlying the antidepressant effect of psilocybin - Establishing an nCounter pipeline for microRNA-quantification in the pig brain

abstract:
Abstract Novel treatment strategies are needed to overcome some of the current challenges related to treatment resistance and treatment latency within the psychiatric field. Recently, psilocybin has shown promise as a novel treatment of major depressive disorder. A single dose of psilocybin is associated with lasting changes in personality and mood. In parallel, various studies have indicated that microRNAs (miRNAs) are regulated after antidepressive interventions. Here, pigs were used to study the transcriptional profiles of miRNAs in the prefrontal cortex (PFC) and hippocampus (HIP), 1 day and 1 week after a single dose of psilocybin. A streamlined process was developed to adapt the Nanostring nCounter technology, specifically the Human v3b miRNA Assay panel, for compatibility with pig tissue samples. The mirmachine tool was used to select miRNAs with complete human-pig sequence conservation to make a conservative reannotation of pig microRNAs. Furthermore, different normalization strategies were employed. Utilizing this pipeline, dysregulation of 12 miRNAs in the PFC and 2 miRNAs in the HIP was ∂identified 1 day after psilocybin administration. Seven days after psilocybin administration, only 4 dysregulated miRNAs were observed in the HIP. Among the 18 identified miRNAs, 9 have previously been linked to depression. Notably, miR-212-3p and miR-107 displayed robust acute regulation across all four normalization strategies in the PFC. The two miRNAs are known to exert anti-inflammatory effects, mirroring previously reported effects of psilocybin. These results suggest that psilocybin may exert its acute and sustained molecular effects through the regulation of specific miRNAs in core brain areas of depression.

raw_json:
{"europe_pmc_id":"PPR786762","source":"PPR","pub_type":null,"publisher":"Research Square","importer":"Europe PMC"}


title: Systematic Review on the Mechanisms of Action of Psilocybin in the Treatment of Depression
authors: Lin M, Lee H, Tsang V, Chai B, Howard A, Uy C, Elefante J.
publication_date: 2023-07-18
source_url: https://europepmc.org/article/PMC/PMC10434693
substance_tags: psilocybin
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
abstract:
Introduction Despite emerging evidence suggesting the efficacy of psilocybin in the treatment of mood disorders such as depression, the exact mechanisms by which psilocybin is able to elicit these antidepressant effects remains unknown. Objectives As the use of psilocybin as a treatment modality for depression has garnered increasing interest, this study aims to summarize the existing evidence of the mechanism of action with which psilocybin alleviates depressive symptoms, focusing specifically on the neurobiological effects of psilocybin in human subjects. Methods Four databases (Ovid MEDLINE, EMBASE, psychINFO, and Web of Science) were searched using a combination of MeSH terms and free text keywords in September 2021. The original search included both human and animal studies and must have included testing of the mechanism of action of psilocybin. Only antidepressant effects were considered, with no other mood disorders or psychiatric diagnoses included. Two independent researchers screened at every stage of the review, with a third researcher resolving any conflicts. Though a full systematic review outlining the current literature on the complete mechanisms of action of psilocybin on depression was conducted, this abstract will focus specifically on the nine papers that included human subjects, disregarding the five animal models. PROSPERO registration number: 282710. Results After removing duplicates, the search identified 2193 papers and forty-nine were selected for full text review. Out of nine papers outlining the mechanisms of action of psilocybin use in human subjects, three papers investigated psilocybin’s effect on serotonin or glutamate receptor activity, two found an increase in synaptogenesis in regions such as the medial frontal cortex and hippocampus. Four found variation in blood flow to the amygdala, two found altered blood flow to the prefrontal cortex, and one found a reduction in delta power during sleep. Four papers found changes in functional connectivity or neurotransmission, most commonly in the hippocampus or prefrontal cortex. Conclusions Overall, the exact mechanism of psilocybin’s potential antidepressant effect remains unclear. Multiple pathways may be involved, including alterations in serotonin and glutamate receptor activity, as well as shifts in amygdala activity, neurogenesis, and functional connectivity in various brain regions. The relative lack of studies, and the variety of neurobiological modalities and endpoints used challenged the consolidation of data into consensus findings. Further studies are needed to better characterize psilocybin’s mechanism of action and to better understand the clinical effects of the use of psilocybin in the treatment of depression. Disclosure of Interest None Declared

topic_tags:
Depression,Neuroplasticity,Neurogenesis,Mechanism of Action,Receptor Pharmacology,Systematic Review,Review Article,Animal Study

raw_json:
{"europe_pmc_id":"PMC10434693","source":"PMC","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Defining ‘psychedelic’
journal: PsyArXiv
publication_date: 2025-12-03
source_url: https://osf.io/preprints/psyarxiv/5ybhk_v1
substance_tags: psilocybin
topic_tags: Pharmacology,Receptor Pharmacology,Consciousness
study_type: Other
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"5ybhk_v1","version":1,"reviews_state":"accepted"}
abstract:
Humphry Osmond coined the term ‘psychedelic’ in 1956, conjoining ‘psyche’ for ‘soul’ and ‘delic’ from ‘dêlos’ for ‘to manifest’ or ‘illuminate.’ Soul-illumination is an adjective that describes a psychological state or process. However, Osmond’s intention was to use the adjective to name- not just a state- but a category of drug that can induce the subjective effect as its principal action; thus, when used in this way, psychedelic becomes a ‘nominalized adjective;’ describing a ‘thing’ (i.e., a drug) that can induce the described state. Consistent with the etymology of psychedelic, the present work is guided by phenomenology, recognizing its fundamental ontology. Accordingly, we examine the main subjective effect of three different psychoactive drugs, psilocybin, ketamine, and MDMA (variable label, Drug). Over two-hundred participants rated Delphi-derived subjective rating scale items based on their personal experiences with all three drugs. Factor analyses revealed 3 or 4 sufficiently independent dimensions of subjective experience (variable label, Effects). A machine learning classifier successfully predicted Drug from Effects, validating the hypothesis that psilocybin, ketamine and MDMA are categorically distinct as determined by their differential ability to induce the following Effects: 1) visions and psychological insight (psilocybin), 2) dissociation (ketamine) and 3) pro-social feelings, epitomized by feelings of love (MDMA). We conclude that psilocybin is an exemplar psychedelic drug- a category of drug definable by the induction of a psychedelic state- the quintessential psychedelic phenomenon. This state is characterized by visions and psychological insight.

keywords:
classic psychedelics, consciousness, hallucinogen, ketamine, mdma, psilocybin, psychedelic, psychedelics, psychedelic therapy, psychedelic trip, serotonin, Psychiatry, Neuroscience, Cognitive Neuroscience, Clinical Neuroscience, Behavioral Neuroscience, Social and Behavioral Sciences, Clinical Psychology, Psychopharmacology


authors: Mortaheb S, Fort LD, Mason NL, Mallaroni P, Ramaekers JG, Demertzi A.
journal: bioRxiv
publication_date: 2023-09-17
doi: 10.1101/2023.09.18.558309
source_url: https://doi.org/10.1101/2023.09.18.558309
substance_tags: psilocybin
topic_tags: Consciousness,Healthy Volunteers
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
Dynamic Functional Hyperconnectivity after Psilocybin Intake is Primarily Associated with Oceanic Boundlessness

abstract:
To provide insights into neurophenomenological richness after psilocybin intake, we investigated the link between dynamical brain patterns and the ensuing phenomenological pattern after psilocybin intake. Healthy participants received either psilocybin (n=22) or placebo (n=27) while in ultra-high field 7T MRI scanning. Changes in the phenomenological patterns were quantified using the 5-Dimensional Altered States of Consciousness (5D-ASC) Rating Scale, revealing alterations across all dimensions under psilocybin. Changes in the neurobiological patterns displayed that psilocybin induced widespread increases in averaged functional connectivity. Time-varying connectivity analysis unveiled a recurrent hyperconnected pattern characterized by low BOLD signal amplitude, suggesting heightened cortical arousal. In terms of neurophenomenology, canonical correlation analysis primarily linked the transition probabilities of the hyperconnected pattern with feelings of oceanic boundlessness (OBN), and secondly with visionary restructuralization. We suggest that the brain’s tendency to enter a hyperconnected-hyperarousal pattern under psilocybin represents the potential to entertain variant mental associations. For the first time, these findings link brain dynamics with phenomenological alterations, providing new insights into the neurophenomenology and neurophysiology of the psychedelic state.

raw_json:
{"europe_pmc_id":"PPR727205","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


authors: Kolbman N, Liu T, Guzzo P, Gilligan JP, Mashour GA, Vanini G, Pal D.
journal: bioRxiv
publication_date: 2023-08-27
doi: 10.1101/2023.08.26.554802
source_url: https://doi.org/10.1101/2023.08.26.554802
substance_tags: psilocybin
topic_tags: Chronic Pain,Animal Study
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
Intravenous psilocybin administration attenuates mechanical hypersensitivity in a rat model of chronic pain

abstract:
There is a renewed interest in the therapeutic potential of psychedelics, including psilocybin, in treating mental health disorders. However, there are no data on the efficacy of psilocybin in alleviating chronic pain. In this study, we investigated the effect of psilocybin on mechanical hypersensitivity and thermal hyperalgesia in a rat model of formalin-induced chronic pain. Adult male and female rats were surgically implanted with a jugular vein catheter for psilocybin or saline administration. After two weeks of post-surgical recovery and conditioning, baseline responses to mechanical (von Frey assay) and thermal (hot plate assay) stimuli were measured. Twenty-four hours after baseline measurements, rats received a subcutaneous injection of formalin (5%, 50µL) into one of the hind paws and 2h later, responses to the mechanical and thermal stimuli were measured. Twenty-four hours after formalin injection, rats received an intravenous bolus of 1 mg/kg psilocybin (n=14) or 10 mg/kg psilocybin (n=12) or saline (n=13), and approximately 3h later, responses to the mechanical and thermal stimuli were measured. Rats were tested every other day during week 1, and then weekly for the next 3 weeks. Formalin injection induced thermal hyperalgesia and bilateral mechanical hypersensitivity in the hind paws of all rats. Intravenous psilocybin produced significant attenuation (p

raw_json:
{"europe_pmc_id":"PPR704236","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


authors: Wojtas A, Bysiek A, Wawrzczak-Bargiela A, Maćkowiak M, Gołembiowska K.
journal: Preprints.org
publication_date: 2023-09-24
doi: 10.20944/preprints202309.1649.v1
source_url: https://doi.org/10.20944/preprints202309.1649.v1
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Receptor Pharmacology
study_type: Clinical Trial
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
Limbic System Response to Psilocybin and Ketamine Administration in Rats: A Neurochemical and Behavioral Study

abstract:
Pathophysiology of depression is related with reduced volume of the hippocampus and amygdala and hypertrophy of the nucleus accumbens. The mechanism of these changes is not well under-stood, but clinical studies have shown that administration of the fast-acting antidepressant keta-mine reversed the decrease in hippocampus and amygdala volume in depressed patients, and the magnitude of this effect correlated with the reduction of depressive symptoms. In the present study, we attempted to find out whether the psychedelic substance psilocybin affects neurotransmission in the limbic system in comparison to ketamine. Psilocybin and ketamine increased the release of dopamine (DA) and serotonin (5-HT) in the nucleus accumbens of naive rats as demonstrated using microdialysis. Both drugs influenced glutamate and GABA release in the nucleus accumbens, hippocampus and amygdala and increased ACh levels in the hippocampus. The changes in D2, 5-HT1A and 5-HT2A receptor density in the nucleus accumbens and hippocampus was observed as a long-lasting effect. A marked anxiolytic effect of psilocybin in acute phase and 24 h post-treatment was shown in the open field test. These data provide the neurobiological background for psilocybin effect on stress, anxiety and structural changes in the limbic system and translate into antidepres-sant effect of psilocybin in depressed patients.

raw_json:
{"europe_pmc_id":"PPR730140","source":"PPR","pub_type":null,"publisher":"Preprints.org","importer":"Europe PMC"}


title: Distinct classes of antidepressants commonly act to shape pallidal structure and function in mice
journal: bioRxiv
publication_date: 2024-09-23
doi: 10.1101/2024.09.23.614626
source_url: https://doi.org/10.1101/2024.09.23.614626
substance_tags: psilocybin,psilocin
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
authors:
Abe Y, Sugiura Y, Maeda R, Taira S, Yoshida K, Ibi D, Moritoh S, Hashimoto K, Yagishita S, Tanaka KF.

abstract:
Antidepressants including selective serotonin reuptake inhibitors, ketamine, and psilocybin are all effective for treating depression despite their distinct primary mechanisms. We hypothesized that these drugs may share a common mechanism that underlies their therapeutic actions. We treated mice with one of the following: escitalopram, R- / S -/ RS- ketamine, or psilocin. Additionally, groups exposed to electroconvulsive stimulation and a saline control were included. Following treatment, fixed brains underwent structural magnetic resonance imaging, and voxel-based morphometry was performed to evaluate brain-wide volumetric changes. Compared with control treatment, we observed greater volumes in the nucleus accumbens, ventral pallidum, and external globus pallidus across all antidepressant treatments, and a smaller volume in the mediodorsal thalamus. Specifically, R -ketamine, RS -ketamine, and psilocin induced more pronounced hypertrophy of the ventral pallidum, whereas selective serotonin reuptake inhibitors and S -ketamine predominantly increased the volume of the external globus pallidus. Further analyses using super-resolution microscopy and imaging mass spectrometry revealed corresponding microstructural and molecular changes. Greater pallidal volume was associated with striatal medium spiny neuron terminal hypertrophy and elevated γ-aminobutyric acid (GABA) levels. Interestingly, all antidepressants were also associated with higher striatal dopamine content. Moreover, striatal vesicular GABA transporter overexpression reproduced the medium spiny neuron terminal hypertrophy and increased pallidal GABA content, and was associated with a reduction in innate anxiety. These findings indicate that despite their pharmacological diversity, antidepressant treatments lead to shared pallidum-centered structural and molecular changes. We propose that these shared changes may potentiate the striato-pallidal inhibitory circuit, thereby contributing to the overall antidepressant effect.

topic_tags:
Depression,Anxiety,End-of-Life Distress,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Aging,Animal Study

raw_json:
{"europe_pmc_id":"PPR914838","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


journal: bioRxiv
publication_date: 2023-12-12
doi: 10.1101/2023.12.12.571374
source_url: https://doi.org/10.1101/2023.12.12.571374
substance_tags: psilocybin
topic_tags: Depression,Eating Disorders,Mechanism of Action,Receptor Pharmacology,Clinical Trial,Animal Study
study_type: Clinical Trial
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
Psilocybin prevents activity-based anorexia in female rats by enhancing cognitive flexibility: contributions from 5-HT1A and 5-HT2A receptor mechanisms

authors:
Conn K, Milton L, Huang K, Munguba H, Ruuska J, Lemus M, Greaves E, Homman-Ludiye J, Oldfield B, Foldi C.

abstract:
Psilocybin has shown promise for alleviating symptoms of depression and is currently in clinical trials for the treatment of anorexia nervosa (AN), a condition that is characterised by persistent cognitive inflexibility. Considering that enhanced cognitive flexibility after psilocybin treatment is reported to occur in individuals with depression, it is plausible that psilocybin could improve symptoms of AN by breaking down cognitive inflexibility. A mechanistic understanding of the actions of psilocybin is required to tailor the clinical application of psilocybin to individuals most likely to respond with positive outcomes. This can only be achieved using incisive neurobiological approaches in animal models. Here, we use the activity-based anorexia (ABA) rat model and comprehensively assess aspects of reinforcement learning to show that psilocybin (post-acutely) improves body weight maintenance in female rats and facilitates cognitive flexibility, specifically via improved adaptation to the initial reversal of reward contingencies. Further, we reveal the involvement of signalling through the serotonin (5-HT) 1A and 5-HT2A receptor subtypes in specific aspects of learning, demonstrating that 5-HT1A antagonism negates the cognitive enhancing effects of psilocybin. Moreover, we show that psilocybin elicits a transient increase and decrease in cortical transcription of these receptors ( Htr2a and Htr1a, respectively), and a further reduction in the abundance of Htr2a transcripts in rats exposed to the ABA model. Together, these findings support the hypothesis that psilocybin could ameliorate cognitive inflexibility in the context of AN and highlight a need to better understand the therapeutic mechanisms independent of 5-HT2A receptor binding.

raw_json:
{"europe_pmc_id":"PPR773743","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


authors: Wall MB, Demetriou L, Giribaldi B, Roseman L, Ertl N, Erritzoe D, Nutt DJ, Carhart-Harris RL.
journal: medRxiv
publication_date: 2023-06-02
doi: 10.1101/2023.05.29.23290667
source_url: https://doi.org/10.1101/2023.05.29.23290667
substance_tags: psilocybin
study_type: Other
source_name: medRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
Reduced brain responsiveness to emotional stimuli with escitalopram but not psilocybin therapy for depression

abstract:
Psilocybin therapy is an emerging intervention for depression that may be at least as effective as standard first-line treatments i.e., Selective Serotonin Reuptake Inhibitors (SSRIs). Here we assess neural responses to emotional faces (fear, happy, and neutral) using Blood Oxygen-Level Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) in two groups with major depressive disorder: 1) a ‘psilocybin group’ that received two dosing sessions with 25mg plus six weeks of daily placebo, and 2) an ‘escitalopram group’ that received six weeks of the SSRI escitalopram, plus two dosing sessions with an inactive/placebo dose of 1mg psilocybin. Both groups had an equal amount of psychological support throughout. An emotional face fMRI paradigm was completed at baseline (pre-treatment) and at the six-week post-treatment primary endpoint (three weeks following psilocybin dosing sessions). An analysis examining the interaction between patient group (psilocybin vs. escitalopram) and time-point (pre-vs. post-treatment) showed a robust effect in a distributed network of cortical brain regions. Follow-up analyses showed that post-treatment BOLD responses to emotional faces of all types were significantly reduced in the escitalopram group, with no change, or even a slight increase, in the psilocybin group. Specific analyses of the amygdala showed a reduction of response to fear faces in the escitalopram group, but no effects for the psilocybin group. Despite large improvements in depressive symptoms in the psilocybin group, psilocybin-therapy had only a minor effect on brain responsiveness to emotional stimuli. We suggest that reduced emotional responsiveness may be a biomarker of SSRIs’ antidepressant action that is not shared by psilocybin-therapy.

topic_tags:
Depression,Brain Imaging,Receptor Pharmacology,Biomarkers,Aging,Emotional Processing,Drug Interactions

raw_json:
{"europe_pmc_id":"PPR670172","source":"PPR","pub_type":null,"publisher":"medRxiv","importer":"Europe PMC"}


journal: medRxiv
publication_date: 2025-11-30
doi: 10.1101/2025.12.01.25341335
source_url: https://doi.org/10.1101/2025.12.01.25341335
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Emotional Processing,Observational Study,Safety,Adverse Events
study_type: Observational Study
source_name: medRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
Real-World Effectiveness and Safety of Psychedelic-Assisted Psychotherapy: Outcomes from a Large-Scale Compassionate Use Cohort in Switzerland

authors:
Aboulafia-Brakha T, Buchard A, Mabilais C, Alaux S, Amberger C, Furtado L, Seragnoli F, Briefer J, Thorens G, Sabé M, Szczesniak L, Iuga R, Zullino D, Penzenstadler L.

abstract:
Background Classic serotonergic psychedelics such as LSD and psilocybin show promising antidepressant effects in controlled trials, but real-world data from routine clinical care remain limited. Methods This study retrospectively analysed routine data from adults with treatment-resistant depressive and/or anxiety disorders who received a first standardized Psychedelic-assisted Psychotherapy (PAP) cycle with 100 µg LSD or 25 mg psilocybin at a Swiss university hospital (May 2024-October 2025). Self-reported depression (BDI) and trait anxiety (STAI-T) were assessed at screening, one month before treatment, and 1-3 months post-treatment. In a subset of participants, cognitive emotion regulation (CERQ) was assessed pre- and post-treatment. Subjective drug effects and adverse events were recorded on the treatment day. Results The sample consisted of 115 patients (56.5% female; Mean age = 47.5 years). Depressive and anxiety symptoms significantly decreased over time (BDI: F(2,178) = 63.50, p < 0.001, partial η 2 = 0.42; STAI-T: F(1.74,145.9) = 16.97, p < 0.001, partial η 2 = 0.17), with no main effect of substance. CERQ analyses indicated reduced self-blame, rumination and catastrophizing, and increased positive refocusing and reappraisal. Perceived intensity followed distinct temporal profiles for LSD and psilocybin, but comparable subjective drug effects and clinical outcomes. Adverse events were mostly mild and transient, with no serious complications or treatment discontinuations. Conclusions In this compassionate-use real-world cohort, a first fully-active dose PAP session with LSD or psilocybin was well tolerated and associated with significant improvements in depressive and anxiety symptoms. These findings support the feasibility and effectiveness of PAP in specialised routine care.

raw_json:
{"europe_pmc_id":"PPR1128175","source":"PPR","pub_type":null,"publisher":"medRxiv","importer":"Europe PMC"}


authors: Kiraga M, Kuypers KPC, Uthaug MV, Ramaekers J, Mason NL.
journal: medRxiv
publication_date: 2022-03-01
doi: 10.1101/2022.03.02.22271743
source_url: https://doi.org/10.1101/2022.03.02.22271743
substance_tags: psilocybin,psilocin
topic_tags: Anxiety,Mechanism of Action,Personality Change,Observational Study,Healthy Volunteers
study_type: Observational Study
source_name: medRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
Persisting decreases in state and trait anxiety post-psilocybin: A naturalistic, observational study among retreat attendees

abstract:
Anxiety disorders are the most common type of psychiatric disorders among Western countries. Evidence-based treatment modalities including pharmacological and cognitive-behavioral therapy result in relatively low response rates (average range: 51 - 58%). Historical and recent research suggests psychedelic drugs may be efficacious in alleviating anxiety-related symptoms among healthy and clinical populations. The main aim of the present study was investigation of the effects of psilocybin-containing truffles, when taken in a supportive group setting, on ratings of state and trait anxiety across self-reported healthy volunteers. Attendees of psilocybin ceremonies were asked to complete a test battery at three separate occasions: before the ceremony (baseline), the morning after, and one week after the ceremony. The test battery included questionnaires assessing state and trait anxiety (State-Trait Anxiety Inventory), mindfulness capacities (Five Facet Mindfulness Questionnaire), and personality (Big Five Inventory). Additionally, the psychedelic experience was quantified with the Persisting Effects Questionnaire and the Ego Dissolution Inventory. The total amount of psilocybin-containing truffles consumed by each participant was recorded, and a sample of the truffles was analyzed to determine psilocin concentrations. Fifty-two attendees (males= 25; females= 25; others= 2) completed parts of the baseline assessment, 46 (males= 21; females= 24; others= 1) completed assessments the morning after the ceremony, and 23 (males= 10; females= 13) completed assessments at the one-week follow-up. Average psilocin consumption across individuals was 27.1 mg. We observed medium to large reductions in anxiety measures (both state and trait) compared to baseline which persisted over a one-week period post-ceremony. At one week post-ceremony, the non-judging facet of the mindfulness scale was increased, while the personality trait neuroticism decreased, when compared to baseline. Additionally, we found neuroticism and ratings of ego dissolution to be the strongest predictors of reductions in trait and state anxiety, respectively. In sum, results indicate rapid and persisting (up to one week) anxiolytic effects in psilocybin retreat attendees, which are related to the acute experience of ego dissolution, as well as lasting changes in trait neuroticism. To understand whether these effects extend to wider populations suffering from heightened anxiety, and the mechanisms involved, further experimental research is needed.

raw_json:
{"europe_pmc_id":"PPR463532","source":"PPR","pub_type":null,"publisher":"medRxiv","importer":"Europe PMC"}


title: Psilocybin in the treatment of obsessive-compulsive disorder: What do we know so far?
authors: Descalço N, Medeiros A, Santos C, Borges G.
publication_date: 2021-08-12
source_url: https://europepmc.org/article/PMC/PMC9476072
substance_tags: psilocybin,psilocin
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
abstract:
Introduction Psilocybin is a naturally occurring plant alkaloid in mushrooms and a prodrug of psilocin. It is a serotonin receptor (5-HT2A) agonist and known psychedelic, with similar hallucinatory properties to lysergic acid diethylamide (LSD). It has been identified as a safe and effective option in treatment-resistant depression. Literature focus mainly on its use on depressive but its interest in other psychiatric disorders such as obsessive-compulsive disorder (OCD) has grown. Objectives To review the clinical evidence for the use of hallucinogens such as psilocybin in OCD. Methods Non-systematic review of literature found on PubMed/MEDLINE, Web of Science and Google Scholar, using the keywords “obsessive-compulsive disorder”, “psilocybin” and “hallucinogens”. Articles may include clinical trials, case report or case series. Articles found were admitted according to their relevance for the topic in review; only articles in English were included. Ongoing research trials on this topic were checked on ClinicalTrials.gov. Results So far, only one open-label non-randomized study directly assessed the effects of psilocybin on OCD patients that found acute reductions of obsessive-compulsive symptoms. Case reports of patients improving with off-label use of psilocybin are reported. There are two ongoing phase I research trials, aiming to explore the effect of the substance on symptomatology, hypothesizing that psilocybin will normalize cerebral connectivity and thus correlate with clinical improvement. Conclusions More research to establish the usefulness of psilocybin in OCD patients is needed; the collected data is encouraging are there may be a role for its use on this disorder.

topic_tags:
Depression,OCD,Receptor Pharmacology,Aging,Clinical Trial,Systematic Review,Review Article,Case Report,Treatment-Resistant Depression

raw_json:
{"europe_pmc_id":"PMC9476072","source":"PMC","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Synergistic Behavioral and Neuroplastic Effects of Psilocybin-NMDAR Modulator Administration
authors: Ben-Tal T, Pogodin I, Botvinnik A, Lifschytz T, Heresco-Levy U, Lerer B.
journal: bioRxiv
publication_date: 2024-11-27
doi: 10.1101/2024.11.28.625811
source_url: https://doi.org/10.1101/2024.11.28.625811
substance_tags: psilocybin
topic_tags: Depression,Neuroplasticity,Receptor Pharmacology,Animal Study,Safety
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
abstract:
The full therapeutic potential of serotonergic psychedelics (SP) in treating neuropsychiatric disorders, such as depression and schizophrenia, is limited by possible adverse effects, including perceptual disturbances and psychosis, which require administration in controlled clinical environments. This study investigates the synergistic benefits of combining psilocybin (PSIL) with N-methyl-D-aspartate receptor (NMDAR) modulators D-serine (DSER) and D-cycloserine (DCS) to enhance both efficacy and safety. Using ICR male mice, we examined head twitch response (HTR), MK-801-induced hyperlocomotion, and neuroplasticity related synaptic protein levels in the frontal cortex, hippocampus, amygdala, and striatum. Our results indicate that PSIL significantly increased HTR-a surrogate measure for hallucinogenic effects-which was reduced by the co-administration of DSER or DCS in a dose-dependent manner. Similarly, combining PSIL with DSER or DCS significantly decreased MK-801-induced hyperactivity, modeling antipsychotic effects. Neuroplasticity-related synaptic protein assays demonstrated that the PSIL-DSER combination enhanced GAP43 expression over all 4 brain examined and overall expression of the 4 assayed synaptic proteins in the hippocampus, while PSIL-DCS elevated PSD95 levels across all 4 brain regions, suggesting a synaptogenic synergy. These findings support the hypothesis that combinations of SP with NMDAR modulators could optimize the therapeutic potential of SP by mitigating adverse effects and enhancing neuroplasticity. Future studies should focus on refining administration protocols and evaluating translational applicability for broader clinical use.

raw_json:
{"europe_pmc_id":"PPR947201","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


journal: PsyArXiv
publication_date: 2023-10-13
doi: 10.31234/osf.io/hm6jn_v1
source_url: https://doi.org/10.31234/osf.io/hm6jn_v1
substance_tags: psilocybin
topic_tags: Chronic Pain,Wellbeing,Emotional Processing,Observational Study
study_type: Observational Study
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
Shame, guilt and psychedelic experience: Results from a prospective, longitudinal survey of real-world psilocybin use

authors:
Mathai DS, Roberts DE, Nayak SM, Sepeda ND, Lehrner A, Johnson M, Lowe MX, Jackson H, Garcia-Romeu A.

abstract:
Introduction: The classic psychedelic psilocybin has attracted special interest across clinical and non-clinical settings as a potential tool for mental health. However, despite increasing attention to challenging psychedelic experiences, few studies have explored the relevance of emotionally painful, shame-related processes with psychedelic use. Methods: This prospective, longitudinal study involved sequential, automated, web-based surveys that collected data from 679 adults planning to use psilocybin in naturalistic settings at timepoints before and after psilocybin use. State and trait shame and feelings of guilt were collected using validated measures and assessed alongside other measurements of psychological health. Results: Participants were primarily college-educated, White individuals residing in the United States with a prior history of psilocybin use; mean age = 38.9-41 years. Most users (89.7%) described their experience of psilocybin as positive, though acute feelings of shame or guilt were commonly reported (i.e., 68.2% of users) and difficult to predict. Ratings of participant ability to constructively work through these feelings predicted wellbeing 2-4 weeks after psilocybin use. Psilocybin on average produced a small but significant decrease in trait shame that was maintained 2-3 months after use (Cohen’s dz = 0.37; adjusted p

raw_json:
{"europe_pmc_id":"PPR1036093","source":"PPR","pub_type":null,"publisher":"PsyArXiv","importer":"Europe PMC"}


journal: PsyArXiv
publication_date: 2023-10-13
doi: 10.31234/osf.io/hm6jn
source_url: https://doi.org/10.31234/osf.io/hm6jn
substance_tags: psilocybin
topic_tags: Chronic Pain,Wellbeing,Emotional Processing,Observational Study
study_type: Observational Study
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
Shame, guilt and psychedelic experience: Results from a prospective, longitudinal survey of real-world psilocybin use

authors:
Mathai DS, Roberts DE, Nayak SM, Sepeda ND, Lehrner A, Johnson M, Lowe MX, Jackson H, Garcia-Romeu A.

abstract:
Introduction: The classic psychedelic psilocybin has attracted special interest across clinical and non-clinical settings as a potential tool for mental health. However, despite increasing attention to challenging psychedelic experiences, few studies have explored the relevance of emotionally painful, shame-related processes with psychedelic use. Methods: This prospective, longitudinal study involved sequential, automated, web-based surveys that collected data from 679 adults planning to use psilocybin in naturalistic settings at timepoints before and after psilocybin use. State and trait shame and feelings of guilt were collected using validated measures and assessed alongside other measurements of psychological health. Results: Participants were primarily college-educated, White individuals residing in the United States with a prior history of psilocybin use; mean age = 38.9-41 years. Most users (89.7%) described their experience of psilocybin as positive, though acute feelings of shame or guilt were commonly reported (i.e., 68.2% of users) and difficult to predict. Ratings of participant ability to constructively work through these feelings predicted wellbeing 2-4 weeks after psilocybin use. Psilocybin on average produced a small but significant decrease in trait shame that was maintained 2-3 months after use (Cohen’s dz = 0.37; adjusted p

raw_json:
{"europe_pmc_id":"PPR742379","source":"PPR","pub_type":null,"publisher":"PsyArXiv","importer":"Europe PMC"}


title: Psilocybin’s effect on human brain synaptic plasticity
journal: Research Square
publication_date: 2025-10-09
doi: 10.21203/rs.3.rs-7469144/v1
source_url: https://doi.org/10.21203/rs.3.rs-7469144/v1
substance_tags: psilocybin
topic_tags: Neuroplasticity,Mechanism of Action,Mystical Experience,Healthy Volunteers
study_type: Other
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
authors:
Johansen A, Plavén-Sigray P, Madsen MK, Søndergaard A, Messel C, Geisler M, Nasser A, McCulloch DE, Beliveau V, Vassilieva A, Lund A, Lehel S, Ozenne B, Stenbæk DS, Fisher PM, Svarer C, Knudsen GM.

abstract:
Abstract Psychedelics such as psilocybin have been linked to enhanced neuroplasticity and symptom relief in affective disorders, but the neurobiological mechanisms and impact of environmen-tal context remain unclear. Here, we tested whether a single dose of psilocybin alters synap-tic density in healthy individuals and whether setting-dependent subjective experience shapes this effect. Fifteen healthy participants had a psilocybin-induced psychedelic experi-ence either inside an MRI scanner or in a therapeutic-like room. We assessed synaptic densi-ty changes by measuring the Synaptic Vesicle glycoprotein 2A in the frontal cortex and hip-pocampus with [¹¹C]UCB-J PET at baseline and one-week post-dose, and assessed subjective experiences immediately afterwards and at three months. Participants treated in the thera-peutic-like setting exhibited more intense mystical-type experiences, longer-lasting psycho-logical benefits, and greater increases in synaptic density than those dosed in the MRI scan-ner. These findings indicate that psilocybin’s neuroplastic effects are modulated by envi-ronmental context, with important implications for psychedelic-assisted therapies.

raw_json:
{"europe_pmc_id":"PPR1099975","source":"PPR","pub_type":null,"publisher":"Research Square","importer":"Europe PMC"}


journal: PsyArXiv
publication_date: 2023-07-05
source_url: https://osf.io/preprints/psyarxiv/ztyxh_v1
substance_tags: psilocybin
study_type: Systematic Review
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"ztyxh_v1","version":1,"reviews_state":"accepted"}
title:
Psychoactive substances in psychotherapy - A vision for the future? - A systematic review on Psilocybin

abstract:
This work is a literature review on the use of psilocybin in psychotherapeutic treatment of mental illnesses. The review answers the question of what opportunities and risks are associated with the use of the psychoactive substance psilocybin. Peer-reviewed studies between 2017 and 2022 were included. Nine studies were found regarding the following indications: tobacco addiction, anxiety and depressive states related to life-threatening cancer, as well as treatment-resistant depression. A rapid clinical improvement of various symptoms was observed. The greatest evidence for the use of psilocybin was found in treating tobacco addiction and anxiety and depression related to life-threatening illnesses. No serious adverse events were reported in the studies. However, current studies have limitations, such as small sample sizes, difficulties with blinding, and a treatment population considered non-representative. The results are not representative but provide indications of effective treatment and are a starting point for further studies.

keywords:
depression, hallucinogens, mental health, Psilocybin, psychedelics, psychotherapy, review, systematic review, Psychiatry, Meta-science, Neuroscience, Computational Neuroscience, Life Sciences, Systems Neuroscience, Clinical Neuroscience

topic_tags:
Depression,Anxiety,Addiction,End-of-Life Distress,Systematic Review,Review Article,Treatment-Resistant Depression,Safety,Adverse Events


title: Acute effects of psilocybin on the dynamics of gaze fixations during visual aesthetic perception
authors: Muller S, Cavanna F, de la Fuente L, Bruno N, D’Amelio TA, Pallavicini C, Tagliazucchi E.
journal: bioRxiv
publication_date: 2023-10-31
doi: 10.1101/2023.10.27.564413
source_url: https://doi.org/10.1101/2023.10.27.564413
substance_tags: psilocybin
topic_tags: Chronic Pain,Consciousness,Emotional Processing
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
abstract:
Rationale Serotonergic psychedelics are remarkable for their capacity to induce variable yet reproducible modifications to human consciousness The most salient acute effects of these compounds include perceptual alterations, predominantly in the visual domain, yet to date these alterations have been mostly documented only by subjective reports. Objectives We used eye-tracking to quantify the effects of low vs. high doses of psilocybin mushrooms on the eye movements that underlie the exploration of complex visual stimuli, focusing on the particular case of aesthetic perception. Results Following a double-blind placebo-controlled design under semi-naturalistic conditions, we demonstrated that high doses of psilocybin result in a more local visual exploration of paintings, and thus in a less entropic fixation probability distribution. Participants reported heightened emotional response and state of flow under the high dose condition. Conclusions These findings are consistent with an effect of psilocybin on gaze fixation mediated by altered perception of low-level visual information, such as textures, shapes and colors. Our work also highlights the possibility of investigating psychedelics by addressing their effect on behavior under complex naturalistic conditions, which contributes to maintaining subject engagement while also increasing the ecological validity of the findings.

raw_json:
{"europe_pmc_id":"PPR752096","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


authors: Masjedi NS, Razi A.
journal: bioRxiv
publication_date: 2025-09-11
doi: 10.1101/2025.09.07.674759
source_url: https://doi.org/10.1101/2025.09.07.674759
substance_tags: psilocybin
topic_tags: Brain Imaging,Mechanism of Action
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
Effective connectivity of the human claustrum: Triple networks, subcortical circuits, and psychedelic modulation

abstract:
Decades of cross-species research highlight the claustrums extensive bidirectional connectivity with cortical and subcortical regions, implicating it in higher-order cognitive processes requiring synchronized brain states. Psychedelics may disrupt this synchrony by modulating claustro-cortical signaling, reflected by the dissolution of cortical network signatures. Using spectral dynamic causal modeling on resting-state fMRI data from the Human Connectome Project and PsiConnect datasets at 7T and 3T, we provide the first in vivo characterization of claustral effective connectivity with triple networks and subcortical regions in humans, both at rest and under the influence of psilocybin. Claustra displayed widespread bidirectional effective connectivity and a strong inhibitory influence on all target regions. Psilocybin enhanced claustral inhibition of cortical networks while disinhibiting subcortical areas, partially associated with psychedelic subjective effect scores. These findings are consistent with cellular and functional cross-species data, supporting the proposed mechanism of claustro-cortical inhibition in regulating network synchrony, while extending this influence to the subcortex, and revealing hierarchical and hemispheric asymmetries in claustral signaling modulation under psilocybin.

raw_json:
{"europe_pmc_id":"PPR1083522","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


journal: Research Square
publication_date: 2023-12-27
doi: 10.21203/rs.3.rs-3474764/v1
source_url: https://doi.org/10.21203/rs.3.rs-3474764/v1
substance_tags: psilocybin
topic_tags: Depression,Neuroplasticity,Brain Imaging,Mechanism of Action,Biomarkers,Aging,Inflammation
study_type: Clinical Trial
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
Engaging Mood Brain Circuits with Psilocybin (EMBRACE): a study protocol for a randomized, proof-of-principle, placebo-controlled and crossover, neuroimaging trial in depression

authors:
Poulin JM, Bigford GE, Lanctot KL, Giacobbe P, Schaffer A, Sinyor M, Rabin JS, Masellis M, Singnurkar A, Pople CB, Lipsman N, MacIntosh BJ, Nestor SM.

abstract:
Abstract Background: Major Depressive Disorder (MDD) is a leading cause of disability worldwide across domains of health and cognition, affecting overall quality of life. Approximately one third of individuals with depression do not fully respond to treatments (e.g., conventional antidepressants, psychotherapy) and alternative strategies are needed. Recent early phase trials suggest psilocybin may be a safe and efficacious intervention with rapid-acting antidepressant properties. Psilocybin is thought to exert therapeutic benefits by altering brain network connectivity and inducing neuroplastic changes that endure for weeks post-treatment. Although early clinical results are encouraging, psilocybin’s acute neurobiological effects on neuroplasticity have not been fully investigated. We aim to examine for the first time how psilocybin acutely (intraday) and subacutely (weeks) alters functional brain networks implicated in depression. Methods: Thirty-six participants diagnosed with MDD or Persistent Depressive Disorder (PDD) will be recruited from a tertiary mood disorders clinic and undergo 1:1 randomization into either an experimental or control arm. Participants will be given either 25 mg psilocybin or active placebo (100 mg niacin) for the first treatment. Three weeks later, those in the control arm will cross over and all participants will receive 25 mg psilocybin. We will investigate whether treatments are associated with changes in arterial spin labelling and blood oxygenation level dependent contrast neuroimaging assessments at acute and subacute timepoints. Primary outcomes include testing whether psilocybin demonstrates acute changes in 1) cerebral blood flow and 2) functional brain activity in networks associated with mood regulation and depression when compared to placebo. Secondary outcomes include changes in MADRS score over time compared to placebo, and changes across complementary clinical psychiatric, cognitive, and functional scales from baseline to final follow-up. Serum peripheral neurotrophic and inflammatory biomarkers will be collected at baseline to examine relationships with clinical response, and neuroimaging measures. Discussion: This study will investigate the acute and additive subacute neuroplastic effects of psilocybin on brain networks affected by depression using advanced serial neuroimaging methods. Results will improve our understanding of psilocybin’s antidepressant mechanisms versus placebo response and whether biological measures of brain function can provide early predictors of treatment response. Trial registration: ClinicalTrials.gov Identifier: NCT06072898. Registered on 6 October 2023.

raw_json:
{"europe_pmc_id":"PPR779931","source":"PPR","pub_type":null,"publisher":"Research Square","importer":"Europe PMC"}


journal: Wellcome Open Res
publication_date: 2024-07-23
doi: 10.12688/wellcomeopenres.22543.1
source_url: https://doi.org/10.12688/wellcomeopenres.22543.1
substance_tags: psilocybin
topic_tags: Brain Imaging,Mechanism of Action,Default Mode Network,Aging
study_type: Other
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
Probing the functional magnetic resonance imaging response to psilocybin in functional neurological disorder (PsiFUND): study protocol

authors:
Butler M, Bird C, Maggio C, Durden A, Modlin N, Campbell-Coker K, Edwards M, Pick S, Millman LM, Lowery E, Bhagavan C, Kanaan R, Golder D, Mildon B, Mehta M, Rucker J, Nicholson TR.

abstract:
Background: Functional neurological disorder (FND) is a common cause of neurological symptoms including paralysis, seizures, and movement disorders. It is often debilitating, is associated with high health and social care costs, and can have a poor prognosis. Functional magnetic resonance imaging (fMRI) has suggested FND is a multi-network disorder; the default mode network (DMN) may be specifically implicated. Converging evidence suggests that other variable mechanisms including dissociation, interoception, and motor agency may be differentially abnormal in people with FND. Psychedelics are currently under investigation for numerous neuropsychiatric disorders and have been shown to disrupt functional networks such as the DMN. Administering psychedelics to people with FND will help us to probe mechanistic theories of the disorder. Protocol In this open-label neuroimaging study, we will administer 25mg oral psilocybin with psychological support to people with chronic FND (target n = 24). Participants will undergo resting-state and task-based (Libet’s clock, a measure of motor agency) fMRI sequences which will be compared in a pre-post manner. Additional mechanistic outcomes including measures of interoception (heartbeat tracking task), somatisation, illness perceptions, imaginative suggestibility, and dissociation will be collected. Data on expectancy, preparedness, and subjective experience of the psychedelic experience will also be gathered. Participants will be followed up for three months following psilocybin administration. fMRI changes in networks such as the DMN will be analysed using seed-based approaches, and additional exploratory analysis of resting-state imaging will take place. Discussion The study will help us to probe the mechanisms thought to potentially underpin FND. As the first modern study of psychedelics in FND, it will also help us to understand whether psychedelic administration alongside psychological support might be safe and feasible in this patient population.

raw_json:
{"europe_pmc_id":"PPR886443","source":"PPR","pub_type":null,"publisher":"Wellcome Open Res","importer":"Europe PMC"}


journal: Research Square
publication_date: 2025-11-30
doi: 10.21203/rs.3.rs-8214817/v1
source_url: https://doi.org/10.21203/rs.3.rs-8214817/v1
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Emotional Processing
study_type: Other
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
Limited prognostic value of early maladaptive schemas for acute psychedelic experience and symptom improvement

authors:
Buchard A, Seragnoli F, Sabe M, Eskinazi M, Aboulafia T, Furtado L, Briefer J, Roediger E, Penzenstadler L, Zullino D, Thorens G.

abstract:
Abstract Early maladaptive schemas (EMS) are highly prevalent in patients seeking psychedelic-assisted psychotherapy and correlate strongly with baseline depression and anxiety. This study characterized EMS in 192 adults and longitudinally followed 74 patients receiving psilocybin- or LSD-assisted therapy. We found that baseline schema burden, particularly related to failure and defectiveness, was linked to cognitive-depressive symptoms but did not predict the quality of the acute psychedelic experience or moderate overall symptom improvement. While patients experienced significant reductions in both depression and anxiety symptoms with each session, these changes were dependent on initial symptom severity, not their schema profile. Treatment effects were comparable between psilocybin and LSD. These findings suggest the clinical utility of EMS lies not in patient selection or outcome prediction, but in identifying key cognitive-emotional themes, such as core beliefs about failure, to be targeted during psychotherapeutic integration.

raw_json:
{"europe_pmc_id":"PPR1128933","source":"PPR","pub_type":null,"publisher":"Research Square","importer":"Europe PMC"}


title: Exposure therapy under psilocybin for general anxiety disorder and claustrophobia
authors: THORENS G, PENZENSTADLER l, FURTADO LCDC, SERAGNOLI F, ROTHEN S, MABILAIS C, ZULLINO D.
journal: Research Square
publication_date: 2023-05-11
doi: 10.21203/rs.3.rs-2859973/v1
source_url: https://doi.org/10.21203/rs.3.rs-2859973/v1
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Case Report
study_type: Case Report
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
abstract:
Case report of a patient with GAD and claustrophobia who underwent exposure therapy using psilocybin-assisted psychotherapy. The patient had failed to respond to conventional psychotherapeutic treatment. After three sessions of psilocybin-assisted psychotherapy, the patient experienced a reduction in anxiety and fear associated with closed spaces, elevators, and planes. The protocol included both an imaginary exposure exercise and a classic exposure therapy in an elevator during the psilocybin-assisted psychotherapy. the patient experienced a significant improvement in his score on the Beck Depression Inventory-II (BDI-II), the State-Trait Anxiety Inventory (STAI), and the Fear Questionnaire before and after therapy. He reported a generalization of the treatment effects, feeling more relaxed and having a greater willingness to confront fearful situations. He also described a shift in his perception of fearful stimuli, which may be explained as the development of new memory representations and a major disconfirmatory experience.

raw_json:
{"europe_pmc_id":"PPR659477","source":"PPR","pub_type":null,"publisher":"Research Square","importer":"Europe PMC"}


journal: Research Square
publication_date: 2023-07-19
doi: 10.21203/rs.3.rs-3146433/v1
source_url: https://doi.org/10.21203/rs.3.rs-3146433/v1
substance_tags: psilocybin
topic_tags: Neuroplasticity,Mechanism of Action,Oxidative Stress,Animal Study,Metabolomics
study_type: Animal Study
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
Distinctive Molecular and Metabolic Profiles of Chemically Synthesized Psilocybin and Psychedelic Mushroom Extract

authors:
Shahar O, Botvinnik A, Shwartz A, Lerer E, Buko A, Hamid E, Kahn D, Guralnick M, Blakolmer K, Wolf G, Lerer L, Lerer B, Lifschytz T.

abstract:
Abstract Psilocybin, a naturally occurring, tryptamine alkaloid prodrug, is currently being investigated for the treatment of a range of psychiatric disorders. Preclinical reports suggest that the biological effects of psilocybin-containing mushroom extract or “full spectrum” (psychedelic) mushroom extract (PME), may differ from those of chemically synthesized psilocybin (PSIL). We compared the effects of PME to those of PSIL on the head twitch response (HTR), neuroplasticity-related synaptic proteins and frontal cortex metabolomic profiles in male C57Bl/6j mice. HTR measurement showed similar effects of PSIL and PME over 20 minutes. Brain specimens (frontal cortex, hippocampus, amygdala, striatum) were assayed for the synaptic proteins, GAP43, PSD95, synaptophysin and SV2A, using western blots. These proteins are indicators of synaptic plasticity. Three days after treatment, there was minimal increase in synaptic proteins. After 11 days, nested analysis of variance (ANOVA) showed a significant increase in each of the 4 proteins over all brain areas studied for PME versus vehicle control, while significant PSIL effects were observed only in the hippocampus and amygdala and were limited to PSD95 and SV2A. Metabolomic analyses of the pre-frontal cortex were performed by untargeted polar metabolomics utilizing capillary electrophoresis - Fourier transform mass spectrometry (CE-FTMS) and showed a differential metabolic separation between PME and vehicle groups. The purines guanosine, hypoxanthine and inosine, associated with oxidative stress and energy production pathways, showed a progressive decline from VEH to PSIL to PME. In conclusion, our synaptic protein findings suggest that PME has a more potent and prolonged effect on synaptic plasticity than PSIL. Our metabolomics data support a gradient of effects from inert vehicle via chemical psilocybin to PME further supporting differential effects. Further studies are needed to confirm and extend these findings and to identify the molecules that may be responsible for the enhanced effects of PME as compared to psilocybin alone.

raw_json:
{"europe_pmc_id":"PPR694814","source":"PPR","pub_type":null,"publisher":"Research Square","importer":"Europe PMC"}


title: Association of Psilocybin Use in Adolescents with Major Depressive Episode
authors: Shah K, Trivedi C, Kamrai D, Akbar M, Tankersley W.
publication_date: 2022-08-31
source_url: https://europepmc.org/article/PMC/PMC9563652
substance_tags: psilocybin
topic_tags: Depression,Observational Study,Adolescents
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
abstract:
Introduction Psilocybin is a psychedelic drug found in mushrooms, often referred to as magic mushrooms due to its visual and auditory hallucinations effects upon ingestion. It is a Schedule I drug per DEA, and the FDA has not approved psilocybin for medicinal purposes. However, recent studies have shown promising therapeutic use to treat depression. Objectives To identify current use, prevalence, and its association with depression in adolescents. Methods The National Survey on Drug Use and Health survey data from 2008-18 studied adolescent data (12-17 years), who responded, “ever used psilocybin (mushrooms)” and “lifetime major depressive episode (MDE).” The association between the psilocybin use and MDE status was analyzed in SAS9.4 through multivariate logistic regression for odds ratio (OR) and 95% confidence interval (CI). Results A total of 172745 adolescents were included in this study, of which 2469 ever used psilocybin in their lifetime, and 170276 responded no lifetime use. The psilocybin ever lifetime users were 17 years old (42%vs.17%,p

raw_json:
{"europe_pmc_id":"PMC9563652","source":"PMC","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Serotonergic antidepressant use is associated with weaker psilocybin effects
journal: PsyArXiv
publication_date: 2022-10-27
source_url: https://osf.io/preprints/psyarxiv/2zys9_v1
keywords: antidepressant, drug interactions, psilocybin, psychedelic, serotonin, Psychiatry
substance_tags: psilocybin
topic_tags: Depression,Receptor Pharmacology,Observational Study,Drug Interactions
study_type: Observational Study
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"2zys9_v1","version":1,"reviews_state":"accepted"}
abstract:
Background: Psilocybin is being studied for depression, but little is known about how it interacts with common antidepressants. Limited data suggests that psilocybin’s effects may be diminished by serotonergic antidepressants acutely and even after a medication washout period. Aims: To learn the extent to which serotonergic antidepressants may diminish psilocybin’s effects both concurrently and after discontinuation of antidepressants. Methods: Online survey of individuals with use of psilocybin 1) with an antidepressant and/or 2) within two years of discontinuing an antidepressant. Participants who took psilocybin with an antidepressant and either took the same dose of psilocybin pre-antidepressant or took the same dose with other people not on antidepressant reported the strength of psilocybin’s effect relative to their expectation. Participants who took psilocybin following discontinuation of a serotonergic antidepressant also reported the presence of weakened effects. Results: In reports (n=595) of taking psilocybin with an antidepressant, probabilities [95% CI] of weaker than expected psilocybin effects were 0.48 [0.41-0.54] (SSRIs), 0.56 [0.44-0.67] (SNRIs) and 0.29 [0.2-0.39] (bupropion). Following serotonergic antidepressant discontinuation (n=1,542 reports), the odds of reduced psilocybin effects were not significantly different from the earliest post-discontinuation timepoint (within 1 week) until 3-6 months OR = 0.42, 95% [0.25-0.72] p = 0.001. Conclusions: Serotonergic antidepressants appear to weaken psilocybin’s effects relative to a non-serotonergic antidepressant. This dampening effect on psilocybin effects may last as long as 3 months following antidepressant discontinuation.


authors: Tolle HM, Farah JC, Mallaroni P, Mason NL, Ramaekers JG, Amico E.
journal: bioRxiv
publication_date: 2023-03-20
doi: 10.1101/2023.03.20.532894
source_url: https://doi.org/10.1101/2023.03.20.532894
substance_tags: psilocybin
topic_tags: Brain Imaging,Default Mode Network,Aging,Healthy Volunteers
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:01
title:
The Unique Neural Signature of Your Trip: Functional Connectome Fingerprints of Subjective Psilocybin Experience

abstract:
The emerging neuroscientific frontier of brain fingerprinting has recently established that human functional connectomes (FCs) exhibit fingerprint-like idiosyncratic features, which map onto heterogeneously distributed behavioural traits. Here, we harness brain-fingerprinting tools to extract FC features that predict subjective drug experience induced by the psychedelic psilocybin. Specifically, in neuroimaging data of healthy volunteers under the acute influence of psilocybin or a placebo, we show that, post psilocybin administration, FCs become more idiosyncratic due to greater inter-subject dissimilarity. Moreover, whereas in placebo subjects idiosyncratic features are primarily found in the frontoparietal network, in psilocybin subjects they concentrate in the default-mode network (DMN). Crucially, isolating the latter revealed an FC pattern that predicts subjective psilocybin experience and is characterised by reduced within-DMN and DMN-limbic connectivity, as well as increased connectivity between the DMN and attentional systems. Overall, these results contribute to bridging the gap between psilocybin-mediated effects on brain and behaviour, while demonstrating the value of a brain-fingerprinting approach to pharmacological neuroimaging. Author summary The trending field of brain fingerprinting focuses on characterising fingerprint-like idiosyncratic features of human functional connectomes (FCs), which have been shown to predict heterogeneously distributed behavioural traits. Here, we apply brain-fingerprinting methods to fMRI data from subjects who were administered the psychedelic psilocybin or a placebo. We find that, compared to the placebo condition, subjects under acute psilocybin effects exhibited more idiosyncratic FCs, with idiosyncratic features being largely concentrated in the default-mode network (DMN). Furthermore, we isolated an idiosyncratic FC pattern that predicted reports of subjective psilocybin experiences. This pattern was characterised by altered DMN connectivity, specifically by reduced within-DMN and DMN-limbic connectivity, and increased connectivity between the DMN and attentional systems. This work paves the way for exciting new research harnessing pharmacological brain fingerprinting.

raw_json:
{"europe_pmc_id":"PPR633592","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: Serotonergic Psychedelics as a Potential Therapeutic Strategy for Anxiety, A Systematic Review
journal: PsyArXiv
publication_date: 2026-05-23
source_url: https://osf.io/preprints/psyarxiv/gf7bq_v1
substance_tags: psilocybin
study_type: Systematic Review
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"gf7bq_v1","version":1,"reviews_state":"accepted"}
abstract:
Background and objective: Anxiety disorders are among the most prevalent psychiatric disorders worldwide and affect all age groups. Current pharmacological treatments, such as selective serotonergic reuptake inhibitors (SSRI’s) and benzodiazepines, have limitations in terms of adverse effects and efficacy, which highlights the need for alternative therapies. Serotonergic psychedelics have demonstrated promising anxiolytic-like behaviors in preclinical studies, primarily thought to be mediated through agonism of the 5-HT2A receptor. This systematic review aimed to investigate the preclinical evidence of anxiolytic-like potential of serotonergic psychedelics in animal models, and to evaluate the validity and limitations of the included behavioral tests. Methods: This systematic review was conducted in accordance with the PRISMA 2020 guidelines. A systematic search was conducted in PubMed and Embase. Inclusion and exclusion criteria were defined prior to screening to ensure a transparent inclusion of studies and minimize bias. The title, abstract and full-text screening were conducted independently by two reviewers, with conflicts being resolved through discussion. In total, 18 studies were included after the final screening. Results: Overall, the results demonstrate that serotonergic psychedelics, such as psilocybin and DOI, exerted anxiolytic-like effects across several behavioral tests. However, anxiogenic and null effects were also reported. This suggests that the effects are context-dependent, influenced by dosage, administration pattern, biological variables, as well as the experimental conditions. The predictive and face validity of the included behavioral models was generally acceptable. However, the construct validity had some limitations, and inconsistencies in the experimental conditions create a need for more standardization to ensure more transparent and reproducible data, and further the research field. Conclusions: The preclinical studies included in this review indicate that the serotonergic psychedelics have therapeutic potential in the treatment of anxiety, especially psilocybin elicited consistent anxiolytic-like effects, possibly due to 5-HT2A receptor agonism. However, future studies should focus on understanding mechanisms, sex-specific effects, and further the combinations of behavioral tests to ensure better interpretation of behavioral outcomes.

keywords:
Anxiety, Preclinical, Psychedelics, Systematic Review, Psychiatry, Social and Behavioral Sciences, Emotion, Neuroscience, Behavioral Neuroscience, Animal Learning and Behavior

topic_tags:
Anxiety,Mechanism of Action,Receptor Pharmacology,Emotional Processing,Systematic Review,Review Article,Animal Study


journal: PsyArXiv
publication_date: 2023-10-10
source_url: https://osf.io/preprints/psyarxiv/jqasf_v1
keywords: Neuroscience, Cognitive Neuroscience, Social and Behavioral Sciences, Cognitive Psychology
substance_tags: psilocybin
topic_tags: Neuroplasticity,Aging,Microdosing
study_type: Other
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"jqasf_v1","version":1,"reviews_state":"accepted"}
title:
Psilocybin-assisted neurofeedback for the improvement of executive functions: a randomised semi-naturalistic-lab feasibility study

abstract:
Executive function deficits, common in psychiatric disorders, hinder daily activities and may be linked to diminished neural plasticity, affecting treatment and training responsiveness. In this pioneering study, we evaluated the feasibility and preliminary efficacy of psilocybin-assisted frontal-midline theta neurofeedback (NF), a neuromodulation technique leveraging neuroplasticity, to improve executive functions (EFs). 37 eligible participants were randomised into an experimental (n=18) and a passive control group (n=19). The experimental group underwent three microdose sessions and then three psilocybin-assisted NF sessions, without requiring psychological support, demonstrating the approach’s feasibility. NF learning showed a statistical trend with large effect size for increases in frontal-midline theta from session-to-session with a large effect size, and non-significant but medium effect size dynamical changes within sessions. Placebo effects were consistent across groups, with no tasks-based EFs improvements, but significant self-reported gains in daily EFs -working memory, shifting, monitoring and inhibition- showing medium and high effect sizes. The experimental group’s significant gains in their key training goals underscored the approach’s external relevance. A thorough study with regular sessions and an active control group is crucial to evaluate EFs improvement and their specificity in future. Psilocybin-enhanced NF could offer significant, lasting benefits across diagnoses, improving daily functioning.


journal: Research Square
publication_date: 2024-01-03
doi: 10.21203/rs.3.rs-3829237/v1
source_url: https://doi.org/10.21203/rs.3.rs-3829237/v1
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Addiction,Neuroplasticity,Mechanism of Action,Clinical Trial,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:02
title:
Psilocybin-Assisted Therapy for Severe Alcohol Use Disorder: Protocol for a Double-Blind, Randomized, Placebo-Controlled, 7-month Parallel-Group Phase II Superiority Trial

authors:
Vanderijst L, Hever F, Buot A, Dauré C, Benoit J, Hanak C, Veeser J, Morgiève M, Campanella S, Kornreich C, Mallet L, Leys C, Noël X.

abstract:
Background: A significant number of individuals with alcohol use disorder remain unresponsive to currently available treatments, which calls for the development of new alternatives. In parallel, psilocybin-assisted therapy for alcohol use disorder has recently yielded promising preliminary results. Building on extant findings, the proposed study is set to evaluate the feasibility and preliminary clinical efficacy of psilocybin-assisted therapy when incorporated as an auxiliary intervention during inpatient rehabilitation for severe alcohol use disorder. Moreover, it intends to pinpoint the modifications in the two core neurocognitive systems underscored by dual-process models of addiction. Methods:: In this double-blind, randomized, placebo-controlled, 7-month parallel-group phase II superiority trial, 62 participants aged 21-64 years will be enrolled to undergo psilocybin-assisted therapy as part of a 4-week inpatient rehabilitation for severe alcohol use disorder. The experimental group will receive a high dose of psilocybin (30 mg), whereas the control group will receive an active placebo dose of psilocybin (5 mg), both within the context of a brief standardized psychotherapeutic intervention drawing from key elements of acceptance and commitment therapy. The primary clinical outcome is the between-group difference regarding the change in percentage of heavy drinking days from baseline to four weeks posthospital discharge, while safety and feasibility metrics will also be reported as primary outcomes. Key secondary assessments include between-group differences in terms of changes in 1) drinking behavior parameters up to six months posthospital discharge, 2) symptoms of depression, anxiety, trauma, and global functioning, 3) neuroplasticity and key neurocognitive mechanisms associated with addiction, and 4) psychological processes and alcohol-related parameters. Discussion: The discussion outlines issues that might arise from our design. Trial registration: EudraCT 2022-002369-14 and NCT06160232

raw_json:
{"europe_pmc_id":"PPR782504","source":"PPR","pub_type":null,"publisher":"Research Square","importer":"Europe PMC"}


journal: PsyArXiv
publication_date: 2026-03-01
source_url: https://osf.io/preprints/psyarxiv/9c6xg_v1
substance_tags: psilocybin
topic_tags: Consciousness,Mystical Experience
study_type: Other
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"9c6xg_v1","version":1,"reviews_state":"accepted"}
title:
Multidimensional Ego-Dissolution Assessment (MEDA): Scale Development and Substance-Specific Comparisons

abstract:
Rationale: Ego-dissolution represents a key therapeutic mechanism in psychedelic-assisted therapy, yet current measurement approaches may inadequately capture its multidimensional nature. Objective: To develop and validate the Multidimensional Ego-Dissolution Assessment (MEDA) and examine substance-specific patterns across classical psychedelics. Methods: Items from three validated scales (Ego-Dissolution Inventory, Mystical Experience Questionnaire, 5D-Altered States of Consciousness) were compiled into a 34-item measure. Exploratory factor analysis was conducted on responses from 207 participants reporting profound experiences with ayahuasca (n=51), DMT (n=28), LSD (n=52), or psilocybin (n=76). Results: Factor analysis revealed a robust 6-factor structure: Dissolving of Identity (α=.94), Experiences of Eternity (α=.89), Dissolving of Physical Body (α=.80), Dissolving into Environment (α=.85), Clarity about Life and Purpose (α=.78), and Pleasure (α=.78). Two distinct substance clusters emerged: ayahuasca/DMT produced significantly higher dissolution scores than LSD/psilocybin across four factors, while all substances showed equivalent high scores on insight and pleasure dimensions. Dosage showed no significant effects. Conclusion: The MEDA provides preliminary evidence for multidimensional ego-dissolution assessment. Substance-specific clustering patterns might inform therapeutic selection, while universal insight and pleasure effects suggest core psychedelic benefits achievable across substances.

keywords:
ego-dissolution, factor analysis, psychedelics, psychometric scale, scale development, Social and Behavioral Sciences, Cultural Psychology, Cross-cultural Psychology


authors: Bennett JN, Blough MD, Mitchell I, Galloway L, Bains R.
journal: medRxiv
publication_date: 2023-04-18
doi: 10.1101/2023.04.12.23288325
source_url: https://doi.org/10.1101/2023.04.12.23288325
substance_tags: psilocybin
topic_tags: Mystical Experience,Clinical Trial,Safety,Adverse Events
study_type: Clinical Trial
source_name: medRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:02
title:
A Phase I trial to inform clinical protocols for the safe administration of psilocybin-assisted psychotherapy

abstract:
This Phase I trial aims to inform the development of safety protocols for psilocybin-assisted therapy. Psychedelics, including psilocybin, are increasingly being recognized as a successful treatment option for many mental health concerns. In order to decrease the risks associated with its clinical use, more data is required regarding its physiological effects in healthy individuals. Safety assessments (heart rate, blood pressure, temperature, and ECG data), as well as adverse event evaluations were the primary outcome measures used to assess the physiological effects of 25 mg of psilocybin extract administered to 14 healthy individuals. We hypothesized that there would be a transient, clinically insignificant rise in both blood pressure and heart rate that would not result in any long-term adverse effects. No unexpected effects were observed, blood pressure and heart rate returned to normal as drug effects waned, and all participants had normal two-month follow-ups. Mean peak systolic and diastolic blood pressures during the psilocybin session were 145.93 ( SD = 19.01) and 93.93 ( SD = 9.75), respectively. While this represents a significant increase from baseline ( p < 0.0001), a healthy cardiovascular system is capable of tolerating such levels for a longer time period than the brief duration of drug effects. Therefore, we suggest implementing focused and limited screening protocols to balance patient safety and accessibility. Secondary outcomes of this trial centered on the subjective effects of psilocybin, assessed via the QIDS-SR16 and the MEQ-30. There was a statistically significant decrease in QIDS-SR16 scores from baseline scores ( M = 3.50, SD = 2.35) to eight-week follow-up scores ( M = 1.86, SD = 0.86), p = 0.018. Mean MEQ-30 scores, assessed on day two and seven after the psilocybin session, indicate participants had full mystical experiences.

raw_json:
{"europe_pmc_id":"PPR648094","source":"PPR","pub_type":null,"publisher":"medRxiv","importer":"Europe PMC"}


title: Electrical spiking of psilocybin fungi
authors: Gandia A, Adamatzky A.
journal: bioRxiv
publication_date: 2022-07-02
doi: 10.1101/2022.07.02.498545
source_url: https://doi.org/10.1101/2022.07.02.498545
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:02
abstract:
Psilocybin fungi, aka “magic” mushrooms, are well known for inducing colourful and visionary states of mind. Such psychoactive properties and the ease of cultivating their basidiocarps within low-tech setups make psilocybin fungi promising pharmacological tools for mental health applications. Understanding of the intrinsic electrical patterns occurring during the mycelial growth can be utilised for better monitoring the physiological states and needs of these species. In this study we aimed to shed light on this matter by characterising the extra-cellular electrical potential of two popular species of psilocybin fungi: Psilo-cybe tampanensis and P. cubensis. As in previous experiments with other common edible mushrooms, the undisturbed fungi have shown to generate electric potential spikes and trains of spiking activity. This short analysis provides a proof of intrinsic electrical communication in psilocybin fungi, and further establishes these fungi as a valuable tool for studying fungal electro-physiology.

raw_json:
{"europe_pmc_id":"PPR513215","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: Effective connectivity of emotion and cognition under psilocybin
authors: Stoliker D, Novelli L, Vollenweider FX, Egan GF, Preller KH, Razi A.
journal: medRxiv
publication_date: 2022-09-08
doi: 10.1101/2022.09.06.22279626
source_url: https://doi.org/10.1101/2022.09.06.22279626
substance_tags: psilocybin
topic_tags: Depression,Addiction,Default Mode Network,Biomarkers,Emotional Processing,Clinical Trial
study_type: Clinical Trial
source_name: medRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:02
abstract:
Classic psychedelics alter sense of self and patterns of self-related thought. These changes are hypothesised to underlie their therapeutic efficacy across internalising pathologies such as addiction and depression. Using resting-state functional MRI images from a randomised, double blinded, placebo-controlled clinical trial of 24 healthy adults under 0.215mg/kg psilocybin, we investigated how psilocybin modulates the effective connectivity between resting state networks and the amygdala that are involved in the appraisal and regulation of emotion and association with clinical symptoms. The networks included the default mode network (DMN), salience network (SN) and central executive network (CEN). Psilocybin decreased top-down effective connectivity from the resting state networks to the amygdala and decreased effective connectivity within the DMN and SN, while the within CEN effective connectivity increased. Effective connectivity changes were also associated with altered emotion and meaning under psilocybin. Our findings identify changes to cognitive-emotional connectivity associated with the subjective effects of psilocybin and the attenuation of the amygdala signal as a potential biomarker of psilocybin’s therapeutic efficacy.

raw_json:
{"europe_pmc_id":"PPR541956","source":"PPR","pub_type":null,"publisher":"medRxiv","importer":"Europe PMC"}


journal: PsyArXiv
publication_date: 2023-08-15
source_url: https://osf.io/preprints/psyarxiv/c9fpj_v1
substance_tags: psilocybin
topic_tags: Neuroplasticity,Wellbeing,Case Report
study_type: Case Report
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"c9fpj_v1","version":1,"reviews_state":"accepted"}
title:
“Diversity makes the richness of humanity”: the emergence of mental imagery after self-reported psilocybin mushrooms intake in an autistic woman with “blind imagination” (aphantasia): a 1-year retrospective case report

abstract:
This retrospective case report explores the impact of psilocybin mushroom intake on the emergence of mental imagery in an autistic woman with aphantasia. Aphantasia refers to the inability to generate visual mental images, which can significantly affect individuals' experiences and cognitive processes. The case study focuses on a 34-year-old autistic woman who had been living with aphantasia since childhood. After consuming psilocybin mushrooms, she reported experiencing vivid mental imagery for the first time, with the ability to manipulate and explore images in her mind. The effects persisted even after the psychedelic effects of psilocybin subsided. The woman's retrospective assessment using the Vividness of Visual Imagery Questionnaire revealed a significant increase in imagery vividness scores post-intake. The findings align with previous research on the effects of psilocybin on brain connectivity, neuroplasticity, and visual processing. The case report highlights the potential of psilocybin to modulate mental imagery in individuals with aphantasia and suggests avenues for further research. Moreover, it raises questions about the classification and pathologization of aphantasia, emphasizing the importance of recognizing cognitive diversity and promoting the well-being of individuals with different cognitive profiles, including aphantasia.

keywords:
Aphantasia, Autism, Blind imagination, Mental imagery, Neurodiversity, Psilocybin, Psychiatry, Neuroscience, Developmental Neuroscience, Cognitive Neuroscience, Social and Behavioral Sciences, Developmental Psychology, Clinical Neuroscience


title: Assessment of the acute effects of 2C-B vs psilocybin on subjective experience, mood and cognition
journal: bioRxiv
publication_date: 2023-02-15
doi: 10.1101/2023.02.16.528808
source_url: https://doi.org/10.1101/2023.02.16.528808
substance_tags: psilocybin
topic_tags: Pharmacology,Consciousness,Emotional Processing,Observational Study,Animal Study
study_type: Observational Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:02
authors:
Mallaroni P, Mason NL, Reckweg JT, Paci R, Ritscher S, Toennes SW, Theunissen EL, Kuypers KP, Ramaekers JG.

abstract:
2,5-dimethoxy-4-bromophenethylamine (2C-B) is a hallucinogenic phenethylamine derived from mescaline. Observational and preclinical data have suggested it to be capable of producing both subjective and emotional effects on par with other classical psychedelics and entactogens. Whereas it is the most prevalently used novel serotonergic hallucinogen to date, it’s acute effects and distinctions from classical progenitors have yet to be characterised in a controlled study. We assessed for the first time the immediate acute subjective, cognitive, and cardiovascular effects of 2C-B (20 mg) in comparison to psilocybin (15mg) and placebo in a within-subjects, double-blind, placebo-controlled study of 22 healthy psychedelic-experienced participants. 2C-B elicited alterations of waking consciousness of a psychedelic nature, with dysphoria, subjective impairment, auditory alterations, and affective elements of ego dissolution largest under psilocybin. Participants demonstrated equivalent psychomotor slowing and spatial memory impairments under either compound compared to placebo, as indexed by the Digit Symbol Substitution Test (DSST), Tower of London (TOL) and Spatial Memory Task (SMT). Neither compound produced empathogenic effects on the Multifaceted Empathy Test (MET). 2C-B induced transient pressor effects to a similar degree as psilocybin. The duration of self-reported effects of 2C-B was shorter than that of psilocybin, largely resolving within 6 hours. Present findings support the categorisation of 2C-B as a subjectively “lighter” psychedelic. Tailored dose-effect studies are needed to discern the pharmacokinetic dependency of 2C-B’s experiential overlaps.

raw_json:
{"europe_pmc_id":"PPR617518","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


authors: Braun D, Rosenberg A, Haruvi R, Malamud D, Barbara R, Kawashima T.
journal: bioRxiv
publication_date: 2023-04-13
doi: 10.1101/2023.04.13.536830
source_url: https://doi.org/10.1101/2023.04.13.536830
substance_tags: psilocybin
topic_tags: Mechanism of Action,Receptor Pharmacology
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:02
title:
High-resolution tracking of unconfined zebrafish behavior reveals stimulatory and anxiolytic effects of psilocybin

abstract:
Serotonergic psychedelics are emerging therapeutics for psychiatric disorders, yet their underlying mechanisms of action in the brain remain largely elusive. Zebrafish have evolutionarily conserved serotonergic circuits and subcortical targets such as the brainstem regions and the cerebellum, providing a promising model for studying the subcortical effects of serotonergic drugs. Here, we developed a wide-field behavioral tracking system for larval zebrafish and investigated the effects of psilocybin, a psychedelic serotonin receptor agonist. Machine learning analyses of precise body kinematics identified latent behavioral states reflecting spontaneous exploration, visually-driven rapid swimming, and irregular swim patterns following stress exposure. Using this method, we identified two main behavioral effects of acute psilocybin treatment: [i] increased rapid swimming in the absence of visual stimuli and [ii] prevention of irregular swim patterns following stress exposure. Together, these effects indicate that psilocybin induces a brain state that is both stimulatory and anxiolytic. These findings pave the way for using larval zebrafish to elucidate subcortical mechanisms underlying the behavioral effects of serotonergic psychedelics.

raw_json:
{"europe_pmc_id":"PPR645777","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


journal: PsyArXiv
publication_date: 2026-02-18
source_url: https://osf.io/preprints/psyarxiv/mdz73_v2
substance_tags: psilocybin
topic_tags: Clinical Trial,Safety
study_type: Clinical Trial
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"mdz73_v2","version":2,"reviews_state":"accepted"}
title:
Ethical Complexities and Best Practices in Informed Consent for Psychedelic Services: A Qualitative Study on Expert Perspectives

abstract:
Background: Informed consent in psychedelic-assisted services is ethically complex, difficult to implement, and remains largely unstudied and unstandardized. Objective: The current study sought expert recommendations from experienced psychedelic facilitators on what constitutes informed consent best practices for supervised psychedelic experiences across various settings. Methods: Participants with expertise in facilitating psilocybin-assisted experiences or other expertise in the psychedelic field were recruited with purposive sampling. Qualitative interviews on informed consent best practices and recommendations were analyzed using Thematic Analysis. Results: Participants (N = 36; 71% white; 56% heterosexual; 53% female) reported facilitating psilocybin services (64%) for a mean of 15.2 (SD = 13.1) years in clinical trial, licensed service center, underground, or ceremonial settings. Participants viewed informed consent as a process (Theme 1), necessitating a strong therapeutic relationship, centering client empowerment, and occurring as an ongoing process. Potential risks and benefits should be comprehensively conveyed (Theme 2), including potential long-term psychological and social changes, and the potential for disappointing experiences. Participants recommended detailed consent processes around touch and boundaries (Theme 3), including explicitly establishing boundaries prior to psychedelic administration, maintaining those boundaries throughout, and recognizing subtle non-verbal cues that may indicate lack of true consent. Within facilitator trainings (Theme 4), participants emphasized cultivating a deep respect for client agency, and experientially learning relational and boundary setting skills. Conclusions: Findings may inform practitioner training, consent practices in varied settings, and policy development for state-regulated psychedelic services.

keywords:
Neuroscience, Clinical Neuroscience, Social and Behavioral Sciences, Clinical Psychology, Psychotherapy, Clinical Ethics, Health Psychology, Mental Health


journal: PsyArXiv
publication_date: 2025-05-15
source_url: https://osf.io/preprints/psyarxiv/6hjkm_v1
keywords: Psychiatry
substance_tags: psilocybin
topic_tags: Depression,Aging,Observational Study,Healthcare Workers,Safety,Adverse Events
study_type: Observational Study
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"6hjkm_v1","version":1,"reviews_state":"accepted"}
title:
Under Pressure: Stronger depressive symptoms are associated with more positive expectations towards experimental treatments

abstract:
Background: Despite significant advancements in the treatment of depression, challenges such as inadequate response rates and high placebo effects highlight the need for improved therapies and a deeper understanding of treatment expectations. Patient expectations play a crucial role in treatment outcomes but have not been systematically investigated in the context of novel interventions like ketamine and psilocybin. Objectives: This study aimed to assess patient acceptance, experiences, and expectations regarding established depression treatments (psychotherapy, psychotherapy plus antidepressants) and novel interventions (ketamine-assisted therapy, psilocybin-assisted therapy, psychotherapy plus placebo). Methods: A web-based survey (N = 404) was conducted using a case vignette depicting a patient diagnosed with severe depression. Participants rated treatment acceptance, ranked treatment preferences, and reported expectations regarding improvement, worsening, and side effects for each intervention. Depression severity was assessed using the Patient Health Questionnaire-9 (PHQ-9). Repeated-measures analyses of variance (RM-ANOVA) and multilevel modeling were used to examine the relationship between treatment expectations and depression severity. Results: Established treatments were more accepted and preferred over novel interventions, with psychotherapy receiving the highest acceptance (98.3%) and psilocybin the lowest (47.5%). Participants expected greater symptom improvement from traditional treatments compared to ketamine and psilocybin, which were associated with higher expectations of worsening and side effects. However, higher depression severity was linked to more favorable expectations of ketamine- and psilocybin-assisted therapy. This effect was specific to novel treatments and was not observed for psychotherapy or antidepressants. Conclusions: Traditional depression treatments are viewed as more acceptable and effective, while novel interventions evoke skepticism, likely due to unfamiliarity and concerns about risks. However, individuals with more severe depressive symptoms exhibit greater openness to innovative treatments. These findings underline the importance of managing patient expectations in psychedelic-assisted therapy and suggest that clinician education and well-balanced informed consent procedures could improve treatment acceptance.


authors: Fluyau D, Kailasam VK, Revadigar N.
journal: medRxiv
publication_date: 2024-06-19
doi: 10.1101/2024.06.17.24308787
source_url: https://doi.org/10.1101/2024.06.17.24308787
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: medRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:02
title:
Rapid and prolonged antidepressant and antianxiety effects of psilocybin, lysergic acid diethylamide, ayahuasca, and 3, 4-methylenedioxy-methamphetamine. A systematic review and meta-analysis of randomized controlled trials

abstract:
Background Hallucinogens attract research as alternatives to the commonly used medications to treat major depressive and anxiety disorders. Aims Assess hallucinogens’ efficacy for managing depressive and anxiety symptoms and evaluate their safety profiles. Method In five databases, we searched for randomized controlled trials of hallucinogens targeting depressive and anxiety symptoms. We performed a meta-analysis using a random effects model when data permitted it. The protocol of the review is registered in PROSPERO; CRD42022341325. Results Psilocybin produced a rapid and sustained reduction in depressive and anxiety symptoms in patients with major depressive disorder, severe, and in patients with life-threatening cancer. A decrease in depressive symptoms was observed with 3, 4-methylenedioxymethamphetamine (MDMA), primarily in patients with life-threatening cancer, autism spectrum disorder, and post-traumatic stress disorder. MDMA reduced social anxiety symptoms. However, MDMA’s effect size was either negligible or negative for anxiety symptoms overall. Ayahuasca reduced depressive symptoms in individuals with treatment-resistant major depressive and personality disorders. Lysergic acid diethylamide (LSD) reduced anxiety symptoms in individuals with life-threatening cancer. Psilocybin’s adverse effects were noticeable for elevated blood pressure, headaches, and panic attacks. For MDMA, elevated blood pressure, headaches, panic attacks, and feeling cold were noticeable. Conclusions Psilocybin, MDMA, ayahuasca, and LSD appear to have the potential to reduce depressive and anxiety symptoms. Adverse effects are noticed. Rigorous randomized controlled studies with larger sample sizes utilizing outcome measures instruments with better reliability and validity are warranted.

topic_tags:
Depression,Anxiety,PTSD,End-of-Life Distress,Headache / Migraine,Aging,Personality Change,Randomized Controlled Trial,Meta-Analysis,Systematic Review,Review Article,Safety

raw_json:
{"europe_pmc_id":"PPR869769","source":"PPR","pub_type":null,"publisher":"medRxiv","importer":"Europe PMC"}


authors: Chwyl C, Bazinet A, Wilson-Poe A, Hoffman K, Pertl K, McCrimmon S, Korthuis P, Luoma JB.
journal: PsyArXiv
publication_date: 2026-02-09
doi: 10.31234/osf.io/mdz73_v1
source_url: https://doi.org/10.31234/osf.io/mdz73_v1
substance_tags: psilocybin
topic_tags: Clinical Trial,Safety
study_type: Clinical Trial
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:47
last_checked: 2026-07-01 11:22:02
title:
Ethical Complexities and Best Practices in Informed Consent for Psychedelic Services: A Qualitative Study on Expert Perspectives

abstract:
Background: Informed consent in psychedelic-assisted services is ethically complex, difficult to implement, and remains largely unstudied and unstandardized. Objective: The current study sought expert recommendations from experienced psychedelic facilitators on what constitutes informed consent best practices for supervised psychedelic experiences across various settings. Methods: Participants with expertise in facilitating psilocybin-assisted experiences or other expertise in the psychedelic field were recruited with purposive sampling. Qualitative interviews on informed consent best practices and recommendations were analyzed using Thematic Analysis. Results: Participants (N = 36; 71% white; 56% heterosexual; 53% female) reported facilitating psilocybin services (64%) for a mean of 15.2 (SD = 13.1) years in clinical trial, licensed service center, underground, or ceremonial settings. Participants viewed informed consent as a process (Theme 1), necessitating a strong therapeutic relationship, centering client empowerment, and occurring as an ongoing process. Potential risks and benefits should be comprehensively conveyed (Theme 2), including potential long-term psychological and social changes, and the potential for disappointing experiences. Participants recommended detailed consent processes around touch and boundaries (Theme 3), including explicitly establishing boundaries prior to psychedelic administration, maintaining those boundaries throughout, and recognizing subtle non-verbal cues that may indicate lack of true consent. Within facilitator trainings (Theme 4), participants emphasized cultivating a deep respect for client agency, and experientially learning relational and boundary setting skills. Conclusions: Findings may inform practitioner training, consent practices in varied settings, and policy development for state-regulated psychedelic services.

raw_json:
{"europe_pmc_id":"PPR1154119","source":"PPR","pub_type":null,"publisher":"PsyArXiv","importer":"Europe PMC"}


journal: PsyArXiv
publication_date: 2023-03-16
source_url: https://osf.io/preprints/psyarxiv/ba42z_v1
substance_tags: psilocybin
topic_tags: OCD,Pharmacology,Mechanism of Action,Safety
study_type: Clinical Trial
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"ba42z_v1","version":1,"reviews_state":"accepted"}
title:
Yale Program for Psychedelic Science (YPPS) Manual for Psilocybin Combined with Non-Directive Support in the Treatment of OCD

abstract:
The Yale Program for Psychedelic Science (YPPS) supports a multi-disciplinary research community dedicated to investigating the effects of psychedelic substances on brain function, cognition, and behavior, including their therapeutic potential in treating neuropsychiatric conditions. In support of this mission, YPPS is testing the safety and efficacy of psilocybin, administered in conjunction with non-directive psychological support, as a treatment for certain neurological and psychiatric conditions. The current study, “Effects of repeated dosing of psilocybin on obsessive-compulsive disorder: A randomized, waitlist-controlled study” (NCT05370911), will investigate the effects of repeated dosing of oral psilocybin on obsessive-compulsive disorder (OCD) symptomatology and assess psychological mechanisms that may mediate psilocybin’s therapeutic effects on OCD. The study will employ a randomized, waitlist-controlled design with blinded ratings, with participants randomized to receive either immediate treatment (two doses of oral psilocybin separated by one week) or delayed treatment (7 weeks post-randomization). An adaptive dose selection strategy will be implemented; the first dose will be fixed at 25 mg of psilocybin, and the second dose will be 25 mg or 30 mg, depending on whether or not a clinically significant response is detected after the first dose. This manual provides background and details for facilitator-related activities at various phases - pre-dosing preparation sessions, dosing sessions, and post-dosing integration sessions. The approach for psychological support by facilitators is unstructured and non-directive. In other words, facilitators do not provide any structured therapy, but rather collaborate and support participants as they prepare for psilocybin dosing sessions, ensure their psychological safety during dosing sessions, and provide them with an unstructured, non-directive context in which to process and consolidate their experiences during and after each dosing at defined time points. In doing so, while no structured therapy program is implemented, the presence and accompaniment by facilitators throughout all study sessions in the treatment phase may be experienced as supportive or even therapeutic by participants. This manual shares several features with a previous YPPS protocol-specific session monitor manual for single-dose psilocybin paired with psychological support for OCD (Ching et al., 2022), including the primary focus on a non-directive approach for preparatory, dosing, and integration sessions. Distinctive additions in this manual include a discussion of psychological processes in OCD that serve as a context for responsive facilitation of study visits, as well as updated facilitator checklists for preparatory, dosing, and integration sessions specific to the current two-dose protocol.

keywords:
manual, non-directive, obsessive-compulsive disorder, psilocybin, psychedelic, psychiatry, psychology, psychopharmacology, therapy, Psychiatry, Social and Behavioral Sciences, Clinical Psychology, Intervention Research, Obsessive-compulsive and Related Disorders, Therapy, Psychotherapy, Psychopharmacology


title: A Bayesian Reanalysis of a Trial of Psilocybin versus Escitalopram for Depression
journal: PsyArXiv
publication_date: 2022-06-30
doi: 10.31234/osf.io/sb5ur
source_url: https://doi.org/10.31234/osf.io/sb5ur
substance_tags: psilocybin
topic_tags: Depression
study_type: Other
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
authors:
Nayak SM, Bari BA, Yaden DB, Spriggs MJ, Rosas F, Peill JM, Giribaldi B, Erritzoe D, Nutt D, Carhart-Harris R.

abstract:
Objectives: To perform a Bayesian reanalysis of a recent trial of psilocybin (COMP360) versus escitalopram for Major Depressive Disorder (MDD) in order to provide a more informative interpretation of the indeterminate outcome of a previous frequentist analysis. Design: Reanalysis of a two-arm double-blind placebo controlled trial.Participants: Fifty-nine patients with MDD.Interventions: Two doses of psilocybin 25mg and daily oral placebo versus daily escitalopram and 2 doses of psilocybin 1mg, with psychological support for both groups.Outcome measures: Quick Inventory of Depressive Symptomatology-Self-Report (QIDS SR-16), and three other depression scales as secondary outcomes: HAMD-17, MADRS, and BDI-1A. Results: Using Bayes factors and ‘skeptical priors’ which bias estimates towards zero, for the hypothesis that psilocybin is superior by any margin, we found indeterminate evidence for QIDS SR-16, strong evidence for BDI-1A and MADRS, and extremely strong evidence for HAMD-17. For the stronger hypothesis that psilocybin is superior by a ‘clinically meaningful amount’ (using literature defined values of the minimally clinically important difference), we found moderate evidence against it for QIDS SR-16, indeterminate evidence for BDI-1A and MADRS, and moderate evidence supporting it for HAMD-17. Furthermore, across the board we found extremely strong evidence for psilocybin’s non-inferiority versus escitalopram. These findings were robust to prior sensitivity analysis. Conclusions: This Bayesian reanalysis supports the following inferences: 1) that psilocybin did indeed outperform escitalopram in this trial, but not to an extent that was clinically meaningful--and 2) that psilocybin is almost certainly non-inferior to escitalopram. The present results provide a more precise and nuanced interpretation to previously reported results from this trial, and support the need for further research into the relative efficacy of psilocybin therapy for depression with respect to current leading treatments.

raw_json:
{"europe_pmc_id":"PPR512763","source":"PPR","pub_type":null,"publisher":"PsyArXiv","importer":"Europe PMC"}


authors: Shinozuka K, Jerotic K, Mediano P, Zhao AT, Preller KH, Carhart-Harris R, Kringelbach ML.
journal: bioRxiv
publication_date: 2023-10-06
doi: 10.1101/2023.10.06.561183
source_url: https://doi.org/10.1101/2023.10.06.561183
substance_tags: psilocybin,psilocin
study_type: Systematic Review
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
title:
Synergistic, Multi-level Understanding of Psychedelics: Three Systematic Reviews and Meta-analyses of Their Pharmacology, Neuroimaging and Phenomenology

abstract:
Serotonergic psychedelics induce altered states of consciousness and have shown potential for treating a variety of neuropsychiatric disorders, including depression and addiction. Yet their modes of action are not fully understood. Here, we provide a novel, synergistic understanding of psychedelics arising from systematic reviews and meta-analyses of three hierarchical levels of analysis: 1) subjective experience (phenomenology), 2) neuroimaging and 3) molecular pharmacology. Phenomenologically, medium and high doses of LSD yield significantly higher ratings of visionary restructuralisation than psilocybin on the 5-dimensional Altered States of Consciousness Scale. Our neuroimaging results reveal that, in general, psychedelics significantly strengthen between-network functional connectivity (FC) while significantly diminishing within-network FC. Pharmacologically, LSD induces significantly more inositol phosphate formation at the 5-HT2A receptor than DMT and psilocin, yet there are no significant between-drug differences in the selectivity of psychedelics for the 5-HT2A, 5-HT2C, or D2 receptors, relative to the 5-HT1A receptor. Our meta-analyses link DMT, LSD, and psilocybin to specific neural fingerprints at each level of analysis. The results show a highly non-linear relationship between these fingerprints. Overall, our analysis highlighted the high heterogeneity and risk of bias in the literature. This suggests an urgent need for standardising experimental procedures and analysis techniques, as well as for more research on the emergence between different levels of psychedelic effects.

topic_tags:
Depression,Addiction,Brain Imaging,Pharmacology,Receptor Pharmacology,Consciousness,Aging,Systematic Review,Review Article,Safety

raw_json:
{"europe_pmc_id":"PPR738055","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


authors: Lerer B, Singh S, Botvinnik A, Shahar O, Wolf G, Yakobi C, Saban M, Salama A, Lotan A, Lifschytz T.
journal: Research Square
publication_date: 2022-09-07
doi: 10.21203/rs.3.rs-2001983/v1
source_url: https://doi.org/10.21203/rs.3.rs-2001983/v1
substance_tags: psilocybin
topic_tags: OCD,Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
title:
Effect of psilocybin on marble-burying in ICR mice: Role of 5-HT1A receptors and implications for the treatment of obsessive-compulsive disorder

abstract:
Abstract Preliminary clinical findings, supported by preclinical studies employing behavioral paradigms such as marble-burying, suggest that psilocybin may be effective in treating obsessive-compulsive disorder. On this background, we set out to explore 1) the role of 5-HT2A and 5-HT1A receptors in the effect of psilocybin on marble-burying; 2) the effect of staggered versus bolus psilocybin administration and persistence of the effect; 3) the effect of the 5-HT1A partial agonist, buspirone, on marble-burying and the head-twitch response (HTR) induced by psilocybin, a rodent correlate of psychedelic effects. Male ICR mice were administered psilocybin 4.4 mg/kg, escitalopram 5 mg/kg, 8-OH-DPAT2 mg/kg, M100907 2 mg/kg, buspirone 5 mg/kg, WAY100635 2 mg/kg or combinations, intraperitoneally, and were tested on the MBT. HTR was examined in a magnetometer-based assay. The results show that 1) Psilocybin and escitalopram significantly reduced marble-burying. The effect of psilocybin was not attenuated by the 5-HT2A antagonist, M100907. The 5-HT1A agonist, 8-OH-DPAT reduced marble-burying as did the 5-HT1A partial agonist, buspirone. The effect of 8-OH-DPAT was additive to that of psilocybin but that of buspirone was not. The 5-HT1A antagonist, WAY100635, attenuated the effect of 8-OH-DPAT and buspirone but not the effect of psilocybin. 2) Psilocybin injections over 3.5 hours had no effect on marble-burying and the effect of bolus injection was not persistent. 3) Co-administration of buspirone with psilocybin blocked its effect on HTR. These data suggest that neither 5-HT2A nor 5-HT1A receptors are pivotally implicated in the effect of psilocybin on marble-burying. Co-administration with buspirone may block the psychedelic effects of psilocybin without impeding its anti-obsessional effects.

raw_json:
{"europe_pmc_id":"PPR541577","source":"PPR","pub_type":null,"publisher":"Research Square","importer":"Europe PMC"}


authors: Nkadimeng SM, Steinmann CM, Eloff JN.
journal: Preprints.org
publication_date: 2023-06-05
doi: 10.20944/preprints202306.0362.v1
source_url: https://doi.org/10.20944/preprints202306.0362.v1
substance_tags: psilocybin
topic_tags: Receptor Pharmacology,Mitochondrial Function,Oxidative Stress,Safety,Toxicity,Inflammation
study_type: Other
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
title:
Cardioprotective Potential of the Ethanol and Water Extracts of Four Psilocybin Mushrooms on Angiotensin II-Induced Hypertrophy and Oxidative Stress on H9C2 Cardiomyocytes

abstract:
Psilocybin-containing mushrooms, commonly known as magic mushrooms have antidepressant effect, however, their safety in cardiovascular diseases such as heart failure is not fully known and needs to be investigated. Cardiac hypertrophy is an independent risk factor for heart failure morbidity and mortality. Angiotensin II (Ang-II) plays a major role in the pathogenesis of cardiac hypertrophy. We investigated the cardiovascular safety of extracts of Panaeolus cyanescens, Psilocybe natalensis, Psilocybe cubensis, and Psilocybe cubensis leucistic A+ strain mushrooms, well-known psilocybin-containing mushrooms in the Panaeolus and Psilocybe genus on Ang II-induced hypertrophy oxidative stress. The four mushrooms were grown, dried and extracted with 70% ethanol, cold and hot water. Extracts were tested for cytotoxicity on H9C2 cardiomyoblast cells. The cardiomyocytes were induced with (10 µM) AngII and treated with the three extracts of the four mushrooms over 48 hours. Control cells were serum starved but neither AngII induced nor treated while AngII cells were serum starved and stimulated with AngII but not treated. Losartan, an inhibitor of AngII type 1 receptor was used as positive control. Effects of the extracts on actin-filament labelling and cell surface area, mitochondrial activity, reactive oxygen species (ROS) and atrial natriuretic peptide levels were determined. Stimulation with AngII lowered cell viability, increased the cell width measurements and intracellular ROS levels significantly compared to control cells. The results indicated that the ethanol and water extracts of the four psilocybin mushrooms did not exacerbate the angiotensin II-induced hypertrophy conditions, but the extracts had cardio-protective activity against angiotensin II-induced oxidative stress. The phytochemical analysis of the extracts confirmed detections of known compounds with antioxidant and anti-inflammatory effects in the water and ethanol extracts of these four psilocybin mushrooms.

raw_json:
{"europe_pmc_id":"PPR672264","source":"PPR","pub_type":null,"publisher":"Preprints.org","importer":"Europe PMC"}


journal: medRxiv
publication_date: 2022-10-31
doi: 10.1101/2022.10.31.22281688
source_url: https://doi.org/10.1101/2022.10.31.22281688
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Biomarkers,Healthy Volunteers,Inflammation,Immune Function
study_type: Other
source_name: medRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
title:
Psilocybin induces acute and persisting alterations in immune status and the stress response in healthy volunteers

authors:
Mason N, Szabo A, Kuypers K, Mallaroni P, de la Torre Fornell R, Reckweg J, Tse D, Hutten N, Feilding A, Ramaekers J.

abstract:
Patients characterized by stress-related disorders such as depression display elevated circulating concentrations of pro-inflammatory cytokines and a hyperactive HPA axis. Psychedelics are demonstrating promising results in treatment of such disorders, however the mechanisms of their therapeutic effects are still unknown. To date the evidence of acute and persisting effects of psychedelics on immune functioning, HPA axis activity in response to stress, and associated psychological outcomes is preliminary. To address this, we conducted a placebo-controlled, parallel group design comprising of 60 healthy participants who received either placebo (n=30) or 0.17 mg/kg psilocybin (n=30). Blood samples were taken to assess acute changes in immune status, and 7 days after drug administration. Seven days’ post-administration, participants in each treatment group were further subdivided: 15 underwent a stress induction protocol, and 15 underwent a control protocol. Ultra-high field magnetic resonance spectroscopy was used to assess whether acute changes in glutamate or glial activity were associated with changes in immune functioning. Finally, questionnaires assessed persisting self-report changes in mood and social behavior. Psilocybin immediately reduced concentrations of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), while other inflammatory markers (interleukin (IL)-1α, IL-1β, IL-6, and C-reactive protein (CRP)) remained unchanged. Seven days later, TNF-α concentrations returned to baseline, while IL-6 and CRP concentrations were persistently reduced in the psilocybin group. Changes in the immune profile were related to acute neurometabolic activity as acute reductions in TNF-α were linked to lower concentrations of glutamate in the hippocampus. Additionally, the more of a reduction in IL-6 and CRP seven days after psilocybin, the more persisting positive mood and social effects participants reported. Regarding the stress response, after a psychosocial stressor, psilocybin blunted the cortisol response compared to placebo. Such acute and persisting changes may contribute to the psychological and therapeutic effects of psilocybin demonstrated in ongoing patient trials.

raw_json:
{"europe_pmc_id":"PPR565752","source":"PPR","pub_type":null,"publisher":"medRxiv","importer":"Europe PMC"}


title: Psilocybin: Systematic review of its use in the treatment of depression
publication_date: 2025-08-25
source_url: https://europepmc.org/article/PMC/PMC12436869
substance_tags: psilocybin
topic_tags: Depression,Systematic Review,Review Article
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
authors:
Andres-Olivera P, de la Iglesia J, Dominguez-Alvarez E, Soto’Gonzalez P, Rodriguez C, Munaiz-Cossio C, Gonzalez-Bolaños R, Brito-Rey R, Marín-Lorenzo C, Arribas-Simon B.

raw_json:
{"europe_pmc_id":"PMC12436869","source":"PMC","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Bradshaw AJ, Ramírez-Cruz V, Awan AR, Furci G, Guzmán-Dávalos L, Stamets P, Dentinger BT.
journal: bioRxiv
publication_date: 2022-12-14
doi: 10.1101/2022.12.13.520147
source_url: https://doi.org/10.1101/2022.12.13.520147
substance_tags: psilocybin
topic_tags: Genomics
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
title:
Phylogenomics of the psychoactive mushroom genus Psilocybe and evolution of the psilocybin biosynthetic gene cluster

abstract:
Psychoactive mushrooms in the genus Psilocybe have immense cultural value and have been used for centuries in Mesoamerica. Despite a recent surge in interest in these mushrooms due to emerging evidence that psilocybin, the main psychoactive compound, is a promising therapeutic for a variety of mental illnesses, their phylogeny and taxonomy remain substantially incomplete. Moreover, the recent elucidation of the psilocybin biosynthetic gene cluster is known for only five species of Psilocybe, four of which belong to only one of two major clades. We set out to improve the phylogeny for Psilocybe using shotgun sequencing of 71 fungarium specimens, including 23 types, and conducting phylogenomic analysis using 2,983 single-copy gene families to generate a fully supported phylogeny. Molecular clock analysis suggests the stem lineage arose ∼66 mya and diversified ∼53 mya. We also show that psilocybin biosynthesis first arose in Psilocybe, with 4-5 possible horizontal transfers to other mushrooms between 40 and 22 mya. Moreover, predicted orthologs of the psilocybin biosynthetic genes revealed two distinct gene orders within the cluster that corresponds to a deep split within the genus, possibly consistent with the independent acquisition of the cluster. This novel insight may predict differences in chemistry between the two major clades of the genus, providing further resources for the development of novel therapeutics.

raw_json:
{"europe_pmc_id":"PPR585520","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


authors: Effinger D, Quadir S, Ramage M, Cone M, Herman M.
journal: bioRxiv
publication_date: 2022-04-28
doi: 10.1101/2022.04.28.489882
source_url: https://doi.org/10.1101/2022.04.28.489882
substance_tags: psilocybin,psilocin
topic_tags: Biomarkers
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
title:
Sex-Specific Effects of Psychedelic Drug Exposure on Central Amygdala Reactivity and Behavioral Responding

abstract:
ABSTRACT Psilocybin, and its active metabolite psilocin, have been shown to elicit rapid and long-lasting symptom improvements in a variety of affective psychiatric illnesses. However, the region-specific alterations underlying these therapeutic effects remain relatively unknown. The central amygdala (CeA) is a primary output region within the extended amygdala that is dysregulated in affective psychiatric disorders. Here, we measured CeA activity using the activity marker c-Fos and CeA reactivity using fiber photometry paired with an aversive air-puff stimulus. We found that psilocin administration acutely increased CeA activity in both males and females and increased stimulus specific CeA reactivity in females, but not males. In contrast, psilocin produced time-dependent decreases in reactivity in males, but not females as early as 2-days and lasting to 28-days post administration. We also measured behavioral responses to the air-puff stimulus and found sex-dependent changes in threat responding but not exploratory behavior or general locomotion. Repeated presentations of the auditory component of the air-puff were also performed and sex-specific effects of psilocin on CeA reactivity to the auditory-alone stimulus were also observed. This study provides new evidence that a single dose of psilocin produces sex-specific, time-dependent, and enduring changes in CeA reactivity and behavioral responding to specific components of an aversive stimulus.

raw_json:
{"europe_pmc_id":"PPR487102","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


authors: Singh S, Botvinnik A, Shahar O, Wolf G, Yakobi C, Saban M, Salama A, Lotan A, Lerer B, Lifschytz T.
journal: bioRxiv
publication_date: 2022-07-13
doi: 10.1101/2022.07.13.498401
source_url: https://doi.org/10.1101/2022.07.13.498401
substance_tags: psilocybin
topic_tags: OCD,Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
title:
Effect of psilocybin on marble-burying in ICR mice: Role of 5-HT1A receptors and implications for the treatment of obsessive-compulsive disorder

abstract:
Background Preliminary clinical findings, supported by preclinical studies employing behavioral paradigms such as marble-burying, suggest that psilocybin may be effective in treating obsessive-compulsive disorder. Aims To explore 1) the role of 5-HT2A and 5-HT1A receptors in the effect of psilocybin on marble-burying; 2) the effect of staggered versus bolus psilocybin administration and persistence of the effect; 3) the effect of the 5-HT1A partial agonist, buspirone, on marble-burying and the head-twitch response (HTR) induced by psilocybin, a rodent correlate of psychedelic effects. Methods Male ICR mice were administered psilocybin 4.4 mg/kg, escitalopram 5 mg/kg, 8-OH-DPAT2 mg/kg, M100907 2 mg/kg, buspirone 5 mg/kg, WAY100635 2 mg/kg or combinations, intraperitoneally, and were tested on the MBT. HTR was examined in a magnetometer-based assay. Results 1) Psilocybin and escitalopram significantly reduced marble-burying. The effect of psilocybin was not attenuated by the 5-HT2A antagonist, M100907. The 5-HT1A agonist, 8-OH-DPAT reduced marble-burying as did the 5-HT1A partial agonist, buspirone. The effect of 8-OH-DPAT was additive to that of psilocybin but that of buspirone was not. The 5-HT1A antagonist, WAY100635, attenuated the effect of 8-OH-DPAT and buspirone but not the effect of psilocybin. 2) Psilocybin injections over 3.5 hours had no effect on marble-burying and the effect of bolus injection was not persistent. 3) Co-administration of buspirone with psilocybin blocked its effect on HTR Conclusions Neither 5-HT2A nor 5-HT1A receptors are pivotally implicated in the effect of psilocybin on marble-burying. Co-administration with buspirone may block the psychedelic effects of psilocybin without impeding its anti-obsessional effects.

raw_json:
{"europe_pmc_id":"PPR519282","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


journal: PsyArXiv
publication_date: 2025-02-27
source_url: https://osf.io/preprints/psyarxiv/26tz7_v1
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Pharmacology,Clinical Trial
study_type: Clinical Trial
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"26tz7_v1","version":1,"reviews_state":"accepted"}
title:
Sociodemographic and mental-health characteristics of psychedelic-assisted therapy participants: Latent class analysis of a cross-sectional, purposive online sample

abstract:
Psychedelic-assisted therapy (PAT) is an emerging treatment approach that often combines pharmacotherapeutic dosing sessions with more traditional psychotherapy. Despite limited formal regulatory approval, treatment seekers can currently access PAT through a variety of avenues, including ketamine treatment centers and “supported adult use” psilocybin centers in the U.S., drug tourism, “underground” therapy, and participation in clinical trials, among other ways. This has created a heterogenous landscape of PAT access in which people self-report PAT utilization with a variety of psychedelic and hallucinogenic drugs. However, there is limited published data on patterns of PAT involvement across drugs among real-world patients. Therefore, the present study investigated patterns of PAT utilization by applying latent class analysis (LCA) to a purposive sample of 244 self-identified PAT patients. Participants were recruited from a variety of sources (e.g., ketamine clinics, social media groups, a large U.S. university) and asked to report lifetime PAT utilization involving six compounds: psilocybin, ketamine, mescaline, ayahuasca/N,N-Dimethyltryptamine (DMT), lysergic acid diethylamide (LSD), and 3,4-methylenedioxymethamphetamine (MDMA). Participants also completed sociodemographic and internalizing measures (e.g., Beck Depression Inventory II, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7), and responses were compared across classes. LCA yielded a three-class solution. In addition to High- (55.7% of the sample) and Medium-PAT classes (29.1%), a unique Psilocybin-Ketamine class (15.2%) was identified-membership in this class was characterized by universal involvement with psilocybin and notable involvement with ketamine PAT compared to other compounds. Between-class comparisons of mental-health assessments indicated that the High-PAT class reported elevated depression and anxiety. These findings suggest that high levels of lifetime involvement in a variety of PAT modalities may be associated with more severe self-reported psychiatric symptoms, raising questions about selection or iatrogenic effects within the current PAT landscape. The emergence of a Psilocybin-Ketamine class implies that these substances may serve as initial entry points into PAT.

keywords:
ketamine, latent class analysis, psilocybin, psychedelic-assisted therapy, purposive sampling methods, underground psychedelic therapy, Psychiatry, Social and Behavioral Sciences, Clinical Psychology, Anxiety Disorders, Depressive Disorders, Therapy, Psychotherapy, Psychopharmacology


title: Interplay of hydrogen bonding in deciding the conformers of psilocin: Computational insights
authors: Bhadoria P, Venkatnarayan R.
journal: Authorea Preprints
publication_date: 2022-08-31
doi: 10.22541/au.166200851.10677416/v1
source_url: https://doi.org/10.22541/au.166200851.10677416/v1
substance_tags: psilocin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
abstract:
Conformational analysis of psilocin, a psychedelic molecule revealed two stable conformers designated as conformer-A and B which were 4.97 kcal/mol apart in energy among many other high energy conformers. AIM analysis revealed that the conformer-A (global minimum) is stable due to intramolecular H-bond formation between ethyl amine nitrogen and indolic hydroxyl group. This is in contradiction to earlier X-ray crystal studies of this molecule reported in literature. Dimers of both conformer-A and B were studied utilizing DFT method and it was observed that even in the dimer of conformer-A the intramolecular H-bond energy dominates over the intermolecular H-bond. Other calculations namely NBO, FMO, charge analysis, ESP mapping corroborated the AIM results in a significant manner. The spectroscopic study including UV, 1H-NMR and vibrational modes calculation were found to be in good agreement with the data reported in literature.

raw_json:
{"europe_pmc_id":"PPR539091","source":"PPR","pub_type":null,"publisher":"Authorea Preprints","importer":"Europe PMC"}


title: Psilocybin Combines Rapid Synaptogenic And Anti-Inflammatory Effects In Vitro
journal: Research Square
publication_date: 2022-03-07
doi: 10.21203/rs.3.rs-1321542/v1
source_url: https://doi.org/10.21203/rs.3.rs-1321542/v1
substance_tags: psilocybin
study_type: Animal Study
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
authors:
Smedfors G, Glotfelty E, Kalani N, Hjelle CP, Horntvedt O, Wellfelt K, Brodin A, von Kieseritzky F, Olson L, Karlsson T.

abstract:
Abstract Psilocybin is a psychedelic substance approaching clinical use. The drug has long-lasting effects after single or multiple administrations and enhances structural plasticity in the brain. Little is known if the plasticity inducing effects of psilocybin could be timed to other treatments and promote a larger effect. We investigated the effect of psilocybin on cultured mouse hippocampal neurons, examining the plasticity promoting effects from 5 min to 72 h post-treatment. We found robust effects on pre- and postsynaptic (Piccolo and Homer1) protein expression 1-3 h following treatment. Presynaptic Synapsin-1 expression mirrored these findings, with peak expression 72 h post-treatment. Our studies suggest psilocybin opens a window of plasticity that rapidly normalizes. As psilocybin has been shown to have an effect treating diseases (e.g. depression and cluster headache) linked with inflammation, we used an immortalized microglia cell line (IMG) to demonstrate its anti-inflammatory effects against a lipopolysaccharide (LPS) challenge (we show reduced tumor necrosis factor-alpha (TNF-α) secretion). Altogether, our studies show discrete and acute cell type specific effects of psilocybin that provides insight into its mechanisms of action and potential therapeutic value.

topic_tags:
Depression,Headache / Migraine,Neuroplasticity,Mechanism of Action,Animal Study,In Vitro Study,Inflammation

raw_json:
{"europe_pmc_id":"PPR465041","source":"PPR","pub_type":null,"publisher":"Research Square","importer":"Europe PMC"}


title: Psychedelics Relax Priors and Reshape Orbitofrontal Dynamics
authors: Delgado-Sallent C, Ahmed SA, Khawaja-Lopez A, Lee BS, Senne R, Scott BB, Ramirez S.
journal: bioRxiv
publication_date: 2025-09-18
doi: 10.1101/2025.09.18.677110
source_url: https://doi.org/10.1101/2025.09.18.677110
substance_tags: psilocybin
topic_tags: Brain Imaging,Mechanism of Action,Aging,Animal Study
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
abstract:
Psychedelics such as psilocybin and ketamine are gaining attention as rapid-acting treatments for psychiatric disorders, yet the mechanisms by which they alter cognition remain unclear. A key hypothesis-the REBUS model-proposes that psychedelics relax high-level priors, allowing bottom-up sensory information to exert greater influence over perception and behavior. Here, we test this model in mice performing a free-response perceptual decision-making task that disambiguates prior-driven and sensory-driven decision strategies. Acute administration of psilocybin or ketamine significantly slowed decision times and improved accuracy. Behavioral modeling that combined drift diffusion and GLM-HMM frameworks revealed that these changes were mediated by increased decision thresholds and a marked shift into sensory-engaged cognitive states. Whole-brain c-Fos mapping identified a distributed decision-making network, with psychedelics selectively modulating cortical and subcortical nodes. Calcium imaging in the orbitofrontal cortex (OFC)-a key region for integrating priors and sensory inputs-revealed preserved decision-related selectivity under psychedelics, while exhibiting reduced neuronal correlations-population-level signatures of weakened top-down influence and relaxed priors. Together, these results provide circuit-level support for the REBUS model, showing that psychedelics reconfigure brain-wide and local dynamics to promote more deliberate, flexible, and sensory-driven decision policies.

raw_json:
{"europe_pmc_id":"PPR1088289","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: Electrodynamics of the Psychedelic Experience
authors: Hunt T.
journal: Preprints.org
publication_date: 2025-09-21
doi: 10.20944/preprints202509.1813.v1
source_url: https://doi.org/10.20944/preprints202509.1813.v1
substance_tags: psilocybin
topic_tags: Brain Imaging,Mechanism of Action,Receptor Pharmacology,Consciousness,Creativity,Drug Interactions
study_type: Other
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
abstract:
Electromagnetic field theories of consciousness propose that consciousness emerges from resonant electromagnetic field interactions rather than purely computational neural processes. This paper examines how psychedelic substances-LSD, psilocybin, ketamine, and 5-MeO-DMT-modulate consciousness through their effects on brain electromagnetic fields, as measured by EEG, ECoG, and local field potential recordings. We present evidence that psychedelics act as "field resonance enhancers," expanding consciousness by increasing electromagnetic field coherence, cross-frequency coupling, and epistemic depth. Our analysis reveals substance-specific field signatures: LSD produces sustained coherence enhancement across frequency bands; psilocybin increases oscillatory flexibility and field entropy; ketamine causes dissociative field fragmentation through NMDA-mediated disruption; and 5-MeO-DMT induces rapid field boundary dissolution. We propose that psychedelics' molecular mechanisms-primarily through 5-HT2A and NMDA receptor modulation-serve as energetic inputs that tune electromagnetic field computation rather than directly encode information. This field-centric perspective offers novel insights into psychedelic phenomenology, including ego dissolution, enhanced creativity, and therapeutic efficacy. The framework predicts specific, testable relationships between receptor activation patterns, field dynamics, and conscious experience, suggesting new approaches for optimizing psychedelic therapy through targeted field modulation.

raw_json:
{"europe_pmc_id":"PPR1088799","source":"PPR","pub_type":null,"publisher":"Preprints.org","importer":"Europe PMC"}


authors: Socoró Garrigosa M, Sanz Perl Y, Kringelbach ML, Carhart-Harris R, Vohryzek J, Deco G.
journal: bioRxiv
publication_date: 2025-01-01
doi: 10.1101/2025.01.01.631011
source_url: https://doi.org/10.1101/2025.01.01.631011
substance_tags: psilocybin
topic_tags: Depression,Neuroplasticity,Clinical Trial
study_type: Clinical Trial
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
title:
Perturbing whole-brain models of brain hierarchy: an application for depression following pharmacological treatment

abstract:
Neural representation can extend beyond localised activity to encompass global patterns, where information is distributed across brain networks in a hierarchical manner. Recent research suggests that the hierarchy of causal influences shaping these patterns can serve as a signature of distinct brain states, with implications for neuropsychiatric disorders. Here, we first delve into how whole-brain models, guided by the Thermodynamics of Mind framework, can estimate the brain hierarchy of specific brain states, and how perturbations of such models can study the in-silico transitions to other states represented by static functional connectivity. We then show an application for major depressive disorder, where different brain hierarchical reconfigurations have been found following psilocybin and escitalopram treatments. We build whole-brain models of depressed patients before and after psilocybin and escitalopram interventions, and we carry a dynamic sensitivity analysis to explore the susceptibility of brain states and their drivability to healthier states. We show that susceptibility is on average reduced by escitalopram and increased by psilocybin, and that both treatments succeed in promoting healthier transitions. These results align with the post-treatment window of plasticity opened by serotonergic psychedelics, as well as with the similar clinical efficacy of both drugs observed in clinical trials. Graphical Abstract We apply whole-brain models of brain hierarchy based on the Thermodynamics of Mind framework to investigate state transitions in depression. Dynamic sensitivity analysis explores how psilocybin and escitalopram affect susceptibility and drivability to healthier states. Results show that psilocybin increases susceptibility, while escitalopram reduces it, with both enabling optimal transitions. This pipeline demonstrates the promise of in-silico approaches to inform neurostimulation protocols, potentially enhancing or complementing antidepressant therapies.

raw_json:
{"europe_pmc_id":"PPR962216","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


journal: bioRxiv
publication_date: 2024-08-08
doi: 10.1101/2024.08.07.606965
source_url: https://doi.org/10.1101/2024.08.07.606965
substance_tags: psilocin
topic_tags: Neuroplasticity,Mechanism of Action,Biomarkers,Animal Study,In Vitro Study
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
title:
Effects of serotonergic psychedelics on synaptogenesis and immediate early genes expression - comparison with ketamine, fluoxetine and lithium

authors:
Vella Y, Syrova K, Petruskova A, Koutrouli I, Kutna V, Pala J, Nikolic M, Sichova K, Mazoch V, Jurok R, Kuchar M, Bendova Z, Palenicek T.

abstract:
Background: Recent evidence suggests that psychedelics are able to induce rapid and long-lasting antidepressant effects. The generally acknowledged explanation for these traits is the phenomenon of neuroplasticity, although exact underlying molecular mechanisms remain unclear. Aims: This study investigates selected neuroplastic effects of psilocin, lysergic acid diethylamide (LSD) and N,N-dimethyltryptamine (DMT) in direct comparison with ketamine, fluoxetine and lithium after acute (1 h) and/or prolonged (24 h) treatment in vitro. Methods: Rat primary cortical cultures were treated with 10 uM psilocin, 1 uM lysergic acid diethylamide (LSD), 90 uM N, N-dimethyltryptamine (DMT), 1 uM ketamine, 10 uM fluoxetine and 5 mM lithium. Analysis of synaptic puncta was performed; puncta of presynaptic marker synapsin I/II, postsynaptic density protein 95 (PSD-95), and their co-localization (established synapse) were assessed 24 h after drug treatment. Next, expressions of immediate early genes (IEGs) encoding activity-regulated cytoskeleton-associated protein (Arc), early growth response 1 (Egr1), and neuronal PAS (Per-ArntSim) domain protein 4 (Npas4) were analysed 1 and 24 h after drug treatments. Results: Psilocin increased synaptic puncta count and induced Arc expression. The effect to promote synaptogenesis was comparable to ketamine and lithium; ketamine additionally increased PSD-95 puncta count. LSD and DMT didn't induce any significant effect. Interestingly, fluoxetine had no effect on synaptic puncta count, but upregulated Egr1 and Npas4. Conclusions: Psilocin demonstrated a significant neuroplastic effect comparable to that of ketamine and lithium, adding another piece of evidence to its profile as a promising therapeutic agent.

raw_json:
{"europe_pmc_id":"PPR892617","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


authors: Thomas CW, Blanco-Duque C, Bréant B, Goodwin GM, Sharp T, Bannerman DM, Vyazovskiy VV.
journal: bioRxiv
publication_date: 2021-02-16
doi: 10.1101/2021.02.16.431276
source_url: https://doi.org/10.1101/2021.02.16.431276
substance_tags: psilocin
topic_tags: Depression,Brain Imaging,Mechanism of Action,Consciousness,Wellbeing,Animal Study
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
title:
Psilocin acutely disrupts sleep and affects local but not global sleep homeostasis in laboratory mice

abstract:
Serotonergic psychedelic drugs, such as psilocin (4-hydroxy-N,N-dimethyltryptamine), profoundly alter the quality of consciousness through mechanisms which are incompletely understood. Growing evidence suggests that a single psychedelic experience can positively impact long-term psychological well-being, with relevance for the treatment of psychiatric disorders, including depression. A prominent factor associated with psychiatric disorders is disturbed sleep, and the sleep-wake cycle is implicated in the regulation of neuronal firing and activity homeostasis. It remains unknown to what extent psychedelic agents directly affect sleep, in terms of both acute arousal and homeostatic sleep regulation. Here, chronic in vivo electrophysiological recordings were obtained in mice to track sleep-wake architecture and cortical activity after psilocin injection. Administration of psilocin led to delayed REM sleep onset and reduced NREM sleep maintenance for up to approximately 3 hours after dosing, and the acute EEG response was associated primarily with an enhanced oscillation around 4 Hz. No long-term changes in sleep-wake quantity were found. When combined with sleep deprivation, psilocin did not alter the dynamics of homeostatic sleep rebound during the subsequent recovery period, as reflected in both sleep amount and EEG slow wave activity. However, psilocin decreased the recovery rate of sleep slow wave activity following sleep deprivation in the local field potentials of electrodes targeting medial prefrontal and surrounding cortex. It is concluded that psilocin affects both global vigilance state control and local sleep homeostasis, an effect which may be relevant for its antidepressant efficacy.

raw_json:
{"europe_pmc_id":"PPR285218","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


journal: PsyArXiv
publication_date: 2022-10-04
source_url: https://osf.io/preprints/psyarxiv/85s9p_v1
substance_tags: psilocybin
topic_tags: OCD,Pharmacology,Safety
study_type: Other
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"85s9p_v1","version":1,"reviews_state":"accepted"}
title:
Yale Program for Psychedelic Science (YPPS) Manual for Psilocybin-OCD Session Monitors for Protocol HIC: 2000020355

abstract:
The Yale Program for Psychedelic Science (YPPS) is testing the safety and efficacy of psilocybin, administered in conjunction with non-directive psychological support, as a treatment for certain neurological and psychiatric conditions. The study, HIC: 200020355 (Neural correlates of the effects of psilocybin in obsessive-compulsive disorder: A double-blind, placebo-controlled study), will explore the safety and efficacy of a single 0.25 mg/kg dose of psilocybin, administered in a supportive clinical environment, to eligible participants with obsessive-compulsive disorder (OCD). Monitors meet with each participant before, during, and after the dosing session. Monitors do not provide any structured therapy, but rather help participants prepare for the experience of psilocybin dosing, ensure psychological safety during dosing, and provide participants with an unstructured context in which to process their experience during and after dosing at defined timepoints. In doing so, while no structured therapy is provided, the presence and accompaniment by monitors throughout all study sessions may be experienced as supportive or even therapeutic by participants. This manual provides background and details for Monitors on the activities that are required at three points - before, during, and after the dosing session.

keywords:
manual, OCD, psilocybin, psychedelic, session monitor, Psychiatry, Social and Behavioral Sciences, Clinical Psychology, Obsessive-compulsive and Related Disorders, Therapy, Psychotherapy, Psychopharmacology


journal: PsyArXiv
publication_date: 2021-11-22
source_url: https://osf.io/preprints/psyarxiv/6f9qp_v1
substance_tags: psilocybin
topic_tags: Pharmacology,Personality Change
study_type: Other
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"6f9qp_v1","version":1,"reviews_state":"accepted"}
title:
Examining attitudes to psilocybin: Should candidates for medical psilocybin be required to pass a contextual suitability test

abstract:
Background: Due to increasing evidence of efficacy in treating mental health disorders, psilocybin may become a legal medicinal drug. This study tested the validity of Carhart-Harris & Nutt (2017) model of extra-pharmacological (EP) factors and examined whether such factors should be taken into account in any psychological suitability test for medicinally prescribed psilocybin. Method: 219 participants (101 self-identified females, 109 males, 7 non-binary people and 2 who preferred not to say), with an age range of 18 to 68, completed three online measures of ‘personality’; ‘set, setting and intention’, and the ‘Attitudes Towards Psilocybin’ (ATP) scale. The sample was equally divided between those who had used psychedelics (52.1%) and those who had no previous psychedelic use (47.5%). A series of stepwise linear regressions were run to examine of extra-pharmcological factor predictors of ATP. Results: The ATP scale was tested in terms of its reliability, construct validity, determinant validity and was deemed an appropriate measure. A model consisting of Set, Openness to Experience and Extraversion significantly predicted ATP scores. Conclusion: These findings supported the EP model and suggest that a suitability test may be a useful tool when determining whether a prescription of psilocybin is an appropriate course of treatment.

keywords:
mental health disorders, personality, psilocybin, psychopharmacology, Social and Behavioral Sciences, Clinical Psychology, Paraphilic Disorders, Psychopharmacology


authors: Davoudian PA, Shao L, Kwan AC.
journal: bioRxiv
publication_date: 2022-03-19
doi: 10.1101/2022.03.18.484437
source_url: https://doi.org/10.1101/2022.03.18.484437
substance_tags: psilocybin
topic_tags: Neuroplasticity,Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
title:
Shared and distinct brain regions targeted for immediate early gene expression by ketamine and psilocybin

abstract:
ABSTRACT Psilocybin is a psychedelic with therapeutic potential. While there is growing evidence that psilocybin exerts its beneficial effects through enhancing neural plasticity, the exact brain regions involved are not completely understood. Determining the impact of psilocybin on plasticity-related gene expression throughout the brain can broaden our understanding of the neural circuits involved in psychedelic-evoked neural plasticity. In this study, whole-brain serial two-photon microscopy and light sheet microscopy were employed to map the expression of the immediate early gene, c-Fos, in male and female mice. The drug-induced c-Fos expression following psilocybin administration was compared to that of subanesthetic ketamine and saline control. Psilocybin and ketamine produced acutely comparable elevations in c-Fos expression in numerous brain regions, including anterior cingulate cortex, locus coeruleus, primary visual cortex, central and basolateral amygdala, medial and lateral habenula, and claustrum. Select regions exhibited drug-preferential differences, such as dorsal raphe and insular cortex for psilocybin and the CA1 subfield of hippocampus for ketamine. To gain insights into the contributions of receptors and cell types, the c-Fos expression maps were related to brain-wide in situ hybridization data. The transcript analyses showed that the endogenous levels of Grin2a and Grin2b are predictive of whether a cortical region is sensitive to drug-evoked neural plasticity for both ketamine and psilocybin. Collectively, the systematic mapping approach produced an unbiased list of brain regions impacted by psilocybin and ketamine. The data are a resource that highlights previously underappreciated regions for future investigations. Furthermore, the robust relationships between drug-evoked c-Fos expression and endogenous transcript distributions suggest glutamatergic receptors as a potential convergent target for how psilocybin and ketamine produce their rapid-acting and long-lasting therapeutic effects.

raw_json:
{"europe_pmc_id":"PPR470947","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


journal: PsyArXiv
publication_date: 2023-03-09
source_url: https://osf.io/preprints/psyarxiv/t6k9b_v1
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Clinical Trial,Treatment-Resistant Depression
study_type: Clinical Trial
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"t6k9b_v1","version":1,"reviews_state":"accepted"}
title:
Underground small-group therapy of treatment-resistant depression and complex post-traumatic stress disorder (C-PTSD) with psilocybin-A retrospective case study

abstract:
While a relatively large body of research exists on many aspects of psychedelic therapy, articles describing a complete, successful treatment process are rarely found. This article therefore presents a case of a woman in her early forties with early complex trauma due to domestic violence, sexual abuse and poverty in her childhood, resulting in approximately three decades of treatment resistant depression. Antidepressive medications did not alleviate her depression but resulted in adverse effects and an eventual discontinuation of the medications. Eventually the woman resorted to 'mixed-method' underground small-group sessions that utilized breathing exercises, cold exposure, physical exercises, music, and psilocybin mushrooms. Psilocybin appeared to interrupt trauma-related dissociation, producing an 'anti-dissociative' effect, allowing the woman to re-experience, in a controlled setting, dissociated physical sensations produced by earlier overwhelming events. After a period of approximately 1.5 years, during which time she had six psilocybin sessions, either individually, in the small group, or with friends, she achieved a remission of her depression. A follow-up interview 2.5 years later indicated permanence of the result. Information was acquired from semi-structured retrospective interviews with a total duration of approximately eight hours. This case study may facilitate an improved understanding of the requirements for and the process of alleviating or resolving treatment-resistant depression with psychedelics. Recent clinical trials have utilized one or two doses of psilocybin. This case illustrates the need for adopting a multi-dose strategy over an extended period of time in order to achieve remission.

keywords:
childhood sexual abuse, C-PTSD, domestic violence, hypnotherapy, psilocybin, psychedelics, psychedelic therapy, treatment-resistant depression, Psychiatry, Social and Behavioral Sciences, Clinical Psychology, Anxiety Disorders, Depressive Disorders, Psychotherapy, Trauma and Stress


title: Psilocybin: the magic medicine for depression?
authors: Corrigan A, Burchill E, Pelton L, Marrocu A, Mazzoleni A, Shackshaft L.
publication_date: 2021-06-17
source_url: https://europepmc.org/article/PMC/PMC8770735
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
abstract:
Aims Depression is the single largest contributor to global disability. However, effective treatments are currently lacking, resulting in a significant burden of treatment-resistant depression (TRD). Psilocybin, a serotonergic psychedelic, found as the active compound in 'magic mushrooms', has been proposed as a novel therapeutic avenue for TRD. We aimed to evaluate the future feasibility and implications of psilocybin as a new antidepressant therapy. Method We reviewed and critically analysed the available literature on the efficacy and safety of psilocybin as a treatment for depression, and the potential pharmacological and psychological mechanisms of the therapeutic benefit. We discussed the relative contributions to this therapeutic effect of the pharmacological drug treatment, placebo effects, and the context and parameters of the psychotherapeutic experience. We reviewed legal, social, and economic barriers to primary research and clinical implementation. Result Psilocybin in combination with psychotherapy has been shown to be safe and effective in TRD. Its mechanism of action in TRD has not been fully elucidated, however reviewing functional neuroimaging studies demonstrated disparate short and long-term modifications of default mode network connectivity, suggested to represent a ‘reset’ mechanism of acute modular disintegration and subsequent reintegration which restores normal function, reviving emotional responsiveness. Research suggests psychedelic treatment induces lasting personality, belief and attitude changes. The psychedelic drug itself, the context of the psychotherapeutic experience, and the post-drug integration therapy all appear to have a significant role. Preparation prior to treatment, the environment, context and support during the psychedelic experience itself, and the following long-term integration and support process must be considered. Despite novel findings Psilocybin is a Schedule I drug; this imposes a persisting ethical barrier to clinical use. Prohibition of psilocybin results in high costs of drug supply, and potential for harmful drug-seeking behaviours. Therefore, complex socio-political factors currently limit wider implementation. Conclusion Psilocybin in combination with psychotherapy is safe and effective in TRD. The interacting and elusive therapeutic mechanisms have implications for clinical implementation. Preparation prior to treatment, the physical and social environment in which the psychedelic experience takes place, and long-term integration and support are considered to play a significant role. Optimisation of these parameters and cost-benefit analyses are required prior to this being feasible as a widely available therapy. Systemic legislative, political and social change will also be key to enable widespread clinical use. The promise of this therapy on a background of inadequate current antidepressant treatments indicates these must be a priority.

topic_tags:
Depression,Brain Imaging,Mechanism of Action,Default Mode Network,Aging,Personality Change,Emotional Processing,Review Article,Treatment-Resistant Depression,Safety

raw_json:
{"europe_pmc_id":"PMC8770735","source":"PMC","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelics Align Brain Activity with Context
journal: bioRxiv
publication_date: 2025-03-10
doi: 10.1101/2025.03.09.642197
source_url: https://doi.org/10.1101/2025.03.09.642197
substance_tags: psilocybin
topic_tags: Brain Imaging,Consciousness,Aging
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
authors:
Stoliker D, Novelli L, Khajehnejad M, Biabani M, Greaves MD, Barta T, Williams M, Chopra S, Bazin O, Simonsson O, Chambers R, Barrett F, Deco G, Preller KH, Carhart-Harris R, Seth A, Sundram S, Egan GF, Razi A.

abstract:
Psychedelics can profoundly alter consciousness by reorganising brain connectivity; however, their effects are context-sensitive. To understand how this reorganisation depends on context, we collected and comprehensively analysed the largest psychedelic neuroimaging dataset to date. Sixty-two adults were scanned with functional MRI and EEG during rest and naturalistic stimuli (meditation, music, and movie), before and after ingesting 19 mg of psilocybin (functional MRI ≈80 min post-dose; EEG ≈150 min post-dose). Half the participants ranked the experience among the most meaningful of their lives. Under psilocybin, functional MRI and EEG signals recorded during eyes-closed conditions became similar to those recorded during an eyes-open condition. Global functional connectivity increased in associative regions and decreased in sensory areas. Using machine learning to represent neural activity as low-dimensional trajectories, we found that psilocybin reorganised these into structured, context-sensitive patterns of brain activity that reflected both experimental condition and the quality of subjective experience, revealing an organisation that was missed by time-averaged connectivity measures. Under psilocybin, brain networks that ordinarily segregate internal and external processing coherently integrated and aligned neural dynamics with context. This context-alignment manifested as distinct and cohesive neural trajectories in participants reporting positively felt self- and boundary-dissolving effects, corresponding to the felt experience of being part of the environment, which we refer to as embeddedness -the subjective experience of being continuous with, rather than separate from, the surrounding environment. The strength of this context-alignment was associated with next-day mindset change, bridging the neural, experiential, and therapeutic dimensions of the psychedelic state. These findings show that the organisation of brain activity covaries with the experiential coherence of the psychedelic state, and provide a systems-level framework for how context-sensitive brain dynamics link neurobiology to subjective experience and behavioural change.

raw_json:
{"europe_pmc_id":"PPR987866","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


journal: PsyArXiv
publication_date: 2026-06-09
source_url: https://osf.io/preprints/psyarxiv/6mj8n_v2
keywords: Neuroscience, Social and Behavioral Sciences, Clinical Psychology
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Mechanism of Action,Consciousness,Randomized Controlled Trial
study_type: Randomized Controlled Trial
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"6mj8n_v2","version":2,"reviews_state":"accepted"}
title:
Aquahenosis: A non-pharmacological altered state of consciousness induced by Floatation-REST in individuals with anxiety and depression

abstract:
Floatation-REST (Reduced Environmental Stimulation Therapy) systematically alters sensory and bodily input by combining neutral buoyancy, thermal and proprioceptive neutrality, attenuation of exteroceptive stimulation, and enhancement of cardiorespiratory signaling to the brain. Here we examined whether this non-pharmacological sensory perturbation induces altered states of consciousness and whether specific experiential dimensions are statistically related to changes in affect. In a secondary analysis of a randomized controlled feasibility trial, 75 treatment-seeking adults with anxiety and depression were assigned to six sessions of Floatation-REST with prescribed scheduling, Floatation-REST with preferred scheduling and duration, or a zero-gravity chair comparison condition. Altered states of consciousness were assessed using the 5-Dimensional Altered States of Consciousness Rating Scale, alongside measures of interoceptive awareness and affect. Compared to the chair condition, Floatation-REST was associated with increased interoceptive awareness of cardiorespiratory sensations and an altered state of consciousness characterized by Oceanic Boundlessness, Disembodiment, and Experience of Unity-a pattern we refer to as "aquahenosis." Effects were strongest among participants who selected longer and more flexible float sessions. Experiential profiles selectively overlapped with those reported for psilocybin and ketamine along boundary-dissolution dimensions. These findings identify Floatation-REST as a tractable, non-pharmacological method for inducing specific altered states of consciousness and highlight oceanic boundlessness as an important mediator of the float-induced changes in positive affect.


title: Effects of psilocybin-assisted therapy on treatment-resistant depression
publication_date: 2021-08-12
source_url: https://europepmc.org/article/PMC/PMC9480034
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Clinical Trial,Review Article,Treatment-Resistant Depression
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
authors:
Fraga A, Esteves-Sousa D, Facucho-Oliveira J, Albuquerque M, Costa M, Dos Santos P, Moura N, Moutinho A.

abstract:
Introduction Major depressive disorder is a highly prevalent clinical condition, affecting more than 300 million individuals worldwide. About 1/3 of patients with MDD fail to achieve remission despite treatment with multiple antidepressants and are considered to have treatment-resistant depression (TRD). Novel antidepressants with rapid and sustained effects on mood and cognition could represent a breakthrough in the TRD and may potentially improve or save lives. Psilocybin, a classic hallucinogen, more commonly found in the Psilocybe mushrooms has a combined serotonergic and glutamatergic action. The preliminary evidence of antidepressant effects of psilocybin-assisted therapy indicates the potential of psilocybin-assisted therapy as a novel antidepressant intervention. Objectives The authors elaborate a narrative literature review about the effects of Psilocybin-based therapy on patients diagnosed with treatment-resistant depression. Methods PubMed database searched using the terms “Treatment-Resistant Depression AND Psilocybin” and targeting clinical trials. References of selected articles and review articles were also assessed. Results 2 articles evaluate psilocybin effects in 32 patients with TRD and showed that two doses of psilocybin alongside psychological support significantly reduces depressive symptoms. All patients presented some reduction in symptoms from baseline to one week after the second dose and reproduced immediate and substantial improvements in depression that ultimately could sustain up to 6 months. Conclusions Psilocybin-assisted therapy is a very appealing new possibility in the treatment of depression. However, due to the small populations of the existing trials, future studies are needed to prove this positive association and to fully understand Psilocybin’s mechanisms of actions and effects. Disclosure No significant relationships.

raw_json:
{"europe_pmc_id":"PMC9480034","source":"PMC","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The DMT and Psilocin Treatment Changes CD11b+ Activated Microglia Immunological Phenotype
authors: Kozłowska U, Klimczak A, Wiatr K, Figiel M.
journal: bioRxiv
publication_date: 2021-03-07
doi: 10.1101/2021.03.07.434103
source_url: https://doi.org/10.1101/2021.03.07.434103
substance_tags: psilocin
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
abstract:
Psychedelics are new, promising candidate molecules for clinical use in psychiatric disorders such as Treatment-Resistant Depression (TRD) and Post Traumatic Stress Disorder (PTSD). They were recently also proposed as molecules supporting neural tissue repair by anti-inflammatory properties. Here we reported that two classic psychedelics, DMT and psilocin, can influence microglial functions by reducing the level of TLR4, p65, CD80 proteins, which are markers of the immune response, and upregulat TREM2 neuroprotective receptor. Psilocin also secured neuronal survival in the neuron-microglia co-culture model by attenuating the phagocytic function of microglia. We conclude that DMT and psilocin regulate the immunomodulatory potential of microglia. Of note, psychedelics were previously reported as a relatively safe treatment approach. The demonstrated regulation of inflammatory molecules and microglia phagocytosis suggests that psychedelics or their analogs are candidates in the therapy of neurological disorders where microglia and inflammation significantly contribute to pathogenic disease mechanisms.

topic_tags:
Depression,PTSD,Mechanism of Action,Receptor Pharmacology,Biomarkers,Treatment-Resistant Depression,Inflammation,Immune Function

raw_json:
{"europe_pmc_id":"PPR293601","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: 597. ARE SIDE EFFECTS NECESSARY FOR ANTIDEPRESSIVE TREATMENT: THE PSILOCYBIN EXPERIENCE
publication_date: 2025-07-31
source_url: https://europepmc.org/article/PMC/PMC12359505
substance_tags: psilocybin
topic_tags: Depression,Adverse Events
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
raw_json:
{"europe_pmc_id":"PMC12359505","source":"PMC","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin for Depression: The ACE Model Manual
journal: PsyArXiv
publication_date: 2021-07-04
source_url: https://osf.io/preprints/psyarxiv/5x2bu_v1
keywords: Social and Behavioral Sciences, Clinical Psychology, Therapy
substance_tags: psilocybin
topic_tags: Depression
study_type: Other
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"5x2bu_v1","version":1,"reviews_state":"accepted"}
abstract:
"The Psilocybin for Depression: The ACE Manual '' describes the structure, procedures, and scripts used in the two Imperial College London studies (Psilodep) researching psilocybin treatment for major depression.


title: 476. ACUTE AND CHRONIC PSILOCYBIN IN MOUSE MODELS OF PSYCHIATRIC DISORDERS
publication_date: 2025-07-31
source_url: https://europepmc.org/article/PMC/PMC12359791
substance_tags: psilocybin
topic_tags: Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
raw_json:
{"europe_pmc_id":"PMC12359791","source":"PMC","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Tolle HM, Luppi AI, Lawn T, Roseman L, Nutt D, Carhart-Harris RL, Mediano PAM.
journal: bioRxiv
publication_date: 2025-07-02
doi: 10.1101/2025.07.02.662710
source_url: https://doi.org/10.1101/2025.07.02.662710
substance_tags: psilocybin
study_type: Clinical Trial
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
title:
Accurate and Interpretable Prediction of Antidepressant Treatment Response from Receptor-informed Neuroimaging

abstract:
Conventional antidepressants show moderate efficacy in treating major depressive disorder. Psychedelic-assisted therapy holds promise, yet individual responses vary, underscoring the need for predictive tools to guide treatment selection. Here, we present graphTRIP (graph-based Treatment Response Interpretability and Prediction) - a geometric deep learning architecture that enables three advances: 1) accurate prediction of post-treatment depression severity using only pretreatment clinical and neuroimaging data; 2) identification of robust biomarkers; and 3) causal analysis of treatment effects and underlying mechanisms. Trained on data from a clinical trial comparing psilocybin and escitalopram ( NCT03429075 ), graphTRIP achieves strong predictive accuracy ( r = 0.72, p = 6.8 ×10 −8 ), and shows clear generalization to both an independent dataset and across brain atlases. The model identifies stronger functional connectivity within sensory networks as a robust predictor of poorer response across both treatments. In contrast, causal analysis implicates frontoparietal and default mode networks as key moderators of differential response, with stronger 5-HT1A- and 5-HT2A-related signalling in the frontoparietal network predicting escitalopram response but psilocybin resistance. Overall, this work advances precision medicine and biomarker discovery in depression.

topic_tags:
Depression,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Default Mode Network,Biomarkers,Aging,Clinical Trial

raw_json:
{"europe_pmc_id":"PPR1046304","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


authors: Nkadimeng SM, Hay L, Steinmann CM, Eloff JN.
journal: Research Square
publication_date: 2023-07-17
doi: 10.21203/rs.3.rs-3088850/v1
source_url: https://doi.org/10.21203/rs.3.rs-3088850/v1
substance_tags: psilocybin
topic_tags: Mechanism of Action,Receptor Pharmacology,Animal Study,In Vitro Study,Safety
study_type: Animal Study
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
title:
Administration effects of four psilocybin mushroom extracts on serotonin levels and endothelial nitric oxide synthase activity levels in vivo and in vitro after one hour

abstract:
Abstract Background Psilocybin-containing mushrooms induce antidepressant and momentary increase in blood pressure (BP) with potential risk to users with cardiovascular diseases. Irregularities in nitric oxide (NO) levels play a key role in endothelial dysfunctions leading to increases in BP. Mushrooms species show large variation in potency which may potentially induce different outcomes and mechanisms of action. Effects of the mushrooms on the endothelial nitric oxide synthase activity is not known. Aim To investigate safety and effects of administration of four psilocybin-containing mushroom species, Panaeolus cyanescens, Psilocybe natalensis, Psilocybe cubensis and Psilocybe cubesis leucistic A + strain, on acute haemodynamic and LV parameters in normal Wistar rat and on serotonin, NO levels and endothelial NO synthase (eNOS) activity in vivo and in vitro on H9C2 cardiomyocytes. Methods Mushrooms were extracted with hot-boiling water and administered (5 mg/kg) through a direct catheterization in anaesthetized rats. Nuzak (0.2 mg/kg) and Nω-Nitro-L-arginine methyl ester hydrochloride (LNAME) were used as positive controls and negative control group given saline. Levels of serotonin, NO and eNOS activities were measured after 1-hour treatment. Results Mushroom treatments incited non-significant increase in LV parameters peaks only after 20 minutes and not immediate like with LNAME. Mushrooms induced a significant increase in serotonin levels and a suppressing effect on the eNOS activity in vivo in rats and in vitro in cardiomyocytes. Conclusion Mushroom treatments were safe on the LV function and induced a significant serotonin level with the concentration investigated. Disturbance in eNOS pathways may be the underlying mechanism involved in the psilocybin-mushroom extracts to inducing temporary BP increase. The four mushrooms exhibited different cardiac effects indicating variations depending on mushroom species.

raw_json:
{"europe_pmc_id":"PPR693606","source":"PPR","pub_type":null,"publisher":"Research Square","importer":"Europe PMC"}


authors: Shahar O, Botvinnik A, Esh-Zuntz N, Brownstien M, Wolf R, Wolf G, Lerer B, Lifschytz T.
journal: bioRxiv
publication_date: 2022-07-22
doi: 10.1101/2022.07.22.501026
source_url: https://doi.org/10.1101/2022.07.22.501026
substance_tags: psilocybin
topic_tags: Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
title:
Role of 5-HT2A, 5-HT2C, 5-HT1A and TAAR1 receptors in the head twitch response induced by 5-hydroxytryptophan and psilocybin: Translational implications

abstract:
There is increasing interest in the therapeutic potential of psilocybin in psychiatric disorders. In common with other serotonergic psychedelics, psilocybin is thought to act via the 5-HT2A receptor (5-HT2AR). Serotonin is the endogenous ligand of 5-HTR. In rodents, the serotonin precursor, 5-hydroxytryptophan (5-HTP), and psilocybin, induce a characteristic head twitch response (HTR), which is correlated with the human psychedelic trip in intensity and duration. We examined the role of other serotonergic receptors and the trace amine associated receptor 1 (TAAR1) in modulating HTR induced by 5-HTP and psilocybin. Male C57BL/6J mice (11 weeks old, ~30g) were administered 5-HTP, 50-250 mg/kg intraperitoneally (i.p.) or 200 mg/kg i.p. after pretreatment with 5-HT/TAAR1 receptor modulators. Psilocybin was administered at 0.1-51.2 mg/kg i.p. or at 4.4 mg/kg i.p. preceded by 5-HT/TAAR1 receptor modulators. HTR was assessed in a custom-built magnetometer. 5-HTP and psilocybin induced a dose dependent increase in the frequency of HTR over 20 minutes with attenuation by the 5-HT2AR antagonist, M100907 (volanserin), and the 5-HT1AR agonist, 8-OH-DPAT. The 5-HT2CR antagonist, RS102221, enhanced HTR at lower doses but reduced it at higher doses for 5-HTP and psilocybin. The TAAR1 antagonist, EPPTB, reduced 5-HTP-but not psilocybin-induced HTR. We have confirmed the key role of 5-HT2AR in HTR and have demonstrated an effect of 5-HT1AR and a bimodal contribution of 5-HT2CR as well as a role of TAAR1 in modulating HTR induced by 5-HTP. Compounds that modulate HTR induced by psychedelics have a potentially important role in the emerging therapeutic use of these compounds. Significance Statement We have confirmed the key role of 5-HT2AR in in the induction of HTR by 5-HTP and psilocybin, have demonstrated the effect of a 5-HT1AR agonist to attenuate HTR and a bimodal contribution of 5-HT2CR as well as a role of TAAR1 in modulating HTR induced by 5-HTP. Compounds that modulate HTR induced by psychedelics have a potentially important role in the emerging therapeutic use of these compounds. Visual Abstract

raw_json:
{"europe_pmc_id":"PPR522905","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


authors: Whelan TP, Daly E, Puts NA, Malievskaia E, Murphy DG, McAlonan GM.
journal: medRxiv
publication_date: 2023-05-25
doi: 10.1101/2023.05.25.23290521
source_url: https://doi.org/10.1101/2023.05.25.23290521
substance_tags: psilocybin
topic_tags: Mechanism of Action,Receptor Pharmacology,Biomarkers,Clinical Trial,Animal Study
study_type: Clinical Trial
source_name: medRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
title:
Bridging the translational neuroscience gap: Development of the ‘shiftability’ paradigm and an exemplar protocol to capture psilocybin-elicited ‘shift’ in neurobiological mechanisms in autism

abstract:
Clinical trials of pharmacological approaches targeting the core features of autism have failed. This is despite evidence from preclinical studies, genetics, post-mortem studies and correlational analyses linking peripheral and central markers of multiple candidate neurochemical systems to brain function in autism. Whilst this has in part been explained by the heterogeneity of the autistic population, the field has largely relied upon association studies to link brain chemistry to function. The only way to directly establish that a neurotransmitter or neuromodulator is involved in a candidate brain function is to change it and observe a shift in that function. This experimental approach dominates preclinical neuroscience, but not human studies. There is very little direct experimental evidence describing how neurochemical systems modulate information processing in the living human brain. As a result, our understanding of how neurochemical differences contribute to neurodiversity is limited and impedes our ability to translate findings from animal studies into humans. Here, we begin by introducing our “shiftability” paradigm, an approach to bridge the translational gap in autism research. We then provide an overview of the methodologies used and explain our most recent choice of psilocybin as a pharmacological probe of the serotonin system in vivo. Finally, we provide a summary of the protocol for ‘PSILAUT’, an exemplar “shiftability” study which uses psilocybin to directly test the hypothesis that the serotonin system functions differently in autistic and non-autistic adults.

raw_json:
{"europe_pmc_id":"PPR666702","source":"PPR","pub_type":null,"publisher":"medRxiv","importer":"Europe PMC"}


journal: medRxiv
publication_date: 2022-07-09
doi: 10.1101/2022.07.10.22277414
source_url: https://doi.org/10.1101/2022.07.10.22277414
substance_tags: psilocybin
topic_tags: Headache / Migraine,Brain Imaging,Mechanism of Action,Aging,Clinical Trial,Safety
study_type: Clinical Trial
source_name: medRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
title:
Psilocybin-induced reduction in chronic cluster headache attack frequency correlates with changes in hypothalamic functional connectivity

authors:
Madsen MK, Petersen AS, Stenbæk DS, Sørensen IM, Schiønning H, Fjeld T, Nykjær CH, Ulv Larsen SM, Grzywacz M, Mathiesen T, Klausen IL, Overgaard-Hansen O, Brendstrup-Brix K, Linnet K, Johansen SS, Fisher PM, Jensen RH, Knudsen GM.

abstract:
Chronic cluster headache (CCH) is an excruciating disorder of unknown pathophysiology, but hypothalamic dysfunction has been implicated. CCH is difficult to treat but on a case-basis, the psychedelic compound psilocybin is said to have beneficial effects. In this first-ever clinical trial ( NCT04280055 ), we evaluate in a small open-label study of CCH patients the feasibility and prophylactic effect of three low-to-moderate doses of psilocybin as well as effects on hypothalamic functional connectivity (FC), using functional magnetic resonance imaging. The treatment was well-tolerated and without serious adverse reactions. Attack frequency was on average reduced by 30% from baseline to follow-up (P FWER =0.008). One patient experienced 21 weeks of complete remission. Changes in hypothalamic-diencephalic FC correlated negatively with relative reduction in attack frequency, implicating this neural pathway in treatment response. Further clinical studies are warranted to confirm the safety and prophylactic efficacy of psilocybin for CCH and hypothalamic involvement in treatment response.

raw_json:
{"europe_pmc_id":"PPR516560","source":"PPR","pub_type":null,"publisher":"medRxiv","importer":"Europe PMC"}


title: A critique of: Skepticism About Recent Evidence that Psilocybin Opens Depressed Minds
journal: PsyArXiv
publication_date: 2022-05-09
source_url: https://osf.io/preprints/psyarxiv/pdbf5_v1
keywords: Psychiatry, Neuroscience
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"pdbf5_v1","version":1,"reviews_state":"accepted"}
abstract:
This document details an authors' response to a critique of their work entitled: Skepticism About Recent Evidence that Psilocybin Opens Depressed Minds.


journal: Research Square
publication_date: 2026-04-27
doi: 10.21203/rs.3.rs-9266175/v1
source_url: https://doi.org/10.21203/rs.3.rs-9266175/v1
substance_tags: psilocybin
topic_tags: Brain Imaging,Drug Interactions
study_type: Other
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
title:
A128-Channel Wireless Wearable Myolink (W2 Myolink): Functional Characteristics and Multidisciplinary Experiments

authors:
Zajaczkowski M, Koutsoftidis S, Sheeraz M, Barsakcioglu DY, Jia T, McGeady CA, Kundu A, Pizzi M, Tatti F, Bashford J, Bhavesh P, Farina D, Drakakis E.

abstract:
Abstract This paper presents Wireless Wearable Myolink (W2 Myolink), a high-density, battery-powered system for wireless acquisition of surface electromyography(EMG) signals, and demonstrates its practicality across diverse experimentalparadigms. The device features a compact form factor (110x70x35 mm), low weight(160 g), and continuous operation for up to 6 h. It supports low-noise (1.34 µVRMS),high-resolution (24 bit) recordings from 128 EMG channels with real-time wireless datatransmission over Wi-Fi. The capabilities of W2 Myolink have been validated througha series of experiments. Conventional EMG studies included the recording and analysisof muscle activity during various gestures and hand movements, as well as concurrentEMG-EEG measurements for the investigation of cortico-muscular coherence. Thesystem’s suitability for clinical and pathological scenarios was examined using surrogateEMG signals representative of healthy subjects and of conditions such as myopathy,neuropathy, and Amyotrophic Lateral Sclerosis (ALS). More complex experimental usecases involved human-robot interaction with ISYBOT robotic arms, intraoperativeEMG monitoring during different types of surgery with and without exoskeletonassistance for the surgeon, and EMG acquisition during psychedelic experiencesinduced by psilocybin. Collectively, these results demonstrate that W2 Myolink canreliably acquire and wirelessly transmit high-quality, high-density EMG data in a broadrange of research and application contexts.

raw_json:
{"europe_pmc_id":"PPR1183277","source":"PPR","pub_type":null,"publisher":"Research Square","importer":"Europe PMC"}


title: Natural language signatures of psilocybin microdosing
journal: bioRxiv
publication_date: 2022-02-21
doi: 10.1101/2022.02.20.481177
source_url: https://doi.org/10.1101/2022.02.20.481177
substance_tags: psilocybin
topic_tags: Microdosing,Wellbeing,Creativity
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
authors:
Sanz C, Cavanna F, Muller S, de la Fuente L, Zamberlan F, Palmucci M, Janeckova L, Kuchar M, Carrillo F, García AM, Pallavicini C, Tagliazucchi E.

abstract:
Serotonergic psychedelics are being studied as novel treatments for mental health disorders and as facilitators of improved well-being, mental function and creativity. Recent studies have found mixed results concerning the effects of low doses of psychedelics (“microdosing”) on these domains. However, microdosing is generally investigated using instruments designed to assess larger doses of psychedelics, which might lack sensitivity and specificity for this purpose. Following a double-blind and placebo-controlled experimental design, we explored natural language as a resource to identify speech produced under the acute effects of psilocybin microdoses, focusing on variables known to be affected by higher doses: verbosity, semantic variability and sentiment scores. Except for semantic variability, these metrics presented significant differences between a typical active microdose of 0.5 g of psilocybin mushrooms and an inactive placebo condition. Moreover, machine learning classifiers trained using these metrics were capable of distinguishing between conditions with high accuracy (AUC≈0.8). Our results constitute first proof that low doses of serotonergic psychedelics can be identified from unconstrained natural speech, with potential for widely applicable, affordable, and ecologically valid monitoring of microdosing schedules.

raw_json:
{"europe_pmc_id":"PPR459897","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


publication_date: 2025-07-31
source_url: https://europepmc.org/article/PMC/PMC12359394
substance_tags: psilocybin
topic_tags: Eating Disorders,Mechanism of Action
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
title:
564. TOWARD AN UNDERSTANDING OF THE THERAPEUTICALLY RELEVANT MECHANISMS OF PSILOCYBIN FOR ANOREXIA NERVOSA

raw_json:
{"europe_pmc_id":"PMC12359394","source":"PMC","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: 205. SYNERGISTIC BEHAVIORAL AND NEUROPLASTIC EFFECTS OF PSILOCYBIN-NMDAR MODULATOR ADMINISTRATION
publication_date: 2025-07-31
source_url: https://europepmc.org/article/PMC/PMC12359736
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
raw_json:
{"europe_pmc_id":"PMC12359736","source":"PMC","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Gaddis A, Lidstone DE, Nebel MB, Griffiths R, Mostofsky SH, Mejia A, Barrett F.
journal: bioRxiv
publication_date: 2022-03-01
doi: 10.1101/2022.02.28.482395
source_url: https://doi.org/10.1101/2022.02.28.482395
substance_tags: psilocybin
topic_tags: Brain Imaging,Receptor Pharmacology,Default Mode Network
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
title:
Psilocybin induces spatially constrained alterations in thalamic functional organizaton and connectivity

abstract:
ABSTRACT Background Serotonin 2A receptor (5-HT 2AR ) agonist psychedelics including psilocybin and LSD (“classic” psychedelics) evoke acute alterations in perception and cognition. Altered thalamocortical connectivity has been proposed to underlie these effects, which is supported by some functional MRI (fMRI) studies. Likely due to sample size limitations, these studies have treated the thalamus as a unitary structure, despite known differential 5-HT 2AR expression and functional specificity of different intrathalamic nuclei. Independent Component Analysis (ICA) has been employed to generate functional subdivisions of the thalamus from resting state fMRI (rsfMRI) data. This report utilizes a novel data-sparing ICA approach in order to examine psilocybin-induced changes in intrathalamic functional organization and thalamocortical connectivity. Methods Baseline rsfMRI data (n=38) was utilized to generate a template, which was then applied in a novel ICA-based analysis of the acute effects of psilocybin on intra- and extra-thalamic functional organization and connectivity in a smaller sample (n=18). Correlations with subjective reports of drug effect and comparisons with a previously reported analytic approach (treating the thalamus as a single functional unit) were conducted. Results Several intrathalamic components showed significant psilocybin-induced alterations in intrathalamic spatial organization, largely localized to the mediodorsal and pulvinar nuclei, and correlated with reported subjective effects. These same components demonstrated alterations in thalamocortical connectivity, largely with visual and default mode networks. Analysis in which the thalamus is treated as a singular unitary structure showed an overall numerical increase in thalamocortical connectivity, consistent with previous literature using this approach, but this increase did not reach statistical significance. Conclusions Utilization of a novel analytic approach demonstrated changes in intra- and extra-thalamic functional organization and connectivity of intrathalamic nuclei and cortical networks known to express the 5-HT 2AR. Given that these changes were not observed using whole-thalamus analyses, it seems that psilocybin may cause widespread but modest increases in thalamocortical connectivity that are offset by strong focal decreases in functionally relevant intrathalamic nuclei.

raw_json:
{"europe_pmc_id":"PPR463548","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: Increased low-frequency brain responses to music after psilocybin therapy for depression
authors: Wall MB, Lam C, Ertl N, Kaelen M, Roseman L, Nutt DJ, Carhart-Harris RL.
journal: bioRxiv
publication_date: 2022-02-14
doi: 10.1101/2022.02.13.480302
source_url: https://doi.org/10.1101/2022.02.13.480302
substance_tags: psilocybin
topic_tags: Depression,Brain Imaging,Aging,Emotional Processing,Treatment-Resistant Depression
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
abstract:
Psychedelic-assisted psychotherapy with psilocybin is an emerging therapy with great promise for depression, and modern psychedelic therapy (PT) methods incorporate music as a key element. Music is an effective emotional/hedonic stimulus that could also be useful in assessing changes in emotional responsiveness following psychedelic therapy. Brain responses to music were assessed before and after PT using functional Magnetic Resonance Imaging (fMRI) and ALFF (Amplitude of Low Frequency Fluctuations) analysis methods. Nineteen patients with treatment-resistant depression underwent two treatment sessions involving administration of psilocybin, with MRI data acquired one week prior and the day after completion of the second of two psilocybin dosing sessions. Comparison of music-listening and resting-state scans revealed significantly greater ALFF in bilateral superior temporal cortex for the post-treatment music scan, and in the right ventral occipital lobe for the post-treatment resting-state scan. ROI analyses of these clusters revealed a significant effect of treatment in the superior temporal lobe for the music scan only. Somewhat consistently, voxelwise comparison of treatment effects showed relative increases for the music scan in the bilateral superior temporal lobes and supramarginal gyrus, and relative decreases in the medial frontal lobes for the resting-state scan. ALFF in these music-related clusters was significantly correlated with intensity of subjective effects felt during the dosing sessions. These data suggest a specific effect of PT on the brain’s response to a hedonic stimulus (music), implying an elevated responsiveness to music after psilocybin therapy that was related to subjective drug effects felt during dosing.

raw_json:
{"europe_pmc_id":"PPR454661","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: Age moderates the relationship between psychedelics use and mental health in naturalistic settings
journal: Research Square
publication_date: 2026-03-09
doi: 10.21203/rs.3.rs-9022170/v1
source_url: https://doi.org/10.21203/rs.3.rs-9022170/v1
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Aging,Longevity,Mystical Experience,Clinical Trial,Observational Study,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
authors:
Gregorio GD, Basset S, Manmohan H, Nixon WC, Pogaku A, Zhou J, Sanderson DJ, Lengieza ML, Bocchio M.

abstract:
Abstract Depression and anxiety affect one in five adults, with age affecting prevalence. While clinical trials suggest classic psychedelics (e.g., psilocybin, LSD) and non-classic psychedelics (e.g., MDMA, ketamine) may alleviate these symptoms, it remains unclear how these relationships function in naturalistic settings or how they vary across the lifespan. We conducted a cross-sectional survey of 1,088 adults (18-55 + years) to assess how lifetime psychedelic use - categorized as classic, non-classic, or mixed - relates to mental health. Using structural equation modeling, we found that age significantly moderates the relationship between psychedelic use and mental health outcomes. Specifically, classic psychedelic use was linked to lower depression and anxiety among younger adults, but these effects diminished with age - even reversing for anxiety in older participants. These age-related effects persisted independently of drug-use parameters - including dosage, frequency, and recency of use - and were moderated by mystical experiences for depression, but not for anxiety. Our findings suggest that age may be a meaningful moderator of mental health outcomes from psychedelic use. This underscores the potential value of age-stratified research to optimize the efficacy and safety of psychedelic-assisted interventions, including in aging populations.

raw_json:
{"europe_pmc_id":"PPR1164283","source":"PPR","pub_type":null,"publisher":"Research Square","importer":"Europe PMC"}


journal: PsyArXiv
publication_date: 2023-06-08
source_url: https://osf.io/preprints/psyarxiv/qyce5_v1
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Emotional Processing
study_type: Other
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"qyce5_v1","version":1,"reviews_state":"accepted"}
title:
Self-treatment of parental neglect-induced mixed anxiety and depressive disorder with psilocybin - A retrospective case study

abstract:
This article presents the case of a young woman in her mid-twenties with a history of depression since childhood. She lived with a mother who failed to take care of her. The patient cared for the emotional needs of the mother instead of the mother caring for the daughter's needs. Her father was mostly absent. Already around the age of thirteen, the patient was severely depressed and was self-harming without anyone interfering with it. Eventually, her parents divorced when she was fourteen. Since then, she and her younger brother lived practically on their own for several years. She was 'unable to either recognize or process' her feelings, and assumed that she was supposed to 'serve others'. At the age of twenty, she moved in with a severely traumatized boyfriend. Compared to his, her childhood appeared 'very happy'. She was 'disconnected from her feelings' and 'could not understand what was wrong'. As she enrolled in a higher education facility, comparisons with other students made her realize that her own upbringing differed from theirs. She was unable to verbalize her problem, and the student healthcare system did not recommend psychotherapy for her. She was prescribed escitalopram, but it 'never worked'. Cannabis somewhat alleviated anxiety but led to passivity. Eventually, she tried psilocybin mushrooms. In the course of two years, she carried out four sessions with lower doses, and three sessions with conventional psychedelic doses of psilocybin. Subsequently, she considered her depression resolved. The mushrooms 'did not provide a swift solution' but 'played a major role' in the resolution of her depression. They enabled her to see that the root of her depression was in her adverse childhood experiences. Later, 'setting boundaries' and 'doing things as she wished' provided 'significant relief'. After this, she was also granted psychotherapy, which she utilized for 'psychedelic integration'. This case, along with previous case studies on the same approach, demonstrates that unsupervised self-treatment is a feasible, cost-effective, and relatively simple method, which could enable societies to overcome the cost and resource crisis of mental health care.

keywords:
psilocybin, psychedelics, psychedelic therapy, Psychiatry, Social and Behavioral Sciences, Clinical Psychology, Anxiety Disorders, Depressive Disorders, Trauma and Stress


title: Decreased brain modularity after psilocybin therapy for depression.
journal: Research Square
publication_date: 2021-05-19
doi: 10.21203/rs.3.rs-513323/v1
source_url: https://doi.org/10.21203/rs.3.rs-513323/v1
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
authors:
Daws R, Timmerman C, Giribaldi B, Sexton J, Wall M, Erritzoe D, Roseman L, Nutt D, Carhart-Harris R.

abstract:
Abstract Importance Psilocybin therapy shows antidepressant potential; our data link its antidepressant effects to decreased brain network modularity post-treatment. Objective To assess the sub-acute impact of psilocybin on brain activity in patients with depression. Design Pre vs post-treatment resting-state functional MRI (fMRI) was recorded in two trials: 1) Open-label treatment-resistant depression (TRD) trial with baseline vs 1 day post-treatment fMRI (April-2015 to April-2016); 2) Two-arm double-blind RCT in major depressive disorder (MDD), fMRI baseline vs 3 week after psilocybin-therapy or 6 weeks of daily escitalopram (January-2019 to March-2020). Setting Study visits occurred at the NIHR Imperial Clinical Research Facility.Participants Adult male and female patients with TRD or MDD. Intervention(s) (for clinical trials) or Exposure(s) (for observational studies)Study 1: Two oral doses of psilocybin (10mg and 25mg, fixed order, 7 days apart). fMRI was recorded at baseline and one day after the 25mg dose. Study 2: either: 2 x 25mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily placebo (‘psilocybin-arm’), or 2 x 1mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily escitalopram [10-20mg] (‘escitalopram-arm’). fMRI was recorded at baseline and 3 weeks after the 2nd psilocybin dose, which was the final day of the 6-week daily capsule ingestion. Main Outcome(s) and Measure(s) Beck Depression Inventory and fMRI network modularity. Results Study 1: In 16 adults (mean age [SD], 42.8 [10.1] years, 4 [25%] female), psilocybin therapy was associated with markedly decreased BDI scores at 1 week (mean difference, -21; 95% CI=[-27.3, -14.7], P

topic_tags:
Depression,Brain Imaging,Clinical Trial,Randomized Controlled Trial,Observational Study,Treatment-Resistant Depression

raw_json:
{"europe_pmc_id":"PPR344499","source":"PPR","pub_type":null,"publisher":"Research Square","importer":"Europe PMC"}


publication_date: 2025-11-30
source_url: https://europepmc.org/article/PMC/PMC12739712
substance_tags: psilocybin
topic_tags: Neurogenesis,Inflammation
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
title:
Psilocybin Maintains Better Brain Function in an Alzheimer’s Disease Model with Reduced Neuroinflammation and Improved Hippocampal Neurogenesis

authors:
Madhu L, Somayaji Y, Kotian S, Attaluri S, Patel J, Panda P, Rao V, Kodali M, Shankar G, Rao S, Weintraub S, Shuai B, Rao X, Shetty A.

raw_json:
{"europe_pmc_id":"PMC12739712","source":"PMC","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Coppola M, Bevione F, Mondola R.
journal: Preprints.org
publication_date: 2021-06-27
doi: 10.20944/preprints202106.0682.v1
source_url: https://doi.org/10.20944/preprints202106.0682.v1
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Addiction,Spirituality
study_type: Other
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:02
title:
Psilocybin for Treating Psychiatric Disorders: Is it a Psychonaut Legend or a Promising Therapeutic Perspective?

abstract:
Psychedelics extracted by plants have been used in religious, spiritual and mystic practices for millennia. In 1957, Dr. Hofmann have identified and synthesized the prodrug psilocybin, a substance present in more than 200 species of psychedelic mushrooms. Although the limitations related to the scientific design of many studies, clinical observations performed during the 1950s and the 1960s have shown a potential therapeutic effect of psilocybin in patients affected by depressive symptoms, anxiety, and conversion disorder. Psilocybin was classed as a schedule I substance in 1970, but the fascination for psychedelics remained almost unchanged over time promoting a new scientific interest starting from the 1990s. Recent studies provided further evidences supporting the suggestive hypothesis of a therapeutic use of psilocybin for treating various psychiatric disorders including: pathological anxiety, mood depressive disorder and addiction.

raw_json:
{"europe_pmc_id":"PPR363172","source":"PPR","pub_type":null,"publisher":"Preprints.org","importer":"Europe PMC"}


journal: PsyArXiv
publication_date: 2023-03-09
source_url: https://osf.io/preprints/psyarxiv/wupvy_v1
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Treatment-Resistant Depression,Healthcare Workers,Safety,Drug Interactions
study_type: Other
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 11:03:48
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"wupvy_v1","version":1,"reviews_state":"accepted"}
title:
Self-treatment of depression and complex post-traumatic stress disorder with psilocybin and LSD-A retrospective case study

abstract:
In medicine, psychedelics were initially considered as a tool for clinicians to understand psychotic states. Based on the presented case data, a reversal of that concept is proposed: psychedelics could be conceptualized as a tool for people chronically anxious and depressed since early childhood to understand ordinary states of mind (e.g. calmness, hopefulness, relaxation, and joy). The case concerns a young man who suffered from early-onset complex trauma due to daily abuse by his comprehensive school teacher and other pupils, resulting in severe anxiety and depression. He refused anti-depressive medication. Supportive psychotherapy failed to alleviate the situation, and interaction with psychiatric personnel subjectively experienced as rejection escalated his symptoms. At the age of 19, he resorted to unsupervised self-treatment with psilocybin. Occasional high-dose psilocybin sessions alone did not produce permanent outcomes in a constantly retraumatizing environment. After becoming unemployed at the age of 25, he dedicated himself to working with psychedelics more intensively, with gradually declining doses. The essence of his method was to relive the originally overwhelming traumatic events, maintaining a conscious focus on somatic sensations and avoiding getting overwhelmed again. In his own estimation, by the age of 30, he had resolved most of his early trauma but had been sensitized to the prevalence of trauma and its consequences (e.g. violence, racism) in the society, and his exposure to these continued to cause him suffering. Regardless, he had gained 'a foundational feeling of peace or stability that could provide safety in the middle of all this'. The information for this case study was acquired in the course of semi-structured retrospective interviews 2.5 years apart. The case illustrates that chronic treatment-resistant depression together with an unsupportive social environment may present a challenge for psychedelic therapy. As with ketamine, chronic administration may be necessary in some cases.

keywords:
Amanita muscaria, bullying, C-PTSD, dissociation, DMT, LSD, major depression, MDMA, muscimol, psilocybin, psychedelics, psychedelic therapy, treatment-resistant depression, Psychiatry, Social and Behavioral Sciences, Clinical Psychology, Dissociative Disorders, Anxiety Disorders, Depressive Disorders, Trauma and Stress


