# publications

title: Brain dynamics predictive of response to psilocybin for treatment-resistant depression.
publication_date: 2024-02-14
doi: 10.1093/braincomms/fcae049
pubmed_id: 38515439
source_url: https://doi.org/10.1093/braincomms/fcae049
substance_tags: psilocybin,psilocin
topic_tags: Depression,Mechanism of Action,Receptor Pharmacology,Treatment-Resistant Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
authors:
Vohryzek J, Cabral J, Lord LD, 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 (10 and 25 mg, 7 days apart) therapy for depression-to gain new insights into regions and networks implicated in the restoration of healthy brain dynamics. We used large-scale 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 healthy 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-hydroxytryptamine 2a and 5-hydroxytryptamine 1a, 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:
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authors: Fang S, Yang X, Zhang W.
publication_date: 2024-02-14
doi: 10.3389/fpsyt.2024.1359088
pubmed_id: 38426002
source_url: https://doi.org/10.3389/fpsyt.2024.1359088
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Efficacy and acceptability of psilocybin for primary or secondary depression: A systematic review and meta-analysis of randomized controlled trials.

abstract:
IntroductionPsilocybin is a classic psychedelics, which has been shown to have antidepressant effects by many studies in recent years. In this study, we aim to evaluate the efficacy, acceptability and tolerability of psilocybin in the treatment of primary (major depressive disorder) or secondary (experiencing distress related to life-threatening diagnoses and terminal illness) depression.MethodsWe searched PubMed, EMBASE, Web of Science, Cochrane Library and ClinicalTrials.gov for clinical trials of psilocybin for depression (updated to 4 October, 2023). Effect size Hedges' g was used as an indicator of efficacy, and other outcomes included response rate, drop-out rate, and adverse events.ResultsA total of 10 studies were finally included in systematic review. 8 studies were included in the meta-analysis, involving a total of 524 adult patients, and produced a large effect size in favor of psilocybin (Hedge's g =-0.89, 95% CI -1.25~-0.53, I² = 70.19%, P

topic_tags:
Depression,End-of-Life Distress,Clinical Trial,Randomized Controlled Trial,Meta-Analysis,Systematic Review,Review Article,Safety,Adverse Events

raw_json:
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title: Psilocybin induces dose-dependent changes in functional network organization in rat cortex
journal: bioRxiv
publication_date: 2024-02-11
doi: 10.1101/2024.02.09.579718
source_url: https://doi.org/10.1101/2024.02.09.579718
substance_tags: psilocybin
topic_tags: Consciousness,Animal Study
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
authors:
Silverstein BH, Kolbman N, Nelson A, Liu T, Guzzo P, Gilligan J, Lee U, Mashour GA, Vanini G, Pal D.

abstract:
Psilocybin produces an altered state of consciousness in humans and is associated with complex spatiotemporal changes in brain networks. Given the emphasis on rodent models for mechanistic studies, there is a need for characterization of the effect of psilocybin on brain-wide network dynamics. Previous rodent studies of psychedelics, using electroencephalogram, have primarily been done with sparse electrode arrays that offered limited spatial resolution precluding network level analysis, and have been restricted to lower gamma frequencies. Therefore, in the study, we used electroencephalographic recordings from 27 sites (electrodes) across rat cortex ( n =6 male, 6 female) to characterize the effect of psilocybin (0.1 mg/kg, 1 mg/kg, and 10 mg/kg delivered over an hour) on network organization as inferred through changes in node degree (index of network density) and connection strength (weighted phase-lag index). The removal of aperiodic component from the electroencephalogram localized the primary oscillatory changes to theta (4-10 Hz), medium gamma (70-110 Hz), and high gamma (110-150 Hz) bands, which were used for the network analysis. Additionally, we determined the concurrent changes in theta-gamma phase-amplitude coupling. We report that psilocybin, in a dose-dependent manner, 1) disrupted theta-gamma coupling [ p

raw_json:
{"europe_pmc_id":"PPR804295","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: Multimodal Neuroimaging of the Effect of Serotonergic Psychedelics on the Brain.
authors: Frautschi PC, Singh AP, Stowe NA, Yu JJ.
publication_date: 2024-02-14
doi: 10.3174/ajnr.a8118
pubmed_id: 38360790
source_url: https://doi.org/10.3174/ajnr.a8118
substance_tags: psilocybin
topic_tags: Depression,PTSD,Addiction,Brain Imaging,Mechanism of Action,Aging,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
abstract:
The neurobiological mechanisms underpinning psychiatric disorders such as treatment-resistant major depression, post-traumatic stress disorder, and substance use disorders, remain unknown. Psychedelic compounds, such as psilocybin, lysergic acid diethylamide, and N,N-dimethyltryptamine, have emerged as potential therapies for these disorders because of their hypothesized ability to induce neuroplastic effects and alter functional networks in the brain. Yet, the mechanisms underpinning the neurobiological treatment response remain obscure. Quantitative neuroimaging is uniquely positioned to provide insight into the neurobiological mechanisms of these emerging therapies and quantify the patient treatment response. This review aims to synthesize our current state-of-the-art understanding of the functional changes occurring in the brain following psilocybin, lysergic acid diethylamide, or N,N-dimethyltryptamine administration in human participants with fMRI and PET. We further aim to disseminate our understanding of psychedelic compounds as they relate to neuroimaging with the goal of improved diagnostics and treatment of neuropsychiatric illness.

raw_json:
{"europe_pmc_id":"38360790","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The Effects of Psychedelics on Neuronal Physiology.
authors: Hatzipantelis CJ, Olson DE
journal: Annual review of physiology
publication_date: 2024-02-11
doi: 10.1146/annurev-physiol-042022-020923
pubmed_id: 37931171
source_url: https://pubmed.ncbi.nlm.nih.gov/37931171/
keywords: 5-HT2A receptor, DMT, LSD, hallucinogen, neuroplasticity, psilocybin, psychedelic
substance_tags: psilocybin
topic_tags: Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Safety
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:37
raw_json: {"pubmed_id":"37931171"}
abstract:
Psychedelics are quite unique among drugs that impact the central nervous system, as a single administration of a psychedelic can both rapidly alter subjective experience in profound ways and produce sustained effects on circuits relevant to mood, fear, reward, and cognitive flexibility. These remarkable properties are a direct result of psychedelics interacting with several key neuroreceptors distributed across the brain. Stimulation of these receptors activates a variety of signaling cascades that ultimately culminate in changes in neuronal structure and function. Here, we describe the effects of psychedelics on neuronal physiology, highlighting their acute effects on serotonergic and glutamatergic neurotransmission as well as their long-lasting effects on structural and functional neuroplasticity in the cortex. We propose that the neurobiological changes leading to the acute and sustained effects of psychedelics might be distinct, which could provide opportunities for engineering compounds with optimized safety and efficacy profiles.


publication_date: 2023-11-14
doi: 10.1016/j.jep.2023.117415
pubmed_id: 37977425
source_url: https://doi.org/10.1016/j.jep.2023.117415
substance_tags: psilocybin,psilocin
topic_tags: Depression,Anxiety,Brain Imaging,Pharmacology,Animal Study,Toxicity
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Antidepressant- and anxiolytic-like activities and acute toxicity evaluation of the Psilocybe cubensis mushroom in experimental models in mice.

authors:
Hernandez-Leon A, Escamilla-Orozco RI, Tabal-Robles AR, Martínez-Vargas D, Romero-Bautista L, Escamilla-Soto G, González-Romero OS, Torres-Valencia M, González-Trujano ME.

abstract:
Ethnopharmacology relevanceCentral nervous system (CNS) diseases can be diverse and usually present with comorbidity, as in the case of depression and anxiety. Despite alternatives like Psilocybe mushrooms for mental health there is no basic research to evidence their CNS benefits.Aim of the studyTo evaluate the anxiolytic- and antidepressant-like effects, as well as the acute toxicity of P. cubensis mushroom.Material and methodsFirst, the acute toxicity (LD50) of P. cubensis (2000 mg/kg) was determined after the esophageal (p.o.) and intraperitoneal (i.p.) route of administration. The rota-rod test and electroencephalogram (EEG) were included to assess CNS toxicity in free moving mice. Anxiolytic (ambulatory or exploratory and rearing behaviors) and antidepressant behavioral responses were assayed in the open-field, plus-maze, and forced swimming test, respectively, after administration of 1000 mg/kg, p.o., of the whole P. cubensis mushroom or the polar aqueous (AQ) or methanolic (MeOH) extractions (1, 10, and/or 100 mg/kg, i.p.) in comparison to the reference drugs buspirone (4 mg/kg, i.p.), fluoxetine and/or imipramine (10 mg/kg, s.c. and i.p., respectively). A chemical analysis of the AQ and MeOH extractions was performed to detect psilocybin and/or psilocin by using UHPLC.ResultsNeurotoxic effects of P. cubensis mushroom administered at high doses were absent in mice assessed in the rota-rod test or for EEG activity. A LD50 > 2000 mg/kg was calculated by p.o. or i.p. administration. While significant and/or dose-response antidepressant-like effects were produced with the whole P. cubensis mushroom, p.o., and after parenteral administration of the AQ or MeOH extractions resembling the effects of the reference drugs. Behavioral responses were associated with an anxiolytic-like effect in the open-field as corroborated in the plus-maze tests. The presence of psilocybin and psilocin was mainly characterized in the AQ extraction.ConclusionOur results provide preclinical evidence of the anxiolytic- and antidepressant-like effects of the P. cubensis mushroom without producing neurotoxicity after enteral or parenteral administration, where psilocybin and psilocin were identified mainly after AQ extraction. This study reinforces the benefits of the P. cubensis mushroom in mental health and therapy for anxiety and depression.

keywords:
Animals, Mice, Agaricales, Methanol, Anti-Anxiety Agents, Antidepressive Agents, Behavior, Animal, Models, Theoretical, Psilocybe, Psilocybin

raw_json:
{"europe_pmc_id":"37977425","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Development and psychometric validation of a novel scale for measuring ‘psychedelic preparedness’
journal: PsyArXiv
publication_date: 2023-04-27
source_url: https://osf.io/preprints/psyarxiv/gw9jp_v1
substance_tags: psilocybin
topic_tags: Wellbeing,Healthcare Workers
study_type: Qualitative Study
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"gw9jp_v1","version":1,"reviews_state":"accepted"}
abstract:
Preparing participants for psychedelic experiences is crucial for ensuring these experiences are safe, and potentially, beneficial. However, there is currently no validated measure to assess the extent to which participants are well-prepared for such experiences. Our study aimed to address this gap by developing, validating, and testing the Psychedelic Preparedness Scale (PPS). Using a novel iterative Delphi-focus group methodology (‘DelFo’) followed by qualitative pre-test interviews, we incorporated the perspectives of expert clinicians/researchers and of psychedelic users, to generate items for the scale. Psychometric validation of the PPS was carried out in two large online samples of psychedelic users (N = 516; N = 716), and the scale was also administered to a group of participants before and after a 5-7-day psilocybin retreat (N = 46). Exploratory and confirmatory factor analysis identified four factors from the 20-item PPS: Knowledge-Expectations, Intention-Preparation, Psychophysical-Readiness, and Support-Planning. The PPS demonstrated excellent reliability (ω = 0.954) and evidence supporting convergent, divergent and discriminant validity was also obtained. Significant differences between those scoring high and low (on psychedelic preparedness) before the psychedelic experience were found on measures of mental health/wellbeing outcomes assessed after the experience, suggesting that the scale has predictive utility. By prospectively measuring modifiable pre-treatment preparatory behaviours and attitudes using the PPS, it may be possible to determine whether a participant has generated the appropriate mental ‘set’ and is therefore likely to benefit from a psychedelic experience, or at least, less likely to be harmed.

keywords:
factor analysis, measurement, preparation, psilocybin, psychedelics, psychedelic therapy, psychometric, scale development, validation, Psychiatry, Social and Behavioral Sciences, Clinical Psychology, Life Sciences, Health Psychology, Prevention, Mental Health


title: Psychedelics and sexual functioning: a mixed-methods study.
publication_date: 2024-02-06
doi: 10.1038/s41598-023-49817-4
pubmed_id: 38326446
source_url: https://doi.org/10.1038/s41598-023-49817-4
substance_tags: psilocybin
topic_tags: Depression,Receptor Pharmacology,Wellbeing,Clinical Trial,Adverse Events
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
authors:
Barba T, Kettner H, Radu C, Peill JM, Roseman L, Nutt DJ, Erritzoe D, Carhart-Harris R, Giribaldi B.

abstract:
Do psychedelics affect sexual functioning postacutely? Anecdotal and qualitative evidence suggests they do, but this has never been formally tested. While sexual functioning and satisfaction are generally regarded as an important aspect of human wellbeing, sexual dysfunction is a common symptom of mental health disorders. It is also a common side effect of selective serotonin reuptake inhibitors (SSRIs), a first line treatment for depression. The aim of the present paper was to investigate the post-acute effects of psychedelics on self-reported sexual functioning, combining data from two independent studies, one large and naturalistic and the other a smaller but controlled clinical trial. Naturalistic use of psychedelics was associated with improvements in several facets of sexual functioning and satisfaction, including improved pleasure and communication during sex, satisfaction with one's partner and physical appearance. Convergent results were found in a controlled trial of psilocybin therapy versus an SSRI, escitalopram, for depression. In this trial, patients treated with psilocybin reported positive changes in sexual functioning after treatment, while patients treated with escitalopram did not. Despite focusing on different populations and settings, this is the first research study to quantitively investigate the effects of psychedelics on sexual functioning. Results imply a potential positive effect on post-acute sexual functioning and highlight the need for more research on this.

keywords:
Humans, Hallucinogens, Sexual Behavior, Psilocybin, Escitalopram, Selective Serotonin Reuptake Inhibitors

raw_json:
{"europe_pmc_id":"38326446","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Pagni BA, Petridis PD, Podrebarac SK, Grinband J, Claus ED, Bogenschutz MP.
publication_date: 2024-02-06
doi: 10.1038/s41598-024-52967-8
pubmed_id: 38326432
source_url: https://doi.org/10.1038/s41598-024-52967-8
substance_tags: psilocybin
topic_tags: Addiction,Brain Imaging,Mechanism of Action,Aging,Emotional Processing,Clinical Trial
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Psilocybin-induced changes in neural reactivity to alcohol and emotional cues in patients with alcohol use disorder: an fMRI pilot study.

abstract:
This pilot study investigated psilocybin-induced changes in neural reactivity to alcohol and emotional cues in patients with alcohol use disorder (AUD). Participants were recruited from a phase II, randomized, double-blind, placebo-controlled clinical trial investigating psilocybin-assisted therapy (PAT) for the treatment of AUD (NCT02061293). Eleven adult patients completed task-based blood oxygen dependent functional magnetic resonance imaging (fMRI) approximately 3 days before and 2 days after receiving 25 mg of psilocybin (n = 5) or 50 mg of diphenhydramine (n = 6). Visual alcohol and emotionally valanced (positive, negative, or neutral) stimuli were presented in block design. Across both alcohol and emotional cues, psilocybin increased activity in the medial and lateral prefrontal cortex (PFC) and left caudate, and decreased activity in the insular, motor, temporal, parietal, and occipital cortices, and cerebellum. Unique to negative cues, psilocybin increased supramarginal gyrus activity; unique to positive cues, psilocybin increased right hippocampus activity and decreased left hippocampus activity. Greater PFC and caudate engagement and concomitant insula, motor, and cerebellar disengagement suggests enhanced goal-directed action, improved emotional regulation, and diminished craving. The robust changes in brain activity observed in this pilot study warrant larger neuroimaging studies to elucidate neural mechanisms of PAT.Trial registration: NCT02061293.

keywords:
Brain, Humans, Alcoholism, Ethanol, Magnetic Resonance Imaging, Pilot Projects, Cues, Adult, Psilocybin

raw_json:
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title: Effects of DMT on mental health outcomes in healthy volunteers.
authors: Timmermann C, Zeifman RJ, Erritzoe D, Nutt DJ, Carhart-Harris RL.
publication_date: 2024-02-06
doi: 10.1038/s41598-024-53363-y
pubmed_id: 38326357
source_url: https://doi.org/10.1038/s41598-024-53363-y
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Wellbeing,Observational Study,Healthy Volunteers
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
Psilocybin, a serotonergic psychedelic, is being increasingly researched in clinical studies for the treatment of psychiatric disorders. The relatively lengthy duration of oral psilocybin's acute effects (4-6 h) may have pragmatic and cost-effectiveness limitations. Here, we explored the effects of intravenous (IV) N,N-Dimethyltryptamine (DMT), a closely related, but faster-acting psychedelic intervention, on mental health outcomes in healthy volunteers. Data is reported from two separate analyses: (1) A comparison of mental health-related variables 1 week after 7, 14, 18, and 20 mg of IV DMT versus IV saline placebo (n = 13) and, (2) A prospective dataset assessing effects before versus 2 weeks after 20 mg of IV DMT (n = 17). Mental health outcomes included measures of depression severity (QIDS-SR16), trait anxiety (STAI-T), Neuroticism (NEO-FFI), wellbeing (WHO-5), meaning in life (MLQ), optimism (LOT-R), and gratitude (GQ-6). In both the prospective and placebo-controlled datasets, significant improvements in scores of depression were found 1-2 weeks after DMT administration. Significant reductions in trait Neuroticism were only found for the placebo-controlled sample. Finally, changes in depression and trait anxiety correlated with acute peak experiences (assessed via 'Oceanic Boundlessness'). While the use of two separate cohorts in pooled analysis limits the generalizability of these correlational findings, these results suggest that DMT may reduce depressive symptomatology by inducing peak experiences. The short half-life of IV DMT and its potential for flexible dosing via controlled infusions makes it an appealing candidate for psychedelic medicine. Further research in clinical samples is needed to corroborate the therapeutic potential of DMT.

keywords:
Humans, N,N-Dimethyltryptamine, Hallucinogens, Prospective Studies, Healthy Volunteers, Psilocybin, Outcome Assessment, Health Care

raw_json:
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title: Keeping the promise: a critique of the current state of microdosing research.
authors: Petranker R, Anderson T, Fewster EC, Aberman Y, Hazan M, Gaffrey M, Seli P
journal: Frontiers in psychiatry
publication_date: 2023-12-31
doi: 10.3389/fpsyt.2024.1217102
pubmed_id: 38374976
source_url: https://pubmed.ncbi.nlm.nih.gov/38374976/
keywords: LSD, microdosing, psilocybin, psychedelics, review
substance_tags: psilocybin
topic_tags: Microdosing,Creativity,Review Article,Safety
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:37
raw_json: {"pubmed_id":"38374976"}
abstract:
The practice of taking small, sub-hallucinogenic doses of psychedelics, known as microdosing, has exploded in popularity over the last decade. Users claim benefits ranging from improved mood and enhanced creativity to an increased sense of meaning and connectedness in life. While research on microdosing is still lagging behind the shift in public opinion, several papers have been published in the last five years which attempted to assess the effects of microdosing.
This review paper aimed to critically analyze the research practices used in the recent wave of microdosing research: We reviewed 15 papers published before the closing date of this review in March 2022.
Our review concludes that it is premature to draw any conclusions about the efficacy or safety of microdosing since the research quality cannot be considered confirmatory.
We propose some potential causes for the current state of the literature and some suggestions for how these causes may be ameliorated.


publication_date: 2024-02-04
doi: 10.1038/s41598-024-53188-9
pubmed_id: 38316896
source_url: https://doi.org/10.1038/s41598-024-53188-9
substance_tags: psilocybin
topic_tags: Depression,Aging,Clinical Trial,Treatment-Resistant Depression,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Patient perspectives and experiences with psilocybin treatment for treatment-resistant depression: a qualitative study.

authors:
Breeksema JJ, Niemeijer A, Krediet E, Karsten T, Kamphuis J, Vermetten E, van den Brink W, Schoevers R.

abstract:
Psilocybin is the most researched classic psychedelic for Treatment-Resistant Depression (TRD). While optimizing set and setting are considered essential for efficacy and safety, patient perspectives on these aspects have rarely been investigated. To address this knowledge gap, the current paper explored the experiences of 11 TRD patients (8 women, 3 men) participating in a double-blind randomized clinical trial with a single session of oral (1, 10 or 25 mg) psilocybin treatment. After qualitative analysis, three major themes were identified: (1) challenges with trust-building and expectation management; (2) navigating the experience; and (3) the need for a more comprehensive treatment. Subthemes of the first theme include a general distrust in mental healthcare, trust in study therapists, limited time for preparation, and managing expectations. The second theme included the following subthemes: trusting to surrender, profound and overwhelming experiences, and music as a guide. The third theme addressed a desire for multiple psilocybin sessions, and challenges with sensemaking. Patients' perspectives provided important insights into potential optimization of psilocybin treatment of TRD, including individualized preparation, investment in trust-building, offering additional psilocybin sessions, providing access to sustained (psycho)therapy with trusted therapists, and personalizing treatment approaches, which may also enhance real-world adaption of these treatments.

keywords:
Humans, Hallucinogens, Depression, Music, Female, Male, Depressive Disorder, Treatment-Resistant, Psilocybin

raw_json:
{"europe_pmc_id":"38316896","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Effects of hallucinogenic drugs on the human heart.
authors: Neumann J, Dhein S, Kirchhefer U, Hofmann B, Gergs U.
publication_date: 2024-02-01
doi: 10.3389/fphar.2024.1334218
pubmed_id: 38370480
source_url: https://doi.org/10.3389/fphar.2024.1334218
substance_tags: psilocybin,psilocin
topic_tags: Receptor Pharmacology,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Hallucinogenic drugs are used because they have effects on the central nervous system. Their hallucinogenic effects probably occur via stimulation of serotonin receptors, namely, 5-HT2A-serotonin receptors in the brain. However, a close study reveals that they also act on the heart, possibly increasing the force of contraction and beating rate and may lead to arrhythmias. Here, we will review the inotropic and chronotropic actions of bufotenin, psilocin, psilocybin, lysergic acid diethylamide (LSD), ergotamine, ergometrine, N,N-dimethyltryptamine, and 5-methoxy-N,N-dimethyltryptamine in the human heart.

raw_json:
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authors: Norred MA, Zuschlag ZD, Hamner MB.
publication_date: 2024-02-27
doi: 10.1007/s40265-023-01983-5
pubmed_id: 38413493
source_url: https://doi.org/10.1007/s40265-023-01983-5
substance_tags: psilocybin
topic_tags: PTSD,Mechanism of Action,Receptor Pharmacology
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
A Neuroanatomic and Pathophysiologic Framework for Novel Pharmacological Approaches to the Treatment of Post-traumatic Stress Disorder.

abstract:
Post-traumatic stress disorder (PTSD) is a debilitating disorder inflicting high degrees of symptomatic and socioeconomic burdens. The development of PTSD results from a cascade of events with contributions from multiple processes and the underlying pathophysiology is complex, involving neurotransmitters, neurocircuitry, and neuroanatomical pathways. Presently, only two medications are US FDA-approved for the treatment of PTSD, both selective serotonin reuptake inhibitors (SSRIs). However, the complex underlying pathophysiology suggests a number of alternative pathways and mechanisms that may be targets for potential drug development. Indeed, investigations and drug development are proceeding in a number of these alternative, non-serotonergic pathways in an effort to improve the management of PTSD. In this manuscript, the authors introduce novel and emerging treatments for PTSD, including drugs in various stages of development and clinical testing (BI1358894, BNC-210, PRAX-114, JZP-150, LU AG06466, NYV-783, PH-94B, SRX246, TNX-102), established agents and known compounds being investigated for their utility in PTSD (brexpiprazole, cannabidiol, doxasoin, ganaxolone, intranasal neuropeptide Y, intranasal oxytocin, tianeptine oxalate, verucerfont), and emerging psychedelic interventions (ketamine, MDMA-assisted psychotherapy, psilocybin-assisted psychotherapy), with an aim to examine and integrate these agents into the underlying pathophysiological frameworks of trauma-related disorders.

keywords:
Humans, Ketamine, Stress Disorders, Post-Traumatic, Psychotherapy, Selective Serotonin Reuptake Inhibitors

raw_json:
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authors: Foster K, Morrison I, Tyler M, Delgoda R.
publication_date: 2023-12-08
doi: 10.1016/j.funbio.2023.12.001
pubmed_id: 38341264
source_url: https://doi.org/10.1016/j.funbio.2023.12.001
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
The effect of casing and gypsum on the yield and psychoactive tryptamine content of Psilocybe cubensis (Earle) Singer.

abstract:
Psychedelic fungi have experienced a surge in interest in recent years. Most notably, the fungal secondary metabolite psilocybin has shown tremendous promise in the treatment of various psychiatric disorders. The mushroom species that produce this molecule are poorly understood. Here we sought to examine for the first time, the response of a psilocybin-producing species Psilocybe cubensis to casing (peat moss and vermiculite) and supplementation with gypsum (calcium sulfate dihydrate), two common practices in commercial mushroom cultivation. Mycelial samples of genetically authenticated P. cubensis were used to inoculate popcorn grain bags. The fully colonized bags of popcorn grain (0.15 kg) were transferred to bins of 0.85 kg pasteurized horse manure, with or without 1 cm thick layer of casing and/or 5 % gypsum. Our results indicate that the use of a casing layer significantly increases the biological efficiency (161.5 %), by approximately four fold, in comparison to control (40.5 %), albeit with a slight delay (∼2 days) for obtaining fruiting bodies and a somewhat reduced total tryptamine content (0.85 %) as gauged by High Performance Liquid Chromatography measurements. Supplementation with both casing and gypsum, however, appears to promote maximal yields (896.6 g/kg of dried substrate), with a biological efficiency of 89.6 %, while also maintaining high total tryptamine expressions (0.95 %). These findings, revealing methods for maximizing yield of harvest and expressions of psychoactive tryptamines, may prove useful for both home growers and commercial cultivators of this species, and ultimately support the growth of a robust industry with high quality natural products.

keywords:
Animals, Horses, Humans, Agaricales, Calcium Sulfate, Tryptamines, Vocalization, Animal, Psilocybe, Psilocybin

raw_json:
{"europe_pmc_id":"38341264","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Cho M, Rosenbaum D, Schneider E, Hales S.
publication_date: 2024-01-31
doi: 10.1089/jpm.2023.0668
pubmed_id: 38301164
source_url: https://doi.org/10.1089/jpm.2023.0668
keywords: Humans, Suicide, Assisted, Incidence, Medical Assistance, Psilocybin
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Letter to the Editor: Will Psilocybin-Assisted Therapy Reduce the Incidence of Medical Assistance in Dying?

raw_json:
{"europe_pmc_id":"38301164","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-01-21
doi: 10.1177/02692163231222430
pubmed_id: 38253521
source_url: https://doi.org/10.1177/02692163231222430
keywords: Humans, Death, Palliative Care, Terminal Care, Adult, Alberta, Psilocybin
substance_tags: psilocybin
topic_tags: End-of-Life Distress,Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Social acceptability of psilocybin-assisted therapy for existential distress at the end of life: A population-based survey.

authors:
Plourde L, Chang SL, Farzin H, Gagnon P, Hébert J, Foxman R, Deschamps P, Provost F, Masse-Grenier M, Stephan JF, Cheung K, Joly Y, Fallu JS, Dorval M, P3A Study Group.

abstract:
BackgroundInternationally, there is a growing interest in the potential benefits of psilocybin-assisted therapy to treat existential distress at the end of life. However, the social acceptability of this therapy is not yet well known.AimThis study assesses the social acceptability of the medical use of psilocybin to treat existential distress at the end of life.DesignAn online survey was conducted in Canada between November 23 and December 4, 2022. The questionnaire included items pertaining to perceptions, attitudes and concerns towards psilocybin-assisted therapy to treat existential distress at the end of life.ParticipantsThe sample (n = 2800) was stratified by province, age and sex. Participants were adults from four provinces of Canada: Québec, Ontario, Alberta and British Columbia.ResultsOverall, 79.3% considered psilocybin-assisted therapy a reasonable medical choice for a patient suffering from existential distress at the end of life, 84.8% agreed that the public health system should cover the costs of the intervention and 63.3% would welcome the legalisation of psilocybin for medical purposes. Previous psilocybin use (p

raw_json:
{"europe_pmc_id":"38253521","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2023-12-17
doi: 10.1016/j.aca.2023.342161
pubmed_id: 38220293
source_url: https://doi.org/10.1016/j.aca.2023.342161
keywords: Agaricales, Chromatography, Liquid, Tandem Mass Spectrometry, Psilocybe, Psilocybin
substance_tags: psilocybin,psilocin
topic_tags: General
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
title:
Determination of psilocybin and psilocin content in multiple Psilocybe cubensis mushroom strains using liquid chromatography - tandem mass spectrometry.

authors:
Goff R, Smith M, Islam S, Sisley S, Ferguson J, Kuzdzal S, Badal S, Kumar AB, Sreenivasan U, Schug KA.

abstract:
A method for clinical potency determination of psilocybin and psilocin in hallucinogenic mushroom species Psilocybe cubensis was developed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Five strains of dried, intact mushrooms were obtained and analyzed: Blue Meanie, Creeper, B-Plus, Texas Yellow, and Thai Cubensis. An extraction protocol was developed; this included an evaluation of sample milling technique, extraction solvents, and recovery/stability. Reversed phase chromatography on fused-core particle phases was developed for the determination of the two analytes using internal standard calibration with deuterated isotopologues of each analyte. The separation takes less than 5 min. Matrix effects were investigated by comparing signal response of calibration samples in neat solution and several mushroom matrices; no significant matrix effects were observed. The limit of detection for psilocybin was 1.5 ng/mL (1.5 pg on-column; 300 ng/g mushroom) and for psilocin was 0.15 ng/mL (0.15 pg on-column; 30 ng/g mushroom) using a Shimadzu LCMS-8050 triple quadrupole mass spectrometer. Assessment of the accuracy and precision of the method indicated percent error and RSD were

raw_json:
{"europe_pmc_id":"38220293","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Synthetic surprise as the foundation of the psychedelic experience.
authors: De Filippo R, Schmitz D.
publication_date: 2024-01-11
doi: 10.1016/j.neubiorev.2024.105538
pubmed_id: 38220035
source_url: https://doi.org/10.1016/j.neubiorev.2024.105538
keywords: Humans, Serotonin, Hallucinogens, Consciousness, Signal Transduction
substance_tags: psilocybin
topic_tags: Mechanism of Action,Receptor Pharmacology,Consciousness,Drug Interactions,Transcriptomics
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
Psychedelic agents, such as LSD and psilocybin, induce marked alterations in consciousness via activation of the 5-HT2A receptor (5-HT2ARs). We hypothesize that psychedelics enforce a state of synthetic surprise through the biased activation of the 5-HTRs system. This idea is informed by recent insights into the role of 5-HT in signaling surprise. The effects on consciousness, explained by the cognitive penetrability of perception, can be described within the predictive coding framework where surprise corresponds to prediction error, the mismatch between predictions and actual sensory input. Crucially, the precision afforded to the prediction error determines its effect on priors, enabling a dynamic interaction between top-down expectations and incoming sensory data. By integrating recent findings on predictive coding circuitry and 5-HT2ARs transcriptomic data, we propose a biological implementation with emphasis on the role of inhibitory interneurons. Implications arise for the clinical use of psychedelics, which may rely primarily on their inherent capacity to induce surprise in order to disrupt maladaptive patterns.

raw_json:
{"europe_pmc_id":"38220035","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Do the therapeutic effects of psilocybin involve actions in the gut?
authors: Reed F, Foldi CJ.
publication_date: 2024-01-10
doi: 10.1016/j.tips.2023.12.007
pubmed_id: 38216431
source_url: https://doi.org/10.1016/j.tips.2023.12.007
keywords: Brain, Humans, Serotonin, Hallucinogens, Mental Disorders, Psilocybin
substance_tags: psilocybin
topic_tags: Receptor Pharmacology
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
The psychedelic compound psilocybin has recently emerged as a therapeutic intervention for various mental health conditions. Psilocybin is a potent agonist of serotonin (5-HT) receptors (5-HTRs), which are expressed in the brain and throughout peripheral tissues, with particularly high expression in the gastrointestinal (GI) tract. However, no studies have investigated the possibility that peripheral actions of psilocybin may contribute to improvements in mental health outcomes. This is despite strong evidence for disturbed gut-brain signalling in conditions in which psilocybin is being tested clinically. In this Opinion, we highlight the likely actions of psychedelics in the gut and provide initial support for the premise that peripheral actions may be involved in rapid and long-term therapeutic effects. A greater understanding of all sites and modes of action will guide more targeted approaches to drug development.

raw_json:
{"europe_pmc_id":"38216431","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Fletcher PJ, Li Z, Ji XD, Lê AD.
publication_date: 2023-12-26
doi: 10.1016/j.pbb.2023.173703
pubmed_id: 38154589
source_url: https://doi.org/10.1016/j.pbb.2023.173703
substance_tags: psilocybin
topic_tags: Addiction,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Established sensitization of ethanol-induced locomotor activity is not reversed by psilocybin or the 5-HT2A receptor agonist TCB-2 in male DBA/2J mice.

abstract:
RationalePsychedelic drugs, which share in common 5-HT2A receptor agonist activity, have shown promise in treating alcohol-use disorders (AUDs). Repeated exposure to ethanol (EtOH) induces molecular and behavioural changes reflective of neuroadaptations that may contribute to addiction. Psychedelic drugs can induce neuroplasticity also, raising the possibility that their potential clinical effects in AUD may involve an action to reverse or offset effects of long-term changes induced by EtOH. This possibility was examined by investigating whether psilocybin, or the 5-HT2A receptor agonist TCB-2, counteracted established sensitization of EtOH-induced locomotor activity.MethodsMale DBA/2J mice received repeated injections of 2.2 g/kg EtOH to induce a sensitized locomotor activity response. In two experiments separate groups of mice were then injected with psilocybin (0, 0.3 and 1 kg/kg) or TCB-2 (0, 1 and 3 mg/kg) on 5 consecutive days. Next, mice were challenged with 1.8 g/kg EtOH and locomotor activity measured for 15 min.ResultsRelative to naïve controls, previously sensitized mice showed enhanced locomotor activity to the challenge dose. Despite reducing locomotor activity in their own right psilocybin and TCB-2 did not alter the strength of this sensitized response.ConclusionPsilocybin and TCB-2 at behaviourally effective doses did not reverse sensitization of EtOH-induced activity. This suggests that mechanisms involved in mediating short-term reductions in EtOH intake by psilocybin or TCB-2 may not involve a capacity of these drugs to offset enduring changes in behaviour and any underlying neural adaptations induced by repeated intermittent exposure to EtOH.

keywords:
Animals, Mice, Inbred DBA, Mice, Ethanol, Receptor, Serotonin, 5-HT2A, Hallucinogens, Motor Activity, Male, Psilocybin

raw_json:
{"europe_pmc_id":"38154589","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Sicignano D, Hernandez AV, Schiff B, Elmahy N, White CM
journal: Current medical research and opinion
publication_date: 2024-01-31
doi: 10.1080/03007995.2023.2296968
pubmed_id: 38111216
source_url: https://pubmed.ncbi.nlm.nih.gov/38111216/
keywords: LSD, alcohol use disorder, meta-analysis, psilocybin
substance_tags: psilocybin
topic_tags: Addiction,Randomized Controlled Trial,Meta-Analysis,Systematic Review,Review Article,Safety
study_type: Randomized Controlled Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:37
raw_json: {"pubmed_id":"38111216"}
title:
The impact of psychedelics on patients with alcohol use disorder: a systematic review with meta-analysis.

abstract:
Critique the available systematic review and de novo assessment of the role of psychedelics in the treatment of alcohol use disorder.
A systematic literature search of PubMed was completed from 1960 to 9/9/2023. We pooled randomized controlled trials comparing psychedelics to control therapy for the treatment of alcohol use disorder.
At the first recorded follow-up, LSD [ = 3, Odds Ratio (OR) 1.99 (95% Confidence interval (CI): 1.10 to 3.61)] and any psychedelic [ = 4, OR2.16 (95%CI: 1.26 to 3.69)] enhanced the odds of patients achieving abstinence or a substantial reduction in drinking alcohol versus placebo in randomized, double-blind, placebo-controlled trials. When the inclusion criteria were relaxed to include controlled trials without double-blinding or placebo control, LSD [ = 5, OR1.79 (95%CI: 1.36 to 2.34)] and any psychedelic therapy [ = 6, OR1.89 (95%CI: 1.42 to 2.50)] still enhanced the odds of patients achieving abstinence or a substantial reduction in drinking alcohol. Four of 6 trials had high risk of bias and other methodological issues. One trial found an instance of suicidal ideation as well as transient increases in blood pressure that requires further exploration before the balance of benefits to harms can be determined.
The use of psychedelics to treat alcohol use disorder is promising, but the weaknesses in the literature base preclude making definitive statements about its value. Future trials with greater methodological rigor are needed.


authors: Videira NB, Nair V, Paquet V, Calhoun D.
publication_date: 2023-08-29
doi: 10.1002/jat.4533
pubmed_id: 37646119
source_url: https://doi.org/10.1002/jat.4533
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
title:
The changing outlook of psychedelic drugs: The importance of risk assessment and occupational exposure limits.

abstract:
Serotonergic psychedelics, such as lysergic acid diethylamide (LSD), psilocybin, dimethyltryptamine (DMT), and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), are currently being investigated for the treatment of psychiatric disorders such as depression and anxiety. Clinical trials with psilocybin and LSD have shown improvement in emotional and psychological scores. Although these drugs are reported to be safe in a controlled environment (such as clinical trials), exposure to low doses of these drugs can result in psychedelic effects, and therefore, occupational safety is an important consideration to prevent adverse effects in the workplace from low daily exposure. This article will discuss the factors involved in the derivation of occupational exposure limits (OELs) and risk assessment of these psychedelic drugs. To support the OEL derivations of psychedelic drugs, information regarding their mechanism of action, adverse effect profiles, pharmacokinetics, clinical effects, and nonclinical toxicity were considered. Additionally, psilocybin and LSD, which are the most extensively researched psychedelic substances, are employed as illustrative examples in case studies. The OELs derived for psilocybin and for LSD are 0.05 and 0.002 μg/m3, respectively, which indicates that these are highly hazardous compounds, and it is important to take into account suitable safety measures and risk-management strategies in order to minimize workplace exposure.

keywords:
Humans, N,N-Dimethyltryptamine, Lysergic Acid Diethylamide, Hallucinogens, Risk Assessment, Psilocybin

topic_tags:
Depression,Anxiety,Pharmacology,Mechanism of Action,Emotional Processing,Clinical Trial,Safety,Toxicity

raw_json:
{"europe_pmc_id":"37646119","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The development of psilocybin therapy for treatment-resistant depression: an update.
authors: Borissova A, Rucker JJ.
publication_date: 2024-01-31
doi: 10.1192/bjb.2023.25
pubmed_id: 37357767
source_url: https://doi.org/10.1192/bjb.2023.25
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Psilocybin is a classic psychedelic drug that has attracted increasing research interest over the past 10 years as a possible treatment for mood, anxiety and related conditions. Initial phase 2 clinical trials of psilocybin given alongside psychological support for major depression and treatment-resistant depression (TRD) demonstrated encouraging signs of basic safety, further confirmed by a large study in groups of healthy volunteers. The first international multi-centre randomised controlled trial was published in 2022, with signs of efficacy for the 25 mg dose condition in people with TRD when compared with an active placebo. Phase 3 trials in TRD are scheduled to start in 2023. Early evidence suggests that single doses of psilocybin given with psychological support induce rapid improvement in depressive symptoms that endure for some weeks. We therefore provide a timely update to psychiatrists on what psilocybin therapy is, what it is not, and the current state of the evidence-base.

topic_tags:
Depression,Anxiety,Aging,Clinical Trial,Randomized Controlled Trial,Healthy Volunteers,Treatment-Resistant Depression,Safety

raw_json:
{"europe_pmc_id":"37357767","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Agin-Liebes G, Nielson EM, Zingman M, Kim K, Haas A, Owens LT, Rogers U, Bogenschutz M.
publication_date: 2023-06-04
doi: 10.1037/adb0000935
pubmed_id: 37276086
source_url: https://doi.org/10.1037/adb0000935
substance_tags: psilocybin
topic_tags: Addiction,Chronic Pain,Mechanism of Action,Emotional Processing,Randomized Controlled Trial
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Reports of self-compassion and affect regulation in psilocybin-assisted therapy for alcohol use disorder: An interpretive phenomenological analysis.

abstract:
ObjectiveThe primary aim of this qualitative study was to delineate psychological mechanisms of change in the first randomized controlled trial of psilocybin-assisted psychotherapy to treat alcohol use disorder (AUD). Theories regarding psychological processes involved in psychedelic therapy remain underdeveloped.MethodParticipants (N = 13) mostly identified as non-Hispanic and White, with approximately equal proportions of cisgender men and women. Participants engaged in semistructured interviews about their subjective experiences in the study. Questions probed the nature of participants' drinking before and after the study as well as coping patterns in response to strong emotions, stress, and cravings for alcohol. Verbatim transcripts were coded using Dedoose software, and content was analyzed with interpretive phenomenological analysis.ResultsParticipants reported that the psilocybin treatment helped them process emotions related to painful past events and helped promote states of self-compassion, self-awareness, and feelings of interconnectedness. The acute states during the psilocybin sessions were described as laying the foundation for developing more self-compassionate regulation of negative affect. Participants also described newfound feelings of belonging and an improved quality of relationships following the treatment.ConclusionOur results support the assertion that psilocybin increases the malleability of self-related processing, and diminishes shame-based and self-critical thought patterns while improving affect regulation and reducing alcohol cravings. These findings suggest that psychosocial treatments that integrate self-compassion training with psychedelic therapy may serve as a useful tool for enhancing psychological outcomes in the treatment of AUD. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

keywords:
Humans, Alcoholism, Hallucinogens, Emotions, Qualitative Research, Female, Male, Randomized Controlled Trials as Topic, Psilocybin, Self-Compassion

raw_json:
{"europe_pmc_id":"37276086","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Gojani EG, Wang B, Li DP, Kovalchuk O, Kovalchuk I.
publication_date: 2024-01-28
doi: 10.3390/genes15020183
pubmed_id: 38397173
source_url: https://doi.org/10.3390/genes15020183
substance_tags: psilocybin
topic_tags: Receptor Pharmacology,Biomarkers,Animal Study,In Vitro Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
The Impact of Psilocybin on High Glucose/Lipid-Induced Changes in INS-1 Cell Viability and Dedifferentiation.

abstract:
Serotonin emerges as a pivotal factor influencing the growth and functionality of β-cells. Psilocybin, a natural compound derived from mushrooms of the Psilocybe genus, exerts agonistic effects on the serotonin 5-HT2A and 5-HT2B receptors, thereby mimicking serotonin's behavior. This study investigates the potential impacts of psilocybin on β-cell viability, dedifferentiation, and function using an in vitro system. The INS-1 832/13 Rat Insulinoma cell line underwent psilocybin pretreatment, followed by exposure to high glucose-high lipid (HG-HL) conditions for specific time periods. After being harvested from treated cells, total transcript and cellular protein were utilized for further investigation. Our findings implied that psilocybin administration effectively mitigates HG-HL-stimulated β-cell loss, potentially mediated through the modulation of apoptotic biomarkers, which is possibly related to the mitigation of TXNIP, STAT-1, and STAT-3 phosphorylation. Furthermore, psilocybin exhibits the capacity to modulate the expression of key genes associated with β-cell dedifferentiation, including Pou5f1 and Nanog, indicating its potential in attenuating β-cell dedifferentiation. This research lays the groundwork for further exploration into the therapeutic potential of psilocybin in Type II diabetes intervention.

keywords:
Animals, Rats, Diabetes Mellitus, Type 2, Serotonin, Glucose, Lipids, Cell Cycle Proteins, Cell Survival, Psilocybin

raw_json:
{"europe_pmc_id":"38397173","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-01-25
doi: 10.1186/s12888-024-05502-y
pubmed_id: 38279085
source_url: https://doi.org/10.1186/s12888-024-05502-y
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
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:
BackgroundA 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.MethodsIn 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.DiscussionThe discussion outlines issues that might arise from our design.Trial registrationEudraCT 2022-002369-14 and NCT06160232.

keywords:
Humans, Alcoholism, Treatment Outcome, Double-Blind Method, Alcohol Drinking, Randomized Controlled Trials as Topic, Clinical Trials, Phase II as Topic, Acceptance and Commitment Therapy, Psilocybin, Equivalence Trials as Topic

topic_tags:
Depression,Anxiety,Addiction,Neuroplasticity,Mechanism of Action,Clinical Trial,Randomized Controlled Trial,Safety

raw_json:
{"europe_pmc_id":"38279085","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2023-11-19
doi: 10.1021/acs.jmedchem.3c01225
pubmed_id: 37983270
source_url: https://doi.org/10.1021/acs.jmedchem.3c01225
keywords: Humans, Hallucinogens, Prodrugs, Anxiety Disorders, Psilocybin
substance_tags: psilocybin,psilocin
topic_tags: Depression,Anxiety,Pharmacology
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
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, Dhananjaya D, Jensen G, Lee JB, Cai C, Gallant J, Bains J, Tucker JE, Facchini PJ.

abstract:
The psychedelic prodrug psilocybin has shown therapeutic benefits for the treatment of numerous psychiatric conditions. Despite positive clinical end points targeting depression and anxiety, concerns regarding the duration of the psychedelic experience produced by psilocybin, associated with enduring systemic exposure to the active metabolite psilocin, pose a barrier to its therapeutic application. Our objective was to create a novel prodrug of psilocin with similar therapeutic benefits but a reduced duration of psychedelic effects compared with psilocybin. Here, we report the synthesis and functional screening of 28 new chemical entities. Our strategy was to introduce a diversity of cleavable groups at the 4-hydroxy position of the core indole moiety to modulate metabolic processing. We identified several novel prodrugs of psilocin with altered pharmacokinetic profiles and reduced pharmacological exposure compared with psilocybin. These candidate prodrugs have the potential to maintain the long-term benefits of psilocybin therapy while attenuating the duration of psychedelic effects.

raw_json:
{"europe_pmc_id":"37983270","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Modlin NL, Creed M, Sarang M, Maggio C, Rucker JJ, Williamson V.
publication_date: 2024-01-19
doi: 10.2147/ndt.s432537
pubmed_id: 38268571
source_url: https://doi.org/10.2147/ndt.s432537
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Addiction,Mechanism of Action,Review Article,Safety
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Trauma-Informed Care in Psychedelic Therapy Research: A Qualitative Literature Review of Evidence-Based Psychotherapy Interventions in PTSD and Psychedelic Therapy Across Conditions.

abstract:
IntroductionPost-traumatic stress disorder (PTSD) is associated with significant patient burden. While pharmacotherapies and evidence-based psychotherapy interventions (EBPI) are effective, studies consistently highlight inadequate outcomes and high treatment dropout. Psychedelic therapy (PT) has shown preliminary promise across difficult-to-treat conditions, including MDMA-assisted therapy for PTSD, however trials of classical psychedelics in PTSD are lacking. Understanding patients' experiences of EBPI could help promote safety in PT.AimTo systematically review qualitative research on patients' subjective experience of EBPI for PTSD, and of PT, and examine areas of overlap and divergence between them.MethodsSystematic literature searches for studies published between 2010 and 2023 were conducted on OVID, PubMed, Web of Science, and PsycInfo. Included were original studies in English that presented qualitative data of patient experiences of EBPI in PTSD, or PT for any indication. Extracted data from included studies were analysed using thematic synthesis. Syntheses were completed separately for EBPI and PT, before similarities and differences between the therapies were identified.Results40 research articles were included for review: 26 studies on EBPI for PTSD, and 14 studies on PT. EBPI studied were CBT, EMDR, CPT and PE. Psychedelic compounds studied were psilocybin, ibogaine, LSD, MDMA and ketamine, for treatment of substance use disorders, anxiety relating to physical illness, depression, and PTSD. Core themes from patient experiences of EBPI: 1) patient burden in PTSD treatment; 2) readiness; 3) key mechanisms of change; 4) psychological safety and trust. Themes identified in the review of PT: 1) indirect trauma processing; 2) reorganisation of self-narratives via processes of relatedness and identification; 3) key treatment characteristics.ConclusionThis study suggests overlap between patients' experience of EBPI and PT in terms of key mechanisms of change, the importance of psychological safety and readiness to engage in treatment. Trauma-informed care paradigms and practices may improve safety and acceptability of PT research.

raw_json:
{"europe_pmc_id":"38268571","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelic-like Activity of Norpsilocin Analogues.
authors: Sherwood AM, Burkhartzmeyer EK, Williamson SE, Baumann MH, Glatfelter GC.
publication_date: 2024-01-07
doi: 10.1021/acschemneuro.3c00610
pubmed_id: 38189238
source_url: https://doi.org/10.1021/acschemneuro.3c00610
keywords: Brain, Animals, Mice, Serotonin, Receptors, Serotonin, Receptor, Serotonin, 5-HT2A, Hallucinogens
substance_tags: psilocybin,psilocin
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Primary metabolites of mushroom tryptamines, psilocybin and baeocystin (i.e., psilocin and norpsilocin), exhibit potent agonist activity at the serotonin 2A receptor (5-HT2A) in vitro but differ in their 5-HT2A-mediated effects in vivo. In particular, psilocin produces centrally mediated psychedelic effects in vivo, whereas norpsilocin, differing only by the loss of an N-methyl group, is devoid of psychedelic-like effects. These observations suggest that the secondary methylamine group in norpsilocin impacts its central nervous system (CNS) bioavailability but not its receptor pharmacodynamics. To test this hypothesis, eight norpsilocin derivatives were synthesized with varied secondary alkyl-, allyl-, and benzylamine groups, primarily aiming to increase their lipophilicity and brain permeability. Structure-activity relationships for the norpsilocin analogues were evaluated using the mouse head-twitch response (HTR) as a proxy for CNS-mediated psychedelic-like effects. HTR studies revealed that extending the N-methyl group of norpsilocin by a single methyl group, to give the corresponding secondary N-ethyl analogue (4-HO-NET), was sufficient to produce psilocin-like activity (median effective dose or ED50 = 1.4 mg/kg). Notably, N-allyl, N-propyl, N-isopropyl, and N-benzyl derivatives also induced psilocin-like HTR activity (ED50 = 1.1-3.2 mg/kg), with variable maximum effects (26-77 total HTR events). By contrast, adding bulkier tert-butyl or cyclohexyl groups in the same position did not elicit psilocin-like HTRs. Pharmacological assessments of the tryptamine series in vitro demonstrated interactions with multiple serotonin receptor subtypes, including 5-HT2A, and other CNS signaling proteins (e.g., sigma receptors). Overall, our data highlight key structural requirements for CNS-mediated psychedelic-like effects of norpsilocin analogues.

topic_tags:
Pharmacology,Mechanism of Action,Receptor Pharmacology,Animal Study,In Vitro Study,Drug Interactions

raw_json:
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title: Modern Psychedelic Microdosing Research on Mental Health: A Systematic Review.
authors: Lo DF, Zia H, Rajkumar P, Thakur A, O'Donnell H.
publication_date: 2024-01-15
doi: 10.4088/pcc.23r03581
pubmed_id: 38228068
source_url: https://doi.org/10.4088/pcc.23r03581
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:06
abstract:
Objective: To investigate the relationship between psychedelic microdosing and its effects on mental health, aiming to understand if microdosing can improve mental well-being.Data Sources: PubMed and Scopus were searched on December 25, 2022, using search terms related to psychedelics, microdosing, and mental health. The inclusion criteria focused on studies published between January 1, 2012, and November 30, 2022. There were no language restrictions for the initial search; however, for the study selection, only articles in English were considered.Study Selection: A total of 45 articles were initially identified. After removing duplicates, 27 unique articles were screened based on their titles and abstracts, resulting in 19 articles included in the final review. The studies were selected based on their relevance to the relationship between mental health and psychedelic microdosing.Data Extraction: The extracted data from the selected studies included sample sizes, demographics, survey designs, and qualitative and quantitative analyses related to the outcomes of individuals with mental health issues who also engaged in psychedelic microdosing. The QualSyst Quality Assessment Checklist was used to assess the methodological rigor and quality of each study. The data extraction process involved systematically reviewing each article and summarizing key findings related to the impact of microdosing on mental health.Results: The review revealed that microdosing psychedelics, such as lysergic acid diethylamide and psilocybin, showed potential benefits on mental health. Users reported positive effects, including improved mood, increased focus, and better daily function. However, there were also challenges reported, such as physiologic discomfort and increased anxiety. Some studies observed that positive expectations about microdosing led to positive outcomes. The studies varied in design, with some being observational, others placebo-controlled, and some relying on self-reported data.Conclusions: There is a growing body of evidence suggesting a positive correlation between psychedelic microdosing and improved mental well-being. However, due to the limited number of controlled studies and the small sample sizes in some of the studies, the causal relationship between microdosing and mental health improvement remains uncertain. The review calls for further research with double-blind experiments, control groups, and larger sample sizes that represent the general population to better understand the potential benefits and risks of psychedelic microdosing on mental health.Prim Care Companion CNS Disord 2024;26(1):23r03581.Author affiliations are listed at the end of this article.

keywords:
Humans, Lysergic Acid Diethylamide, Hallucinogens, Anxiety, Mental Health, Randomized Controlled Trials as Topic, Psilocybin

topic_tags:
Anxiety,Microdosing,Wellbeing,Randomized Controlled Trial,Systematic Review,Review Article,Observational Study,Safety

raw_json:
{"europe_pmc_id":"38228068","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Bradshaw AJ, Ramírez-Cruz V, Awan AR, Furci G, Guzmán-Dávalos L, Dentinger BTM.
publication_date: 2024-01-08
doi: 10.1073/pnas.2311245121
pubmed_id: 38194448
source_url: https://doi.org/10.1073/pnas.2311245121
keywords: Agaricales, Phylogeny, Multigene Family, Psilocybe, Psilocybin
substance_tags: psilocybin
topic_tags: Genomics
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
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 the recent surge of interest in these mushrooms due to the psychotherapeutic potential of their natural alkaloid psilocybin, their phylogeny and taxonomy remain substantially incomplete. Moreover, the recent elucidation of the psilocybin biosynthetic gene cluster is known for only five of ~165 species of Psilocybe, four of which belong to only one of two major clades. We set out to improve the phylogeny of Psilocybe using shotgun sequencing of fungarium specimens, from which we obtained 71 metagenomes including from 23 types, and conducting phylogenomic analysis of 2,983 single-copy gene families to generate a fully supported phylogeny. Molecular clock analysis suggests the stem lineage of Psilocybe arose ~67 mya and diversified ~56 mya. We also show that psilocybin biosynthesis first arose in Psilocybe, with 4 to 5 possible horizontal transfers to other mushrooms between 40 and 9 mya. Moreover, predicted orthologs of the psilocybin biosynthetic genes revealed two distinct gene orders within the biosynthetic gene cluster that corresponds to a deep split within the genus, possibly a signature of two independent acquisitions of the cluster within Psilocybe.

raw_json:
{"europe_pmc_id":"38194448","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelics, epilepsy, and seizures: a review.
authors: Freidel N, Kreuder L, Rabinovitch BS, Chen FY, Huang RST, Lewis EC
journal: Frontiers in pharmacology
publication_date: 2022-12-31
doi: 10.3389/fphar.2023.1326815
pubmed_id: 38283836
source_url: https://pubmed.ncbi.nlm.nih.gov/38283836/
keywords: LSD, MDMA, epilepsy, ketamine, magic mushrooms, psilocybin, psychedelics, seizures
substance_tags: psilocybin
topic_tags: Clinical Trial,Review Article,Observational Study,Animal Study
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:37
raw_json: {"pubmed_id":"38283836"}
abstract:
Psychedelic compounds have been utilized by humans for centuries for medicinal, religious, and tribal purposes. Clinical trial data starting from the early 2000s and continuing today indicates that psychedelics are a clinically efficacious treatment for a variety of neurological and psychiatric disorders. However, all clinical trials examining these substances have excluded any individual with a past or current history of seizures, leaving a large cohort of epilepsy and non-epilepsy chronic seizure disorder patients without anywhere to turn for psychedelic-assisted therapy. These exclusions were made despite any significant evidence that clinically supervised psychedelic use causes or exacerbates seizures in this population. To date, no clinical trial or preclinical seizure model has demonstrated that psychedelics induce seizures. This review highlights several cases of individuals experiencing seizures or seizure remission following psychedelic use, with the overall trend being that psychedelics are safe for use in a controlled, supervised clinical setting. We also suggest future research directions for this field.


title: Knowledge gaps in psychedelic medicalisation: Clinical studies and regulatory aspects.
publication_date: 2024-01-10
doi: 10.1016/j.nsa.2024.103938
pubmed_id: 40656112
source_url: https://doi.org/10.1016/j.nsa.2024.103938
substance_tags: psilocybin
topic_tags: Depression,Pharmacology,Clinical Trial
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
authors:
E-Wen McCulloch D, Liechti ME, Kuypers KP, Nutt D, Lundberg J, Stenbæk DS, Goodwin GM, Gründer G, Butlen-Ducuing F, Haberkamp M, Thirstrup S, Knudsen GM.

abstract:
Psychedelic drugs including psilocybin and LSD are undergoing clinical trials for a range of psychiatric and neurological conditions, and have particularly shown substantial promise in phase 2 studies of depression. In this article we outline key knowledge gaps that may be imperative for a successful implementation of psychedelic drugs as medicines as identified by members of the European College of Neuropsychopharmacology at the New Frontiers Meeting in Nice (2023). Key themes include pharmacokinetic and pharmacodynamic characterisation, comparisons between psychedelics, the relation between the duration of subjective effects and therapeutic outcomes, polypharmacology, and the impact of psychological support. We conclude with a perspective from the European Medicines Agency and Heath Technology Assessors on the most pressing requirements for medical implementation in Europe.

raw_json:
{"europe_pmc_id":"40656112","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Aesthetic chills mitigate maladaptive cognition in depression.
authors: Schoeller F, Jain A, Adrien V, Maes P, Reggente N.
publication_date: 2024-01-09
doi: 10.1186/s12888-023-05476-3
pubmed_id: 38200491
source_url: https://doi.org/10.1186/s12888-023-05476-3
keywords: Humans, Depression, Cognition, Esthetics, Databases, Factual, Major Depressive Disorder
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Consciousness,Emotional Processing,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
BackgroundDepression is a major global health challenge, affecting over 300 million people worldwide. Current pharmacological and psychotherapeutic interventions have limited efficacy, underscoring the need for novel approaches. Emerging evidence suggests that peak emotional experiences characterized by awe, transcendence, and meaning hold promise for rapidly shifting maladaptive cognitive patterns in depression. Aesthetic chills, a peak positive emotion characterized by physical sensations such as shivers and goosebumps, may influence reward-related neural pathways and hold promise for modifying core maladaptive beliefs rooted in early adverse experiences.MethodsWe enrolled 96 patients diagnosed with major depressive disorder. A validated database of multimedia known to elicit chills responses (ChillsDB) was used for stimulus presentation. Participants' emotional responses were assessed using the Emotional Breakthrough Inventory (EBI), while shifts in self-schema were measured via the Young Positive Schema Questionnaire (YSPQ).ResultsThe study found that chill-inducing stimuli have the potential to positively influence the core schema of individuals with depression, impacting areas of self-related beliefs. The associated phenomenology triggered by chills appears to share similarities with the altered states of consciousness induced by psychedelic substances like psilocybin.ConclusionsThese preliminary results suggest that the biological processes involved in aesthetic chills could be harnessed as a non-pharmacological intervention for depression. However, further investigation is necessary to comprehensively understand the neurophysiological responses to chills and to evaluate the practicality, effectiveness, and safety of utilizing aesthetic chills as a preventive measure in mental health care.

raw_json:
{"europe_pmc_id":"38200491","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Rapid-acting antidepressant drugs modulate affective bias in rats.
publication_date: 2024-01-09
doi: 10.1126/scitranslmed.adi2403
pubmed_id: 38198569
source_url: https://doi.org/10.1126/scitranslmed.adi2403
substance_tags: psilocybin
topic_tags: Depression,Neuroplasticity,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
authors:
Hinchcliffe JK, Stuart SA, Wood CM, Bartlett J, Kamenish K, Arban R, Thomas CW, Selimbeyoglu A, Hurley S, Hengerer B, Gilmour G, Robinson ESJ.

abstract:
How rapid-acting antidepressants (RAADs), such as ketamine, induce immediate and sustained improvements in mood in patients with major depressive disorder (MDD) is poorly understood. A core feature of MDD is the prevalence of cognitive processing biases associated with negative affective states, and the alleviation of negative affective biases may be an index of response to drug treatment. Here, we used an affective bias behavioral test in rats, based on an associative learning task, to investigate the effects of RAADs. To generate an affective bias, animals learned to associate two different digging substrates with a food reward in the presence or absence of an affective state manipulation. A choice between the two reward-associated digging substrates was used to quantify the affective bias generated. Acute treatment with the RAADs ketamine, scopolamine, or psilocybin selectively attenuated a negative affective bias in the affective bias test. Low, but not high, doses of ketamine and psilocybin reversed the valence of the negative affective bias 24 hours after RAAD treatment. Only treatment with psilocybin, but not ketamine or scopolamine, led to a positive affective bias that was dependent on new learning and memory formation. The relearning effects of ketamine were dependent on protein synthesis localized to the rat medial prefrontal cortex and could be modulated by cue reactivation, consistent with experience-dependent neural plasticity. These findings suggest a neuropsychological mechanism that may explain both the acute and sustained effects of RAADs, potentially linking their effects on neural plasticity with affective bias modulation in a rodent model.

keywords:
Animals, Humans, Rats, Ketamine, Scopolamine, Antidepressive Agents, Psilocybin, Bias, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"38198569","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Duan W, Cao D, Wang S, Cheng J.
publication_date: 2023-11-29
doi: 10.1021/acs.chemrev.3c00375
pubmed_id: 38033123
source_url: https://doi.org/10.1021/acs.chemrev.3c00375
keywords: Serotonin, Receptor, Serotonin, 5-HT2A, Hallucinogens, Antidepressive Agents
substance_tags: psilocybin
topic_tags: Depression,Pharmacology,Mechanism of Action,Receptor Pharmacology,Aging,Clinical Trial
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants.

abstract:
Psychedelics make up a group of psychoactive compounds that induce hallucinogenic effects by activating the serotonin 2A receptor (5-HT2AR). Clinical trials have demonstrated the traditional psychedelic substances like psilocybin as a class of rapid-acting and long-lasting antidepressants. However, there is a pressing need for rationally designed 5-HT2AR agonists that possess optimal pharmacological profiles in order to fully reveal the therapeutic potential of these agonists and identify safer drug candidates devoid of hallucinogenic effects. This Perspective provides an overview of the structure-activity relationships of existing 5-HT2AR agonists based on their chemical classifications and discusses recent advancements in understanding their molecular pharmacology at a structural level. The encouraging clinical outcomes of psychedelics in depression treatment have sparked drug discovery endeavors aimed at developing novel 5-HT2AR agonists with improved subtype selectivity and signaling bias properties, which could serve as safer and potentially nonhallucinogenic antidepressants. These efforts can be significantly expedited through the utilization of structure-based methods and functional selectivity-directed screening.

raw_json:
{"europe_pmc_id":"38033123","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-01-08
doi: 10.3389/fpsyt.2023.1278823
pubmed_id: 38264632
source_url: https://doi.org/10.3389/fpsyt.2023.1278823
substance_tags: psilocybin
topic_tags: OCD,Mechanism of Action,Clinical Trial,Randomized Controlled Trial,Review Article,Safety
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Safety, feasibility, tolerability, and clinical effects of repeated psilocybin dosing combined with non-directive support in the treatment of obsessive-compulsive disorder: protocol for a randomized, waitlist-controlled trial with blinded ratings.

authors:
Ching THW, Amoroso L, Bohner C, D'Amico E, Eilbott J, Entezar T, Fitzpatrick M, Fram G, Grazioplene R, Hokanson J, Kichuk SA, Martins B, Patel P, Schaer H, Shnayder S, Witherow C, Pittenger C, Kelmendi B.

abstract:
BackgroundTo date, few randomized controlled trials of psilocybin with non-directive support exist for obsessive-compulsive disorder (OCD). Results and participant feedback from an interim analysis of an ongoing single-dose trial (NCT03356483) converged on the possibility of administering a higher fixed dose and/or more doses of psilocybin in future trials for presumably greater benefits.ObjectivesThis trial aims to evaluate the safety, feasibility, tolerability, and clinical effects of two doses of psilocybin paired with non-directive support in the treatment of OCD. This trial also seeks to examine whether two doses of psilocybin lead to greater OCD symptom reduction than a single dose, and to elucidate psychological mechanisms underlying the effects of psilocybin on OCD.DesignA randomized (1:1), waitlist-controlled design with blinded ratings will be used to examine the effects of two doses of oral psilocybin paired with non-directive support vs. waitlist control on OCD symptoms. An adaptive dose selection strategy will be implemented (i.e., first dose: 25 mg; second dose: 25 or 30 mg).Methods and analysisThis single-site trial will enroll 30 adult participants with treatment-refractory OCD. Aside from safety, feasibility, and tolerability metrics, primary outcomes include OCD symptoms assessed on the Yale-Brown Obsessive-Compulsive Scale - Second Edition (Y-BOCS-II). A blinded independent rater will assess primary outcomes at baseline and the primary endpoint at the end of the second dosing week. Participants will be followed up to 12 months post-second dosing. Participants randomized to waitlist will be rescreened after 7 weeks post-randomization, and begin their delayed treatment phase thereafter if still eligible.EthicsWritten informed consent will be obtained from participants. The institutional review board has approved this trial (protocol v. 1.7; HIC #2000032623).DiscussionThis study seeks to advance our ability to treat refractory OCD, and catalyze future research seeking to optimize the process of psilocybin treatment for OCD through understanding relevant psychological mechanisms.Clinical trial registration: ClinicalTrials.gov, identifier NCT05370911.

raw_json:
{"europe_pmc_id":"38264632","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Jones NT, Wagner L, Hahn MCP, Scarlett CO, Wenthur CJ.
publication_date: 2024-01-07
doi: 10.3389/fpsyt.2023.1303365
pubmed_id: 38264637
source_url: https://doi.org/10.3389/fpsyt.2023.1303365
substance_tags: psilocybin,psilocin
topic_tags: Mechanism of Action,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
title:
In vivo validation of psilacetin as a prodrug yielding modestly lower peripheral psilocin exposure than psilocybin.

abstract:
IntroductionThe use of the psychedelic compound psilocybin in conjunction with psychotherapy has shown promising results in the treatment of psychiatric disorders, though the underlying mechanisms supporting these effects remain unclear. Psilocybin is a Schedule I substance that is dephosphorylated in vivo to form an active metabolite, psilocin. Psilacetin, also known as O-acetylpsilocin or 4-acetoxy-N,N-dimethyltryptamine (4-AcO-DMT), is an unscheduled compound that has long been suggested as an alternative psilocin prodrug, though direct in vivo support for this hypothesis has thus far been lacking.MethodsThis study employed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assess the time-course and plasma concentrations of psilocin following the intraperitoneal (IP) administration of psilacetin fumarate or psilocybin to male and female C57Bl6/J mice.ResultsDirect comparisons of the time courses for psilocin exposure arising from psilocybin and psilacetin found that psilocybin led to 10-25% higher psilocin concentrations than psilacetin at 15-min post-injection. The half-life of psilocin remained approximately 30 min, irrespective of whether it came from psilocybin or psilacetin. Overall, the relative amount of psilocin exposure from psilacetin fumarate was found to be approximately 70% of that from psilocybin.DiscussionThese findings provide the first direct support for the long-standing assumption in the field that psilacetin functions as a prodrug for psilocin in vivo. In addition, these results indicate that psilacetin fumarate results in lower peripheral psilocin exposure than psilocybin when dosed on an equimolar basis. Thoughtful substitution of psilocybin with psilacetin fumarate appears to be a viable approach for conducting mechanistic psychedelic research in C57Bl6/J mice.

raw_json:
{"europe_pmc_id":"38264637","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Knowledge gaps in psychedelic medicalisation: Preclinical and neuroimaging mechanisms.
publication_date: 2023-12-14
doi: 10.1016/j.nsa.2023.103929
pubmed_id: 40656118
source_url: https://doi.org/10.1016/j.nsa.2023.103929
substance_tags: psilocybin
topic_tags: Brain Imaging,Mechanism of Action,Receptor Pharmacology,Aging,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
authors:
McCulloch DE, Lopez JP, Dalla C, Castrén E, Erritzoe D, Frokjaer VG, Lundberg J, Preller KH, Fisher PM, Knudsen GM.

abstract:
Classical psychedelic drugs, e.g., psilocybin and LSD, stimulate the serotonin 2A receptor (5-HT2AR) and have recently been intensely investigated for their clinical effects in various brain disorders. At the ECNP "New Frontiers meeting" in March 2023, scientific experts in psychedelics met to identify key knowledge gaps in the mechanism of action of psychedelics as investigated using preclinical models and clinical neuroimaging. Key themes included the development of appropriate behavioural models for measuring acute and persisting effects, dose optimisation, molecular mechanisms of action, sex differences, and the acute and persisting effects of psychedelics on neurotransmitter release and functional brain activity.

raw_json:
{"europe_pmc_id":"40656118","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Armand S, Larsen K, Madsen MK, Ozenne B, Preller KH, Knudsen GM, Stenbæk DS, Fisher PM.
publication_date: 2023-12-29
doi: 10.1016/j.nsa.2023.103934
pubmed_id: 40656071
source_url: https://doi.org/10.1016/j.nsa.2023.103934
substance_tags: psilocybin,psilocin
topic_tags: Depression,Brain Imaging,Aging,Emotional Processing
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
title:
Amygdala response to emotional faces following acute administration of psilocybin in healthy individuals.

abstract:
The serotonergic psychedelic psilocybin acutely induces changes in emotional states. However, it remains unresolved whether psilocybin acutely modulates amygdala reactivity to emotions, a brain region critically involved in emotion processing. Using functional magnetic resonance imaging (fMRI), we examined in 26 healthy individuals whether amygdala responses to angry, fearful and neutral faces differ between acute exposure to psilocybin and at baseline. We also evaluated whether plasma psilocin levels (PPL) and subjective drug intensity (SDI) during psilocybin are related to amygdala responses to the emotional faces. We found that amygdala response to angry faces was significantly reduced during exposure to psilocybin as compared to baseline (mean difference = -0.54, PFWER = 0.03), whereas no significant changes in amygdala responses to fearful or neutral faces were observed. We further found that the amygdala response to fearful faces was significantly negatively associated with SDI (slope = -0.13, PFWER = 0.04), whereas no significant association with PPL was observed. Our findings indicate that psilocybin attenuates amygdala reactivity to angry faces and that a more intense subjective psilocybin response (SDI) is associated with attenuated amygdala reactivity to fearful faces, in accordance with previously reported results. Future studies should investigate whether exposure to psilocybin acutely changes emotion processing in individuals with depression and whether such changes are related to therapeutic outcomes.

raw_json:
{"europe_pmc_id":"40656071","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: Journal of addiction psychiatry
publication_date: 2023-12-31
pubmed_id: 39634920
source_url: https://pubmed.ncbi.nlm.nih.gov/39634920/
substance_tags: psilocybin
topic_tags: PTSD,Mechanism of Action,Personality Change
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:37
raw_json: {"pubmed_id":"39634920"}
title:
Theorizing that Psychedelic Assisted Therapy May Play a Role in the Treatment of Trauma-Induced Personality Disorders.

authors:
Martire G, Sipple D, Baron D, Gold MS, Lewandowski KU, Dennen CA, Sharafshah A, Elman I, Thanos PK, Modestino EJ, Badgaiyan RD, Pinhasov A, Bowirrat A, Makale M, Roy AK, Sunder K, Murphy KT, Mahajan S, Mahajan Y, Levin C, Blum K

abstract:
Borderline personality disorder (BPD) and post-traumatic stress disorder (PTSD) share overlapping neurobiological mechanisms particularly reward deficiency and stress-like anti-reward processes. And so, BPD may be reclassified as a "traumatic personality stress disorder" (TPSD) with ensuing common therapeutic strategies that may stabilize dopaminergic reward function such as psychedelic-assisted therapy. Integrated therapeutic strategies may be further supported by genetic studies aimed at assessing similarities between the two therapeutic entities. In this perspective we theorize that psychedelic assisted therapy (PAT) may play a role in the treatment of trauma induced personality disorders. This study identifies PAT as a pathway for treating both BPD and PTSD, proposing that reframing BPD as TPSD could lead to more effective, personalized interventions, ultimately improving the quality of life for those affected by trauma. Such a reclassification might also mitigate stigma, enhance our understanding of the underlying mechanisms, and optimize therapeutic interventions for a broader range of diagnostic categories characterized by anhedonia, negative affective states, hypervigilance, and dissociation.

keywords:
Borderline personality disorder, Post-traumatic stress disorder, Psilocybin, Psychedelic assisted therapy, Trauma


title: Ayahuasca for the treatment of alcohol use disorder.
authors: Marinho EAV, Serra YA, Oliveira-Lima AJ, Marcourakis T, Berro LF.
publication_date: 2024-08-09
doi: 10.1016/bs.irn.2024.07.007
pubmed_id: 39523057
source_url: https://doi.org/10.1016/bs.irn.2024.07.007
keywords: Animals, Humans, Banisteriopsis, Psychotria, Alcoholism, Hallucinogens
substance_tags: psilocybin
topic_tags: Addiction,Mechanism of Action,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
For decades, psychedelics have been investigated for the treatment of psychiatric disorders. Specifically, evidence suggests that psychedelics may have therapeutic potential for the treatment of alcohol use disorder. Several studies with classic psychedelics, including LSD and psilocybin, show promising results, with psychedelics decreasing alcohol drinking and promoting abstinence in individuals with alcohol use disorder. In the last two decades, ayahuasca has emerged as another psychedelic with therapeutic potential for alcohol use disorder. Although its use by indigenous people from South America has been reported for thousands of years, ayahuasca, an Amazonian brewed beverage used in rituals, has gained attention in recent decades due to its reported effects in the central nervous system. Ayahuasca is a hallucinogenic beverage produced from the decoction of Banisteriopsis caapi and Psychotria viridis, plants that contain β-carbolines and N,N-dimethyltryptamine (DMT), respectively. The majority of clinical studies investigating ayahuasca for the treatment of alcohol use disorder are retrospective, and all show a significant decrease in alcohol use among ayahuasca users. Corroborating the clinical evidence, pre-clinical studies also have demonstrated that ayahuasca can block several of the abuse-related effects of alcohol. This chapter reviews the accumulating evidence from clinical and pre-clinical studies suggesting that ayahuasca may be a promising new pharmacotherapy for the treatment of alcohol use disorders, and discusses the potential mechanisms involved in these and other effects of ayahuasca.

raw_json:
{"europe_pmc_id":"39523057","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelics: From Cave Art to 21st-Century Medicine for Addiction.
authors: Vamvakopoulou IA, Nutt DJ.
publication_date: 2024-09-24
doi: 10.1159/000540062
pubmed_id: 39321788
source_url: https://doi.org/10.1159/000540062
substance_tags: psilocybin
topic_tags: Addiction,Pharmacology,Mechanism of Action,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
BackgroundPsychedelic substance use in ritualistic and ceremonial settings dates back as early as 8,500 BCE. Only in recent years, from the mid-20th century, we have seen the re-emergence of psychedelics in a therapeutic setting and more specifically for the treatment of addiction. This article aims to review research over the past 40 years using classic (psilocybin, lysergic acid diethylamide [LSD], dimethyltryptamine [DMT], mescaline) and atypical (ketamine, ibogaine, 5-MeO-DMT, 3,4-methylenedioxymethamphetamine) psychedelics for the treatment of addiction.SummaryWe will start with an overview of the pharmacology and physiological and psychological properties of psychedelic substances from pre-clinical and clinical research. We will then provide an overview of evidence gathered by studies conducted in controlled research environments and naturalistic and ceremonial settings, while we identify the proposed therapeutic mechanisms of each psychedelic substance.Key messagesClassic and atypical psychedelics show promise as therapeutic alternatives for the treatment of addiction, through the improvement of psychological and physiological symptoms of dependence. A more comprehensive understanding of the ancient and present-day knowledge of the therapeutic potential of psychedelics can facilitate hope for psychedelic therapeutics in the treatment of addiction, especially for individuals who have failed other conventional treatment methods.

keywords:
Animals, Humans, Substance-Related Disorders, N,N-Dimethyltryptamine, N-Methyl-3,4-methylenedioxyamphetamine, Mescaline, Ketamine, Lysergic Acid Diethylamide, Hallucinogens, Behavior, Addictive, History, Ancient, History, 20th Century, History, 21st Century, Psilocybin

raw_json:
{"europe_pmc_id":"39321788","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Efficacy, Safety, and Tolerability of Psychedelics in Treatment-Resistant Depression (TRD).
authors: Olivier B, Olivier JDA.
publication_date: 2023-12-31
doi: 10.1007/978-981-97-4402-2_3
pubmed_id: 39261423
source_url: https://doi.org/10.1007/978-981-97-4402-2_3
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Treatment-Resistant Depression,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
abstract:
Major depressive disorder (MDD) is a highly prevalent psychiatric disorder, associated with substantial burden and large economical costs. Notwithstanding various conventional antidepressant treatment options, a large portion of depressed people (ca. 30%) fails to respond to first-line treatment, resulting in treatment-resistant depression (TRD). Although non-response to multiple antidepressant interventions is a common outcome, a consensus definition of TRD is not yet available. In practice, TRD is applied when two or more successive treatments with different antidepressants are not working. The last decade's intense research into new medicines for TRD has led to two developments, using typical or serotonergic (psilocybin, ayahuasca) and atypical (glutamatergic) psychedelics (ketamine, esketamine). Both approaches, although via different entrance mechanism, exhibit a fast onset but also long-lasting antidepressant effect far beyond the biological presence of the drug in the body, strongly indicating that downstream mechanisms activated by signaling cascades in the brain are involved. The present chapter describes the clinical development of psilocybin and esketamine for TRD and discusses the problems involved in the use of a proper placebo because of the psychotomimetic (psilocybin) or dissociative (ketamine) effects that interfere with performing "blind" studies. Nevertheless, intranasal esketamine was developed and approved for TRD, whereas psilocybin has shown positive results. Adverse effects and tolerability of both drugs in the dose ranges used are generally acceptable. The emergence of anti-TRD medicines for treatment of a very severe disease is a breakthrough in psychiatry.

keywords:
Humans, Ketamine, Hallucinogens, Antidepressive Agents, Treatment Outcome, Depressive Disorder, Treatment-Resistant, Psilocybin, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"39261423","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: [Up-to-Date on clinical and preclinical studies of psilocybin therapy].
authors: Ibi D.
publication_date: 2023-12-31
doi: 10.1254/fpj.24007
pubmed_id: 38945903
source_url: https://doi.org/10.1254/fpj.24007
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Major Depressive Disorder (MDD) poses a significant global health burden, with 30-40% patients developing resistance to standard clinical antidepressants, such as selective serotonin reuptake inhibitors and tricyclic antidepressants. In 2016, Carhart-Harris and colleagues reported that psilocybin, the hallucinogenic compound derived from magic mushrooms, exhibits rapid and enduring antidepressant effects in patients with treatment-resistant depression. Subsequent clinical studies have found the therapeutic potential of psilocybin in MDD, depressive episode in bipolar disorder, anorexia, and drug addiction. In 2018 and 2019, the U.S. Food and Drug Administration designated psilocybin as a "breakthrough medicine" for treatment-resistant depression and MDD, respectively. Notably, the side effects of psilocybin are limited to transient and mild issues, such as headache and fatigue, suggesting its safety. In 2023, we published a review on the role of serotonin 5-HT2A receptors in the antidepressant effects of serotonergic psychedelics (Nihon Yakurigaku Zasshi, Volume 158, Issue 3, Page 229-232). Here, we present our study alongside the latest clinical and preclinical research on the antidepressant effects of psilocybin and provide an overview of the potential and issues related to psilocybin therapy.

keywords:
Animals, Humans, Receptor, Serotonin, 5-HT2A, Hallucinogens, Antidepressive Agents, Psilocybin, Major Depressive Disorder

topic_tags:
Depression,Addiction,Eating Disorders,Headache / Migraine,Receptor Pharmacology,Review Article,Animal Study,Treatment-Resistant Depression,Safety,Adverse Events

raw_json:
{"europe_pmc_id":"38945903","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Valuing the Acute Subjective Experience.
authors: Cheung K, Earp BD, Yaden DB.
publication_date: 2023-12-31
doi: 10.1353/pbm.2024.a919717
pubmed_id: 38662070
source_url: https://doi.org/10.1353/pbm.2024.a919717
keywords: Humans, N-Methyl-3,4-methylenedioxyamphetamine, Hallucinogens, Consciousness, Psilocybin
substance_tags: psilocybin
topic_tags: Consciousness,Wellbeing
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
Psychedelics, including psilocybin, and other consciousness-altering compounds such as 3,4-methylenedioxymethamphetamine (MDMA), currently are being scientifically investigated for their potential therapeutic uses, with a primary focus on measurable outcomes: for example, alleviation of symptoms or increases in self-reported well-being. Accordingly, much recent discussion about the possible value of these substances has turned on estimates of the magnitude and duration of persisting positive effects in comparison to harms. However, many have described the value of a psychedelic experience with little or no reference to such therapeutic benefits, instead seeming to find the experience valuable in its own right. How can we make sense of such testimony? Could a psychedelic experience be valuable even if there were no persisting beneficial effects? If so, how? Using the concept of psychological richness, combined with insights from the philosophy of aesthetics and the enhancement literature, this essay explores potential sources of value in the acute subjective experience, apart from the value derived from persisting beneficial effects.

raw_json:
{"europe_pmc_id":"38662070","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The Psychedelic Future of Post-Traumatic Stress Disorder Treatment.
publication_date: 2023-12-31
doi: 10.2174/1570159x22666231027111147
pubmed_id: 38284341
source_url: https://doi.org/10.2174/1570159x22666231027111147
substance_tags: psilocybin
topic_tags: PTSD,Pharmacology,Mechanism of Action,Receptor Pharmacology,Clinical Trial,Review Article,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
authors:
Zaretsky TG, Jagodnik KM, Barsic R, Antonio JH, Bonanno PA, MacLeod C, Pierce C, Carney H, Morrison MT, Saylor C, Danias G, Lepow L, Yehuda R.

abstract:
Post-traumatic stress disorder (PTSD) is a mental health condition that can occur following exposure to a traumatic experience. An estimated 12 million U.S. adults are presently affected by this disorder. Current treatments include psychological therapies (e.g., exposure-based interventions) and pharmacological treatments (e.g., selective serotonin reuptake inhibitors (SSRIs)). However, a significant proportion of patients receiving standard-of-care therapies for PTSD remain symptomatic, and new approaches for this and other trauma-related mental health conditions are greatly needed. Psychedelic compounds that alter cognition, perception, and mood are currently being examined for their efficacy in treating PTSD despite their current status as Drug Enforcement Administration (DEA)- scheduled substances. Initial clinical trials have demonstrated the potential value of psychedelicassisted therapy to treat PTSD and other psychiatric disorders. In this comprehensive review, we summarize the state of the science of PTSD clinical care, including current treatments and their shortcomings. We review clinical studies of psychedelic interventions to treat PTSD, trauma-related disorders, and common comorbidities. The classic psychedelics psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltryptamine (DMT) and DMT-containing ayahuasca, as well as the entactogen 3,4-methylenedioxymethamphetamine (MDMA) and the dissociative anesthetic ketamine, are reviewed. For each drug, we present the history of use, psychological and somatic effects, pharmacology, and safety profile. The rationale and proposed mechanisms for use in treating PTSD and traumarelated disorders are discussed. This review concludes with an in-depth consideration of future directions for the psychiatric applications of psychedelics to maximize therapeutic benefit and minimize risk in individuals and communities impacted by trauma-related conditions.

keywords:
Humans, N,N-Dimethyltryptamine, N-Methyl-3,4-methylenedioxyamphetamine, Lysergic Acid Diethylamide, Hallucinogens, Stress Disorders, Post-Traumatic, Adult, Psilocybin

raw_json:
{"europe_pmc_id":"38284341","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Older adults in psychedelic-assisted therapy trials: A systematic review.
authors: Bouchet L, Sager Z, Yrondi A, Nigam KB, Anderson BT, Ross S, Petridis PD, Beaussant Y.
publication_date: 2024-01-18
doi: 10.1177/02698811231215420
pubmed_id: 38240068
source_url: https://doi.org/10.1177/02698811231215420
keywords: Humans, Hallucinogens, Mental Disorders, Aged, Clinical Trials as Topic
substance_tags: psilocybin
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
BackgroundGrowing clinical interest in psychedelic-assisted therapies has led to a second wave of research involving psilocybin, lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA) and other substances. Data suggests that these compounds have the potential to treat mental health conditions that are especially prevalent in older adults such as depression, anxiety, existential distress, and posttraumatic stress disorder.AimsThe goal of this study was to quantify the prevalence of older adults enrolled in psychedelic clinical trials and explore safety data in this population.MethodsA systematic review was conducted following the 2020 PRISMA guidelines. Search criteria included all trials published in English using psychedelic substances to treat psychiatric conditions, including addiction as well as existential distress related to serious illness. Articles were identified from literature searches on PubMed, EBSCO, and EMBASE.Results4376 manuscripts were identified, of which 505 qualified for further review, with 36 eventually meeting eligibility criteria. Of the 1400 patients enrolled in the 36 studies, only 19 were identified as 65 or older, representing less than 1.4% of all trial participants. For 10 of these 19 older adults, detailed safety data was obtained. No serious adverse events (AEs) occurred in any older adults and only transient mild-to-moderate AEs related to anxiety, gastrointestinal upset, and hypertension were reported during the psychedelic dosing sessions.ConclusionsWhile existing data in older adults is limited, it suggests that psychedelic-assisted psychotherapy can be safe and well tolerated in older adults. Therefore, psychedelic-assisted psychotherapy should be more rigorously investigated for the treatment of psychiatric conditions in this population.

topic_tags:
Depression,Anxiety,PTSD,Addiction,Aging,Clinical Trial,Systematic Review,Review Article,Older Adults,Safety,Adverse Events

raw_json:
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publication_date: 2023-12-31
doi: 10.1111/head.14656
pubmed_id: 38238974
source_url: https://doi.org/10.1111/head.14656
keywords: Hypothalamus, Neural Pathways, Humans, Cluster Headache, Magnetic Resonance Imaging, Psilocybin
substance_tags: psilocybin
topic_tags: Headache / Migraine,Brain Imaging,Mechanism of Action,Aging,Clinical Trial
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
CCH attack frequency reduction after psilocybin correlates with hypothalamic functional connectivity.

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

abstract:
ObjectiveTo evaluate the feasibility and prophylactic effect of psilocybin as well as its effects on hypothalamic functional connectivity (FC) in patients with chronic cluster headache (CCH).BackgroundCCH is an excruciating and difficult-to-treat disorder with incompletely understood pathophysiology, although hypothalamic dysfunction has been implicated. Psilocybin may have beneficial prophylactic effects, but clinical evidence is limited.MethodsIn this small open-label clinical trial, 10 patients with CCH were included and maintained headache diaries for 10 weeks. Patients received three doses of peroral psilocybin (0.14 mg/kg) on the first day of weeks five, six, and seven. The first 4 weeks served as baseline and the last 4 weeks as follow-up. Hypothalamic FC was determined using functional magnetic resonance imaging the day before the first psilocybin dose and 1 week after the last dose.ResultsThe treatment was well tolerated. Attack frequency was reduced by mean (standard deviation) 31% (31) from baseline to follow-up (pFWER = 0.008). One patient experienced 21 weeks of complete remission. Changes in hypothalamic-diencephalic FC correlated negatively with a percent change in attack frequency (pFWER = 0.03, R = -0.81), implicating this neural pathway in treatment response.ConclusionOur results indicate that psilocybin may have prophylactic potential and implicates the hypothalamus in possible treatment response. Further clinical studies are warranted.

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title: The safety of supported psilocybin use in Oregon.
authors: Smith WR, Sisti DA, Appelbaum PS.
publication_date: 2023-12-31
doi: 10.1038/s41591-023-02727-4
pubmed_id: 38238619
source_url: https://doi.org/10.1038/s41591-023-02727-4
keywords: Hallucinogens, Oregon, Psilocybin
substance_tags: psilocybin
topic_tags: Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
raw_json:
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title: Psychological Support for Psilocybin Treatment: Reply to Letters on Our Commentary.
authors: Goodwin GM, Malievskaia E, Fonzo GA, Nemeroff CB.
publication_date: 2023-12-31
doi: 10.1176/appi.ajp.20230905
pubmed_id: 38161302
source_url: https://doi.org/10.1176/appi.ajp.20230905
keywords: Humans, Hallucinogens, Counseling, Psilocybin
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
raw_json:
{"europe_pmc_id":"38161302","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin Without Psychotherapy: A Cart Without a Horse?
authors: Earleywine M, De Leo J, Bhayana D, Rajanna B, Scott K.
publication_date: 2023-12-31
doi: 10.1176/appi.ajp.20230572
pubmed_id: 38161299
source_url: https://doi.org/10.1176/appi.ajp.20230572
keywords: Animals, Horses, Humans, Hallucinogens, Psychotherapy, Psilocybin
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
raw_json:
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title: Is Poorly Assisted Psilocybin Treatment an Increasing Risk?
authors: Schenberg EE, King F, da Fonseca JE, Roseman L.
publication_date: 2023-12-31
doi: 10.1176/appi.ajp.20230664
pubmed_id: 38161296
source_url: https://doi.org/10.1176/appi.ajp.20230664
keywords: Humans, Lysergic Acid Diethylamide, Hallucinogens, Psychotherapy, Psilocybin
substance_tags: psilocybin
topic_tags: Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
raw_json:
{"europe_pmc_id":"38161296","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2023-12-31
doi: 10.1176/appi.ajp.20230661
pubmed_id: 38161295
source_url: https://doi.org/10.1176/appi.ajp.20230661
keywords: Humans, Lysergic Acid Diethylamide, Hallucinogens, Psychotherapy, Psilocybin
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Misinterpretations and Omissions: A Critical Response to Goodwin and Colleagues' Commentary on Psilocybin-Assisted Therapy.

authors:
O'Donnell KC, Anderson BT, Barrett FS, Bogenschutz MP, Grob CS, Hendricks PS, Kelmendi B, Nayak SM, Nicholas CR, Paleos CA, Stauffer CS, Gukasyan N.

raw_json:
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authors: Simonsson O, Hendricks PS, Stenfors CU, Goldberg SB, Honk L, Osika W
journal: Journal of psychopharmacology (Oxford, England)
publication_date: 2023-12-31
doi: 10.1177/02698811231218931
pubmed_id: 38140891
source_url: https://pubmed.ncbi.nlm.nih.gov/38140891/
keywords: HPPD, LSD, Psychedelics, mescaline, psilocybin, risks, visual
substance_tags: psilocybin
topic_tags: Case Report,Observational Study,Safety,Drug Interactions
study_type: Case Report
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:37
raw_json: {"pubmed_id":"38140891"}
title:
Longitudinal associations between psychedelic use and unusual visual experiences in the United States and the United Kingdom.

abstract:
Whereas findings from case reports and cross-sectional studies suggest that naturalistic psychedelic use may be associated with unusual visual experiences that occur after the acute pharmacological effects have subsided, such findings need to be replicated in longitudinal studies to better understand potential cause-and-effect relationships.
To investigate longitudinal associations between naturalistic psychedelic use and unusual visual experiences.
Using a longitudinal observational research design with samples representative of the US and UK adult populations with regard to sex, age, and ethnicity ( = 9732), we investigated the relationship between psychedelic use during the 2-month study period and changes in past-week unusual visual experiences.
The follow-up survey was completed by 79% of respondents ( = 7667), with 100 respondents reporting psychedelic use during the 2-month study period (1.3% of those who responded at follow-up). In covariate-adjusted regression models, the results showed that, as hypothesized, psychedelic use during the 2-month study period was associated with greater increases in unusual visual experiences. Notably, there was an interaction between lifetime psychedelic use and psychedelic use during the study period on unusual visual experiences such that those who used psychedelics for the first time reported greater increases in unusual visual experiences.
Psychedelic use may elicit unusual visual experiences that occur after the acute pharmacological effects have subsided, especially among those who have not used psychedelics previously. Future longitudinal studies are warranted to further elucidate these relationships.


title: Is there credible evidence to assert psilocybin-assisted therapy for depression?
authors: Nogueira GN, Vasconcelos MMA, Souza FGM, Bisol LW.
publication_date: 2023-12-19
doi: 10.1016/j.euroneuro.2023.11.003
pubmed_id: 38128153
source_url: https://doi.org/10.1016/j.euroneuro.2023.11.003
keywords: Hallucinogens, Depression, Anxiety, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Anxiety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
raw_json:
{"europe_pmc_id":"38128153","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Borkel LF, Rojas-Hernández J, Henríquez-Hernández LA, Santana Del Pino Á, Quintana-Hernández DJ.
publication_date: 2024-01-28
doi: 10.1080/17512433.2023.2295997
pubmed_id: 38108102
source_url: https://doi.org/10.1080/17512433.2023.2295997
keywords: Humans, Salvia, Substance-Related Disorders, Mescaline, Hallucinogens, Psilocybin
substance_tags: psilocybin
topic_tags: Addiction,Wellbeing,Personality Change,Clinical Trial,Observational Study
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Set and setting predict psychopathology, wellbeing and meaningfulness of psychedelic experiences: a correlational study.

abstract:
BackgroundIn psychedelic therapy, the importance of set and setting is a fundamental but under-researched assumption. The aim of this study is to correlate variables of set (psychedelic use motivation) and setting (psychedelic use location and type of companion) with psychopathology, wellbeing and personality variables.Research design and methodsA sample of 1022 participants of the Spanish-speaking population was collected through an online survey. A novel instrument, the Psychedelic Use Scale (PUS), was developed to measure substance use variables of LSD, mescaline, psilocybin, DMT, 5-Meo-DMT, ketamine, Salvia divinorum, ibogaine and MDMA. Various personality, well-being and psychopathology instruments were implemented to measure outcome variables.ResultsGrowth motivations, natural settings and presence of significant others predicted less psychopathology, greater wellbeing and meaningfulness of psychedelic experiences, whereas problematic motivations predicted greater psychopathology, lower wellbeing and did not predict meaningfulness of psychedelic experiences.ConclusionsBased on these results, we suggest experimental hypotheses for future clinical trials and longitudinal studies with potential clinical implications.

raw_json:
{"europe_pmc_id":"38108102","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: Pharmacological research
publication_date: 2023-12-31
doi: 10.1016/j.phrs.2023.106998
pubmed_id: 38029805
source_url: https://pubmed.ncbi.nlm.nih.gov/38029805/
keywords: Medication Assisted Treatment, Psilocybin, Psychedelics, Substance Use Disorder
substance_tags: psilocybin
topic_tags: Addiction,Review Article
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:37
raw_json: {"pubmed_id":"38029805"}
title:
IUPHAR-review: The integration of classic psychedelics into current substance use disorder treatment models.

authors:
Yaden DB, Berghella AP, Hendricks PS, Yaden ME, Levine M, Rohde JS, Nayak S, Johnson MW, Garcia-Romeu A

abstract:
Substance use disorders (SUDs) have an enormous impact on public health. With classic psychedelic-assisted therapies showing initial promise in treating multiple SUDs, it is possible that these treatments will become legally available options for patients with SUDs in the future. This article highlights how classic psychedelic-assisted therapies might be integrated into current clinical practice. We first describe contemporary evidence-based treatments for SUDs and highlight how classic psychedelic-assisted therapies might fit within each treatment. We suggest that classic psychedelic-assisted therapies can be integrated into most mainstream evidence-based SUD treatments that are currently used in clinical settings, indicating broad compatibility of classic psychedelics with contemporary SUD treatment paradigms.


title: Psychedelia: The interplay of music and psychedelics.
authors: Jerotic K, Vuust P, Kringelbach ML
journal: Annals of the New York Academy of Sciences
publication_date: 2023-12-31
doi: 10.1111/nyas.15082
pubmed_id: 37983198
source_url: https://pubmed.ncbi.nlm.nih.gov/37983198/
keywords: DMT, LSD, ayahuasca, music, psilocybin, psychedelic
substance_tags: psilocybin
topic_tags: Consciousness,Drug Interactions
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:37
raw_json: {"pubmed_id":"37983198"}
abstract:
Music and psychedelics have been intertwined throughout the existence of Homo sapiens, from the early shamanic rituals of the Americas and Africa to the modern use of psychedelic-assisted therapy for a variety of mental health conditions. Across such settings, music has been highly prized for its ability to guide the psychedelic experience. Here, we examine the interplay between music and psychedelics, starting by describing their association with the brain's functional hierarchy that is relied upon for music perception and its psychedelic-induced manipulation, as well as an exploration of the limited research on their mechanistic neural overlap. We explore music's role in Western psychedelic therapy and the use of music in indigenous psychedelic rituals, with a specific focus on ayahuasca and the Santo Daime Church. Furthermore, we explore work relating to the evolution and onset of music and psychedelic use. Finally, we consider music's potential to lead to altered states of consciousness in the absence of psychedelics as well as the development of psychedelic music. Here, we provide an overview of several perspectives on the interaction between psychedelic use and music-a topic with growing interest given increasing excitement relating to the therapeutic efficacy of psychedelic interventions.


title: Drug-drug interactions involving classic psychedelics: A systematic review.
authors: Halman A, Kong G, Sarris J, Perkins D.
publication_date: 2023-11-19
doi: 10.1177/02698811231211219
pubmed_id: 37982394
source_url: https://doi.org/10.1177/02698811231211219
substance_tags: psilocybin
topic_tags: Mechanism of Action,Systematic Review,Review Article,Case Report,Drug Interactions
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
Classic psychedelics, including lysergic acid diethylamide (LSD), psilocybin, mescaline, N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), are potent psychoactive substances that have been studied for their physiological and psychological effects. However, our understanding of the potential interactions and outcomes when using these substances in combination with other drugs is limited. This systematic review aims to provide a comprehensive overview of the current research on drug-drug interactions between classic psychedelics and other drugs in humans. We conducted a thorough literature search using multiple databases, including PubMed, PsycINFO, Web of Science and other sources to supplement our search for relevant studies. A total of 7102 records were screened, and studies involving human data describing potential interactions (as well as the lack thereof) between classic psychedelics and other drugs were included. In total, we identified 52 studies from 36 reports published before September 2, 2023, encompassing 32 studies on LSD, 10 on psilocybin, 4 on mescaline, 3 on DMT, 2 on 5-MeO-DMT and 1 on ayahuasca. These studies provide insights into the interactions between classic psychedelics and a range of drugs, including antidepressants, antipsychotics, anxiolytics, mood stabilisers, recreational drugs and others. The findings revealed various effects when psychedelics were combined with other drugs, including both attenuated and potentiated effects, as well as instances where no changes were observed. Except for a few case reports, no serious adverse drug events were described in the included studies. An in-depth discussion of the results is presented, along with an exploration of the potential molecular pathways that underlie the observed effects.

keywords:
Humans, Lysergic Acid Diethylamide, Hallucinogens, Psychotropic Drugs, Drug Interactions, Psilocybin

raw_json:
{"europe_pmc_id":"37982394","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Hovmand OR, Poulsen ED, Arnfred S.
publication_date: 2023-11-15
doi: 10.1177/02698811231200019
pubmed_id: 37969069
source_url: https://doi.org/10.1177/02698811231200019
substance_tags: psilocybin
topic_tags: Consciousness,Clinical Trial,Review Article
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Assessment of the acute subjective psychedelic experience: A review of patient-reported outcome measures in clinical research on classical psychedelics.

abstract:
BackgroundThe classical psychedelics psilocybin, peyote, ayahuasca/ N, N-dimethyltryptamine, and lysergic acid diethylamide can temporarily produce altered states of consciousness, characterized by changes in sensory perception, thought, mood, and the sense of self-reality and meaning. It is important to have reliable instruments for quantifying these altered states in trials, due to a plausible link between the acute subjective experience and treatment outcome.MethodsWe conducted a review of outcome measures applied in research on classical psychedelics to assess one or more dimensions of the acute subjective psychedelic experience. Three relevant databases were searched electronically. Two reviewers independently conducted article selection and data extraction regarding the instruments, dimensions, geography, population, and psychedelic substance investigated in the included studies. We identified the five most utilized instruments for the most recent 6 years, as well as the five most utilized instruments for each psychedelic.ResultsWe included 93 papers, which reported on 93 unique trials and utilized 17 different rating scales. Of these, the most utilized were the Five-Dimensional Altered States of Consciousness Questionnaire, visual analog or Likert scales specially developed for the trials, the Hallucinogen Rating Scale, the States of Consciousness Questionnaire, and the Abnormer Psychischer Zustand.DiscussionConsiderable variability was found in the instruments utilized in clinical trials on classical psychedelics. We advise and encourage the development of a core outcome set for psychedelic research to enable altered state comparisons across compounds, participants, and settings. We further advise that instruments be designed to assess the "setting" of a psychedelic experience.

keywords:
Humans, N,N-Dimethyltryptamine, Lysergic Acid Diethylamide, Hallucinogens, Psilocybin, Patient Reported Outcome Measures

raw_json:
{"europe_pmc_id":"37969069","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin and Other Classic Psychedelics in Depression.
authors: Nutt DJ, Peill JM, Weiss B, Godfrey K, Carhart-Harris RL, Erritzoe D.
publication_date: 2023-12-31
doi: 10.1007/7854_2023_451
pubmed_id: 37955822
source_url: https://doi.org/10.1007/7854_2023_451
keywords: Brain, Humans, Hallucinogens, Depression, Psilocybin
substance_tags: psilocybin
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Psychedelic drugs such as psilocybin and ketamine are returning to clinical research and intervention across several disorders including the treatment of depression. This chapter focusses on psychedelics that specifically target the 5-HT2A receptor such as psilocybin and DMT. These produce plasma-concentration related psychological effects such as hallucinations and out of body experiences, insightful and emotional breakthroughs as well as mystical-type experiences. When coupled with psychological support, effects can produce a rapid improvement in mood among people with depression that can last for months. In this chapter, we summarise the scientific studies to date that explore the use of psychedelics in depressed individuals, highlighting key clinical, psychological and neuroimaging features of psychedelics that may account for their therapeutic effects. These include alterations in brain entropy that disrupt fixed negative ruminations, a period of post-treatment increased cognitive flexibility, and changes in self-referential psychological processes. Finally, we propose that the brain mechanisms underlying the therapeutic effect of serotonergic psychedelics might be distinct from those underlying classical serotonin reuptake-blocking antidepressants.

topic_tags:
Depression,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Aging,Emotional Processing,Mystical Experience

raw_json:
{"europe_pmc_id":"37955822","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The psychedelic effects of cannabis: A review of the literature.
authors: Wolinsky D, Barrett FS, Vandrey R.
publication_date: 2023-11-09
doi: 10.1177/02698811231209194
pubmed_id: 37947321
source_url: https://doi.org/10.1177/02698811231209194
keywords: Humans, Cannabis, Hallucinogens, Consciousness, Mental Disorders, Psilocybin
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
Cannabis and classic psychedelics are controlled substances with emerging evidence of efficacy in the treatment of a variety of psychiatric illnesses. Cannabis has largely not been regarded as having psychedelic effects in contemporary literature, despite many examples of historical use along with classic psychedelics to attain altered states of consciousness. Research into the "psychedelic" effects of cannabis, and delta-9-tetrahydrocannabinol (THC) in particular, could prove helpful for assessing potential therapeutic indications and elucidating the mechanism of action of both cannabis and classic psychedelics. This review aggregates and evaluates the literature assessing the capacity of cannabis to yield the perceptual changes, aversiveness, and mystical experiences more typically associated with classic psychedelics such as psilocybin. This review also provides a brief contrast of neuroimaging findings associated with the acute effects of cannabis and psychedelics. The available evidence suggests that high-THC cannabis may be able to elicit psychedelic effects, but that these effects may not have been observed in recent controlled research studies due to the doses, set, and settings commonly used. Research is needed to investigate the effects of high doses of THC in the context utilized in therapeutic studies of psychedelics aimed to occasion psychedelic and/or therapeutic experiences. If cannabis can reliably generate psychedelic experiences under these conditions, high-THC dose cannabis treatments should be explored as potential adjunctive treatments for psychiatric disorders and be considered as an active comparator in clinical trials involving traditional psychedelic medications.

topic_tags:
Brain Imaging,Mechanism of Action,Consciousness,Aging,Mystical Experience,Clinical Trial,Review Article

raw_json:
{"europe_pmc_id":"37947321","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Synergistic psychedelic - NMDAR modulator treatment for neuropsychiatric disorders.
authors: Heresco-Levy U, Lerer B.
publication_date: 2023-11-08
doi: 10.1038/s41380-023-02312-8
pubmed_id: 37945694
source_url: https://doi.org/10.1038/s41380-023-02312-8
substance_tags: psilocybin
topic_tags: Depression,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Safety,Drug Interactions
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
Modern research data suggest a therapeutic role for serotonergic psychedelics in depression and other neuropsychiatric disorders, although psychotomimetic effects may limit their widespread utilization. Serotonergic psychedelics enhance neuroplasticity via serotonin 2 A receptors (5HT2AR) activation and complex serotonergic-glutamatergic interactions involving the ionotropic glutamate receptors, tropomyosin receptor kinase B (TrkB) and the mammalian target of rapamycin (mTOR). N-methyl-d-aspartate receptors (NMDAR) channel antagonists, i.e. ketamine, and glycine modulatory site full and partial agonists, i.e., D-serine (DSR) and D-cycloserine (DCS), share some of these mechanisms of action and have neuroplastic and antidepressant effects. Moreover, procognitive effects have been reported for DSR and DCS and 5HT2AR-NMDAR interactions modulate neuronal excitability in prefrontal cortex and represent a target for new antipsychotics. We hypothesize that the synchronous administration of a psychedelic and a NMDAR modulator may increase the therapeutic impact of each of the treatment components and allow for dose adjustments and improved safety. We propose to initially focus research on the acute concurrent administration of psilocybin and DSR or DCS in depression.

keywords:
Animals, Humans, Ketamine, Cycloserine, Receptors, N-Methyl-D-Aspartate, Hallucinogens, Mental Disorders, Neuronal Plasticity, Drug Synergism

raw_json:
{"europe_pmc_id":"37945694","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: When the Trial Ends: The Case for Post-Trial Provisions in Clinical Psychedelic Research.
authors: Jacobs E, Murphy-Beiner A, Rouiller I, Nutt D, Spriggs MJ
journal: Neuroethics
publication_date: 2023-12-31
doi: 10.1007/s12152-023-09536-z
pubmed_id: 37942467
source_url: https://pubmed.ncbi.nlm.nih.gov/37942467/
keywords: Clinical trials, Post-trial access, Psilocybin, Psychedelic, Research ethics
substance_tags: psilocybin
topic_tags: Clinical Trial
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:37
raw_json: {"pubmed_id":"37942467"}
abstract:
The ethical value-and to some scholars, necessity-of providing trial patients with post-trial access (PTA) to an investigational drug has been subject to significant attention in the field of research ethics. Although no consensus has emerged, it seems clear that, in some trial contexts, various factors make PTA particularly appropriate. We outline the atypical aspects of psychedelic clinical trials that support the case for introducing the provision of PTA within research in this field, including the broader legal status of psychedelics, the nature of the researcher-therapist/participant relationship, and the extended time-frame of the full therapeutic process. As is increasingly understood, the efficacy of psychedelic-assisted psychotherapy is driven as much by extrapharmacological elements and the cultural therapeutic container as by the drug itself. As such, we also advocate for a refocusing of attention from post-trial access to a broader concept encompassing other elements of post-trial care. We provide an overview of some of the potential post-trial care provisions that may be appropriate in psychedelic clinical trials. Although the World Medical Association's Declaration of Helsinki calls on researchers, sponsors, and governments to make provisions for post-trial access, such provision may feel impracticable or out-of-reach within psychedelic trials that are already constrained by a high resource demand and significant bureaucratic burden. We show how conceiving of post-trial provision as an integral site of the research process, and an appropriate destination for research funding, will serve to develop the infrastructure necessary for the post-legalisation psychedelic medicine ecosystem.


authors: Stocker K, Hartmann M, Ley L, Becker AM, Holze F, Liechti ME.
publication_date: 2023-10-30
doi: 10.1177/02698811231199112
pubmed_id: 37905369
source_url: https://doi.org/10.1177/02698811231199112
substance_tags: psilocybin
topic_tags: Consciousness,Mystical Experience,Healthy Volunteers
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
title:
The revival of the psychedelic experience scale: Revealing its extended-mystical, visual, and distressing experiential spectrum with LSD and psilocybin studies.

abstract:
BackgroundResearch with the Psychedelic Experience Questionnaire/Scale (PES) focuses on questions relating to mystical experience (Mystical Experience Questionnaire (MEQ)). The psychometric potential of the non-MEQ items of the PES remains largely unexplored.AimsWe investigated whether the PES also yields subscales besides the MEQ30 subscales.MethodsData from 239 PES measurements (140 healthy participants) from six studies with moderate to high doses of lysergic acid diethylamide and/or psilocybin were included. New subscales (with items other than MEQ30) were created and validated as follows: (1) theoretical derivation of candidate items; (2) removal of items with rare experiences; (3) exploratory factor analysis; and (4) confirmatory factor analysis. Correlations of subscales within the PES and between the PES and the 5-Dimensional Altered States of Consciousness Scale (5D-ASC) were performed. In addition, a cluster analysis using all items (except rare experiences) was performed.ResultsThe reliability of the four original factors of the MEQ30 was confirmed and four additional factors for the non-MEQ items were revealed: paradoxicality, connectedness, visual experience, and distressing experience. The first two additional factors were strongly correlated with the MEQ30 mystical subscale. Adding the new subscales to the MEQ30 subscales increased the explained variance with the 5D-ASC. The cluster analysis confirmed our main results and provided additional insights for future psychedelic psychometrics.ConclusionThe study yields a new validated 6-factor structure for extended mystical experience (MEQ40: MEQ30 + Paradoxicality + Connectedness) and covers psychedelic experience as a whole more comprehensively than has hitherto been possible within a single questionnaire (PES48). The entire PES (PES100) can also be used for further future psychedelic-psychometric research.

keywords:
Humans, Lysergic Acid Diethylamide, Hallucinogens, Reproducibility of Results, Consciousness, Mysticism, Psilocybin

raw_json:
{"europe_pmc_id":"37905369","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Potential Benefits of Psilocybin for Lupus Pain: A Case Report.
authors: Gonzales SAB, Alexopoulos C, Arkfeld DG.
publication_date: 2023-12-31
doi: 10.2174/1573397119666230904150750
pubmed_id: 37670693
source_url: https://doi.org/10.2174/1573397119666230904150750
substance_tags: psilocybin
study_type: Case Report
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
IntroductionOutcomes of treatment for patients with Lupus have shown overall improvement and benefit from the more aggressive use of immunosuppressants and biological agents through a treat-to-target approach. However, chronic musculoskeletal pain can be refractory to treatment despite the use of non-steroidal anti-inflammatory drugs, corticosteroids, and other analgesic agents, leading to patient dissatisfaction. The concept of new neural pathways from psilocybin usage has been proposed in a variety of pain syndromes; however, it is not trialed for patients with Lupus pain.Case presentationThe patient was a 67-year-old male with positive anti-dsDNA antibody Lupus with a predominance of chronic polyarticular joint pain treated with hydroxychloroquine and non-steroidal anti-inflammatory drugs without pain relief. Pain dramatically improved after a one-time macro-dosing of 6 grams of Psilocybin cubensis in Oregon, which he expected would only provide a sense of enlightenment. After 12 months, he continued without debilitating joint pain.ConclusionThe serotonin-2A receptor's activation triggers an array of neurophysiological reactions that disrupt the functional connections in areas of the brain that are associated with chronic pain. These neuroplastic effects can generate healthy connections, resulting in long-lasting pain relief. However, this is a process that has not been fully analyzed. While there is anecdotal evidence to suggest the therapeutic benefits for autoimmune diseases, including rheumatoid arthritis and psoriasis, there is no specific research that explores its use for lupus-related pain. Since this is the first case that shows the benefit of psilocybin in a patient with Lupus, further studies on macro-dosing psilocybin to treat Lupus pain are warranted.

keywords:
Humans, Arthralgia, Pain, Lupus Erythematosus, Systemic, Anti-Inflammatory Agents, Non-Steroidal, Antibodies, Antinuclear, Treatment Outcome, Aged, Male, Psilocybin

topic_tags:
Chronic Pain,Mechanism of Action,Receptor Pharmacology,Biological Age,Case Report,Inflammation,Immune Function

raw_json:
{"europe_pmc_id":"37670693","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Potential analgesic effects of psychedelics on select chronic pain conditions: A survey study.
authors: Cavarra M, Mason NL, Kuypers KPC, Bonnelle V, Smith WJ, Feilding A, Kryskow P, Ramaekers JG.
publication_date: 2023-08-19
doi: 10.1002/ejp.2171
pubmed_id: 37599279
source_url: https://doi.org/10.1002/ejp.2171
substance_tags: psilocybin
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
BackgroundChronic pain is a major cause of suffering and disability and is often associated with psychiatric complications. Current treatments carry the risk of severe side effects and may lead to limited or no relief at all in a relevant portion of this patient population. Preliminary evidence suggests that classical psychedelics (e.g. LSD and psilocybin) may have analgesic effects in healthy volunteers, and in certain chronic pain conditions and observational studies reveal that they are used in naturalistic settings as a means to manage pain.MethodsIn order to gain insight on the effectiveness of such compounds in chronic pain conditions, we set up a survey addressed to chronic pain patients inquiring about psychedelic use and the relief levels achieved with both conventional treatments, full psychedelic doses and microdoses. We analysed data related to five conditions selected based on diagnostic homogeneity within each of them: fibromyalgia, arthritis, migraine, tension-type headache and sciatica.ResultsExcept for sciatica, volunteers reported that psychedelics led to better pain relief compared to conventional medication in all examined conditions. More specifically, full doses performed better than conventional medication. Microdoses led to significantly better relief compared to conventional medication in migraines and achieved comparable relief in the remaining three categories. Implications for future research are discussed.ConclusionsFull doses and microdoses may hold value in the treatment of some specific chronic pain conditions.SignificancePsychedelic substances are receiving increasing attention from the scientific literature because of evidence showing beneficial effects on several measures related to mental health in clinical samples and healthy volunteers samples. Previous evidence suggests that people suffering from chronic pain are using psychedelics to seek relief and the present paper presents the results of a survey study investigating their use and analgesic effects among individuals suffering from fibromyalgia, arthritis, migraine, tension-type headache and sciatica.

keywords:
Humans, Arthritis, Fibromyalgia, Sciatica, Chronic Disease, Analgesics, Hallucinogens, Migraine Disorders, Tension-Type Headache, Chronic Pain

topic_tags:
Chronic Pain,Headache / Migraine,Microdosing,Observational Study,Healthy Volunteers,Safety,Adverse Events

raw_json:
{"europe_pmc_id":"37599279","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2023-07-18
doi: 10.1017/s0033291723002039
pubmed_id: 37466289
source_url: https://doi.org/10.1017/s0033291723002039
substance_tags: psilocybin
topic_tags: Depression,Personality Change
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Personality Change in a Trial of Psilocybin Therapy vs Escitalopram Treatment for Depression - CORRIGENDUM.

authors:
Weiss B, Ginige I, Shannon L, Giribaldi B, Murphy-Beiner A, Murphy R, Baker-Jones M, Martell J, Nutt DJ, Carhart-Harris RL, Erritzoe D.

keywords:
Humans, Citalopram, Hallucinogens, Depression, Personality, Personality Disorders, Psilocybin, Escitalopram

raw_json:
{"europe_pmc_id":"37466289","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Must Psilocybin Always "Assist Psychotherapy"?
authors: Goodwin GM, Malievskaia E, Fonzo GA, Nemeroff CB.
publication_date: 2023-07-11
doi: 10.1176/appi.ajp.20221043
pubmed_id: 37434509
source_url: https://doi.org/10.1176/appi.ajp.20221043
keywords: Humans, Hallucinogens, Psychotherapy, Psilocybin
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
raw_json:
{"europe_pmc_id":"37434509","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Personality change in a trial of psilocybin therapy v. escitalopram treatment for depression.
publication_date: 2023-06-01
doi: 10.1017/s0033291723001514
pubmed_id: 37264814
source_url: https://doi.org/10.1017/s0033291723001514
keywords: Humans, Depression, Personality, Psilocybin, Neuroticism, Escitalopram, Major Depressive Disorder
substance_tags: psilocybin
topic_tags: Depression,Personality Change,Clinical Trial
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
authors:
Weiss B, Ginige I, Shannon L, Giribaldi B, Murphy-Beiner A, Murphy R, Baker-Jones M, Martell J, Nutt DJ, Carhart-Harris RL, Erritzoe D.

abstract:
BackgroundPsilocybin Therapy (PT) is being increasingly studied as a psychiatric intervention. Personality relates to mental health and can be used to probe the nature of PT's therapeutic action.MethodsIn a phase 2, double-blind, randomized, active comparator controlled trial involving patients with moderate-to-severe major depressive disorder, we compared psilocybin with escitalopram, over a core 6-week trial period. Five-Factor model personality domains, Big Five Aspect Scale Openness aspects, Absorption, and Impulsivity were measured at Baseline, Week 6, and Month 6 follow-up.ResultsPT was associated with decreases in neuroticism (B = -0.63), introversion (B = -0.38), disagreeableness (B = -0.47), impulsivity (B = -0.40), and increases in absorption (B = 0.32), conscientiousness (B = 0.30), and openness (B = 0.23) at week 6, with neuroticism (B = -0.47) and disagreeableness (B = -0.41) remaining decreased at month 6. Escitalopram Treatment (ET) was associated with decreases in neuroticism (B = -0.38), disagreeableness (B = -0.26), impulsivity (B = -0.35), and increases in openness (B = 0.28) at week 6, with neuroticism (B = -0.46) remaining decreased at month 6. No significant between-condition differences were observed.ConclusionsPersonality changes across both conditions were in a direction consistent with improved mental health. With the possible exception of trait absorption, there were no compelling between-condition differences warranting conclusions regarding a selective action of PT (v. ET) on personality; however, post-ET changes in personality were significantly moderated by pre-trial positive expectancy for escitalopram, whereas expectancy did not moderate response to PT.

raw_json:
{"europe_pmc_id":"37264814","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Koning E, Brietzke E.
publication_date: 2023-06-05
doi: 10.47626/2237-6089-2022-0597
pubmed_id: 37126863
source_url: https://doi.org/10.47626/2237-6089-2022-0597
substance_tags: psilocybin
topic_tags: Eating Disorders,Emotional Processing,Clinical Trial,Review Article
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Psilocybin-assisted psychotherapy as a potential treatment for eating disorders: a narrative review of preliminary evidence.

abstract:
Eating disorders (ED) are a group of potentially severe mental disorders characterized by abnormal energy balance, cognitive dysfunction, and emotional distress. Cognitive inflexibility is a major challenge to successful ED treatment and dysregulated serotonergic function has been implicated in this symptomatic dimension. Moreover, there are few effective treatment options and long-term remission of ED symptoms is difficult to achieve. There is emerging evidence for the use of psychedelic-assisted psychotherapy (PAP) for a range of mental disorders. Psilocybin is a serotonergic psychedelic that has demonstrated therapeutic benefit in a variety of psychiatric illnesses characterized by rigid thought patterns and treatment resistance. The current paper presents a narrative review of the hypothesis that psilocybin may be an effective adjunctive treatment for individuals with EDs, based on biological plausibility, transdiagnostic evidence, and preliminary results. Limitations of the PAP model and proposed future directions for its application to eating behavior are also discussed. Although the literature to date is not sufficient to propose the incorporation of psilocybin in the treatment of disordered eating behaviors, preliminary evidence supports the need for more rigorous clinical trials as an important avenue for future investigation.

keywords:
Humans, Hallucinogens, Combined Modality Therapy, Psychotherapy, Feeding and Eating Disorders, Psilocybin

raw_json:
{"europe_pmc_id":"37126863","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Menstrual Changes and Reversal of Amenorrhea Induced by Classic Psychedelics: A Case Series.
authors: Gukasyan N, Narayan SK
journal: Journal of psychoactive drugs
publication_date: 2023-12-31
doi: 10.1080/02791072.2022.2157350
pubmed_id: 36682064
source_url: https://pubmed.ncbi.nlm.nih.gov/36682064/
substance_tags: psilocybin
topic_tags: Mechanism of Action,Receptor Pharmacology,Case Report
study_type: Case Report
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:37
raw_json: {"pubmed_id":"36682064"}
abstract:
There has been little research on the effects of psychedelics on menstrual and reproductive function, though anecdotal evidence suggests that these compounds may have striking effects on menstrual function in at least a subset of users. Social media and word of mouth were used to seek out individuals who had a history of changes in menstrual function following psychedelic use. Case histories were elicited from three respondents following informed consent. A literature search on the effects of classic psychedelics and related compounds was completed. Three women ranging from 27 to 34 years of age were interviewed and reported three distinct phenomena following the use of classic psychedelics: 1) resumption of menses following amenorrhea, 2) early onset of menses, in particular when psychedelics were used in the mid to late luteal period, and 3) improved menstrual regularity in a woman with irregular cycles who was eventually diagnosed with polycystic ovarian syndrome. The mechanisms behind these effects remain unclear, though they may be mediated via direct or indirect effects of 5-HT agonism on the hypothalamic-pituitary-gonadal axis. Although phenomena related to menstrual and reproductive function have been largely overlooked in the psychedelic literature to date, these effects may have therapeutic utility and warrant further study.

keywords:
LSD, menstruation, psilocybin, psychedelics, psychoneuroendocrinology, reproductive health, serotonin


title: Educational Materials and Image Induction Increase Treatment Credibility.
authors: Low F, Earleywine M.
publication_date: 2023-01-21
doi: 10.1080/02791072.2022.2154722
pubmed_id: 36682063
source_url: https://doi.org/10.1080/02791072.2022.2154722
substance_tags: psilocybin
topic_tags: Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
Patient-perceived treatment credibility is linked to important outcome measures including symptom reduction, therapeutic alliance, patient satisfaction, and attrition rates. However, few studies have tested strategies to enhance treatment credibility. The present study investigates the effect of brief, written educational materials and the use of an image induction prime on perceptions of credibility for cognitive behavioral therapy and psilocybin-assisted therapy for depression. Participants (N = 493) rated the perceived credibility of depression treatments before and after reading brief educational materials. Half of the participants were asked an image induction question containing the construct of open-mindedness. Results indicate that brief educational materials of about 300 words significantly increased perceived treatment credibility for both therapies, with a large effect size (Cohen's d =.91). The use of an image induction prime further increased perceived credibility for psilocybin-assisted therapy for depression (Cohen's d =.38). These strategies offer an efficient and cost-effective way to enhance treatment credibility. Future studies testing variations of the image induction prime might prove fruitful for optimizing the technique.

keywords:
Humans, Treatment Outcome, Patient Satisfaction, Psilocybin, Cognitive Behavioral Therapy, Outcome Assessment, Health Care

raw_json:
{"europe_pmc_id":"36682063","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Madrid-Gambin F, Fabregat-Safont D, Gomez-Gomez A, Olesti E, Mason NL, Ramaekers JG, Pozo OJ.
publication_date: 2023-11-06
doi: 10.1016/j.biopha.2023.115775
pubmed_id: 37944438
source_url: https://doi.org/10.1016/j.biopha.2023.115775
substance_tags: psilocybin
topic_tags: Pharmacology,Mechanism of Action,Consciousness,Review Article,Drug Interactions,Metabolomics
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Present and future of metabolic and metabolomics studies focused on classical psychedelics in humans.

abstract:
Psychedelics are classical hallucinogen drugs that induce a marked altered state of consciousness. In recent years, there has been renewed attention to the possible use of classical psychedelics for the treatment of certain mental health disorders. However, further investigation to better understand their biological effects in humans, their mechanism of action, and their metabolism in humans is needed when considering the development of future novel therapeutic approaches. Both metabolic and metabolomics studies may help for these purposes. On one hand, metabolic studies aim to determine the main metabolites of the drug. On the other hand, the application of metabolomics in human psychedelics studies can help to further understand the biological processes underlying the psychedelic state and the mechanisms of action underlying their therapeutic potential. This review presents the state of the art of metabolic and metabolomic studies after lysergic acid diethylamide (LSD), mescaline, N,N-dimethyltryptamine (DMT) and β-carboline alkaloids (ayahuasca brew), 5-methoxy-DMT and psilocybin administrations in humans. We first describe the characteristics of the published research. Afterward, we reviewed the main results obtained by both metabolic and metabolomics (if available) studies in classical psychedelics and we found out that metabolic and metabolomics studies in psychedelics progress at two different speeds. Thus, whereas the main metabolites for classical psychedelics have been robustly established, the main metabolic alterations induced by psychedelics need to be explored. The integration of metabolomics and pharmacokinetics for investigating the molecular interaction between psychedelics and multiple targets may open new avenues in understanding the therapeutic role of psychedelics.

keywords:
Humans, N,N-Dimethyltryptamine, Lysergic Acid Diethylamide, Hallucinogens, Mental Disorders, Psilocybin

raw_json:
{"europe_pmc_id":"37944438","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Danias G, Appel J.
publication_date: 2023-12-28
doi: 10.2196/43850
pubmed_id: 38064635
source_url: https://doi.org/10.2196/43850
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Addiction
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Public Interest in Psilocybin and Psychedelic Therapy in the Context of the COVID-19 Pandemic: Google Trends Analysis.

abstract:
BackgroundPsychedelic substances have demonstrated promise in the treatment of depression, anxiety, and substance use disorders. Significant media coverage has been dedicated to psychedelic medicine, but it is unclear whether the public associates psilocybin with its potential therapeutic benefits. The COVID-19 pandemic led to an increase in depression, anxiety, and substance abuse in the general population.ObjectiveThis study attempts to link increases in interest in these disorders with increases in interest in psilocybin using Google Trends.MethodsWeekly interest-over-time Google Trends data for 4 years, from the week of March 11, 2018, to the week of March 6, 2022, were obtained for the following terms: "psilocybin," "psychedelic therapy," "cannabis," "cocaine," "antidepressant," "depression," "anxiety," and "addiction." Important psilocybin-related news and the declaration of the pandemic were noted. Trends data for each of the queried terms were plotted, and multiple regression analysis was performed to determine the slope of the prepandemic and postpandemic data with 95% CIs. Nonparametric Tau-U analysis was performed correcting for baseline trends. Results from this test were used to make inferences about the pre- and postpandemic trends and inferences about the change in overall level of searches between the 2 groups.ResultsTau values for prepandemic data were significant for stable trends, all ranging -0.4 to 0.4. Tau values for postpandemic data showed positive trends for "psilocybin," "psychedelic therapy," and "antidepressant." All other trends remained stable in the range of -0.4 to 0.4. When comparing Tau values for pre- and postpandemic data, overall increases in relative search volume (RSV) were seen for "psilocybin," "psychedelic therapy," and "anxiety," and overall decreases in RSV were seen for "depression," "addiction," and "cocaine." Overall RSVs for "cannabis" and "antidepressant" remained stable as Tau values ranged between -0.4 and 0.4. In the immediate aftermath of the declaration of the pandemic, drop-offs in interest were seen for all terms except for "anxiety" and "cannabis." After the initial shock of a global pandemic, "psilocybin" and "psychedelic therapy" groups demonstrated increases in interest trends and overall RSV.ConclusionsThese data suggest that overall interest in "psilocybin" and "psychedelic therapy" increased at higher rates and to higher levels after than before the declaration of the pandemic. This is consistent with our hypothesis that interest increased for these treatments after the pandemic as incidence of depression, anxiety, and addiction increased. However, there may be other drivers of interest for these topics, since interest in antidepressants-the typical pharmacologic treatments for depression and anxiety-followed the expected pattern of drop-off and accelerated interest back to prepandemic levels. Interest in "psilocybin" and "psychedelic therapy" may have also been partially driven by popular culture hype and novelty, explaining why interest increased at a higher rate post pandemic and continued to grow, surpassing prior interest.

raw_json:
{"europe_pmc_id":"38064635","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Molecular and Medical Aspects of Psychedelics.
authors: Wojtas A, Gołembiowska K.
publication_date: 2023-12-22
doi: 10.3390/ijms25010241
pubmed_id: 38203411
source_url: https://doi.org/10.3390/ijms25010241
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
abstract:
Psychedelics belong to the oldest psychoactive drugs. They arouse recent interest due to their therapeutic applications in the treatment of major depressive disorder, substance use disorder, end-of-life anxiety,= and anxiety symptoms, and obsessive-compulsive disorder. In this review, the current state of preclinical research on the mechanism of action, neurotoxicity, and behavioral impact of psychedelics is summarized. The effect of selective 5-HT2A receptor agonists, 25I- and 25B-NBOMe, after acute and repeated administration is characterized and compared with the effects of a less selective drug, psilocybin. The data show a significant effect of NBOMes on glutamatergic, dopaminergic, serotonergic, and cholinergic neurotransmission in the frontal cortex, striatum, and nucleus accumbens. The increases in extracellular levels of neurotransmitters were not dose-dependent, which most likely resulted from the stimulation of the 5-HT2A receptor and subsequent activation of the 5-HT2C receptors. This effect was also observed in the wet dog shake test and locomotor activity. Chronic administration of NBOMes elicited rapid development of tolerance, genotoxicity, and activation of microglia. Acute treatment with psilocybin affected monoaminergic and aminoacidic neurotransmitters in the frontal cortex, nucleus accumbens, and hippocampus but not in the amygdala. Psilocybin exhibited anxiolytic properties resulting from intensification of GABAergic neurotransmission. The data indicate that NBOMes as selective 5-HT2A agonists exert a significant effect on neurotransmission and behavior of rats while also inducing oxidative DNA damage. In contrast to NBOMes, the effects induced by psilocybin suggest a broader therapeutic index of this drug.

keywords:
Animals, Rats, Receptor, Serotonin, 5-HT2A, Neurotransmitter Agents, Hallucinogens, Psilocybin, Major Depressive Disorder

topic_tags:
Depression,Anxiety,Addiction,OCD,End-of-Life Distress,Mechanism of Action,Receptor Pharmacology,Review Article,Animal Study,Toxicity

raw_json:
{"europe_pmc_id":"38203411","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Wojtas A, Bysiek A, Wawrzczak-Bargiela A, Maćkowiak M, Gołembiowska K.
publication_date: 2023-12-19
doi: 10.3390/ijms25010100
pubmed_id: 38203271
source_url: https://doi.org/10.3390/ijms25010100
keywords: Limbic System, Animals, Humans, Rats, Ketamine, Glutamic Acid, Antidepressive Agents, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Receptor Pharmacology
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
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:
The pathophysiology of depression is related to the reduced volume of the hippocampus and amygdala and hypertrophy of the nucleus accumbens. The mechanism of these changes is not well understood; however, clinical studies have shown that the administration of the fast-acting antidepressant ketamine reversed the decrease in hippocampus and amygdala volume in depressed patients, and the magnitude of this effect correlated with the reduction in 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 were observed as a long-lasting effect. A marked anxiolytic effect of psilocybin in the acute phase and 24 h post-treatment was shown in the open field test. These data provide the neurobiological background for psilocybin's effect on stress, anxiety and structural changes in the limbic system and translate into the antidepressant effect of psilocybin in depressed patients.

raw_json:
{"europe_pmc_id":"38203271","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin facilitates fear extinction in mice by promoting hippocampal neuroplasticity.
authors: Du Y, Li Y, Zhao X, Yao Y, Wang B, Zhang L, Wang G.
publication_date: 2023-03-29
doi: 10.1097/cm9.0000000000002647
pubmed_id: 37000971
source_url: https://doi.org/10.1097/cm9.0000000000002647
substance_tags: psilocybin
topic_tags: Depression,PTSD,Neuroplasticity,Neurogenesis,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
BackgroundPosttraumatic stress disorder (PTSD) and depression are highly comorbid. Psilocybin exerts substantial therapeutic effects on depression by promoting neuroplasticity. Fear extinction is a key process in the mechanism of first-line exposure-based therapies for PTSD. We hypothesized that psilocybin would facilitate fear extinction by promoting hippocampal neuroplasticity.MethodsFirst, we assessed the effects of psilocybin on percentage of freezing time in an auditory cued fear conditioning (FC) and fear extinction paradigm in mice. Psilocybin was administered 30 min before extinction training. Fear extinction testing was performed on the first day; fear extinction retrieval and fear renewal were tested on the sixth and seventh days, respectively. Furthermore, we verified the effect of psilocybin on hippocampal neuroplasticity using Golgi staining for the dendritic complexity and spine density, Western blotting for the protein levels of brain derived neurotrophic factor (BDNF) and mechanistic target of rapamycin (mTOR), and immunofluorescence staining for the numbers of doublecortin (DCX)- and bromodeoxyuridine (BrdU)-positive cells.ResultsA single dose of psilocybin (2.5 mg/kg, i.p.) reduced the increase in the percentage of freezing time induced by FC at 24 h, 6th day and 7th day after administration. In terms of structural neuroplasticity, psilocybin rescued the decrease in hippocampal dendritic complexity and spine density induced by FC; in terms of neuroplasticity related proteins, psilocybin rescued the decrease in the protein levels of hippocampal BDNF and mTOR induced by FC; in terms of neurogenesis, psilocybin rescued the decrease in the numbers of DCX- and BrdU-positive cells in the hippocampal dentate gyrus induced by FC.ConclusionsA single dose of psilocybin facilitated rapid and sustained fear extinction; this effect might be partially mediated by the promotion of hippocampal neuroplasticity. This study indicates that psilocybin may be a useful adjunct to exposure-based therapies for PTSD and other mental disorders characterized by failure of fear extinction.

keywords:
Hippocampus, Animals, Humans, Mice, Brain-Derived Neurotrophic Factor, Bromodeoxyuridine, Fear, Neuronal Plasticity, Extinction, Psychological, TOR Serine-Threonine Kinases, Psilocybin

raw_json:
{"europe_pmc_id":"37000971","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Intravenous psilocybin attenuates mechanical hypersensitivity in a rat model of chronic pain.
authors: Kolbman N, Liu T, Guzzo P, Gilligan J, Mashour GA, Vanini G, Pal D.
publication_date: 2023-11-30
doi: 10.1016/j.cub.2023.10.016
pubmed_id: 38113836
source_url: https://doi.org/10.1016/j.cub.2023.10.016
substance_tags: psilocybin
topic_tags: Depression,Addiction,Chronic Pain,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
There is a renewed interest in psychedelic drugs as potential therapeutic agents for the treatment of psychiatric disorders. In particular, psilocybin has shown promise for the treatment of refractory depression1 and major depressive disorder2, and has also been explored as a treatment for tobacco and alcohol abuse3,4. However, despite suggestive evidence5,6, there has been no systematic study to investigate the effectiveness of psilocybin in attenuating indices of chronic pain. To address this gap, we investigated the effect of psilocybin on mechanical hypersensitivity and thermal hyperalgesia in a well-established rat model of formalin-induced, centralized chronic pain7,8 and demonstrate that a single intravenous bolus administration of psilocybin can attenuate mechanical hypersensitivity for 28 days.

keywords:
Animals, Humans, Rats, Formaldehyde, Hallucinogens, Chronic Pain, Psilocybin, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"38113836","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin and Eugenol Reduce Inflammation in Human 3D EpiIntestinal Tissue.
authors: Robinson GI, Li D, Wang B, Rahman T, Gerasymchuk M, Hudson D, Kovalchuk O, Kovalchuk I.
publication_date: 2023-12-14
doi: 10.3390/life13122345
pubmed_id: 38137946
source_url: https://doi.org/10.3390/life13122345
substance_tags: psilocybin
topic_tags: Mechanism of Action,Receptor Pharmacology,Biomarkers,Inflammation,Immune Function
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Inflammation plays a pivotal role in the development and progression of inflammatory bowel disease (IBD), by contributing to tissue damage and exacerbating the immune response. The investigation of serotonin receptor 2A (5-HT2A) ligands and transient receptor potential (TRP) channel ligands is of significant interest due to their potential to modulate key inflammatory pathways, mitigate the pathological effects of inflammation, and offer new avenues for therapeutic interventions in IBD. This study investigates the anti-inflammatory effects of 5-HT2A ligands, including psilocybin, 4-AcO-DMT, and ketanserin, in combination with TRP channel ligands, including capsaicin, curcumin, and eugenol, on the inflammatory response induced by tumor necrosis factor (TNF)-α and interferon (IFN)-γ in human 3D EpiIntestinal tissue. Enzyme-linked immunosorbent assay was used to assess the expression of pro-inflammatory markers TNF-α, IFN-γ, IL-6, IL-8, MCP-1, and GM-CSF. Our results show that psilocybin, 4-AcO-DMT, and eugenol significantly reduce TNF-α and IFN-γ levels, while capsaicin and curcumin decrease these markers to a lesser extent. Psilocybin effectively lowers IL-6 and IL-8 levels, but curcumin, capsaicin, and 4-AcO-DMT have limited effects on these markers. In addition, psilocybin can significantly decrease MCP-1 and GM-CSF levels. While ketanserin lowers IL-6 and GM-CSF levels, there are no effects seen on TNF-α, IFN-γ, IL-8, or MCP-1. Although synergistic effects between 5-HT2A and TRP channel ligands are minimal in this study, the results provide further evidence of the anti-inflammatory effects of psilocybin and eugenol. Further research is needed to understand the mechanisms of action and the feasibility of using these compounds as anti-inflammatory therapies for conditions like IBD.

raw_json:
{"europe_pmc_id":"38137946","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin-induced default mode network hypoconnectivity is blunted in alcohol-dependent rats.
authors: Reinwald JR, Schmitz CN, Skorodumov I, Kuchar M, Weber-Fahr W, Spanagel R, Meinhardt MW.
publication_date: 2023-12-13
doi: 10.1038/s41398-023-02690-1
pubmed_id: 38097569
source_url: https://doi.org/10.1038/s41398-023-02690-1
substance_tags: psilocybin
topic_tags: Addiction,Brain Imaging,Default Mode Network,Aging,Clinical Trial,Animal Study
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Alcohol Use Disorder (AUD) adversely affects the lives of millions of people, but still lacks effective treatment options. Recent advancements in psychedelic research suggest psilocybin to be potentially efficacious for AUD. However, major knowledge gaps remain regarding (1) psilocybin's general mode of action and (2) AUD-specific alterations of responsivity to psilocybin treatment in the brain that are crucial for treatment development. Here, we conducted a randomized, placebo-controlled crossover pharmaco-fMRI study on psilocybin effects using a translational approach with healthy rats and a rat model of alcohol relapse. Psilocybin effects were quantified with resting-state functional connectivity using data-driven whole-brain global brain connectivity, network-based statistics, graph theory, hypothesis-driven Default Mode Network (DMN)-specific connectivity, and entropy analyses. Results demonstrate that psilocybin induced an acute wide-spread decrease in different functional connectivity domains together with a distinct increase of connectivity between serotonergic core regions and cortical areas. We could further provide translational evidence for psilocybin-induced DMN hypoconnectivity reported in humans. Psilocybin showed an AUD-specific blunting of DMN hypoconnectivity, which strongly correlated to the alcohol relapse intensity and was mainly driven by medial prefrontal regions. In conclusion, our results provide translational validity for acute psilocybin-induced neural effects in the rodent brain. Furthermore, alcohol relapse severity was negatively correlated with neural responsivity to psilocybin treatment. Our data suggest that a clinical standard dose of psilocybin may not be sufficient to treat severe AUD cases; a finding that should be considered for future clinical trials.

keywords:
Brain, Animals, Humans, Rats, Alcoholism, Recurrence, Ethanol, Hallucinogens, Magnetic Resonance Imaging, Psilocybin, Default Mode Network

raw_json:
{"europe_pmc_id":"38097569","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Nicholas CR, Horton DM, Malicki J, Baltes A, Hutson PR, Brown RT.
publication_date: 2023-12-12
doi: 10.1089/psymed.2023.0012
pubmed_id: 40046866
source_url: https://doi.org/10.1089/psymed.2023.0012
substance_tags: psilocybin
topic_tags: Addiction,Safety,Adverse Events,Drug Interactions
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Psilocybin for Opioid Use Disorder in Two Adults Stabilized on Buprenorphine: A Technical Report on Study Modifications and Preliminary Findings.

abstract:
BackgroundPsilocybin has demonstrated promising clinical outcomes for nicotine and alcohol use disorders, yet its potential clinical utility in the treatment of opioid use disorder (OUD) remains unreported in modern literature. This technical report presents methodological considerations and preliminary data from a safety-feasibility trial examining the interaction between psilocybin and buprenorphine in two adults diagnosed with OUD.ProceduresTwo adults meeting eligibility criteria for long-term stabilization of buprenorphine/naloxone (≥6 months) enrolled and underwent two psilocybin dosing sessions in a supportive setting. Preliminary data pertaining to the safety, clinical outcomes, and subjective effects of psilocybin were collected.Main findingsTwo participants received psilocybin and completed all study visits. Feasibility considerations were identified, including limitations in provider-based recruitment strategies, participant accessibility, flexibility of the study schedule, and initial eligibility criteria. There were no serious adverse events or significant baseline changes on measures of opioid craving or withdrawal, and the subjective effects associated with psilocybin were consistent with previous studies.Principal conclusionsCoadministration of psilocybin and buprenorphine was safely tolerated and did not demonstrate contraindicating effects vis-à-vis effectiveness of buprenorphine or the subjective effects of psilocybin. Challenges in feasibility led to modifications in the sample population and eligibility criteria and strategies to improve accessibility, minimize burden, and enhance overall generalizability.clinicaltrials.gov ID: NCT05242029.

raw_json:
{"europe_pmc_id":"40046866","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Brennan W, Kelman AR, Belser AB.
publication_date: 2023-12-12
doi: 10.1089/psymed.2023.0007
pubmed_id: 40046864
source_url: https://doi.org/10.1089/psymed.2023.0007
substance_tags: psilocybin
topic_tags: Clinical Trial,Systematic Review,Review Article,Safety
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
A Systematic Review of Reporting Practices in Psychedelic Clinical Trials: Psychological Support, Therapy, and Psychosocial Interventions.

abstract:
BackgroundPsychedelic-assisted therapy has gained significant attention in recent years. However, there is a lack of empirical clarity on the role of psychosocial interventions (PIs) in clinical trials of psychedelic treatment due in part to deficiencies in reporting practices found in the existing literature. These PI include non-drug support or interventions provided by psychotherapists or facilitators during all phases of treatment, sometimes called "psychological support," "monitoring," "psychedelic-assisted therapy," or "psychedelic-assisted psychotherapy." A brief review of recent research, historical studies, safety considerations, and participant perspectives suggests that PI has a substantive and critical impact on treatment outcomes.MethodsThis systematic review examines the reporting practices on PI in published clinical trial results. The review employs a search of PubMed/Medline and PSYCinfo databases to identify relevant articles. It includes quantitative clinical studies treating patients with psychiatric indications using classic psychedelics (psilocybin, LSD, DMT, ayahuasca) or empathogenic drugs (MDMA) since 2000. The analytic approach follows a modified version of assessment items based on CONSORT extension statement and TIDieR checklist.ResultsThirty-three published psychedelic clinical trials met criteria. The review reveals that many published reports on psychedelic clinical trials did not report basic aspects of the intervention: 33% did not report the number of sessions, 45% did not report the duration of sessions, 42% did not report provider credentials, 52% did not report whether their intervention used a therapy manual, 64% did not reference a manual that was available to readers, and 82% did not report that they assessed treatment fidelity. A comparison with non-psychedelic trials shows that psychedelic trial reports underreport on key items related to PI.DiscussionThe study highlights the problems of underreporting and the importance of improving reporting practices regarding PI in psychedelic clinical trials to enhance research standardization and improve treatment outcomes. Recommendations for improving reporting practices are provided.

raw_json:
{"europe_pmc_id":"40046864","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Weintraub MJ, Jeffrey JK, Grob CS, Ichinose MC, Bergman RL, Cooper ZD, Miklowitz DJ.
publication_date: 2023-12-12
doi: 10.1089/psymed.2023.0018
pubmed_id: 40046861
source_url: https://doi.org/10.1089/psymed.2023.0018
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Clinical Trial,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Psilocybin-Assisted Cognitive Behavioral Therapy for Adults with Major Depressive Disorder: Rationale and Treatment Development.

abstract:
BackgroundRecent studies suggest that one to two administrations of psilocybin have acute antidepressant effects for people with major depressive disorder. These data on psilocybin have generated considerable enthusiasm, but little empirical attention has been paid to the therapy that adjoins psilocybin treatment (psychedelic-assisted therapy, or PAT).Materials and methodsIn this study, we present the initial protocol and plans to empirically test the psychosocial therapy that adjoins psilocybin treatment with the goal of optimizing this therapeutic approach for adults with major depressive disorder. The psychotherapy is based on the principles of cognitive-behavioral therapy (CBT), an evidence-based treatment for major depressive disorder. Participants will be 30 adults with a history of major depressive disorder and current, active depressive symptoms. Following psychiatric and medical safety evaluations, eligible participants will be enrolled in a 12-session CBT that includes classic PAT safety elements (termed psilocybin-assisted CBT; PA-CBT). Following the third and sixth PA-CBT sessions, participants will engage in two psilocybin drug administration sessions (10 and 25 mg, respectively). Participants will provide feedback about the PA-CBT and complete measures of mood symptoms, psychosocial functioning, cognitive schemas, and affective experiences immediately following each drug administration session, at the completion of PA-CBT, and 3 months following treatment completion.ConclusionsThe trial will provide preliminary data on the feasibility, safety, acceptability, and psychosocial effects of PA-CBT. Results will inform randomized clinical trials to test the effects of PA-CBT for patients with depression and other mental health conditions, as well as hypotheses concerning mediating mechanisms at the cognitive and affective levels. ClinicalTrials.gov ID: NCT05227612.

raw_json:
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authors: Cardoso MS, da Cunha KF, Silva IG, Fiorentin TR, de Campos EG, Costa JL.
publication_date: 2023-11-30
doi: 10.1093/jat/bkad064
pubmed_id: 37642343
source_url: https://doi.org/10.1093/jat/bkad064
keywords: Humans, Chromatography, Liquid, Tandem Mass Spectrometry, Psilocybin
substance_tags: psilocybin,psilocin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
title:
Development and validation of a sensitive LC-MS-MS method to quantify psilocin in authentic oral fluid samples.

abstract:
Psilocin is an active substance and a dephosphorylated product of psilocybin formed after the ingestion of mushrooms. The low stability caused by the quick oxidation of this analyte requires sensitive methods for its determination in biological matrices. In this work, we described the development, optimization and validation of a method for the quantification of psilocin in authentic oral fluid samples by liquid chromatography-tandem mass spectrometry. Liquid-liquid extraction was performed using 100 µL of oral fluid samples collected with a Quantisal™ device and t-butyl methyl ether as the extraction solvent. The method showed acceptable performance, with limits of detection and quantification of 0.05 ng/mL, and the calibration model was achieved between 0.05 and 10 ng/mL. Bias and imprecision results were below -14.2% and 10.7%, respectively. Ionization suppression/enhancement was lower than -30.5%, and recovery was >54.5%. Dilution integrity bias was

raw_json:
{"europe_pmc_id":"37642343","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Drugs for depressionr.
journal: The Medical letter on drugs and therapeutics
publication_date: 2023-12-10
doi: 10.58347/tml.2023.1691a
pubmed_id: 38133585
source_url: https://pubmed.ncbi.nlm.nih.gov/38133585/
substance_tags: psilocybin
topic_tags: Depression,Safety,Drug Interactions
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:37
raw_json: {"pubmed_id":"38133585"}
keywords:
Abilify, Aplenzin, Auvelity, Buspar, Celexa, Cymbalta, Deplin, Effexor, Emsam, Exxua, Fetzima, Forfivo, L-methylfolate, Lexapro, Marplan, Nardil, Norpramin, PamelorZurzuvae, Parnate, Paxil, Pristiq, Prozac, Remeron, SNRIs, SSRIs, Seroquel, Spravato, St. John’s wort, Symbyax, Trintellix, Viibryd, Wellbutrin, Zoloft, Zulresso, Zurzuvae, adverse effects, amitriptyline, amoxapine, antipsychotics, aripiprazole, brexanolone, bupropion, buspirone, citalopram, cognitive behavioral therapy, deep brain stimulation, depression, desipramine, desvenlafaxine, dextromethorphan, dosage, drug interactions, duloxetine, efficacy, electroconvulsive therapy, escitalopram, esketamine, fluoxetine, gepirone, imipramine, isocarboxazid, ketamine, lactation, levomilnacipran, lithium, mirtazapine, nefazodone, nortriptyline, olanzapine, paroxetine, phenelzine, pregnancy, psilocybin, quetiapine, safety, selegiline, sertraline, transcranial magnetic stimulation, tranylcypromine, trazodone, tricyclic antidepressants, triiodothyronine, venlafaxine, vilazodone, vortioxetine, zuranolone


title: Group psychedelic therapy: empirical estimates of cost-savings and improved access.
authors: Marseille E, Stauffer CS, Agrawal M, Thambi P, Roddy K, Mithoefer M, Bertozzi SM, Kahn JG.
publication_date: 2023-12-05
doi: 10.3389/fpsyt.2023.1293243
pubmed_id: 38125286
source_url: https://doi.org/10.3389/fpsyt.2023.1293243
substance_tags: psilocybin
topic_tags: Depression,PTSD,Healthcare Workers
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
abstract:
ObjectiveTo compare group and individual psychedelic-assisted therapy in terms of clinician time, costs and patient access.MethodsUsing 2023 data from two group therapy trial sites, one using 3,4-Methylenedioxymethamphetamine (MDMA) to treat posttraumatic stress disorder (PTSD), and one using psilocybin to treat major depressive disorder (MDD), we compared overall variable costs, clinician costs and clinician time required by therapy protocols utilizing groups versus individual patient therapy. Using published literature, we estimated the prevalence of adults with PTSD and MDD eligible for treatment with psychedelic therapy and projected the savings in time and cost required to treat these prevalent cases.ResultsGroup therapy saved 50.9% of clinician costs for MDMA-PTSD and 34.7% for psilocybin-MDD, or $3,467 and $981 per patient, respectively. To treat all eligible PTSD and MDD patients in the U.S. in 10 years with group therapy, 6,711 fewer full-time equivalent (FTE) clinicians for MDMA-PTSD and 1,159 fewer for FTE clinicians for psilocybin-MDD would be needed, saving up to $10.3 billion and $2.0 billion respectively, discounted at 3% annually.ConclusionAdopting group therapy protocols where feasible would significantly reduce the cost of psychedelic-assisted therapies. By enhancing the number of patients served per clinician, group therapy could also ameliorate the anticipated shortage of appropriately trained clinicians, thereby accelerating access to these promising new therapies.

raw_json:
{"europe_pmc_id":"38125286","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2023-11-30
doi: 10.1016/j.cub.2023.10.059
pubmed_id: 38052161
source_url: https://doi.org/10.1016/j.cub.2023.10.059
substance_tags: psilocybin
topic_tags: Genomics
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
title:
Domestication through clandestine cultivation constrained genetic diversity in magic mushrooms relative to naturalized populations.

authors:
McTaggart AR, McLaughlin S, Slot JC, McKernan K, Appleyard C, Bartlett TL, Weinert M, Barlow C, Warne LN, Shuey LS, Drenth A, James TY.

abstract:
Fungi that are edible or fermentative were domesticated through selective cultivation of their desired traits. Domestication is often associated with inbreeding or selfing, which may fix traits other than those under selection, and causes an overall decrease in heterozygosity. A hallucinogenic mushroom, Psilocybe cubensis, was domesticated from its niche in livestock dung for production of psilocybin. It has caused accidental poisonings since the 1940s in Australia, which is a population hypothesized to be introduced from an unknown center of origin. We sequenced genomes of 38 isolates from Australia and compared them with 86 genomes of commercially available cultivars to determine (1) whether P. cubensis was introduced to Australia, and (2) how domestication has impacted commercial cultivars. Our analyses of genome-wide SNPs and single-copy orthologs showed that the Australian population is naturalized, having recovered its effective population size after a bottleneck when it was introduced, and it has maintained relatively high genetic diversity based on measures of nucleotide and allelic diversity. In contrast, domesticated cultivars generally have low effective population sizes and hallmarks of selfing and clonal propagation, including low genetic diversity, low heterozygosity, high linkage disequilibrium, and low allelic diversity of mating-compatibility genes. Analyses of kinship show that most cultivars are founded from related populations. Alleles in the psilocybin gene cluster are identical across most cultivars of P. cubensis with low diversity across coding sequence; however, unique allelic diversity in Australia and some cultivars may translate to differences in biosynthesis of psilocybin and its analogs.

keywords:
Hallucinogens, Polymorphism, Single Nucleotide, Australia, Genetic Variation, Psilocybe, Psilocybin, Domestication

raw_json:
{"europe_pmc_id":"38052161","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Perceptions of psychedelic-assisted therapy among Black Americans.
authors: Carter S, Packard G, Coghlan C, George JR, Brown AJ, Ching THW, Julian J, Maples-Keller JL.
publication_date: 2023-09-25
doi: 10.1016/j.xjmad.2023.100023
pubmed_id: 40656968
source_url: https://doi.org/10.1016/j.xjmad.2023.100023
substance_tags: psilocybin
topic_tags: Depression,PTSD,Clinical Trial,Observational Study,Drug Interactions
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
The present study investigated differences in perceptions of psychedelic-assisted therapy between Black and White Americans, as well as factors that may influence these perceptions. A final sample of 294 adults (42% female, 44% Black/African American or Mixed Race (of Black/African ancestry), 56% White American; Mage = 36.3 years) completed an online survey which assessed baseline knowledge and views of psychedelic-assisted therapy. Participants were then provided brief psychoeducation related to MDMA and psilocybin-assisted therapy. After psychoeducation, participants were queried on their perceptions of psychedelic-assisted therapy and factors potentially influencing these perceptions, including trauma history, current depressive and PTSD symptoms, perceived stress, and perceived barriers to psychological treatments. Psychoeducation had a positive impact on both level of interest and positivity of views of psychedelic-assisted therapy across groups. Black American participants reported more positive views of psychedelic-assisted therapy than White participants following psychoeducation. Greater depression and PTSD symptom severity was associated with greater baseline interest in Black and White Americans and there was significant interactions in predicting baseline view and interest, such that Black participants who reported greater depression symptom severity were more interested and had more positive views of PAT. Despite historical exclusion from psychedelic clinical trials and experiences of unethical treatment in research, Black Americans demonstrate more positive views of psychedelic therapy, and Black Americans more in need of novel mental health care demonstrate more interest and more positive views. Our findings demonstrate that the onus for diversification of psychedelic research samples is on research groups. These findings also provide an impetus for the psychedelic research community to rebuild trust in psychedelic research among Black Americans, conduct outreach, and provide culturally attuned psychedelic-assisted interventions that are accessible to Black Americans.

raw_json:
{"europe_pmc_id":"40656968","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Mathai DS, Hilbert S, Sepeda ND, Strickland JC, Griffiths RR, Garcia-Romeu A.
publication_date: 2023-12-12
doi: 10.1089/psymed.2023.0035
pubmed_id: 38152462
source_url: https://doi.org/10.1089/psymed.2023.0035
substance_tags: psilocybin
topic_tags: Receptor Pharmacology,Consciousness,Wellbeing,Spirituality,Healthy Volunteers,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Double-Blind Comparison of the Two Hallucinogens Dextromethorphan and Psilocybin: Experience-Dependent and Enduring Psychological Effects in Healthy Volunteers.

abstract:
RationaleN-methyl-D-aspartate receptor-mediated dissociatives and serotonergic hallucinogens are being increasingly used in therapeutic interventions that involve nonordinary states of consciousness and may represent a unique mental health paradigm wherein pharmacologically induced experiences are conducive to psychological well-being.ObjectiveThe aim of this study was to further understand how the phenomenological and health-promoting effects of high-dose dextromethorphan (DXM) compared to psilocybin in the same participants when administered under experimental conditions that are typical of therapeutic psychedelic trials.MethodsSingle, acute oral doses of DXM (400 mg/70 kg), psilocybin (10, 20, 30 mg/70 kg), and inactive placebo were administered under double-blind and psychologically supportive conditions to 20 healthy participants with histories of hallucinogen use. Ratings of personal meaning, spiritual significance, psychological challenge, and psychological insight attributed to acute drug experiences were assessed 7 h (at session end) and 1 week after each drug administration. Persisting psychological effects were assessed 1 week after each drug administration.ResultsHigh-dose DXM and psilocybin produced similar increases over placebo in ratings of drug experience that was predictive of psychological benefit at 1 week, even when expectancy effects were minimized. These effects tended to favor psilocybin in a dose-dependent manner and were limited by poor physical tolerability for DXM.ConclusionsThis analysis suggests the utility of exploring clinical applications of dissociatives that occur within the supportive contexts that are characteristic of psychedelic research and that prioritize the optimization of psychologically valuable drug experiences. This study was registered with ClinicalTrials.gov (NCT02033707).

raw_json:
{"europe_pmc_id":"38152462","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin's Erasure of EGO.
authors: Ahlskog G.
publication_date: 2023-11-30
doi: 10.1521/prev.2023.110.4.457
pubmed_id: 38117518
source_url: https://doi.org/10.1521/prev.2023.110.4.457
keywords: Humans, Ego, Psychoanalysis, Psilocybin, Psychotherapists
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
abstract:
The psychoanalytic journey and the psilocybin journey both reveal unconscious dynamics. In this article a psychoanalyst discusses his own psilocybin journey. Similarities and differences between these journeys are discussed. Possibilities are offered for a dialogue in which psilocybin may contribute to psychoanalytic understanding and psychoanalysis may contribute to the understanding of psychedelic sessions. Patients may benefit from this cross-fertilization.

raw_json:
{"europe_pmc_id":"38117518","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin therapy to reduce depression following a terminal diagnosis.
authors: Boudreau E, Orlowski K.
publication_date: 2023-11-30
doi: 10.1097/01.jaa.0000994952.07847.2d
pubmed_id: 37989175
source_url: https://doi.org/10.1097/01.jaa.0000994952.07847.2d
keywords: Humans, Depression, Anxiety, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Anxiety,End-of-Life Distress
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
raw_json:
{"europe_pmc_id":"37989175","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The possible place for psychedelics in pharmacotherapy of mental disorders.
authors: Wojtas A.
publication_date: 2023-11-06
doi: 10.1007/s43440-023-00550-9
pubmed_id: 37934320
source_url: https://doi.org/10.1007/s43440-023-00550-9
keywords: Humans, Serotonin, Ketamine, Hallucinogens, Antidepressive Agents, Mental Disorders, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Receptor Pharmacology,Review Article,Adverse Events
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
Since its emergence in the 1960s, the serotonergic theory of depression bore fruit in the discovery of a plethora of antidepressant drugs affecting the lives of millions of patients. While crucial in the history of drug development, recent studies undermine the effectiveness of currently used antidepressant drugs in comparison to placebo, emphasizing the long time it takes to initiate the therapeutic response and numerous adverse effects. Thus, the scope of contemporary pharmacological research shifts from drugs affecting the serotonin system to rapid-acting antidepressant drugs. The prototypical representative of the aforementioned class is ketamine, an NMDA receptor antagonist capable of alleviating the symptoms of depression shortly after the drug administration. This discovery led to a paradigm shift, focusing on amino-acidic neurotransmitters and growth factors. Alas, the drug is not perfect, as its therapeutic effect diminishes circa 2 weeks after administration. Furthermore, it is not devoid of some severe side effects. However, there seems to be another, more efficient, and safer way to target the glutamatergic system. Hallucinogenic agonists of the 5-HT2A receptor, commonly known as psychedelics, are nowadays being reconsidered in clinical practice, shedding their infamous 1970s stigma. More and more clinical studies prove their clinical efficacy and rapid onset after a single administration while bearing fewer side effects. This review focuses on the current state-of-the-art literature and most recent clinical studies concerning the use of psychedelic drugs in the treatment of mental disorders. Specifically, the antidepressant potential of LSD, psilocybin, DMT, and 5-MeO-DMT will be discussed, together with a brief summary of other possible applications.

raw_json:
{"europe_pmc_id":"37934320","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Chruścicka-Smaga B, Machaczka A, Szewczyk B, Pilc A.
publication_date: 2023-11-06
doi: 10.1007/s43440-023-00547-4
pubmed_id: 37932583
source_url: https://doi.org/10.1007/s43440-023-00547-4
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Interaction of hallucinogenic rapid-acting antidepressants with mGlu2/3 receptor ligands as a window for more effective therapies.

abstract:
The desire to find a gold-standard therapy for depression is still ongoing. Developing one universal and effective pharmacotherapy remains troublesome due to the high complexity and variety of symptoms. Over the last decades, the understanding of the mechanism of pathophysiology of depression and its key consequences for brain functioning have undergone significant changes, referring to the monoaminergic theory of the disease. After the breakthrough discovery of ketamine, research began to focus on the modulation of glutamatergic transmission as a new pharmacological target. Glutamate is a crucial player in mechanisms of a novel class of antidepressants, including hallucinogens such as ketamine. The role of glutamatergic transmission is also suggested in the antidepressant (AD) action of scopolamine and psilocybin. Despite fast, robust, and sustained AD action hallucinogens belonging to a group of rapid-acting antidepressants (RAA) exert significant undesired effects, which hamper their use in the clinic. Thus, the synergistic action of more than one substance in lower doses instead of monotherapy may alleviate the likelihood of adverse effects while improving therapeutic outcomes. In this review, we explore AD-like behavioral, synaptic, and molecular action of RAAs such as ketamine, scopolamine, and psilocybin, in combination with mGlu2/3 receptor antagonists.

keywords:
Ketamine, Scopolamine, Receptors, Metabotropic Glutamate, Hallucinogens, Antidepressive Agents, Depression, Psilocybin

topic_tags:
Depression,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Review Article,Drug Interactions

raw_json:
{"europe_pmc_id":"37932583","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Mindfulness meditation and psychedelics: potential synergies and commonalities.
authors: Holas P, Kamińska J
journal: Pharmacological reports : PR
publication_date: 2023-11-30
doi: 10.1007/s43440-023-00551-8
pubmed_id: 37926796
source_url: https://pubmed.ncbi.nlm.nih.gov/37926796/
substance_tags: psilocybin
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:37
raw_json: {"pubmed_id":"37926796"}
abstract:
There has been increasing scientific and clinical interest in studying psychedelic and meditation-based interventions in recent years, both in the context of improving mental health and as tools for understanding the mind. Several authors suggest neurophysiological and phenomenological parallels and overlaps between psychedelic and meditative states and suggest synergistic effects of both methods. Both psychedelic-assisted therapy and meditation training in the form of mindfulness-based interventions have been experimentally validated with moderate to large effects as alternative treatments for a variety of mental health problems, including depression, addictions, and anxiety disorders. Both demonstrated significant post-acute and long-term decreases in clinical symptoms and enhancements in well-being in healthy participants, in addition. Postulated shared salutogenic mechanisms, include, among others the ability to alter self-consciousness, present-moment awareness and antidepressant action via corresponding neuromodulatory effects. These shared mechanisms between mindfulness training and psychedelic intervention have led to scientists theorizing, and recently demonstrating, positive synergistic effects when both are used in combination. Research findings suggest that these two approaches can complement each other, enhancing the positive effects of both interventions. However, more theoretical accounts and methodologically sound research are needed before they can be extended into clinical practice. The current review aims to discuss the theoretical rationale of combining psychedelics with mindfulness training, including the predictive coding framework as well as research findings regarding synergies and commonalities between mindfulness training and psychedelic intervention. In addition, suggestions how to combine the two modalities are provided.

keywords:
Decentering, Meditation, Mindfulness, Mindfulness-based interventions, Mystical experiences, Predictive coding, Psilocybin, Psychedelics

topic_tags:
Depression,Anxiety,Addiction,Mechanism of Action,Consciousness,Wellbeing,Mystical Experience,Review Article,Healthy Volunteers


title: Psychedelic renaissance: Revitalized potential therapies for psychiatric disorders.
authors: Rhee TG, Davoudian PA, Sanacora G, Wilkinson ST.
publication_date: 2023-11-01
doi: 10.1016/j.drudis.2023.103818
pubmed_id: 37925136
source_url: https://doi.org/10.1016/j.drudis.2023.103818
substance_tags: psilocybin
topic_tags: Clinical Trial,Review Article,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
Psychiatric disorders represent the largest cause of disability worldwide. Global interests in psychedelic substances as potentially therapeutic agents for psychiatric disorders has recently re-emerged. Here, we review progress in the development of psychedelic compounds that have potential therapeutic effects as well as the safety concerns. We include psilocybin, N,N-dimethyltryptamine (DMT), lysergic acid diethylamide (LSD), and the entactogen 3,4-methyl-enedioxy-methamphetamine (MDMA). We also review the potential interactive effects these compounds can have with psychotherapeutic approaches. We provide a cutting-edge review of active and recently completed clinical trials based on the published literature (from MEDLINE), published abstracts at citable conferences, clinical trials from the US Clinical Trials registry (clinicaltrials.gov) and media press releases.

keywords:
Humans, N,N-Dimethyltryptamine, Lysergic Acid Diethylamide, Hallucinogens, Mental Disorders, Psilocybin

raw_json:
{"europe_pmc_id":"37925136","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Preclinical models of treatment-resistant depression: challenges and perspectives.
authors: Kolasa M, Faron-Górecka A
journal: Pharmacological reports : PR
publication_date: 2023-11-30
doi: 10.1007/s43440-023-00542-9
pubmed_id: 37882914
source_url: https://pubmed.ncbi.nlm.nih.gov/37882914/
substance_tags: psilocybin
topic_tags: Depression,Pharmacology,Review Article,Animal Study,Treatment-Resistant Depression
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:37
raw_json: {"pubmed_id":"37882914"}
abstract:
Treatment-resistant depression (TRD) is a subgroup of major depressive disorder in which the use of classical antidepressant treatments fails to achieve satisfactory treatment results. Although there are various definitions and grading models for TRD, common criteria for assessing TRD have still not been established. However, a common feature of any TRD model is the lack of response to at least two attempts at antidepressant pharmacotherapy. The causes of TRD are not known; nevertheless, it is estimated that even 60% of TRD patients are so-called pseudo-TRD patients, in which multiple biological factors, e.g., gender, age, and hormonal disturbances are concomitant with depression and involved in antidepressant drug resistance. Whereas the phenomenon of TRD is a complex disorder difficult to diagnose and successfully treat, the search for new treatment strategies is a significant challenge of modern pharmacology. It seems that despite the complexity of the TRD phenomenon, some useful animal models of TRD meet the construct, the face, and the predictive validity criteria. Based on the literature and our own experiences, we will discuss the utility of animals exposed to the stress paradigm (chronic mild stress, CMS), and the Wistar Kyoto rat strain representing an endogenous model of TRD. In this review, we will focus on reviewing research on existing and novel therapies for TRD, including ketamine, deep brain stimulation (DBS), and psychedelic drugs in the context of preclinical studies in representative animal models of TRD.

keywords:
Animal models, Chronic mild stress, DBS, Ketamine, Psilocybin, Treatment-resistant depression, Wistar Kyoto rats


title: Cardiovascular safety of psychedelic medicine: current status and future directions.
authors: Wsół A.
publication_date: 2023-10-23
doi: 10.1007/s43440-023-00539-4
pubmed_id: 37874530
source_url: https://doi.org/10.1007/s43440-023-00539-4
keywords: Humans, Mescaline, Lysergic Acid Diethylamide, Hallucinogens, Anxiety Disorders, Psilocybin
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
Psychedelics are powerful psychoactive substances that alter perception and mood processes. Their effectiveness in the treatment of psychiatric diseases was known before their prohibition. An increasing number of recent studies, due to the indisputable resurgence of serotonergic hallucinogens, have shown their efficacy in alleviating depression, anxiety, substance abuse therapies, and existential distress treatment in patients facing life-threatening illness. Psychedelics are generally considered to be physiologically safe with low toxicity and low addictive potential. However, their agonism at serotonergic receptors should be considered in the context of possible serotonin-related cardiotoxicity (5-HT2A/2B and 5-HT4 receptors), influence on platelet aggregation (5-HT2A receptor), and their proarrhythmic potential. The use of psychedelics has also been associated with significant sympathomimetic effects in both experimental and clinical studies. Therefore, the present review aims to provide a critical discussion of the cardiovascular safety of psilocybin, d-lysergic acid diethylamide (LSD), N,N-dimethyltryptamine, ayahuasca, and mescaline, based on the results of experimental research and clinical trials in humans. Experimental studies provide inconsistent information on the potential cardiovascular effects and toxicity of psychedelics. Data from clinical trials point to the relative cardiovascular safety of psychedelic-assisted therapies in the population of "healthy" volunteers. However, there is insufficient evidence from therapies carried out with microdoses of psychedelics, and there is still a lack of data on the safety of psychedelics in the population of patients with cardiovascular disease. Therefore, the exact determination of the cardiovascular safety of psychedelic therapies (especially long-term therapies) requires further research.

topic_tags:
Depression,Anxiety,End-of-Life Distress,Receptor Pharmacology,Microdosing,Clinical Trial,Review Article,Safety,Toxicity

raw_json:
{"europe_pmc_id":"37874530","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Potential use of psilocybin drugs in the treatment of depression.
authors: Śladowska K, Kawalec P, Brzostek T, Pilc A.
publication_date: 2023-12-25
doi: 10.1080/14728214.2023.2264180
pubmed_id: 37817501
source_url: https://doi.org/10.1080/14728214.2023.2264180
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
IntroductionDepression is a common disabling psychiatric disorder, which - in extreme cases - may lead to suicide if untreated or inadequately treated. Despite the availability of various treatments for depression, including pharmacotherapy, there is still a need to search for new agents with higher effectiveness and faster onset of action, especially for patients with treatment-resistant depression.Areas coveredA substance that has attracted considerable attention for nearly a decade is psilocybin, a natural psychedelic found in psilocybin mushrooms. In this study, we evaluated the efficacy and safety of psilocybin in the treatment of depression, based on pivotal randomized clinical trials. Moreover, we used findings from observational studies regarding recreational use. We also looked at ongoing clinical trials and discussed the registration status and clinical potential of the drug.Expert opinionClinical phase I-II trials published to date reported promising results for psilocybin in the treatment of patients with major depressive disorder and treatment-resistant depression, in a relatively short time after administration. However, before psilocybin is approved for use and administered to patients with depression, the results of large ongoing phase III clinical trials are needed to confirm its efficacy and safety and to change the way it is perceived by physicians and patients.

keywords:
Humans, Hallucinogens, Pharmaceutical Preparations, Depression, Randomized Controlled Trials as Topic, Psilocybin, Major Depressive Disorder

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

raw_json:
{"europe_pmc_id":"37817501","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Pepe M, Hesami M, de la Cerda KA, Perreault ML, Hsiang T, Jones AMP.
publication_date: 2023-08-31
doi: 10.1016/j.biotechadv.2023.108247
pubmed_id: 37659744
source_url: https://doi.org/10.1016/j.biotechadv.2023.108247
keywords: Humans, Agaricales, Tryptamines, Hallucinogens, Biology, Biotechnology, Psilocybin
substance_tags: psilocybin
topic_tags: Pharmacology,Mechanism of Action,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
title:
A journey with psychedelic mushrooms: From historical relevance to biology, cultivation, medicinal uses, biotechnology, and beyond.

abstract:
Psychedelic mushrooms containing psilocybin and related tryptamines have long been used for ethnomycological purposes, but emerging evidence points to the potential therapeutic value of these mushrooms to address modern neurological, psychiatric health, and related disorders. As a result, psilocybin containing mushrooms represent a re-emerging frontier for mycological, biochemical, neuroscience, and pharmacology research. This work presents crucial information related to traditional use of psychedelic mushrooms, as well as research trends and knowledge gaps related to their diversity and distribution, technologies for quantification of tryptamines and other tryptophan-derived metabolites, as well as biosynthetic mechanisms for their production within mushrooms. In addition, we explore the current state of knowledge for how psilocybin and related tryptamines are metabolized in humans and their pharmacological effects, including beneficial and hazardous human health implications. Finally, we describe opportunities and challenges for investigating the production of psychedelic mushrooms and metabolic engineering approaches to alter secondary metabolite profiles using biotechnology integrated with machine learning. Ultimately, this critical review of all aspects related to psychedelic mushrooms represents a roadmap for future research efforts that will pave the way to new applications and refined protocols.

raw_json:
{"europe_pmc_id":"37659744","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Jones G, Herrmann F, Wang E.
publication_date: 2023-08-11
doi: 10.1016/j.abrep.2023.100513
pubmed_id: 37649653
source_url: https://doi.org/10.1016/j.abrep.2023.100513
substance_tags: psilocybin
topic_tags: Observational Study,Safety
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Associations between individual hallucinogens and hallucinogen misuse among U.S. Adults who recently initiated hallucinogen use.

abstract:
Hallucinogen dependence and abuse are DSM-IV diagnoses that are associated with significant morbidity, yet the specific hallucinogens that are most strongly linked to dependence and abuse are understudied. We used recent data from the National Survey on Drug Use and Health (2015-2020) and multivariable logistic regression to test the relationships that lifetime use of seven individual hallucinogens (MDMA/ecstasy, PCP, ketamine, psilocybin, LSD, peyote, and mescaline) shares with hallucinogen dependence and abuse among individuals who initiated hallucinogen use within the past two years (N = 5,252). We controlled for various demographic factors (sex, age, race/ethnicity, educational attainment, self-reported engagement in risky behavior, annual household income, marital status) and lifetime use of various substances. Lifetime PCP use was associated with increased odds of hallucinogen dependence or abuse (aOR [95% CI]: 6.27 [1.51, 26.0]). Additionally, PCP increased the odds of three main hallucinogen dependence and abuse criteria measures (aOR [95% CI]: 4.45 [1.11, 17.8], 5.58 [1.42, 22.0], and 7.01 [1.87, 26.3]). LSD conferred increased odds of two criteria (aOR: 2.33 [1.37, 3.98] and 2.53 [1.48, 4.33]), while ketamine and mescaline each conferred increased odds of one criterion (aOR: 2.12 [1.03, 4.39]; 5.39 [1.05, 27.7]). Future longitudinal studies and Bayesian statistical analyses can further assess the relationships between hallucinogens and disordered hallucinogen use.

raw_json:
{"europe_pmc_id":"37649653","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2023-08-16
doi: 10.1089/jpm.2023.0189
pubmed_id: 37590474
source_url: https://doi.org/10.1089/jpm.2023.0189
keywords: Humans, Feasibility Studies, Emotions, Consciousness, Psilocybin
substance_tags: psilocybin
topic_tags: Mechanism of Action,Consciousness,Emotional Processing,Clinical Trial,Drug Interactions
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Developing a Direct Observation Measure of Therapeutic Connection in Psilocybin-Assisted Therapy: A Feasibility Study.

authors:
Gramling R, Bennett E, Curtis K, Richards W, Rizzo DM, Arnoldy F, Hegg L, Porter J, Honstein H, Pratt S, Tarbi E, Reblin M, Thambi P, Agrawal M.

abstract:
Context: Measuring therapeutic connection during psilocybin-assisted therapy is essential to understand underlying mechanisms, inform training, and guide quality improvement. Purpose: To evaluate the feasibility of directly observing indicators of therapeutic connection during psilocybin administration encounters. Methods: We evaluated audio and video data from a recent clinical trial for observable expressions of therapeutic connection as defined in proposed best-practice competencies (i.e., empathic abiding presence and interpersonal grounding). We selected the first four 8-hour encounters involving unique participants, therapists, and gender pairs. Each video was independently coded by three members of an interprofessional six-person team. Using a structured checklist, coders recorded start-stop times, the audible (i.e., speech prosody or words) and visible (i.e., body movements, eye gaze, and touch) cues marking the event, and the qualities of the interaction (e.g., expression of awe, trust, distress, and calmness). We assessed feasibility by observing the frequency, distribution, and overlap of cues and qualities coders used to identify and define moments of therapeutic connection. Results: Among the 2074 minutes of video, coders recorded 372 moments of therapeutic connection. Eighty-three percent were identified by at least two coders and 41% by all three. Coders used a combination of audible and visual cues to identify therapeutic connection in 51% of observed events (190/372). Both the cues and qualities of therapeutic connection expressions varied over the course of psilocybin temporal effects on states of consciousness. Conclusion: Direct observation of therapeutic human connection is feasible, sensitive to changes in states of consciousness and requires evaluation of audible and visual data.

raw_json:
{"europe_pmc_id":"37590474","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin-assisted psychotherapy for treatment-resistant depression: Which psychotherapy?
authors: Crowe M, Manuel J, Carlyle D, Lacey C.
publication_date: 2023-08-16
doi: 10.1111/inm.13214
pubmed_id: 37589380
source_url: https://doi.org/10.1111/inm.13214
keywords: Humans, Hallucinogens, Depression, Emotions, Psychotherapy, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Emotional Processing,Review Article,Treatment-Resistant Depression
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
This perspective paper explores the choice of psychotherapy for psilocybin-assisted psychotherapy for treatment-resistant depression. There is evidence to support the use of some psychotherapies in treating 'treatment-resistant' depression, and emerging evidence for the efficacy of psilocybin. The next step which is the focus of this paper is to identify psychotherapies that are both effective and congruent with the psilocybin experience. The evidence for the efficacy of the psychotherapies is drawn from a Cochrane review and the analysis of their congruence with the psilocybin experience is drawn from a qualitative meta-synthesis of the experience of psilocybin. The paper will examine whether three one-to-one psychotherapies identified as effective in the treatment of treatment-resistant depression are compatible with the psilocybin experience. Each psychotherapy will be examined in relation to its congruence with the qualitative evidence that suggests the choice of psychotherapy needs to give priority to the subjective experience, facilitate emotional processing, support connectedness with others, acceptance of the self as emotional and support change based on the person's insights into their relationships with others and the world in which they live. We conclude that interpersonal psychotherapy and intensive short-term dynamic psychotherapy align with that experience, although others are currently being trialled.

raw_json:
{"europe_pmc_id":"37589380","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Hallucinogen use among young adults ages 19-30 in the United States: Changes from 2018 to 2021.
authors: Keyes KM, Patrick ME.
publication_date: 2023-06-06
doi: 10.1111/add.16259
pubmed_id: 37287110
source_url: https://doi.org/10.1111/add.16259
substance_tags: psilocybin
topic_tags: Observational Study,Safety
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
Background and aimsGiven the shifting landscape of hallucinogen use, particularly with increased therapeutic use, understanding current changes in use is a necessary part of examining the potential risk hallucinogens pose to vulnerable populations, such as young adults. This study aimed to measure hallucinogen use among young adults aged 19-30 years from 2018 to 2021.Design, setting and participantsThis was a longitudinal cohort study among young adults aged 19-30 years from the US general population, interviewed between 2018 and 2021. Participants comprised 11 304 unique respondents, with an average number of follow-ups of 1.46 (standard deviation = 0.50). Of the observed data points, 51.9% were among females.MeasurementsWe examined past 12-month self-reported use of lysergic acid diethylamide (LSD), as well as hallucinogens besides LSD (e.g. psilocybin), monitoring any use as well as frequency, overall and by sex.FindingsFrom 2018 to 2021, past 12-month use of LSD among young adults in the US remained relatively unchanged, from 3.7% [95% confidence interval (CI) = 3.1-4.3] in 2018 to 4.2% in 2021 (95% CI = 3.4-5.0). Non-LSD hallucinogen [e.g. 'shrooms', psilocybin or PCP (phenylcyclohexyl piperidine)] use, however, increased in prevalence from 3.4% (95% CI = 2.8-4.1) to 6.6% from 2018 to 2021 (95% CI = 5.5-7.6). Across years, the odds of non-LSD use were higher for males [odds ratio (OR) = 1.86, 95% CI = 1.52-2.26] and lower for black than white participants (OR = 0.29, 95% CI = 0.19-0.47) and those without a college-educated parent (OR = 0.80, 95% CI = 0.64-0.99). Demographic disparities were similar for LSD use.ConclusionPrevalence of past-year use non-lysergic acid diethylamide (LSD) hallucinogen was twice as high in 2021 as in 2018 among US young adults. Correlates of non-LSD hallucinogen use included being male, white and from higher socio-economic status backgrounds.

keywords:
Humans, Lysergic Acid Diethylamide, Hallucinogens, Prevalence, Longitudinal Studies, United States, Female, Male, Young Adult, Psilocybin

raw_json:
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authors: McCrone P, Fisher H, Knight C, Harding R, Schlag AK, Nutt DJ, Neill JC.
publication_date: 2023-06-01
doi: 10.1017/s0033291723001411
pubmed_id: 37264950
source_url: https://doi.org/10.1017/s0033291723001411
substance_tags: psilocybin
topic_tags: Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Cost-effectiveness of psilocybin-assisted therapy for severe depression: exploratory findings from a decision analytic model.

abstract:
BackgroundThere is growing evidence to support the use of the psychedelic drug psilocybin for difficult-to-treat depression. This paper compares the cost-effectiveness of psilocybin-assisted psychotherapy (PAP) with conventional medication, cognitive behavioural therapy (CBT), and the combination of conventional medication and CBT.MethodsA decision model simulated patient events (response, remission, and relapse) following treatment. Data on probabilities, costs and quality-adjusted life years (QALYs) were derived from previous studies or from best estimates. Expected healthcare and societal costs and QALYs over a 6-month time period were calculated. Sensitivity analyses were used to address uncertainty in parameter estimates.ResultsThe expected healthcare cost of PAP varied from £6132 to £7652 depending on the price of psilocybin. This compares to £3528 for conventional medication alone, £4250 for CBT alone, and £4197 for their combination. QALYs were highest for psilocybin (0.310), followed by CBT alone (0.283), conventional medication alone (0.278), and their combination (0.287). Psilocybin was shown to be cost-effective compared to the other therapies when the cost of therapist support was reduced by 50% and the psilocybin price was reduced from its initial value to £400 to £800 per person. From a societal perspective, psilocybin had improved cost-effectiveness compared to a healthcare perspective.ConclusionsPsilocybin has the potential to be a cost-effective therapy for severe depression. This depends on the level of psychological support that is given to patients receiving psilocybin and the price of the drug itself. Further data on long-term outcomes are required to improve the evidence base.

keywords:
Humans, Depression, Psychotherapy, Quality-Adjusted Life Years, Cost-Benefit Analysis, Psilocybin, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"37264950","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Exploring Psilocybe spp. mycelium and fruiting body chemistry for potential therapeutic compounds.
authors: Waldbillig A, Baranova M, Neumann S, Andrade J, Sidhu S.
publication_date: 2023-11-28
doi: 10.3389/ffunb.2023.1295223
pubmed_id: 38094868
source_url: https://doi.org/10.3389/ffunb.2023.1295223
substance_tags: psilocybin,psilocin
topic_tags: Receptor Pharmacology,Metabolomics
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Psilocybe mushrooms, otherwise known as "magic" mushrooms, owe their psychedelic effect to psilocin, a serotonin subtype 2A (5-HT2A) receptor agonist and metabolite of psilocybin, the primary indole alkaloid found in Psilocybe species. Metabolomics is an advanced fingerprinting tool that can be utilized to identify the differences among fungal life stages that may otherwise be unaccounted for. In this study, by using targeted and untargeted (metabolomic) multivariate analysis, we demonstrate that the chemical composition of Psilocybe differs among mycelia, grain mycelia, and fruiting bodies. The preferential accumulation of psilocybin, baeocystin, tryptophan, ergothioneine, and phenylethylamine in fruiting bodies differentiated them from mycelia; however, the levels of alpha-glycerylphosphorylcholine (α-GPC), N-acetylglucosamine, and trimethylglycine were found to be proportionally higher in mycelia than in fruiting bodies based on Pareto-scaled data. Considering the wealth of compounds with therapeutic potential that have been isolated from various fungal genera, it would be pertinent to study the compounds found in Psilocybe mycelia as potential naturally derived therapeutic targets.

raw_json:
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title: [Feeling unwell after eating a piece of chocolate].
authors: van der Schuur-Saleem R, Visser E, Robben H, Zwols M, den Besten-Berthololee D.
publication_date: 2023-11-22
pubmed_id: 38175555
source_url: https://europepmc.org/article/MED/38175555
keywords: Humans, Dizziness, Emotions, Fear, Food, Male, Psilocybin, Chocolate
substance_tags: psilocybin,psilocin
topic_tags: Emotional Processing
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
abstract:
BackgroundSince 2006 chocolate containing psilocin is circulating in The Netherlands. Psilocin is a psychoactive substance derived from psychedelic mushrooms and known to be hard drugs. Consuming psilocin can cause symptoms such as hallucinations, fear and panic attacks and sympathomimetic effects. These effects can last for approximately 6 hours.Case descriptionA man presented to the ED after eating a piece of chocolate. He was complaining of agitation, dizziness, a dry mouth and nausea. He was hypertensive and had wide light-responsive pupils. An analysis of the chocolate in the hospital pharmacy laboratory indicated the presence of psilocin.ConclusionsFood, like chocolate, can contain toxic ingredients that are not mentioned on the ingredients lists. Therefore, in unexplained symptoms, it could be useful to exclude an intoxication with polluted food.

raw_json:
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title: Biological studies of clavine alkaloids targeting CNS receptors.
authors: Tasker NR, Pazur EJ, Wipf P.
publication_date: 2023-11-20
doi: 10.3389/fpsyt.2023.1286941
pubmed_id: 38076698
source_url: https://doi.org/10.3389/fpsyt.2023.1286941
substance_tags: psilocybin
topic_tags: Pharmacology,Receptor Pharmacology
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
In contrast to well established psychedelics such as lysergic acid diethylamide (LSD) and psilocybin, ergot alkaloids of the clavine subclass have not been thoroughly investigated, in spite of their broad occurrence in nature and their well-established potent physiological effects. This study presents the current knowledge on the biological properties of clavine alkaloids, draws comparisons to the pharmacology of ergolines and related psychedelics, and demonstrates opportunities to develop novel structure-activity relationship (SAR) profiles. The latter could usher in a new stage of medicinal chemistry studies that enable an expansion of the currently structurally limited portfolio of psychedelic therapeutics.

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title: Psychedelic Drugs or Hallucinogens: Exploring Their Medicinal Potential.
authors: Raj P, Rauniyar S, Sapkale B.
publication_date: 2023-11-12
doi: 10.7759/cureus.48719
pubmed_id: 38094517
source_url: https://doi.org/10.7759/cureus.48719
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Neuroplasticity,Receptor Pharmacology,Consciousness,Aging
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
Serotonergic hallucinogens also referred to as psychedelics, are psychoactive substances that profoundly alter perception, mood, and cognitive processes. These substances, historically intertwined with religious and cultural rituals, offer profound effects that extend beyond mere hallucinations to profoundly altered states of consciousness. Notable compounds like Lysergic acid diethylamide (LSD) and psilocybin, potent in their action on serotonin receptors, play pivotal roles in influencing brain functions. Despite societal misconceptions that have overshadowed their potential, contemporary research increasingly recognizes their therapeutic value. These substances have shown promise in treating neuropsychiatric disorders such as depression, post-traumatic stress disorder (PTSD), and anxiety, leveraging their influence on neuroplasticity. Furthermore, they exhibit therapeutic potential across various conditions, challenging conventional treatment methodologies. Compared to substances like alcohol, traditional psychedelics like LSD and psilocybin emerge as relatively safer substances. The modern revival of scientific interest in psychedelics necessitates a renewed perspective, viewing them not just as recreational entities but as potent therapeutic tools. Harnessing their actual value mandates rigorous scientific investigations and a receptive societal discourse. A re-evaluation of their classification following international criteria is necessary in light of this increasing understanding. Hallucinogens or psychedelic drugs, if used correctly, can potentially be potential treatments for mental illness, signalling a paradigm shift from traditional techniques. To dispel myths and use their therapeutic advantages, embracing this potential necessitates thorough scientific investigation together with an open societal discourse.

raw_json:
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authors: Kvam TM, Uthaug MV, Andersen KAA, Refsum BB, Tunstad PA, Stewart LH, Jacobsen HB, Grønnerød C.
publication_date: 2023-11-12
doi: 10.3389/fpsyt.2023.1287196
pubmed_id: 38025484
source_url: https://doi.org/10.3389/fpsyt.2023.1287196
substance_tags: psilocybin
topic_tags: Addiction,Clinical Trial,Observational Study,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Epidemiology of classic psychedelic substances: results from a Norwegian internet convenience sample.

abstract:
ObjectiveIn recent years, there has been a renewed interest in investigating the use of classic psychedelics such as psilocybin and lysergic acid diethylamide (LSD) in the treatment of mental disorders and substance use disorders. However, knowledge about the epidemiology of classic psychedelics in the Nordic countries is limited.MethodsWe recruited adult, Norwegian participants who have had a memorable experience after taking a classic psychedelic substance. They filled in an anonymous internet survey with 119 items covering matters related to recreational use of psychedelics using a secure, web-based application. Data are presented by using descriptive statistics (frequencies, means, and standard deviations).ResultsWe recruited 841 participants, 770 (72% male; 88% 45 years or younger) of which were included in the data analysis. The intentions behind taking the psychedelic substance were mainly recreational (46.1%) or therapeutic (42.3%). Most participants reported that their most memorable experience was with psilocybin. As in modern era clinical trials, most participants were well-prepared before, did processing during, and did integration work after the experience, whereas only a minority were supported by a therapist. Self-perceived symptoms of various mental disorders and substance use disorders were prevalent in the sample. Most subjects reported improvements in their condition. Although adverse reactions were usually mild and short-lived, 4.2% lasted for 1 year or more. Persisting flashbacks were present for a year or more among 2.9% of the participants.ConclusionIn this cross-sectional sample of Norwegian, self-selecting adults, we shed light on what characterizes the most memorable experience with a classic psychedelic substance, including short- and long-term risks and benefits. For the most part, the psychedelic experience led to improvements in self-perceived symptoms of mental disorders and substance use disorders. However, a small subset experienced persisting adverse reactions.

raw_json:
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title: Beyond the 5-HT2A Receptor: Classic and Nonclassic Targets in Psychedelic Drug Action.
publication_date: 2023-10-31
doi: 10.1523/jneurosci.1384-23.2023
pubmed_id: 37940583
source_url: https://doi.org/10.1523/jneurosci.1384-23.2023
keywords: Humans, Serotonin, Receptor, Serotonin, 5-HT2A, Hallucinogens, Anxiety, Psilocybin
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
authors:
Cameron LP, Benetatos J, Lewis V, Bonniwell EM, Jaster AM, Moliner R, Castrén E, McCorvy JD, Palner M, Aguilar-Valles A.

abstract:
Serotonergic psychedelics, such as psilocybin and LSD, have garnered significant attention in recent years for their potential therapeutic effects and unique mechanisms of action. These compounds exert their primary effects through activating serotonin 5-HT2A receptors, found predominantly in cortical regions. By interacting with these receptors, serotonergic psychedelics induce alterations in perception, cognition, and emotions, leading to the characteristic psychedelic experience. One of the most crucial aspects of serotonergic psychedelics is their ability to promote neuroplasticity, the formation of new neural connections, and rewire neuronal networks. This neuroplasticity is believed to underlie their therapeutic potential for various mental health conditions, including depression, anxiety, and substance use disorders. In this mini-review, we will discuss how the 5-HT2A receptor activation is just one facet of the complex mechanisms of action of serotonergic psychedelics. They also interact with other serotonin receptor subtypes, such as 5-HT1A and 5-HT2C receptors, and with neurotrophin receptors (e.g., tropomyosin receptor kinase B). These interactions contribute to the complexity of their effects on perception, mood, and cognition. Moreover, as psychedelic research advances, there is an increasing interest in developing nonhallucinogenic derivatives of these drugs to create safer and more targeted medications for psychiatric disorders by removing the hallucinogenic properties while retaining the potential therapeutic benefits. These nonhallucinogenic derivatives would offer patients therapeutic advantages without the intense psychedelic experience, potentially reducing the risks of adverse reactions. Finally, we discuss the potential of psychedelics as substrates for post-translational modification of proteins as part of their mechanism of action.

topic_tags:
Depression,Anxiety,Addiction,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Emotional Processing,Review Article,Safety,Drug Interactions

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authors: Van Der Walt J, Parker R.
publication_date: 2023-11-05
doi: 10.7196/samj.2023.v113i11.814
pubmed_id: 38525640
source_url: https://doi.org/10.7196/samj.2023.v113i11.814
substance_tags: psilocybin
topic_tags: Depression,Chronic Pain,Mechanism of Action,Aging,Review Article,Healthcare Workers
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
LSD and psilocybin for chronic nociplastic pain: A narrative review of the literature supporting the use of classic psychedelic agents in chronic pain.

abstract:
Healthcare providers face the challenging task of managing patients who suffer from chronic nociplastic pain conditions. Pain is a multidimensional experience, and the current approach to managing people in chronic pain often fails to meet the needs of these patients. Novel ways of treating people who suffer from chronic nociplastic pain with classic psychedelic agents may offer a new lens through which to approach their pain. Lysergic acid diethylamide (LSD) and psilocybin are both serotonergic agents with a long history of use in treating people with chronic pain and mental health disorders. The new wave of research into psychedelics for major depressive disorder provides an opportunity to investigate and understand the potential for incorporating these drugs into chronic pain management pathways. This narrative review presents healthcare workers with a framework to understand the method of action of these drugs in chronic nociplastic pain pathways and a brief history into their use. We conducted an online search using Pubmed with keywords 'chronic pain' AND/OR 'psilocybin' AND/OR 'lysergic acid diethylamide' AND/OR 'psychedelics' with no date limit applied. We identified further articles that contained information on the neuroscience of psychedelics and the serotonergic system using Google Scholar. During the final stages of writing the article, the latest publications on psychedelics and chronic pain in leading pain journals were again included to update the information.

keywords:
Humans, Lysergic Acid Diethylamide, Hallucinogens, South Africa, Chronic Pain, Psilocybin, Major Depressive Disorder

raw_json:
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authors: Gray JC, Murphy M, Carter SE, Johnson MW, Wolfgang AS, Roy MJ, Maples-Keller JL.
publication_date: 2023-10-31
doi: 10.1093/milmed/usac400
pubmed_id: 36564939
source_url: https://doi.org/10.1093/milmed/usac400
substance_tags: psilocybin
topic_tags: Depression,PTSD,Aging,Personality Change,Veterans
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:06
title:
Beliefs and Perceived Barriers Regarding Psychedelic-assisted Therapy in a Pilot Study of Service Members and Veterans With a History of Traumatic Brain Injury.

abstract:
IntroductionPosttraumatic stress disorder (PTSD) and depression are common in service members and veterans, and the response to currently available treatments is often modest at best. Recent studies suggest potential benefit with psychedelic-assisted therapies (PATs), particularly 3,4-methylenedioxymethamphetamine-assisted therapy for PTSD and psilocybin-assisted therapy for depression. This study examined beliefs and perceived barriers regarding PAT among service members and veterans to inform the delivery of these treatments if they are approved by the FDA.Materials and methodsTwenty-one service members and veterans (67% male, 81% White, and 43% active duty) with a history of traumatic brain injury and co-occurring cognitive and psychological symptoms completed a measure assessing baseline knowledge and views of PAT, read a brief psychoeducation regarding PAT, and then responded to questions related to their beliefs and perceived barriers to PAT.ResultsBefore psychoeducation, participants reported a neutral view of psychedelic drugs (M = 2.76; range: 1-5), PAT (M = 3.33), and interest in PAT (M = 3.10). After psychoeducation, participants reported a significantly more positive view of psychedelic drugs (M = 3.24, P =.014) and interest in PAT (M = 3.67, P =.016). Overall, participants indicated that they would support PAT availability in medical settings if proven beneficial (M = 4.52; 5 = "agree strongly") and they would support a loved one engaging in PAT (M = 4.29). The most frequently reported health concerns were concern of long-term effects (43%), fear of losing their mind (33%), fear of personality changes (33%), and fear of traumatic brain injury complications (24%). The most frequently endorsed barriers were time commitment, transportation, financial concerns, work, and childcare (33%-19%), with 48% reporting no barriers.ConclusionsThis is the first study to explore beliefs and perceived barriers regarding PAT among service members and veterans. These results indicate that military populations may be interested in PAT, particularly if psychoeducation and outreach regarding these treatments occurred. If FDA approved, it will be important to facilitate command support and address logistical barriers to ensure appropriate access within military contexts.

keywords:
Humans, Hallucinogens, Pilot Projects, Stress Disorders, Post-Traumatic, Military Personnel, Veterans, Female, Male, Brain Injuries, Traumatic

raw_json:
{"europe_pmc_id":"36564939","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: A "Magic Mushroom" Multi-Product Sesquiterpene Synthase.
journal: Chembiochem : a European journal of chemical biology
publication_date: 2023-11-01
doi: 10.1002/cbic.202300511
pubmed_id: 37614035
source_url: https://pubmed.ncbi.nlm.nih.gov/37614035/
keywords: Psilocybe, biosynthesis, enzyme, sesquiterpene, terpene synthase
substance_tags: psilocybin
topic_tags: In Vitro Study,Genomics
study_type: In Vitro Study
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:37
raw_json: {"pubmed_id":"37614035"}
authors:
Schäfer E, Seibold PS, Bartram S, Trottmann F, Haensch VG, Gressler M, Chadeayne AR, Hertweck C, O'Connor SE, Hoffmeister D

abstract:
Psilocybe "magic mushrooms" are chemically well understood for their psychotropic tryptamines. However, the diversity of their other specialized metabolites, in particular terpenoids, has largely remained an open question. Yet, knowledge on the natural product background is critical to understand if other compounds modulate the psychotropic pharmacological effects. CubA, the single clade II sesquiterpene synthase of P. cubensis, was heterologously produced in Escherichia coli and characterized in vitro, complemented by in vivo product formation assays in Aspergillus niger as a heterologous host. Extensive GC-MS analyses proved a function as multi-product synthase and, depending on the reaction conditions, cubebol, β-copaene, δ-cadinene, and germacrene D were detected as the major products of CubA. In addition, mature P. cubensis carpophores were analysed chromatographically which led to the detection of β-copaene and δ-cadinene. Enzymes closely related to CubA are encoded in the genomes of various Psilocybe species. Therefore, our results provide insight into the metabolic capacity of the entire genus.


authors: Liu LQ, Chen JZ, Fu WS, Tang CY.
publication_date: 2023-10-31
doi: 10.3724/sp.j.1123.2023.07013
pubmed_id: 37968816
source_url: https://doi.org/10.3724/sp.j.1123.2023.07013
substance_tags: psilocybin
topic_tags: Safety,Toxicity
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
[Determination of amanita peptide and tryptamine toxins in wild mushrooms by high performance liquid chromatography-tandem mass spectrometry].

abstract:
The discovery and identification of mushroom toxins has long been an important area in the fields of toxicology and food safety. Mushrooms are widely favored for their culinary and medicinal value; however, the presence of potentially lethal toxins in some species poses a substantial challenge in ensuring their safe consumption. Therefore, the development of a robust and sensitive analytical method is necessary for accurately identifying the risks associated with mushroom consumption. The study of mushroom toxins, which are characterized by their diversity and substantial variations in chemical structures, present a considerable challenge for achieving precise and high-throughput analysis. To address this issue, the present study employed a robust approach combining a solid-phase extraction (SPE) purification technique with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to establish an analytical method for the detection and quantification of five amatoxins and two tryptamines (psilocybin and bufotenine) present in some mushrooms. Several optimization procedures were undertaken, including optimizing the chromatographic conditions, mass spectrometric parameters, and sample extraction and purification. The procedure involved the extraction of dry mushroom powder with methanol containing 0.3% formic acid, followed by purification using a strong cation exchange cartridge (SCX). The analytes were separated on a T3 chromatographic column (100 mm×2.1 mm, 1.8 μm) using mobile phases of acetonitrile and 5 mmol/L ammonium acetate solution containing 0.1% formic acid. The multiple reaction monitoring (MRM) mode was employed for data acquisition. Amatoxins were quantified using matrix-matched standard calibration curves, whereas isotopic internal standards were used to quantify tryptamine. The results showed that all seven toxins exhibited good linearities (r2>0.99) within the optimized concentration range. The limits of detection (LODs) for bufotenine, psilocybin, and amatoxins were determined as 2.0, 5.0, and 10 μg/kg, respectively, while the limits of quantification (LOQs) were determined as 5.0, 10, and 20 μg/kg, respectively. The LOD and LOQ values further underscore the ability of the method to detect minute quantities of toxins, making it particularly well suited for screening food samples for potential contamination. Using dried shiitake mushroom powder as the matrix, the recoveries of the two tryptamines ranged from 80.6% to 117%, with relative standard deviations (RSDs) ranging from 1.73% to 5.98%, while the recoveries of amatoxins ranged from 71.8% to 115%, with RSDs varying from 2.14% to 9.92% at the three concentration levels. The consistent and satisfactory recoveries of amatoxins and tryptamines demonstrated the ability of this method to accurately quantify the target analytes even in a complex matrix. Comparison with the results of supplementary test method recognized by State Administration for Market Regulation for food (BJS202008) demonstrated comparable results, indicating no significant differences (p>0.05) in amatoxin contents. The newly developed method is rapid, accurate, precise, meets the required standards, and is suitable for the detection of seven toxins in wild mushrooms. As part of the application of this method, a comprehensive investigation of the distribution of toxins in wild mushrooms from Fujian Province was undertaken. In this study, 59 wild mushroom samples from nine cities were collected in the Fujian province. Species identification was conducted using rDNA-internal transcribed space (rDNA-ITS) molecular barcode technology, which revealed the presence of toxins in the two samples. Notably, one specimen named Amanita fuligineoides contained α-amanitin, β-amanitin, and phalloidin in quantities of 607, 377, and 69.0 mg/kg, respectively. Additionally, another sample, identified as Tricholomataceae, had a psilocybin concentration of 12.6 mg/kg.

keywords:
Amanita, Tryptamines, Formates, Bufotenin, DNA, Ribosomal, Mycotoxins, Powders, Chromatography, High Pressure Liquid, Tandem Mass Spectrometry, Psilocybin

raw_json:
{"europe_pmc_id":"37968816","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Olafsson RP, Kvaran K, Ketilsdottir K, Hallgrimsdottir K, Sigurdsson EL, Sigurdsson E.
publication_date: 2023-10-31
doi: 10.17992/lbl.2023.11.766
pubmed_id: 37909445
source_url: https://doi.org/10.17992/lbl.2023.11.766
substance_tags: psilocybin
topic_tags: Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
[Psychedelics and treatment of mental disorders: A survey of attitudes and knowledge among psychiatrists, general practitioners and psychologists in Iceland].

abstract:
IntroductionInterest in the use of psychedelics has increased following reports of their possible therapeutic potential. However, little is known about the knowledge of and attitudes towards the substances among health care professional who provide treatment for mental disorders in Iceland. An online survey was therefore conducted among members of the Icelandic associations of psychiatrists, general practitioners and psychologists.MethodsRespondents were 256 in total, including 177 psychologists, 38 psychiatrists and 41 general practitioners that provided information on their background, type of work, knowledge of and attitude towards different types of psychedelic substances and their views on optimal service delivery if psychedelics were approved by licencing authorities and used for treatment.ResultsAround half of psychiatrists reported having received questions about treatment with psychedelics in their clinical work, compared to only 14,6% of general practitioners and 17,5% of psychologists. The majority of respondents had little, or no knowledge of the substances targeted in the survey. A majority also expressed negative attitudes towards treatment with psilocybin mushrooms, but was positive towards ongoing scientific research and felt that such a treatment should be prescribed and provided by psychiatrists. Moreover, the majority view was that psilocybin treatment should be provided in specialised clinics or psychiatric units in a hospital setting. Scientific articles on the topic, discussions with colleagues and information in the media were identified as having had most influence on respondents´ attitudes towards psychedelics. Most respondents were interested in further education on psychedelics.ConclusionsRespondents among these three professions felt that the time has not yet come to use psychedelics in the treatment of mental disorders in Iceland but thought more education on psychedelics, their potential efficacy and adverse health effects is important given the increased interest in psychedelics.

keywords:
Humans, Hallucinogens, Mental Disorders, Psychiatry, Iceland, General Practitioners, Surveys and Questionnaires, Psilocybin

raw_json:
{"europe_pmc_id":"37909445","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin-assisted therapy for depression: A systematic review and meta-analysis.
publication_date: 2023-10-10
doi: 10.1016/j.psychres.2023.115531
pubmed_id: 37844352
source_url: https://doi.org/10.1016/j.psychres.2023.115531
substance_tags: psilocybin
topic_tags: Depression,End-of-Life Distress,Clinical Trial,Meta-Analysis,Systematic Review,Review Article
study_type: Meta-Analysis
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
authors:
Haikazian S, Chen-Li DCJ, Johnson DE, Fancy F, Levinta A, Husain MI, Mansur RB, McIntyre RS, Rosenblat JD.

abstract:
The aim of this review was to determine the effect of psilocybin on depressive symptoms in patients diagnosed with life-threatening illnesses or major depressive disorder. Systematic searches were conducted to search for randomized clinical trials and open-label trials that evaluated depression symptoms after psilocybin therapy. Data was pooled using a random-effects model. The primary outcome was the standardized mean difference (SMD) in depression severity, determined by calculating the change in depression ratings from baseline to the primary endpoint in the psilocybin arm versus the control arm. The literature search yielded 1734 studies, and 13 studies (n = 686) were included in either qualitative and/or quantitative analyses. The meta-analysis included 9 studies (pooled n = 596) and yielded a large effect size in favour of psilocybin (SMD = -0.78; p

keywords:
Humans, Hallucinogens, Antidepressive Agents, Depression, Psychotherapy, Psilocybin, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"37844352","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Malikowska-Racia N, Koniewski M, Golebiowska J, Popik P.
publication_date: 2023-10-15
doi: 10.1177/02698811231205692
pubmed_id: 37842884
source_url: https://doi.org/10.1177/02698811231205692
substance_tags: psilocybin
topic_tags: Depression,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Acute but not long-lasting antidepressant-like effect of psilocybin in differential reinforcement of low-rate 72 schedule in rats.

abstract:
BackgroundIn clinical studies, psychedelics including psilocybin and D-lysergic acid diethylamide (LSD) demonstrate rapid and persistent antidepressant effects. Since the effective treatment with psychedelics is usually provided with psychotherapy, it is debatable whether their prolonged efficacy can be observed in infrahuman species. Preclinical reports on psychedelics' effects most often address their acute actions, and different tests and models provide inconsistent results. The goal of this study was to examine whether the treatment with psilocybin and/or LSD would demonstrate immediate and/or sustained antidepressant-like effects in the differential reinforcement of low-rate responding (DRL) schedule in rats. In contrast to the antidepressant screening tools, the DRL 72s test is known to detect antidepressants with high predictive validity as it differentiates clinically effective antidepressants from other psychoactive drugs in non-stressed animals.MethodsAdult male Sprague Dawley rats were injected over three consecutive days with psilocybin (1 mg/kg), LSD (0.08 mg/kg), or saline and then tested in DRL 72s for the following 4 weeks.ResultsTreatment with psilocybin but not LSD demonstrated an immediate antidepressant-like effect, manifested as an increased number of reinforced presses and response efficiency. By contrast, neither of the drugs showed a long-term (up to 4 weeks following administration) antidepressant-like effect.ConclusionsUsing DRL 72s schedule of reinforcement, we demonstrated the acute antidepressant-like effect of psilocybin but not of LSD, and failed to detect their persistent antidepressant-like efficacy. The present study suggests that the detection of long-lasting antidepressant-like activity in rats could be challenging and may require entirely novel behavioral methods.

keywords:
Animals, Rats, Rats, Sprague-Dawley, Lysergic Acid Diethylamide, Hallucinogens, Antidepressive Agents, Reinforcement Schedule, Male, Psilocybin, Reinforcement, Psychology

raw_json:
{"europe_pmc_id":"37842884","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2023-10-04
doi: 10.1016/j.neubiorev.2023.105421
pubmed_id: 37802267
source_url: https://doi.org/10.1016/j.neubiorev.2023.105421
keywords: Brain, Humans, N-Methyl-3,4-methylenedioxyamphetamine, Ketamine, Hallucinogens, Psilocybin
substance_tags: psilocybin
topic_tags: Brain Imaging,Aging,Systematic Review,Review Article
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Functional imaging studies of acute administration of classic psychedelics, ketamine, and MDMA: Methodological limitations and convergent results.

authors:
Linguiti S, Vogel JW, Sydnor VJ, Pines A, Wellman N, Basbaum A, Eickhoff CR, Eickhoff SB, Edwards RR, Larsen B, McKinstry-Wu A, Scott JC, Roalf DR, Sharma V, Strain EC, Corder G, Dworkin RH, Satterthwaite TD.

abstract:
Functional magnetic resonance imaging (fMRI) is increasingly used to non-invasively study the acute impact of psychedelics on the human brain. While fMRI is a promising tool for measuring brain function in response to psychedelics, it also has known methodological challenges. We conducted a systematic review of fMRI studies examining acute responses to experimentally administered psychedelics in order to identify convergent findings and characterize heterogeneity in the literature. We reviewed 91 full-text papers; these studies were notable for substantial heterogeneity in design, task, dosage, drug timing, and statistical approach. Data recycling was common, with 51 unique samples across 91 studies. Fifty-seven studies (54%) did not meet contemporary standards for Type I error correction or control of motion artifact. Psilocybin and LSD were consistently reported to moderate the connectivity architecture of the sensorimotor-association cortical axis. Studies also consistently reported that ketamine administration increased activation in the dorsomedial prefrontal cortex. Moving forward, use of best practices such as pre-registration, standardized image processing and statistical testing, and data sharing will be important in this rapidly developing field.

raw_json:
{"europe_pmc_id":"37802267","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2023-09-06
doi: 10.1016/j.bbi.2023.09.004
pubmed_id: 37689275
source_url: https://doi.org/10.1016/j.bbi.2023.09.004
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Biomarkers,Healthy Volunteers,Inflammation,Immune Function
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Psilocybin induces acute and persisting alterations in immune status in healthy volunteers: An experimental, placebo-controlled study.

authors:
Mason NL, Szabo A, Kuypers KPC, Mallaroni PA, de la Torre Fornell R, Reckweg JT, Tse DHY, Hutten NRPW, Feilding A, Ramaekers JG.

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 and persisting (7 day) changes in immune status. 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 (7-Tesla) 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)- 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 did not significantly alter the stress response. Results are discussed in regards to the psychological and therapeutic effects of psilocybin demonstrated in ongoing patient trials.

keywords:
Hypothalamo-Hypophyseal System, Humans, Glutamic Acid, Tumor Necrosis Factor-alpha, Hallucinogens, Interleukin-6, Cytokines, Double-Blind Method, Stress, Psychological, Affect, Adult, Female, Male, Young Adult, Healthy Volunteers, Psilocybin

raw_json:
{"europe_pmc_id":"37689275","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Kovacevich A, Weleff J, Claytor B, Barnett BS.
publication_date: 2023-08-30
doi: 10.1080/02791072.2023.2253538
pubmed_id: 37650700
source_url: https://doi.org/10.1080/02791072.2023.2253538
substance_tags: psilocybin
topic_tags: Neuroplasticity,Mechanism of Action,Microdosing,Inflammation
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Three Cases of Reported Improvement in Microsmia and Anosmia Following Naturalistic Use of Psilocybin and LSD.

abstract:
Cultural awareness of anosmia and microsmia has recently increased due to their association with COVID-19, though treatment for these conditions is limited. A growing body of online media claims that individuals have noticed improvement in anosmia and microsmia following classic psychedelic use. We report what we believe to be the first three cases recorded in the academic literature of improvement in olfactory impairment after psychedelic use. In the first case, a man who developed microsmia after a respiratory infection experienced improvement in smell after the use of 6 g of psilocybin containing mushrooms. In the second case, a woman with anosmia since childhood reported olfactory improvement after ingestion of 100 µg of lysergic acid diethylamide (LSD). In the third case, a woman with COVID-19-related anosmia reported olfactory improvement after microdosing 0.1 g of psilocybin mushrooms three times. Following a discussion of these cases, we explore potential mechanisms for psychedelic-facilitated improvement in olfactory impairment, including serotonergic effects, increased neuroplasticity, and anti-inflammatory effects. Given the need for novel treatments for olfactory dysfunction, increasing reports describing improvement in these conditions following psychedelic use and potential biological plausibility, we believe that the possible therapeutic benefits of psychedelics for these conditions deserve further investigation.

keywords:
Humans, Olfaction Disorders, Lysergic Acid Diethylamide, Hallucinogens, Child, Female, Male, Psilocybin, COVID-19, Anosmia

raw_json:
{"europe_pmc_id":"37650700","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2023-08-17
doi: 10.1080/02791072.2023.2246459
pubmed_id: 37594163
source_url: https://doi.org/10.1080/02791072.2023.2246459
keywords: Animals, Humans, Mice, Agaricales, Hallucinogens, Psilocybe, Psilocybin, Major Depressive Disorder
substance_tags: psilocybin
topic_tags: Depression,Pharmacology,Animal Study,Safety,Toxicity
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
A Proposal to Study the Safety and Efficacy of Psilocybe cubensis in Preclinical and Clinical Studies as a Therapeutic Alternative for Major Depressive Disorder.

authors:
Escamilla R, González-Trujano ME, González Mariscal JM, Torres-Valencia JM, Guzmán-González H, Vega JL, Loizaga-Velder A.

abstract:
The pharmacological treatment of depression consists of taking antidepressant drugs for prolonged periods; its modest therapeutic effect can often be associated with significant adverse effects, while its discontinuation can lead to relapses. Psilocybin is today a novel and breakthrough therapy for major depression. It is a natural alkaloid in Psilocybe mushrooms, which are endemic to Mexico. Research on a larger scale is lacking in various populations, including the Mexican people. This proposal contemplates the experimental design of a preclinical (toxicity and pharmacological evaluation of an extract in mice) and clinical study by including the chemical analysis of a species of Psilocybe cubensis mushroom to characterize its main constituents. The clinical study will consider the safety evaluation by exploring tolerated doses of Psilocybe cubensis by measuring pharmacokinetic parameters after oral administration in healthy adults and an open trial on a sample of patients with major depressive disorder to assess the safety and efficacy of fully characterized Psilocybe cubensis in a two-single doses treatment, (with assisted psychotherapy), compared with the traditional care model at the Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz in Mexico City. This report presents the design of a research project with preclinical and clinical experimental components.

raw_json:
{"europe_pmc_id":"37594163","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2023-08-06
doi: 10.1016/j.euroneuro.2023.07.011
pubmed_id: 37557019
source_url: https://doi.org/10.1016/j.euroneuro.2023.07.011
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Psilocybin-assisted therapy for depression: A systematic review and dose-response meta-analysis of human studies.

authors:
Perez N, Langlest F, Mallet L, De Pieri M, Sentissi O, Thorens G, Seragnoli F, Zullino D, Kirschner M, Kaiser S, Solmi M, Sabé M.

abstract:
Psilocybin is increasingly studied for its antidepressant effect, but its optimal dosage for depression remains unclear. We conducted a systematic review and a dose-response meta-analysis to find the optimal dosage of psilocybin to reduce depression scores. Following our protocol (CRD42022220190) multiple electronic databases were searched from their inception until February 2023, to identify double-blind randomized placebo-controlled (RCTs) fixed-dose trials evaluating the use of psilocybin for adult patients with primary or secondary depression. A one-stage dose-response meta-analysis with restricted cubic splines was used. Cochrane risk of bias was used to assess risk of bias. Our analysis included seven studies with a total of 489 participants. Among these, four studies focused on primary depression (N = 366), including one study with patients suffering from treatment-resistant depression. The remaining three studies examined secondary depression (N = 123). The determined 95% effective doses per day (ED95) were 8.92, 24.68, and 36.08 mg/70 kg for patients with secondary depression, primary depression, and both subgroups, respectively. We observed significant dose-response associations for all curves, each plateauing at different levels, except for the bell-shaped curve observed in the case of secondary depression. Additionally, we found significant dose-response associations for various side effects, including physical discomfort, blood pressure increase, nausea/vomiting, headache/migraine, and the risk of prolonged psychosis. In conclusion, we discovered specific ED95 values for different populations, indicating higher ED95 values for treatment-resistant depression, primary depression, and secondary depression groups. Further RCTs are necessary for each population to determine the optimal dosage, allowing for maximum efficacy while minimizing side effects.

keywords:
Humans, Antidepressive Agents, Depression, Psychotic Disorders, Adult, Randomized Controlled Trials as Topic, Psilocybin

topic_tags:
Depression,Headache / Migraine,Randomized Controlled Trial,Meta-Analysis,Systematic Review,Review Article,Treatment-Resistant Depression,Safety,Adverse Events

raw_json:
{"europe_pmc_id":"37557019","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Downey AE, Boyd M, Chaphekar AV, Woolley J, Raymond-Flesch M.
publication_date: 2023-08-07
doi: 10.1002/eat.24041
pubmed_id: 37551650
source_url: https://doi.org/10.1002/eat.24041
keywords: Humans, Focus Groups, Psychotherapy, Qualitative Research, Feeding and Eating Disorders, Psilocybin
substance_tags: psilocybin
topic_tags: Eating Disorders,Clinical Trial,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
"But the reality is it's happening": A qualitative study of eating disorder providers about psilocybin-assisted psychotherapy.

abstract:
ObjectiveThis study invited providers who care for patients with eating disorders to inform engagement, communication, and collaboration with psilocybin-assisted psychotherapy interventions.MethodMedical and mental health providers who treat patients with eating disorders were recruited via professional referral networks and participant driven sampling from across California to participate in one of five focus groups. Discussion topics included prior knowledge of psychedelic therapy, interest/concerns related to psilocybin therapy, and opportunities for collaboration. Study team members completed iterative rounds of coding with a grounded theory approach.ResultsA total of 32 participants reported a range of familiarity with psychedelics. Some raised concerns about the risks of administering psilocybin to malnourished patients and to those with psychological comorbidities. Despite these concerns, participants were hopeful to see psilocybin therapy as a treatment for patients with eating disorders. In anticipating challenges, providers had concerns about equity in access to care among publicly insured and non-English speaking patients. They requested opportunities for continuing education about psilocybin therapy.DiscussionOur findings demonstrate provider interest in psilocybin therapy for the treatment of patients with eating disorders. As psilocybin therapy interventions are developed, providers caring for patients with eating disorders value collaboration to improve longitudinal patient outcomes.Public significanceThis study invited healthcare providers of patients with eating disorders to discuss their thoughts around the use of psilocybin-assisted psychotherapy in this population. Findings will help inform emerging psilocybin therapy clinical trials with the goal of successful translation and adoption in real world clinical settings.

raw_json:
{"europe_pmc_id":"37551650","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: bioRxiv
publication_date: 2023-02-20
doi: 10.1101/2023.02.19.528997
source_url: https://doi.org/10.1101/2023.02.19.528997
substance_tags: psilocybin
topic_tags: Brain Imaging,Aging,Animal Study,Drug Interactions
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
UNRAVELing the synergistic effects of psilocybin and environment on brain-wide immediate early gene expression in mice

authors:
Rijsketic DR, Casey AB, Barbosa DA, Zhang X, Hietamies TM, Ramirez-Ovalle G, Pomrenze M, Halpern CH, Williams LM, Malenka RC, Heifets BD.

abstract:
The effects of context on the subjective experience of serotonergic psychedelics have not been fully examined in human neuroimaging studies, partly due to limitations of the imaging environment. Here, we administered saline or psilocybin to mice in their home cage or an enriched environment, immunofluorescently-labeled brain-wide c-Fos, and imaged cleared tissue with light sheet microscopy to examine the impact of context on psilocybin-elicited neural activity at cellular resolution. Voxel-wise analysis of c-Fos-immunofluorescence revealed differential neural activity, which we validated with c-Fos + cell density measurements. Psilocybin increased c-Fos expression in the neocortex, caudoputamen, central amygdala, and parasubthalamic nucleus and decreased c-Fos in the hypothalamus, cortical amygdala, striatum, and pallidum. Main effects of context and psilocybin-treatment were robust, widespread, and spatially distinct, whereas interactions were surprisingly sparse.

raw_json:
{"europe_pmc_id":"PPR619153","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


authors: Kruger DJ, Enghoff O, Herberholz M, Barron J, Boehnke KF
journal: Journal of psychoactive drugs
publication_date: 2022-12-31
doi: 10.1080/02791072.2023.2201263
pubmed_id: 37078418
source_url: https://pubmed.ncbi.nlm.nih.gov/37078418/
keywords: LSD, Psychedelics, information, media, psilocybin, trust
substance_tags: psilocybin
topic_tags: Review Article,Observational Study,Safety
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:37
raw_json: {"pubmed_id":"37078418"}
title:
"How Do I Learn More About this?": Utilization and Trust of Psychedelic Information Sources Among People Naturalistically Using Psychedelics.

abstract:
There is a surge of interest in psychedelics, including new stakeholders and greater media attention. There is a need to examine the information-seeking behavior of people using psychedelics naturalistically, given the importance of preparation and harm-reduction. We examined sources of information for people using psychedelics naturalistically, and the degree to which they are trusted in a large, anonymous, online survey ( = 1221). The most common source of participants' information on psychedelics was their own experimentation and experiences (79.52%). Most also sought information from Internet websites (61.67%), friends (61.02%), Internet discussion forums (57.08%), books (57%), and articles in peer-reviewed scientific journals (54.55%). Few sought information from their primary health care provider (4.83%). Articles published in scientific journals, psychedelic nonprofits, and researchers based in colleges or universities were the most trusted sources of psychedelic information. Government agencies and pharmaceutical companies were the least trusted. Few participants thought that the popular media accurately stated the benefits and risks of psychedelics and most thought that the popular media failed to distinguish between different types of psychedelics. Our results indicate a high level of information seeking among psychedelic users, with a diverse array of information sources typically outside of mainstream health and medical care systems.


authors: Sharma R, Batchelor R, Sin J.
publication_date: 2023-03-17
doi: 10.1080/02791072.2023.2190319
pubmed_id: 36933948
source_url: https://doi.org/10.1080/02791072.2023.2190319
substance_tags: psilocybin
topic_tags: Addiction,Systematic Review,Review Article
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Psychedelic Treatments for Substance Use Disorder and Substance Misuse: A Mixed Methods Systematic Review.

abstract:
Renewed interest in psychedelic substances in the 21st century has seen the exploration of psychedelic treatments for various psychiatric disorders including substance use disorder (SUD). This review aimed to assess the effectiveness of psychedelic treatments for people with SUD and those falling below diagnostic thresholds (i.e. substance misuse). We systematically searched 11 databases, trial registries, and psychedelic organization websites for empirical studies examining adults undergoing psychedelic treatment for SUD or substance misuse, published in the English language, between 2000 and 2021. Seven studies investigating treatment using psilocybin, ibogaine, and ayahuasca, alone or adjunct with psychotherapy reported across 10 papers were included. Measures of abstinence, substance use, psychological and psychosocial outcomes, craving, and withdrawal reported positive results, however, this data was scarce among studies examining a wide range of addictions including opioid, nicotine, alcohol, cocaine and unspecified substance. The qualitative synthesis from three studies described subjective experience of psychedelic-assisted treatments enhanced self-awareness, insight, and confidence. At present, there is no sufficient research evidence to suggest effectiveness of any of the psychedelics on any specific substance use disorder or substance misuse. Further research using rigorous effectiveness evaluation methods with larger sample sizes and longer-term follow-up is required.

keywords:
Humans, Substance-Related Disorders, Lysergic Acid Diethylamide, Ibogaine, Hallucinogens, Psychotherapy, Adult, Psilocybin

raw_json:
{"europe_pmc_id":"36933948","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Baker KM, Ulrich CM, Meghani SH.
publication_date: 2023-01-04
doi: 10.1177/10499091221147700
pubmed_id: 36604312
source_url: https://doi.org/10.1177/10499091221147700
keywords: Humans, Hallucinogens, Spirituality, Mysticism, Adult, Surveys and Questionnaires, Psilocybin
substance_tags: psilocybin
topic_tags: Wellbeing,Spirituality,Mystical Experience,Review Article,Observational Study
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
An Integrative Review of Measures of Spirituality in Experimental Studies of Psilocybin in Serious Illness Populations.

abstract:
Background: Psilocybin-assisted therapies (PAT) are reemerging as a treatment for complex distress often prompting mystical experiences, enhanced meaning, and spiritual wellbeing. We sought to investigate how measures of spirituality are employed in experimental studies of PAT conducted with seriously ill adults. Methods: We included experimental studies of psilocybin conducted with seriously ill adults, which employed measures that contained spirituality and mysticism concepts within their domains or subdomains. Included studies were peer-reviewed and published in English language (up to December 2021). Results: Seven articles met our inclusion criteria. A total of 12 unique instruments were identified. The most frequently used instruments were the Mystical Experience Questionnaire (MEQ30), the Functional Assessment of Chronic Illness Therapy-Spirituality (FACIT-Sp-12), and the Demoralization Scale (DS-I/II) (used in four studies each), followed by the Persisting Effects Questionnaire (PEQ) (used in three studies). Overall, studies did not consistently define and contextualize spirituality domains and subdomains studied. Conclusions: Despite well-recognized significance of spirituality in PAT, there was considerable heterogeneity in number and types of spirituality measures employed across studies. There also seemed a lack of attention to defining and operationalizing spirituality and its domains and subdomains. This is notable as spirituality and overlapping concepts (eg mystical experiences) contributes substantially to this body of research and patients' therapeutic outcomes. Towards developing more rigorous science of spirituality in PAT research, there is a critical need to evaluate and refine measures of spirituality to enhance their utility and replicability, limit participant burden, and better contextualize spirituality-related findings and outcomes.

raw_json:
{"europe_pmc_id":"36604312","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: A Comprehensive Review of the Current Status of the Cellular Neurobiology of Psychedelics.
authors: Banushi B, Polito V
journal: Biology
publication_date: 2023-10-27
doi: 10.3390/biology12111380
pubmed_id: 37997979
source_url: https://pubmed.ncbi.nlm.nih.gov/37997979/
substance_tags: psilocybin
topic_tags: Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Review Article,Inflammation
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:37
raw_json: {"pubmed_id":"37997979"}
abstract:
Psychedelic substances have gained significant attention in recent years for their potential therapeutic effects on various psychiatric disorders. This review delves into the intricate cellular neurobiology of psychedelics, emphasizing their potential therapeutic applications in addressing the global burden of mental illness. It focuses on contemporary research into the pharmacological and molecular mechanisms underlying these substances, particularly the role of 5-HT2A receptor signaling and the promotion of plasticity through the TrkB-BDNF pathway. The review also discusses how psychedelics affect various receptors and pathways and explores their potential as anti-inflammatory agents. Overall, this research represents a significant development in biomedical sciences with the potential to transform mental health treatments.

keywords:
5-HT2A, BDNF, LSD, TrkB, hallucinogen, neuroplasticity, psilocybin, psychedelic therapy, psychedelics, serotonergic


authors: Barnett BS, Bassir Nia A, Sackett NB, Weleff J
journal: Frontiers in psychiatry
publication_date: 2022-12-31
doi: 10.3389/fpsyt.2023.1305478
pubmed_id: 37928914
source_url: https://pubmed.ncbi.nlm.nih.gov/37928914/
keywords: addiction, ketamine, psilocybin, psychedelics, substance use disorder
substance_tags: psilocybin
topic_tags: Addiction,Mechanism of Action,Safety
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"37928914"}
title:
Editorial: Psychedelics as treatments for substance use disorders: exploring therapeutic potential, risks, underlying mechanisms of action, and implementation challenges.


authors: Rieser NM, Gubser LP, Moujaes F, Duerler P, Lewis CR, Michels L, Vollenweider FX, Preller KH.
publication_date: 2023-10-13
doi: 10.1038/s41598-023-44153-z
pubmed_id: 37838755
source_url: https://doi.org/10.1038/s41598-023-44153-z
keywords: Brain, Humans, Hallucinogens, Individuality, Cerebrovascular Circulation, Psilocybin
substance_tags: psilocybin
topic_tags: Mechanism of Action,Biomarkers,Healthy Volunteers
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Psilocybin-induced changes in cerebral blood flow are associated with acute and baseline inter-individual differences.

abstract:
Research into the use of psilocybin for the treatment of psychiatric disorders is a growing field. Nevertheless, robust brain-behavior relationships linking psilocybin-induced brain changes to subjective drug-induced effects have not been established. Furthermore, it is unclear if the acute neural effects are dependent on individual heterogeneity in baseline characteristics. To address this, we assessed the effects of three oral doses of psilocybin vs. placebo on cerebral blood flow (CBF) using arterial spin labeling in healthy participants (N = 70; n = 31, 0.16 mg/kg; n = 10, 0.2 mg/kg; n = 29, 0.215 mg/kg). First, we quantified psilocybin-induced changes in relative and absolute CBF. Second, in an exploratory analysis, we assessed whether individual baseline characteristics and subjective psychedelic experience are associated with changes in CBF. Psychological and neurobiological baseline characteristics correlated with the psilocybin-induced reduction in relative CBF and the psilocybin-induced subjective experience. Furthermore, the psilocybin-induced subjective experience was associated with acute changes in relative and absolute CBF. The results demonstrated that inter-individual heterogeneity in the neural response to psilocybin is associated with baseline characteristics and shed light on the mechanisms underlying the psychedelic-induced altered state. Overall, these findings help guide the search for biomarkers, paving the way for a personalized medicine approach within the framework of psychedelic-assisted therapy.

raw_json:
{"europe_pmc_id":"37838755","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Tyagi R, Saraf TS, Canal CE.
publication_date: 2023-09-17
doi: 10.1021/acsptsci.3c00137
pubmed_id: 37854624
source_url: https://doi.org/10.1021/acsptsci.3c00137
substance_tags: psilocybin
topic_tags: Pharmacology,Receptor Pharmacology,Animal Study,In Vitro Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:06
title:
The Psychedelic N,N-Dipropyltryptamine Prevents Seizures in a Mouse Model of Fragile X Syndrome via a Mechanism that Appears Independent of Serotonin and Sigma1 Receptors.

abstract:
The serotonergic psychedelic psilocybin shows efficacy in treating neuropsychiatric disorders, though the mechanism(s) underlying its therapeutic effects remain unclear. We show that a similar psychedelic tryptamine, N,N-dipropyltryptamine (DPT), completely prevents audiogenic seizures (AGS) in an Fmr1 knockout mouse model of fragile X syndrome at a 10 mg/kg dose but not at lower doses (3 or 5.6 mg/kg). Despite showing in vitro that DPT is a serotonin 5-HT2A, 5-HT1B, and 5-HT1A receptor agonist (with that rank order of functional potency, determined with TRUPATH Gα/βγ biosensors), pretreatment with selective inhibitors of 5-HT2A/2C, 5-HT1B, or 5-HT1A receptors did not block DPT's antiepileptic effects; a pan-serotonin receptor antagonist was also ineffective. Because 5-HT1A receptor activation blocks AGS in Fmr1 knockout mice, we performed a dose-response experiment to evaluate DPT's engagement of 5-HT1A receptors in vivo. DPT elicited 5-HT1A-dependent effects only at doses greater than 10 mg/kg, further supporting that DPT's antiepileptic effects were not 5-HT1A-mediated. We also observed that the selective sigma1 receptor antagonist, NE-100, did not impact DPT's antiepileptic effects, suggesting DPT engagement of sigma1 receptors was not a crucial mechanism. Separately, we observed that DPT and NE-100 at high doses caused convulsions on their own that were qualitatively distinct from AGS. In conclusion, DPT dose-dependently blocked AGS in Fmr1 knockout mice, but neither serotonin nor sigma1 receptor antagonists prevented this action. Thus, DPT might have neurotherapeutic effects independent of its serotonergic psychedelic properties. However, DPT also caused seizures at high doses, showing that DPT has complex dose-dependent in vivo polypharmacology.

raw_json:
{"europe_pmc_id":"37854624","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Tryptamines and Mental Health: Activating the 5-HT Receptor for Therapeutic Potential.
authors: Kargbo RB.
publication_date: 2023-09-14
doi: 10.1021/acsmedchemlett.3c00390
pubmed_id: 37849550
source_url: https://doi.org/10.1021/acsmedchemlett.3c00390
substance_tags: psilocybin
topic_tags: Depression,PTSD,Receptor Pharmacology,Clinical Trial,Treatment-Resistant Depression
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
abstract:
Tryptamines, a class of 3-aminoethyl-indoles that activate the serotonin receptor, show potential for novel mental health treatments. The FDA has granted "breakthrough therapy designation" to psilocybin and MDMA for treatment-resistant depression, major depressive disorder, and post-traumatic stress disorder, sparking global research efforts. Various clinical trials are currently investigating the therapeutic value of psilocybin for several mental health disorders. Results thus far indicate significant improvements in patient-reported outcomes via reductions in experiential avoidance. These advancements highlight a promising future for tryptamines in mental health therapy.

raw_json:
{"europe_pmc_id":"37849550","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Ko K, Carter B, Cleare AJ, Rucker JJ.
publication_date: 2023-10-04
doi: 10.2147/ndt.s426193
pubmed_id: 37818448
source_url: https://doi.org/10.2147/ndt.s426193
substance_tags: psilocybin
topic_tags: Depression,Personality Change,Mystical Experience,Clinical Trial,Healthy Volunteers
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
title:
Predicting the Intensity of Psychedelic-Induced Mystical and Challenging Experience in a Healthy Population: An Exploratory Post-Hoc Analysis.

abstract:
IntroductionIn psychedelic therapy, mystical as well as challenging experience may influence therapeutic outcome. However, predictors of such experience have not been sufficiently established. Determining predictors of their intensity is, therefore, potentially beneficial in targeting psilocybin therapy for depression.MethodsIn a post hoc data analysis of a Phase 1, randomised, double-blind, placebo-controlled, between-groups clinical trial, dosage, personality traits, affect, and individual data were analysed as possible clinical predictors. Eighty-nine healthy volunteers were randomised to receive a single dose of placebo, 10 mg of psilocybin, or 25 mg of psilocybin. ANOVA was used to analyse the relationship between dosage and mystical and/or challenging experience, and correlation analysis for all other variables.ResultsThe intensity of both mystical and challenging experience was strongly associated with higher dosage. Age was negatively correlated with intensity of challenging experience. Correlation between identified personality traits and either mystical or challenging experience was minimal, with the exception of positive correlation between neuroticism and challenging experience at higher dose. Neither positive nor negative affect indicated correlation with the intensity of either type of experience.DiscussionA limitation of this study is its post hoc, exploratory design; recommendations for further research are provided.

raw_json:
{"europe_pmc_id":"37818448","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2023-10-04
doi: 10.1186/s40814-023-01399-8
pubmed_id: 37798662
source_url: https://doi.org/10.1186/s40814-023-01399-8
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
An open-label pilot trial assessing tolerability and feasibility of LSD microdosing in patients with major depressive disorder (LSDDEP1).

authors:
Donegan CJ, Daldegan-Bueno D, Sumner R, Menkes D, Evans W, Hoeh N, Sundram F, Reynolds L, Ponton R, Cavadino A, Smith T, Roop P, Allen N, Abeysinghe B, Svirskis D, Forsyth A, Bansal M, Muthukumaraswamy S.

abstract:
BackgroundGlobally, an estimated 260 million people suffer from depression [1], and there is a clear need for the development of new, alternative antidepressant therapies. In light of problems with the tolerability and efficacy of available treatments [2], a global trend is emerging for patients to self-treat depression with microdoses of psychedelic drugs such as lysergic acid diethylamide (LSD) and psilocybin [3]. Beyond anecdotal reports from those who self-medicate in this way, few clinical trials have evaluated this practice. In our recently published phase 1 study in healthy volunteers [4], we determined that LSD microdosing was relatively safe and well tolerated in that cohort. Furthermore, the data demonstrated that conducting such microdosing trials is broadly feasible, with excellent adherence and compliance to the regimen observed. In this open-label pilot trial of patients with major depressive disorder (LSDDEP1), we will test the tolerability and feasibility of an 8-week regimen of LSD microdosing in this patient group prior to a larger subsequent randomised controlled trial (LSDDEP2).MethodsTwenty patients meeting the DSM-5 criteria for major depressive disorder will receive an 8-week LSD microdosing treatment regimen. The treatment protocol will use a sublingual formulation of LSD (MB-22001) delivered twice per week under a titration schedule using a dose of 5-15 µg. Tolerability will be assessed by quantifying the percentage of participants who withdraw from the trial due to adverse events attributable to the treatment regimen, while feasibility will be assessed by quantifying the percentage of attended clinic visits once enrolled. To determine whether there is any antidepressant response to the LSD microdosing regimen, MADRS scores will be assessed at baseline and 2, 4, 6, and 8 weeks after the commencement of the regimen.DiscussionThe results of LSDDEP1 will provide valuable information regarding the tolerability and feasibility of a proposed LSD microdosing regimen in patients with MDD. Such information is critically important to optimise trial design prior to commencing a subsequent and more resource-intensive randomised controlled trial.Trial registrationANZCTR, ACTRN12623000486628. Registered on 12 May 2023.

topic_tags:
Depression,Microdosing,Clinical Trial,Randomized Controlled Trial,Observational Study,Healthy Volunteers,Safety,Adverse Events

raw_json:
{"europe_pmc_id":"37798662","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Bedside to bench: the outlook for psychedelic research.
authors: Acero VP, Cribas ES, Browne KD, Rivellini O, Burrell JC, O'Donnell JC, Das S, Cullen DK
journal: Frontiers in pharmacology
publication_date: 2022-12-31
doi: 10.3389/fphar.2023.1240295
pubmed_id: 37869749
source_url: https://pubmed.ncbi.nlm.nih.gov/37869749/
keywords: DMT, MDMA, ayahuasca, ketamine, mechanism of action (MOA), psilocybin, psychedelics, salvinorin
substance_tags: psilocybin
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"37869749"}
abstract:
There has recently been a resurgence of interest in psychedelic compounds based on studies demonstrating their potential therapeutic applications in treating post-traumatic stress disorder, substance abuse disorders, and treatment-resistant depression. Despite promising efficacy observed in some clinical trials, the full range of biological effects and mechanism(s) of action of these compounds have yet to be fully established. Indeed, most studies to date have focused on assessing the psychological mechanisms of psychedelics, often neglecting the non-psychological modes of action. However, it is important to understand that psychedelics may mediate their therapeutic effects through multi-faceted mechanisms, such as the modulation of brain network activity, neuronal plasticity, neuroendocrine function, glial cell regulation, epigenetic processes, and the gut-brain axis. This review provides a framework supporting the implementation of a multi-faceted approach, incorporating, and modeling, to aid in the comprehensive understanding of the physiological effects of psychedelics and their potential for clinical application beyond the treatment of psychiatric disorders. We also provide an overview of the literature supporting the potential utility of psychedelics for the treatment of brain injury (e.g., stroke and traumatic brain injury), neurodegenerative diseases (e.g., Parkinson's and Alzheimer's diseases), and gut-brain axis dysfunction associated with psychiatric disorders (e.g., generalized anxiety disorder and major depressive disorder). To move the field forward, we outline advantageous experimental frameworks to explore these and other novel applications for psychedelics.

topic_tags:
Depression,Anxiety,PTSD,Neuroplasticity,Mechanism of Action,Epigenetics,Clinical Trial,Review Article,Treatment-Resistant Depression


title: Use of Psychedelics for Pain: A Scoping Review.
authors: Goel A, Rai Y, Sivadas S, Diep C, Clarke H, Shanthanna H, Ladha KS.
publication_date: 2023-09-30
doi: 10.1097/aln.0000000000004673
pubmed_id: 37698433
source_url: https://doi.org/10.1097/aln.0000000000004673
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
Chronic pain is a public health concern that affects approximately 1.5 billion people globally. Conventional therapeutic agents including opioid and non-opioid analgesics have been associated with adverse side effects, issues with addiction, and ineffective analgesia. Novel agents repurposed to treat pain via different mechanisms are needed to fill the therapeutic gap in chronic pain management. Psychedelics such as lysergic acid diethylamide and psilocybin (the active ingredient in psychedelic mushrooms) are thought to alter pain perception through direct serotonin receptor agonism, anti-inflammatory effects, and synaptic remodeling. This scoping review was conducted to identify human studies in which psychedelic agents were used for the treatment of pain. Twenty-one articles that assessed the effects of psychedelics in treating various pain states were included. The present scarcity of clinical trials and small sample sizes limit their application for clinical use. Overall, psychedelics appear to show promise for analgesia in patients with certain headache disorders and cancer pain diagnoses. Future studies must aim to examine the combined effects of psychotherapy and psychedelics on chronic pain.

keywords:
Humans, Hallucinogens, Analgesia, Pain Perception, Pain Management, Chronic Pain, Drug-Related Side Effects and Adverse Reactions

topic_tags:
Addiction,Chronic Pain,Headache / Migraine,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Clinical Trial,Review Article,Adverse Events,Inflammation

raw_json:
{"europe_pmc_id":"37698433","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The zebrafish for preclinical psilocybin research.
authors: Syed OA, Tsang B, Gerlai R.
publication_date: 2023-09-06
doi: 10.1016/j.neubiorev.2023.105381
pubmed_id: 37689090
source_url: https://doi.org/10.1016/j.neubiorev.2023.105381
keywords: Animals, Zebrafish, Hallucinogens, Anxiety, Anxiety Disorders, Psilocybin
substance_tags: psilocybin
topic_tags: Anxiety,Mechanism of Action,Review Article,Animal Study,Safety,Toxicity
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
In this review, we discuss the possible utility of zebrafish in research on psilocybin, a psychedelic drug whose recreational use as well as possible clinical application are gaining increasing interest. First, we review behavioral tests with zebrafish, focussing on anxiety and social behavior, which have particular relevance in the context of psilocybin research. Next, we briefly consider methods of genetic manipulations with which psilocybin's phenotypical effects and underlying mechanisms may be investigated in zebrafish. We briefly review the known mechanisms of psilocybin, and also discuss what we know about its safety and toxicity profile. Last, we discuss examples of how psilocybin may be employed for testing treatment efficacy in preclinical research for affective disorders in zebrafish. We conclude that zebrafish has a promising future in preclinical research on psychedelic drugs.

raw_json:
{"europe_pmc_id":"37689090","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Wolfgang AS, Hoge CW.
publication_date: 2023-09-07
doi: 10.1007/s11920-023-01446-4
pubmed_id: 37682446
source_url: https://doi.org/10.1007/s11920-023-01446-4
substance_tags: psilocybin
topic_tags: Depression,PTSD,Mechanism of Action,Clinical Trial,Review Article,Veterans,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Psychedelic-Assisted Therapy in Military and Veterans Healthcare Systems: Clinical, Legal, and Implementation Considerations.

abstract:
Purpose of reviewThis review discusses the current and projected landscape of psychedelic-assisted therapy (PAT), with a focus on clinical, legal, and implementation considerations in Department of Defense (DoD) and Department of Veterans Affairs (VA) healthcare systems.Recent findings3,4-Methylenedioxymethamphetamine (MDMA)- and psilocybin-assisted therapy have shown promising outcomes in efficacy, safety, tolerability, and durability for PTSD and depression, respectively. MDMA-assisted therapy is already approved by the Food and Drug Administration (FDA) on an Expanded Access ("compassionate use") basis for PTSD, with full approval projected for 2024. Psilocybin-assisted therapy is projected to be FDA-approved for depression soon thereafter. Other psychedelics are in earlier stages of development. The VA is currently conducting PAT clinical trials. Although there are clear legal pathways for the VA and DoD to conduct PAT trials, a number of implementation barriers exist, such as the very high number of clinical hours necessary to treat each patient, resource requirements to support treatment infrastructure, military-specific considerations, and the high level of evidence necessary for PAT to be recommended in clinical practice guidelines. Ongoing considerations are whether and how PAT will be made available to VA and DoD beneficiaries, feasibility and cost-effectiveness, and ethical safeguards that must be implemented to prioritize access to PAT given the likelihood of extremely limited initial availability. However, with imminent FDA approval of PATs and considerable national interest in these treatments, DoD and VA policymakers must be prepared with clearly delineated policies and plans for how these healthcare systems will approach PAT.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Hallucinogens, United States Department of Veterans Affairs, Veterans, Delivery of Health Care, United States, Psilocybin

raw_json:
{"europe_pmc_id":"37682446","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelics in the treatment of eating disorders: Rationale and potential mechanisms.
authors: Calder A, Mock S, Friedli N, Pasi P, Hasler G.
publication_date: 2023-06-20
doi: 10.1016/j.euroneuro.2023.05.008
pubmed_id: 37352816
source_url: https://doi.org/10.1016/j.euroneuro.2023.05.008
substance_tags: psilocybin
topic_tags: PTSD,Addiction,Eating Disorders,Mechanism of Action,Review Article,Case Report,Safety
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
Eating disorders are serious illnesses showing high rates of mortality and comorbidity with other mental health problems. Psychedelic-assisted therapy has recently shown potential in the treatment of several common comorbidities of eating disorders, including mood disorders, post-traumatic stress disorder, and substance use disorders. The theorized therapeutic mechanisms of psychedelic-assisted therapy suggest that it could be beneficial in the treatment of eating disorders as well. In this review, we summarize preliminary data on the efficacy of psychedelic-assisted therapy in people with anorexia nervosa, bulimia nervosa, and binge eating disorder, which include studies and case reports of psychedelic-assisted therapy with ketamine, MDMA, psilocybin, and ayahuasca. We then discuss the potential therapeutic mechanisms of psychedelic-assisted therapy in these three eating disorders, including both general therapeutic mechanisms and those which are relatively specific to eating disorders. We find preliminary evidence that psychedelic-assisted therapy may be effective in the treatment of anorexia nervosa and bulimia nervosa, with very little data available on binge eating disorder. Regarding mechanisms, psychedelic-assisted therapy may be able to improve beliefs about body image, normalize reward processing, promote cognitive flexibility, and facilitate trauma processing. Just as importantly, it appears to promote general therapeutic factors relevant to both eating disorders and many of their common comorbidities. Lastly, we discuss potential safety concerns which may be associated with these treatments and present recommendations for future research.

keywords:
Humans, Hallucinogens, Anorexia Nervosa, Bulimia Nervosa, Binge-Eating Disorder, Feeding and Eating Disorders

raw_json:
{"europe_pmc_id":"37352816","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Brown O.
publication_date: 2023-05-28
doi: 10.1016/j.jad.2023.05.088
pubmed_id: 37257781
source_url: https://doi.org/10.1016/j.jad.2023.05.088
keywords: Brain, Humans, Hallucinogens, Depression, Music, Psilocybin
substance_tags: psilocybin
topic_tags: Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Letter to the editor on "Increased low-frequency brain responses to music after psilocybin therapy for depression".

abstract:
The recent publication in the Journal of Affective Disorders titled "Increased low-frequency brain responses to music after psilocybin therapy for depression" identified significant region-of-interest based effects of treatment in the task scans. In this letter to the editor, I am hoping to raise methodological concerns with regards to the ANOVA ROI analysis that were otherwise not acknowledged in this study. These concerns raise questions as to the impact of confounds, including as age and biological sex, on the reported proportion variance explained by the effects of psilocybin treatment for depression.

raw_json:
{"europe_pmc_id":"37257781","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2023-05-24
doi: 10.1038/s41386-023-01607-2
pubmed_id: 37231080
source_url: https://doi.org/10.1038/s41386-023-01607-2
substance_tags: psilocybin
topic_tags: Pharmacology,Consciousness,Healthy Volunteers,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Comparative acute effects of mescaline, lysergic acid diethylamide, and psilocybin in a randomized, double-blind, placebo-controlled cross-over study in healthy participants.

authors:
Ley L, Holze F, Arikci D, Becker AM, Straumann I, Klaiber A, Coviello F, Dierbach S, Thomann J, Duthaler U, Luethi D, Varghese N, Eckert A, Liechti ME.

abstract:
Mescaline, lysergic acid diethylamide (LSD), and psilocybin are classic serotonergic psychedelics. A valid, direct comparison of the effects of these substances is lacking. The main goal of the present study was to investigate potential pharmacological, physiological and phenomenological differences at psychoactive-equivalent doses of mescaline, LSD, and psilocybin. The present study used a randomized, double-blind, placebo-controlled, cross-over design to compare the acute subjective effects, autonomic effects, and pharmacokinetics of typically used, moderate to high doses of mescaline (300 and 500 mg), LSD (100 µg), and psilocybin (20 mg) in 32 healthy participants. A mescaline dose of 300 mg was used in the first 16 participants and 500 mg was used in the subsequent 16 participants. Acute subjective effects of 500 mg mescaline, LSD, and psilocybin were comparable across various psychometric scales. Autonomic effects of 500 mg mescaline, LSD, and psilocybin were moderate, with psilocybin causing a higher increase in diastolic blood pressure compared with LSD, and LSD showing a trend toward an increase in heart rate compared with psilocybin. The tolerability of mescaline, LSD, and psilocybin was comparable, with mescaline at both doses inducing slightly more subacute adverse effects (12-24 h) than LSD and psilocybin. Clear distinctions were seen in the duration of action between the three substances. Mescaline had the longest effect duration (mean: 11.1 h), followed by LSD (mean: 8.2 h), and psilocybin (mean: 4.9 h). Plasma elimination half-lives of mescaline and LSD were similar (approximately 3.5 h). The longer effect duration of mescaline compared with LSD was due to the longer time to reach maximal plasma concentrations and related peak effects. Mescaline and LSD, but not psilocybin, enhanced circulating oxytocin. None of the substances altered plasma brain-derived neurotrophic factor concentrations. In conclusion, the present study found no evidence of qualitative differences in altered states of consciousness that were induced by equally strong doses of mescaline, LSD, and psilocybin. The results indicate that any differences in the pharmacological profiles of mescaline, LSD, and psilocybin do not translate into relevant differences in the subjective experience. ClinicalTrials.gov identifier: NCT04227756.

keywords:
Humans, Mescaline, Lysergic Acid Diethylamide, Hallucinogens, Cross-Over Studies, Healthy Volunteers, Psilocybin

raw_json:
{"europe_pmc_id":"37231080","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Gold ND, Mallard AJ, Hermann JC, Zeifman RJ, Pagni BA, Bogenschutz MP, Ross S
journal: Journal of palliative medicine
publication_date: 2023-09-30
doi: 10.1089/jpm.2022.0604
pubmed_id: 37167080
source_url: https://pubmed.ncbi.nlm.nih.gov/37167080/
substance_tags: psilocybin
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"37167080"}
title:
Exploring the Potential Utility of Psychedelic Therapy for Patients With Amyotrophic Lateral Sclerosis.

abstract:
Amyotrophic lateral sclerosis (ALS) is an aggressive, terminal neurodegenerative disease that causes death of motor neurons and has an average survival time of 3-4 years. ALS is the most common motor neuron degenerative disease and is increasing in prevalence. There is a pressing need for more effective ALS treatments as available pharmacotherapies do not reverse disease progression or provide substantial clinical benefit. Furthermore, despite psychological distress being highly prevalent in ALS patients, psychological treatments remain understudied. Psychedelics (i.e., serotonergic psychedelics and related compounds like ketamine) have seen a resurgence of research into therapeutic applications for treating a multitude of neuropsychiatric conditions, including psychiatric and existential distress in life-threatening illnesses. We conducted a narrative review to examine the potential of psychedelic assisted-psychotherapy (PAP) to alleviate psychiatric and psychospiritual distress in ALS. We also discussed the safety of using psychedelics in this population and proposed putative neurobiological mechanisms that may therapeutically intervene on ALS neuropathology. PAP has the potential to treat psychological dimensions and may also intervene on neuropathological dimensions of ALS. Robust improvements in psychiatric and psychospiritual distress from PAP in other populations provide a strong rationale for utilizing this therapy to treat ALS-related psychiatric and existential distress. Furthermore, relevant neuroprotective properties of psychedelics warrant future preclinical trials to investigate this area in ALS models. PAP has the potential to serve as an effective treatment in ALS. Given the lack of effective treatment options, researchers should rigorously explore this therapy for ALS in future trials.

keywords:
amyotrophic lateral sclerosis, ketamine, neurodegenerative, psilocybin, psychedelic-assisted psychotherapy

topic_tags:
End-of-Life Distress,Mechanism of Action,Spirituality,Clinical Trial,Review Article,Animal Study,Safety


title: A suite of engineered mice for interrogating psychedelic drug actions
journal: bioRxiv
publication_date: 2023-09-25
doi: 10.1101/2023.09.25.559347
source_url: https://doi.org/10.1101/2023.09.25.559347
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Headache / Migraine,Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
authors:
Chiu Y, Deutch AY, Wang W, Schmitz GP, Huang KL, Kocak DD, Llorach P, Bowyer K, Liu B, Sciaky N, Hua K, Chen C, Mott SE, Niehaus J, DiBerto JF, English J, Walsh JJ, Scherrer G, Herman MA, Wu Z, Wetsel WC, Roth BL.

abstract:
ABSTRACT Psychedelic drugs like lysergic acid diethylamide (LSD) and psilocybin have emerged as potentially transformative therapeutics for many neuropsychiatric diseases, including depression, anxiety, post-traumatic stress disorder, migraine, and cluster headaches. LSD and psilocybin exert their psychedelic effects via activation of the 5-hydroxytryptamine 2A receptor (HTR2A). Here we provide a suite of engineered mice useful for clarifying the role of HTR2A and HTR2A-expressing neurons in psychedelic drug actions. We first generated Htr2a -EGFP-CT-IRES-CreERT2 mice (CT:C-terminus) to independently identify both HTR2A-EGFP-CT receptors and HTR2A-containing cells thereby providing a detailed anatomical map of HTR2A and identifying cell types that express HTR2A. We also generated a humanized Htr2a mouse line and an additional constitutive Htr2A -Cre mouse line. Psychedelics induced a variety of known behavioral changes in our mice validating their utility for behavioral studies. Finally, electrophysiology studies revealed that extracellular 5-HT elicited a HTR2A-mediated robust increase in firing of genetically-identified pyramidal neurons--consistent with a plasma membrane localization and mode of action. These mouse lines represent invaluable tools for elucidating the molecular, cellular, pharmacological, physiological, behavioral, and other actions of psychedelic drugs in vivo.

raw_json:
{"europe_pmc_id":"PPR730960","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: Manic episode following psilocybin use in a man with bipolar II disorder: a case report.
authors: Halim HJ, Burk BG, Fargason RE, Birur B.
publication_date: 2023-09-21
doi: 10.3389/fpsyt.2023.1221131
pubmed_id: 37810598
source_url: https://doi.org/10.3389/fpsyt.2023.1221131
substance_tags: psilocybin
topic_tags: Depression,Addiction,OCD,End-of-Life Distress,Case Report,Treatment-Resistant Depression,Safety
study_type: Case Report
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
There has been an increase in research on the topic of psychedelic substances and their effects as treatment options in neuropsychiatric conditions. Psilocybin is a psychedelic drug that has recently garnered increased interest as an effective treatment modality for treatment-resistant depression, depression associated with terminal conditions, certain substance use disorders, and obsessive-compulsive disorder. However, sparse data exist as to the effects that psilocybin might have on patients at risk for mania, in large part secondary to the exclusion of this patient population from studies due to the concern for inducing mania or worsening illness course. We describe a case of a 21-year-old male with a recent diagnosis of bipolar II disorder who developed a manic episode following the ingestion of psilocybin in the form of hallucinogenic mushrooms. Given the incidence of depression in those with bipolar disorder, impulsivity, and a tendency to abuse substances associated with the illness, further research is needed into the risks of psilocybin and other psychedelic use in those with bipolar disorder.

raw_json:
{"europe_pmc_id":"37810598","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Black T.
publication_date: 2023-09-19
doi: 10.3389/fpsyt.2023.1159843
pubmed_id: 37799400
source_url: https://doi.org/10.3389/fpsyt.2023.1159843
substance_tags: psilocybin
topic_tags: Addiction,Wellbeing,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Lifeboat ethics, risk, and therapeutic opportunity: an appeal for equitable psychedelic therapy access in the "high-risk" addiction patient.

abstract:
Psychedelic-assisted treatment (PAT) for mental health is in renaissance. Psilocybin and MDMA stand near FDA approval, and US cities and states are decriminalizing or regulating the non-clinical use of psilocybin. However, neither FDA indications nor a regulated use model sufficiently address the complex needs and opportunities for an improved treatment of addiction. When paired with disability and social dispossession, addiction increasingly burdens informal care networks, public safety, and particularly healthcare systems. Stigma and mistreatment alienate people from opportunities for care and multiply the costs of providing care. This dynamic worsens socially determined resource limitations, enforcing stark ethical choices and perpetuating socioeconomic inequities, isolation, mental illness, medical illness, overdose, suicide, and violence. In order for psychedelic treatments to achieve their greatest utility to population health, we must intentionally develop regulatory, clinical, and payment systems supporting clinical research, rigorous safety monitoring, and implementation to address these immense needs and reduce the barriers to engagement for those who now bear the costs, including those who work at the front lines of addiction care. To achieve full fruition, I advocate for a collaborative approach, built from within networks of mutual social support but linked and accountable to public institutions charged with the equitable dissemination of these therapies for the greatest social and health equities. Rather than relegating PAT to the needs of the commercially insured or wellness markets, this is the moment to learn from ancient traditions of ritualized sacramental use, organized around faith in our mutual dependency and accountability, and to capture an opportunity to improve population health and equity. To miss this opportunity is to accept the status quo in the midst of a growing emergency, for lack of moral vision and intention to change our habits.

raw_json:
{"europe_pmc_id":"37799400","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2023-09-18
doi: 10.3389/fpsyt.2023.1199642
pubmed_id: 37795509
source_url: https://doi.org/10.3389/fpsyt.2023.1199642
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Wellbeing,Emotional Processing,Spirituality,Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Naturalistic psilocybin use is associated with persisting improvements in mental health and wellbeing: results from a prospective, longitudinal survey.

authors:
Nayak SM, Jackson H, Sepeda ND, Mathai DS, So S, Yaffe A, Zaki H, Brasher TJ, Lowe MX, Jolly DRP, Barrett FS, Griffiths RR, Strickland JC, Johnson MW, Jackson H, Garcia-Romeu A.

abstract:
IntroductionThe classic psychedelic psilocybin, found in some mushroom species, has received renewed interest in clinical research, showing potential mental health benefits in preliminary trials. Naturalistic use of psilocybin outside of research settings has increased in recent years, though data on the public health impact of such use remain limited.MethodsThis prospective, longitudinal study comprised six sequential automated web-based surveys that collected data from adults planning to take psilocybin outside clinical research: at time of consent, 2 weeks before, the day before, 1-3 days after, 2-4 weeks after, and 2-3 months after psilocybin use.ResultsA sample of 2,833 respondents completed all baseline assessments approximately 2 weeks before psilocybin use, 1,182 completed the 2-4 week post-use survey, and 657 completed the final follow-up survey 2-3 months after psilocybin use. Participants were primarily college-educated White men residing in the United States with a prior history of psychedelic use; mean age = 40 years. Participants primarily used dried psilocybin mushrooms (mean dose = 3.1 grams) for "self-exploration" purposes. Prospective longitudinal data collected before and after a planned psilocybin experience on average showed persisting reductions in anxiety, depression, and alcohol misuse, increased cognitive flexibility, emotion regulation, spiritual wellbeing, and extraversion, and reduced neuroticism and burnout after psilocybin use. However, a minority of participants (11% at 2-4 weeks and 7% at 2-3 months) reported persisting negative effects after psilocybin use (e.g., mood fluctuations, depressive symptoms).DiscussionResults from this study, the largest prospective survey of naturalistic psilocybin use to date, support the potential for psilocybin to produce lasting improvements in mental health symptoms and general wellbeing.

raw_json:
{"europe_pmc_id":"37795509","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2023-09-17
doi: 10.3389/fpsyt.2023.1215972
pubmed_id: 37795513
source_url: https://doi.org/10.3389/fpsyt.2023.1215972
substance_tags: psilocybin
topic_tags: Anxiety,Addiction,Clinical Trial,Randomized Controlled Trial,Safety,Adverse Events
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Nature-themed video intervention may improve cardiovascular safety of psilocybin-assisted therapy for alcohol use disorder.

authors:
Heinzerling KG, Sergi K, Linton M, Rich R, Youssef B, Bentancourt I, Bramen J, Siddarth P, Schwartzberg L, Kelly DF.

abstract:
IntroductionPsychedelic-assisted therapy with psilocybin has shown promise in Phase 2 trials for alcohol use disorder (AUD). Set and setting, particularly factors facilitating a connection with nature, may positively influence the psychedelic experience and therapeutic outcomes. But to date, randomized controlled trials of interventions to enhance set and setting for psychedelic-assisted therapy are lacking.MethodsThis was a pilot randomized, controlled trial of Visual Healing, a nature-themed video intervention to optimize set and setting, versus Standard set and setting procedures with two open-label psilocybin 25 mg dosing sessions among 20 participants with AUD. For the first session, participants randomized to Visual Healing viewed nature-themed videos during the preparation session and the "ascent" and "descent" phases of the psilocybin dosing session while participants randomized to the Standard condition completed a meditation during the preparatory session and wore eyeshades and listened to a music playlist throughout the dosing session. For the second session 4 weeks later, participants chose either Visual Healing or Standard procedures. Primary outcomes were feasibility, safety, and tolerability of Visual Healing. Secondary and exploratory outcomes were changes in alcohol use, psychedelic effects, anxiety and stress.ResultsNineteen of 20 (95%) randomized participants (mean age 49 ± 11 years, 60% female) completed the 14-week study. During the first psilocybin session, participants viewed an average of 37.9 min of the 42-min video and there were no video-related adverse events. Peak increase in post-psilocybin blood pressure was significantly less for participants randomly assigned to Visual Healing compared to Standard procedures. Alcohol use decreased significantly in both Visual Healing and Standard groups and psychedelic effects, stress, and anxiety were similar between groups.DiscussionIn this open-label pilot study, viewing Visual Healing videos during preparation and psilocybin dosing sessions was feasible, safe, and well-tolerated among participants with AUD. Preliminary findings suggest that Visual Healing has potential to reduce the cardiovascular risks of psychedelic therapy, without interfering with the psychedelic experience or alcohol-related treatment outcomes. Studies to replicate our findings as well as studies of different set and setting interventions with other psychedelic medications and indications are warranted.

raw_json:
{"europe_pmc_id":"37795513","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelics: Threshold of a Therapeutic Revolution.
authors: Heal DJ, Smith SL, Belouin SJ, Henningfield JE.
publication_date: 2023-05-26
doi: 10.1016/j.neuropharm.2023.109610
pubmed_id: 37247807
source_url: https://doi.org/10.1016/j.neuropharm.2023.109610
keywords: Humans, Substance-Related Disorders, Hallucinogens, Anxiety, Psilocybin, Major Depressive Disorder
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
abstract:
This Special Issue of Neuropharmacology on psychedelics provides a timely and comprehensive update on progress following the previous Neuropharmacology Special Issue "Psychedelics: New Doors, Altered Perceptions". Remarkable advances have been made in basic and clinical research on psychedelics in the five years since 2018. It is partly based on the seminar series focused on psilocybin organized by the National Institutes of Health (NIH), USA from April to June 2021, the "NIH Psilocybin Research Speaker Series". Participants were world leading experts, including scientists, medical practitioners, clinical psychologists and oncologists, and attendees from additional disciplines of patient advocacy, law, government science policy and regulatory policy. To provide a global perspective, their contributions are complemented with reviews by some of the world's most eminent scientists in the field. The US Food and Drug Administration (FDA) has granted two breakthrough therapy designations for psilocybin in treatment resistant depression (TRD) in 2018 and major depressive disorder (MDD) in 2019, as well as for MDMA for the treatment of post-traumatic stress disorder (PTSD) in 2017. Clinical trials are in progress to assess the therapeutic value of psilocybin in MDD and TRD, and in other indications such as cancer-related anxiety and depression, anorexia, PTSD, substance use disorders and various types of chronic pain. The contributors' insights should assist basic and applied science for transition of psychedelics from bench to potential mainstream therapies. The implications are global, because FDA approval of these new medicines will increase international interest and efforts.

topic_tags:
Depression,Anxiety,PTSD,Addiction,Eating Disorders,Chronic Pain,Pharmacology,Clinical Trial,Review Article,Cancer Patients,Treatment-Resistant Depression

raw_json:
{"europe_pmc_id":"37247807","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Herrmann Z, Levin AW, Cole SP, Slabaugh S, Barnett B, Penn A, Jain R, Raison C, Rajanna B, Jain S
journal: Psychedelic medicine (New Rochelle, N.Y.)
publication_date: 2023-08-31
doi: 10.1089/psymed.2023.0030
pubmed_id: 40046570
source_url: https://pubmed.ncbi.nlm.nih.gov/40046570/
keywords: anxiety, depression, prescriber, psilocybin, psychedelics, wellness
substance_tags: psilocybin
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"40046570"}
title:
Psychedelic Use Among Psychiatric Medication Prescribers: Effects on Well-Being, Depression, Anxiety, and Associations with Patterns of Use, Reported Harms, and Transformative Mental States.

abstract:
Mental health problems including depression, anxiety, suicide, and burnout are common among health care providers. Resilience and well-being are factors thought to protect against these incidents. Clinical trials and naturalistic studies of psychedelic compounds have shown decreases in depression, anxiety, and suicidality while suggesting improvements in well-being. This secondary analysis of a large cross-sectional online survey consisting of participants with at least one lifetime psychedelic use sought to examine how use affects health care providers who treat psychiatric disorders with medications. In total, 228 respondents retrospectively completed measures of depression, anxiety, and well-being before and after psychedelic exposure. They also reported lifetime use, harms attributed to use, and preferred psychedelic agent. Psychedelic use was associated with improvements in depression, anxiety, and well-being. Reported suicidality decreased and resilience increased. A factor analysis suggested that a cluster of mystical, interpersonal, and personal items predicted improvement in depression, anxiety, well-being, suicidality, and resilience. Preferred psychedelic agent did not affect outcomes. Frequency of use was not associated with outcomes although differences in effect sizes were seen. Harm reported was consistent with the general population, with 13.2% ( = 30) reporting at least one harm. Pre-exposure alcohol use, aggressive impulses, and desire to die by suicide improved most often while marijuana use most often worsened or did not change. These results are consistent with clinical trials and naturalistic studies examining psychedelic use in the general population and suggest that health care providers who treat psychiatric disorders with medications may benefit from psychedelic use, although some harm was reported. Given the current mental health crisis among health care providers, further research is warranted to examine whether interventions utilizing psychedelics could improve well-being and effectiveness of health care providers while decreasing adverse mental health outcomes associated with working in health care. ClinicalTrials.gov (ID: NCT04040582).

topic_tags:
Depression,Anxiety,Addiction,Wellbeing,Resilience,Mystical Experience,Clinical Trial,Observational Study


authors: Pagán AF, Lex C, Soares JC, Meyer TD.
publication_date: 2023-09-12
doi: 10.1089/psymed.2023.0022
pubmed_id: 40046569
source_url: https://doi.org/10.1089/psymed.2023.0022
substance_tags: psilocybin
topic_tags: Depression,Observational Study
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Medical Students' Attitudes and Beliefs Toward Psilocybin: Does Terminology and Personal Experience with Psychedelics Matter?

abstract:
BackgroundPsilocybin and psychedelic-assisted therapy (PAT) have gained renewed interest due to recent findings that PAT can enhance therapeutic outcomes. In 2019, the U.S. Food & Drug Administration (FDA) approved breakthrough therapy status to psilocybin for the treatment of depression, but PAT has yet to be approved as a therapeutic treatment for mental health disorders. Should the FDA approve PAT, medical students will serve as gatekeepers to PAT.MethodsMedical students (n = 295) were surveyed and randomized to two terminology conditions (i.e., "psilocybin" or "magic mushrooms, MMs") assessing their attitudes, knowledge, and beliefs.ResultsRegardless of the terminology utilized, medical students held overall positive attitudes but their attitudes were significantly more positive when the term "psilocybin" was used. Furthermore, experience with psychedelics was associated with significantly more positive attitudes, beliefs, and higher self-rated knowledge. Finally, attitudes and beliefs were significant predictors of medical students' willingness to recommend PAT, if FDA approved, after controlling for covariates (e.g., personal experience with psychedelics).ConclusionsDespite some limitations, based on this study, using the term "psilocybin" might be preferable over "MMs" in a research or educational context. Although personal experience positively affects opinions toward psychedelics, beliefs and attitudes seem to be more relevant when it comes to actual medical advice.

raw_json:
{"europe_pmc_id":"40046569","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Predictors of Pharmacy Students' Attitudes About the Therapeutic Use of Psilocybin.
authors: Bhuiya NMA, Jacobs RJ, Wang K, Sun Y, Nava B, Sampiere L, Yerubandi A, Caballero J.
publication_date: 2023-09-12
doi: 10.7759/cureus.45169
pubmed_id: 37842360
source_url: https://doi.org/10.7759/cureus.45169
substance_tags: psilocybin
topic_tags: Depression,Anxiety,OCD,Review Article,Observational Study,Safety
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Background Psilocybin has been studied for its potential therapeutic benefits, particularly for the treatment of psychiatric disorders such as anxiety, depression, and obsessive-compulsive disorder. While more research is needed as psilocybin-assisted therapy becomes more prevalent, future pharmacists will probably be involved at some level. At present, pharmacists receive minimal training on psilocybin, and little is known about their attitudes toward its use for medical purposes. Findings from recent clinical studies have attempted to establish the safety and medical efficacy of psilocybin, leading to an increased interest in therapeutic psilocybin use in the United States. This study aimed to assess if self-assessed knowledge of psilocybin, concerns about adverse effects, and opinions about legalization will make statistically significant contributions to pharmacy students' attitudes about psilocybin use in practice. Methods Pharmacy students' self-assessed knowledge, concern for potential adverse effects, and perceptions of psilocybin were investigated using a cross-sectional survey study design. Data were collected from March 13 to April 7, 2023, from a convenience sample of 161 pharmacy students enrolled in an accredited pharmacy school in the southern region of the United States using a 41-item anonymous quantitative survey developed by the researchers that contained validated scales. The survey was delivered electronically. Multiple regression modeling was conducted to determine if self-assessed knowledge, concerns for adverse effects, and opinions about legalization would predict pharmacy students' attitudes about therapy-assisted psilocybin use. This study was approved by the Institutional Review Board of the authors' university. Results The mean age of the 161 participants was 24 years (SD = 2.981; range 20-40 years). Twenty (12.4%) participants reported previous use of psilocybin for recreational purposes and two (1.2%) reported having used it therapeutically. Many (n =121; 75.2%) of the participants believed that psilocybin should be decriminalized for therapeutic use, but only 54 (33.5%) thought it should be decriminalized for recreational use. A multiple linear regression model predicting "attitudes about psilocybin" (dependent variable) produced significant results: (F(4, 122) = 40.575, p < 0.001), with an R2 = 0.571 (adjusted R2 = 0.557). Greater "self-assessed knowledge about psilocybin," less "concern about possible negative effects," greater "belief in the decriminalization of psilocybin for recreational use," and greater "belief in the decriminalization of psilocybin for therapeutic use" (all independent variables) were associated with more positive perceptions about medical psilocybin. The percentage of variance in the scores accounted for by the model was 57%. Conclusions Pharmacy students may lack information and training regarding psilocybin and report a desire to learn more about it. Their attitudes about medical psilocybin may be driven by this desire to learn in addition to concerns about adverse effects and legalization issues. Due to the dearth of published information regarding the knowledge and acceptance of psilocybin as a viable treatment option for patients, further research in psychedelic-assisted treatments may be warranted.

raw_json:
{"europe_pmc_id":"37842360","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin for anorexia nervosa: If it helps, let's learn how.
authors: Attia E, Steinglass JE.
publication_date: 2023-08-31
doi: 10.1016/j.medj.2023.08.003
pubmed_id: 37689054
source_url: https://doi.org/10.1016/j.medj.2023.08.003
keywords: Humans, Brain Diseases, Learning, Anorexia Nervosa, Adult, Psilocybin
substance_tags: psilocybin
topic_tags: Eating Disorders,Mechanism of Action,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Existing treatments for adults with anorexia nervosa (AN) have limited effectiveness. AN is a brain-based disorder with behavioral and cognitive features leading to severe undernourishment. Peck et al. conducted a small open trial suggesting safety and tolerability of psilocybin for AN,1 opening an avenue for further investigation into the neural mechanisms involved.

raw_json:
{"europe_pmc_id":"37689054","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial.
publication_date: 2023-08-31
doi: 10.1001/jama.2023.14530
pubmed_id: 37651119
source_url: https://doi.org/10.1001/jama.2023.14530
substance_tags: psilocybin
topic_tags: Depression,Addiction,Clinical Trial,Safety,Adverse Events
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
authors:
Raison CL, Sanacora G, Woolley J, Heinzerling K, Dunlop BW, Brown RT, Kakar R, Hassman M, Trivedi RP, Robison R, Gukasyan N, Nayak SM, Hu X, O'Donnell KC, Kelmendi B, Sloshower J, Penn AD, Bradley E, Kelly DF, Mletzko T, Nicholas CR, Hutson PR, Tarpley G, Utzinger M, Lenoch K, Warchol K, Gapasin T, Davis MC, Nelson-Douthit C, Wilson S, Brown C, Linton W, Ross S, Griffiths RR.

abstract:
ImportancePsilocybin shows promise as a treatment for major depressive disorder (MDD).ObjectiveTo evaluate the magnitude, timing, and durability of antidepressant effects and safety of a single dose of psilocybin in patients with MDD.Design, setting, and participantsIn this phase 2 trial conducted between December 2019 and June 2022 at 11 research sites in the US, participants were randomized in a 1:1 ratio to receive a single dose of psilocybin vs niacin placebo administered with psychological support. Participants were adults aged 21 to 65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of MDD of at least 60 days' duration and moderate or greater symptom severity. Exclusion criteria included history of psychosis or mania, active substance use disorder, and active suicidal ideation with intent. Participants taking psychotropic agents who otherwise met inclusion/exclusion criteria were eligible following medication taper. Primary and secondary outcomes and adverse events (AEs) were assessed at baseline (conducted within 7 days before dosing) and at 2, 8, 15, 29, and 43 days after dosing.InterventionsInterventions were a 25-mg dose of synthetic psilocybin or a 100-mg dose of niacin in identical-appearing capsules, each administered with psychological support.Main outcomes and measuresThe primary outcome was change in central rater-assessed Montgomery-Asberg Depression Rating Scale (MADRS) score (range, 0-60; higher scores indicate more severe depression) from baseline to day 43. The key secondary outcome measure was change in MADRS score from baseline to day 8. Other secondary outcomes were change in Sheehan Disability Scale score from baseline to day 43 and MADRS-defined sustained response and remission. Participants, study site personnel, study sponsor, outcome assessors (raters), and statisticians were blinded to treatment assignment.ResultsA total of 104 participants (mean [SD] age, 41.1 [11.3] years; 52 [50%] women) were randomized (51 to the psilocybin group and 53 to the niacin group). Psilocybin treatment was associated with significantly reduced MADRS scores compared with niacin from baseline to day 43 (mean difference,-12.3 [95% CI, -17.5 to -7.2]; P

keywords:
Humans, Niacin, Hallucinogens, Mental Health, Adult, Female, Male, Psilocybin, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"37651119","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelics for treatment resistant depression: are they game changers?
authors: Kalfas M, Taylor RH, Tsapekos D, Young AH.
publication_date: 2023-08-31
doi: 10.1080/14656566.2023.2281582
pubmed_id: 37947195
source_url: https://doi.org/10.1080/14656566.2023.2281582
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
abstract:
IntroductionA new era of treatment for adults with treatment-resistant depression (TRD), which involves psychedelic substances, is dawning. Emerging evidence indicates that psychedelics can exert antidepressant effects through multiple neurobiological and psychological mechanisms. However, it remains to be seen if these new treatments will revolutionize the treatment of TRD.Areas coveredThe present review focuses on the efficacy of serotoninergic psychedelics psilocybin, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), ayahuasca, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and mescaline (3,4,5-trimethoxyphenethylamine), as well as 3,4-methylenedioxymethamphetamine (MDMA), for TRD. A systematic search was conducted for psilocybin in TRD as emerging trials had not yet been subject to review. A narrative review summarized findings on other psychedelics.Expert opinionPsychedelic therapy has created a paradigm shift in the treatment of TRD, as it can maximize therapeutic benefits and minimize potential risks. Psilocybin holds promise as a potential game-changer in the treatment of TRD, with initial evidence suggesting a rapid antidepressant effect sustained for some responders for at least 3 months. Nevertheless, further adequately powered, double-blind, comparator-controlled trials are required to explore and clarify the mechanisms of action and long-term effects of psychedelics in TRD. Psychedelics also hold promise for other psychiatric conditions, such as bipolar depression and post-traumatic stress disorder.

keywords:
Humans, N,N-Dimethyltryptamine, Mescaline, Lysergic Acid Diethylamide, Hallucinogens, Antidepressive Agents, Adult, Randomized Controlled Trials as Topic, Depressive Disorder, Treatment-Resistant, Psilocybin

topic_tags:
Depression,PTSD,Mechanism of Action,Receptor Pharmacology,Randomized Controlled Trial,Review Article,Treatment-Resistant Depression,Safety

raw_json:
{"europe_pmc_id":"37947195","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Self-administration of Psilocybin for the Acute Treatment of Migraine: A Case Report.
authors: Lawrence DW.
publication_date: 2023-06-30
pubmed_id: 37817818
source_url: https://europepmc.org/article/MED/37817818
substance_tags: psilocybin
topic_tags: Headache / Migraine,Pharmacology,Receptor Pharmacology,Case Report,Safety
study_type: Case Report
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
BackgroundMigraine is a common neurovascular disorder with a pathophysiology related to the serotonin (5-hydroxytryptamine; 5-HT) system. Pharmacologic modulation of 5-HT receptors has demonstrated efficacy in the acute treatment of migraines. Psilocybin, a classic psychedelic with 5-HT receptor activity, has demonstrated therapeutic potential in the management of neuropsychiatric conditions. To date, no reports have investigated the effect of psilocybin administered acutely during a migraine episode.Case presentationThe case of a 33-year-old male patient with a history of migraines with aura, who had acute administration of oral psilocybin (in the form of the dried fruiting body of Psilocybe cubensis mushrooms) at migraine onset is presented. Headache intensity was rated hourly using the Numerical Rating Scale (NRS) and compared to three previous migraines. Profound reductions in headache intensity and emetic episodes were reported during the migraine treated acutely with oral psilocybin administration, compared to three previous migraines.DiscussionThe severe, disabling, and treatment-resistant nature of migraines warrants continued surveillance for novel pharmacologic interventions. The established congruous pathophysiology of migraine and pharmacology of psilocybin, via the 5-HT receptor system, positions psilocybin as a potential therapeutic target.ConclusionWhile this report highlights the potential role of psilocybin in the acute management of migraines, it is essential to note that it should not be considered a basis for guiding clinical practice at this point. Further research is necessary to establish the safety and efficacy of psilocybin as a treatment option for migraines.

raw_json:
{"europe_pmc_id":"37817818","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2023-08-31
doi: 10.1038/s41380-023-02280-z
pubmed_id: 37783788
source_url: https://doi.org/10.1038/s41380-023-02280-z
substance_tags: psilocybin
topic_tags: Anxiety,Neuroplasticity,Receptor Pharmacology,Microdosing,Resilience,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Repeated low doses of psilocybin increase resilience to stress, lower compulsive actions, and strengthen cortical connections to the paraventricular thalamic nucleus in rats.

authors:
Kiilerich KF, Lorenz J, Scharff MB, Speth N, Brandt TG, Czurylo J, Xiong M, Jessen NS, Casado-Sainz A, Shalgunov V, Kjaerby C, Satała G, Bojarski AJ, Jensen AA, Herth MM, Cumming P, Overgaard A, Palner M.

abstract:
Psilocybin (a classic serotonergic psychedelic drug) has received appraisal for use in psychedelic-assisted therapy of several psychiatric disorders. A less explored topic concerns the use of repeated low doses of psychedelics, at a dose that is well below the psychedelic dose used in psychedelic-assisted therapy and often referred to as microdosing. Psilocybin microdose users frequently report increases in mental health, yet such reports are often highly biased and vulnerable to placebo effects. Here we establish and validate a psilocybin microdose-like regimen in rats with repeated low doses of psilocybin administration at a dose derived from occupancy at rat brain 5-HT2A receptors in vivo. The rats tolerated the repeated low doses of psilocybin well and did not manifest signs of anhedonia, anxiety, or altered locomotor activity. There were no deficits in pre-pulse inhibition of the startle reflex, nor did the treatment downregulate or desensitize the 5-HT2A receptors. However, the repeated low doses of psilocybin imparted resilience against the stress of multiple subcutaneous injections, and reduced the frequency of self-grooming, a proxy for human compulsive actions, while also increasing 5-HT7 receptor expression and synaptic density in the paraventricular nucleus of the thalamus. These results establish a well-validated regimen for further experiments probing the effects of repeated low doses of psilocybin. Results further substantiate anecdotal reports of the benefits of psilocybin microdosing as a therapeutic intervention, while pointing to a possible physiological mechanism.

keywords:
Midline Thalamic Nuclei, Animals, Humans, Rats, Serotonin, Hallucinogens, Compulsive Behavior, Resilience, Psychological, Psilocybin

raw_json:
{"europe_pmc_id":"37783788","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Neuroimaging in psychedelic drug development: Past, present, and future
journal: PsyArXiv
publication_date: 2022-06-29
source_url: https://osf.io/preprints/psyarxiv/xwu4j_v1
substance_tags: psilocybin
topic_tags: Depression,PTSD,Addiction,Eating Disorders,Brain Imaging,Pharmacology,Aging
study_type: Other
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"xwu4j_v1","version":1,"reviews_state":"accepted"}
abstract:
Psychedelic therapy (PT) is an emerging paradigm with great transdiagnostic potential for treating a range of psychiatric disorders, including depression, addiction, eating disorders, post-traumatic stress disorder, and others. ‘Classic’ serotonergic psychedelics, such as psilocybin, lysergic acid diethylamide (LSD), N, N-Dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), form the main focus of this movement, but other substances including ketamine, 3,4-Methylenedioxymethamphetamine (MDMA) and ibogaine also hold promise. The development of these novel treatment modalities in the early 21st century has occurred concurrently with the wider use of advanced human neuroscientific research methods; principally neuroimaging. This has enabled assessment of drug and therapy brain effects with greater precision and quantification than any previous novel development in psychiatric pharmacology. We outline some of the major trends in existing data and suggest that the modern development of PT has benefitted greatly from the use of neuroimaging. Important gaps in existing knowledge are identified which can be addressed by future neuroimaging work, principally using combined Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) methods, plus other adjunct techniques. Suggestions for future multimodal imaging studies are discussed, which would resolve some of these questions and provide a firmer foundation for the development of PT.

keywords:
fMRI, Ketamine, LSD, MDMA, Neuroimaging, PET, Psilocybin, Psychedelics, Psychiatry, Neuroscience, Clinical Neuroscience


authors: Miller M, Rosa WE, Doerner Rinaldi A, Addicott K, Spence D, Beaussant Y
journal: Psychedelic medicine (New Rochelle, N.Y.)
publication_date: 2023-08-31
doi: 10.1089/psymed.2022.0009
pubmed_id: 37753521
source_url: https://pubmed.ncbi.nlm.nih.gov/37753521/
substance_tags: psilocybin
topic_tags: End-of-Life Distress,Spirituality
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"37753521"}
title:
Applying Key Lessons from the Hospice and Palliative Care Movement to Inform Psychedelic-Assisted Therapy.

abstract:
Psychedelic-assisted therapy (PAT) has re-emerged as a promising intervention for addressing mental health conditions and existential concerns. Despite growing enthusiasm, PAT may be difficult to integrate into mainstream health systems. The rich sacramental traditions of psychedelics, their centering of the human experience, proposed substrates of action, context-dependent outcomes, and highly relational method of therapy all challenge dominant reductionistic approaches of the biomedical model. Hospice and palliative care are well established as holistic evidence-based standards of care, yet they began as a radical grassroots movement. Hospice and palliative care models may offer unique insights to support the growing field of PAT.
The intention of this commentary is to articulate the deep synergies between hospice and palliative care and PAT, with the intention of fostering interdisciplinary dialogue that may aid in implementation of human-centered high-quality PAT.
Various aspects of hospice and palliative care models were identified and explored, which may support the implementation of human-centered high-quality PAT at scale. These include a focus on truly interdisciplinary care, applying a holistic lens to health and illness, bearing witness to suffering and healing, customized care, centering human relationships, decentralized models of care, generalist/specialist competencies, fostering spirituality, organizing as a social moment around shared goals, and growth from grassroots community organizations to mature care systems. Although hospice and palliative care can offer practical lessons for scaling human-centered experiential therapies, PAT, with its radical centering of meaning-making and relationship in the healing process, may also mutually innovate the fields of hospice and palliative care.

keywords:
holistic, palliative care, supportive care, hospice, psilocybin, psychedelic-assisted therapy, psychedelics, psychosocial, spiritual care


title: History of the administration of psychedelics in France.
authors: Dubus Z, Grandgeorge E, Verroust V.
publication_date: 2023-08-31
doi: 10.3389/fpsyg.2023.1131565
pubmed_id: 37744588
source_url: https://doi.org/10.3389/fpsyg.2023.1131565
substance_tags: psilocybin
topic_tags: Anxiety,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
This article reviews the historical protocols for the administration of "classic" psychedelics in France, from the 1920s to the 1960s. Taking a chronological approach, it investigates the way mescaline, LSD, and psilocybin were administered, the subjects involved, the route of administration, the dosage, and the epistemological context of the research. From the 1930s, the Sainte-Anne school dominated French experimentation with psychedelics, inserting these studies on "hallucinogens" into a biological conception of therapeutics, where the notion of "shock" dominated. The sessions show particularly anxious experiences, sometimes described as "torture" by the patients who underwent them. With just a few rare cases of recovery reported, these substances were not considered as medicines, but rather as tools for exploration in the context of experimental research; thought of not as psychedelics ("mind manifesters") but as psychodysleptics ("mind disruptors"). While these tools could be useful for the diagnosis of sick patients, French physicians did not manage to demonstrate clear therapeutic benefits in the use of psychedelics, perhaps because of their reluctance, in most cases, to determine an optimum dose, and also very often to appreciate the context of administration and the relationship with the patient. This article allows us to understand the reasons for the therapeutic failures reported by these early French psychedelic researchers, but also to help explain the current reluctance of French health professionals who in the face of the "psychedelic renaissance" remain strongly influenced by the very negative early representations of these substances.

raw_json:
{"europe_pmc_id":"37744588","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelics, With a Focus on Psilocybin: Issues for the Clinician.
authors: Garakani A, Alexander JL, Sumner CR, Pine JH, Gross LS, Raison CL, Aaronson ST, Baron DA.
publication_date: 2023-08-31
doi: 10.1097/pra.0000000000000729
pubmed_id: 37678363
source_url: https://doi.org/10.1097/pra.0000000000000729
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
There has been a burgeoning interest in psychedelics among the public, state legislatures, psychiatrists and other clinical providers, and within the research community. Increasing numbers of studies evaluating psychedelics for depression, anxiety, posttraumatic stress disorder, and substance use disorders have been conducted or are underway. While discussing psychedelics in general, the focus of this paper is on psilocybin and its mechanism, how it exerts a psychedelic effect, dosing, and a review of the treatment studies of psilocybin, which were primarily for treatment-resistant depression and cancer-related anxiety. Future directions and potential limitations of studying and regulating psilocybin and other psychedelics are also discussed.

keywords:
Humans, Hallucinogens, Anxiety, Anxiety Disorders, Depressive Disorder, Treatment-Resistant, Psilocybin

topic_tags:
Depression,Anxiety,PTSD,Addiction,Review Article,Cancer Patients,Treatment-Resistant Depression,Healthcare Workers

raw_json:
{"europe_pmc_id":"37678363","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin history, action and reaction: A narrative clinical review.
authors: Sharma P, Nguyen QA, Matthews SJ, Carpenter E, Mathews DB, Patten CA, Hammond CJ.
publication_date: 2023-08-30
doi: 10.1177/02698811231190858
pubmed_id: 37650489
source_url: https://doi.org/10.1177/02698811231190858
keywords: Humans, Alcoholism, Hallucinogens, Affect, Anxiety Disorders, Psilocybin
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Hallucinogenic mushrooms have been used in religious and cultural ceremonies for centuries. Of late, psilocybin, the psychoactive compound in hallucinogenic mushrooms, has received increased public interest as a novel drug for treating mood and substance use disorders (SUDs). In addition, in recent years, some states in the United States have legalized psilocybin for medical and recreational use. Given this, clinicians need to understand the potential benefits and risks related to using psilocybin for therapeutic purposes so that they can accurately advise patients. This expert narrative review summarizes the scientific basis and clinical evidence on the safety and efficacy of psilocybin-assisted therapy for treating psychiatric disorders and SUDs. The results of this review are structured as a more extensive discussion about psilocybin's history, putative mechanisms of action, and recent legislative changes to its legal status. There is modest evidence of psilocybin-assisted therapy for treating depression and anxiety disorders. In addition, early data suggest that psilocybin-assisted therapy may effectively reduce harmful drinking in patients with alcohol use disorders. The evidence further suggests psilocybin, when administered under supervision (psilocybin-assisted therapy), the side effects experienced are mild and transient. The occurrence of severe adverse events following psilocybin administration is uncommon. Still, a recent clinical trial found that individuals in the psilocybin arm had increased suicidal ideations and non-suicidal self-injurious behaviors. Given this, further investigation into the safety and efficacy of psilocybin-assisted therapy is warranted to determine which patient subgroups are most likely to benefit and which are most likely to experience adverse outcomes related to its use.

topic_tags:
Depression,Anxiety,Addiction,Mechanism of Action,Clinical Trial,Review Article,Healthcare Workers,Safety,Adverse Events

raw_json:
{"europe_pmc_id":"37650489","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The risk of chronic psychedelic and MDMA microdosing for valvular heart disease.
authors: Tagen M, Mantuani D, van Heerden L, Holstein A, Klumpers LE, Knowles R.
publication_date: 2023-08-11
doi: 10.1177/02698811231190865
pubmed_id: 37572027
source_url: https://doi.org/10.1177/02698811231190865
substance_tags: psilocybin
topic_tags: Receptor Pharmacology,Microdosing,In Vitro Study,Safety
study_type: In Vitro Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
Psychedelic microdosing is the practice of taking very low doses of psychedelic substances, typically over a longer period of time. The long-term safety of chronic microdosing is relatively uncharacterized, but valvular heart disease (VHD) has been proposed as a potential risk due to activation of the serotonin 5-HT2B receptor. However, this risk has not yet been comprehensively assessed. This analysis searched for all relevant in vitro, animal, and clinical studies related to the VHD risk of lysergic acid diethylamide (LSD), psilocybin, mescaline, N,N-dimethyltryptamine (DMT), and the non-psychedelic 3,4-methylenedioxymethamphetamine (MDMA). All five compounds and some metabolites could bind to the 5-HT2B receptor with potency equal to or greater than that of the 5-HT2A receptor, the primary target of psychedelics. All compounds were partial agonists at the 5-HT2B receptor with the exception of mescaline, which could not be adequately assessed due to low potency. Safety margins relative to the maximum plasma concentrations from typical microdoses were greater than known valvulopathogens, but not without potential risk. No animal or clinical studies appropriately designed to evaluate VHD risk were found for the four psychedelics. However, there is some clinical evidence that chronic ingestion of full doses of MDMA is associated with VHD. We conclude that VHD is a potential risk with chronic psychedelic microdosing, but further studies are necessary to better define this risk.

keywords:
Humans, Heart Valve Diseases, Serotonin, N-Methyl-3,4-methylenedioxyamphetamine, Mescaline, Lysergic Acid Diethylamide, Hallucinogens, Psilocybin

raw_json:
{"europe_pmc_id":"37572027","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The Potential of Psychedelics for the Treatment of Episodic Migraine.
authors: Schindler EAD.
publication_date: 2023-08-03
doi: 10.1007/s11916-023-01145-y
pubmed_id: 37540398
source_url: https://doi.org/10.1007/s11916-023-01145-y
keywords: Humans, Cluster Headache, Hallucinogens, Mental Disorders, Migraine Disorders, Psilocybin
substance_tags: psilocybin
topic_tags: Chronic Pain,Headache / Migraine,Clinical Trial,Review Article,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
Purpose of reviewThis review presents the existing literature of and a framework for how psychedelic drugs might be applied as therapeutic agents in episodic migraine.Recent findingsThe therapeutic effects of psychedelics in headache disorders have been reported for decades and controlled investigations are now beginning. In the first and only clinical trial of a psychedelic drug in migraine, the single administration of low-dose psilocybin reduced weekly migraine days and pain intensity for the following 2 weeks in episodic subjects. These transitional effects, along with abortive effects in two subjects and additional findings in cluster headache, offer insight into the potential medicinal use of this and other psychedelic drugs in episodic migraine. The existing evidence supports the continued investigation of psilocybin and other psychedelics as transitional treatments in episodic migraine. Acute and preventive effects also exist, but the risks may outweigh benefits with these applications. Future research of psychedelics in episodic migraine should be tailored for this condition and not modeled after protocols used in other medical or psychiatric conditions.

raw_json:
{"europe_pmc_id":"37540398","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2023-07-22
doi: 10.1016/j.psychres.2023.115349
pubmed_id: 37523886
source_url: https://doi.org/10.1016/j.psychres.2023.115349
keywords: Humans, Hallucinogens, Sample Size, Depression, Symptom Flare Up, Psilocybin, Escitalopram
substance_tags: psilocybin
topic_tags: Depression,Meta-Analysis,Systematic Review,Review Article,Safety
study_type: Meta-Analysis
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Assessing the risk of symptom worsening in psilocybin-assisted therapy for depression: A systematic review and individual participant data meta-analysis.

authors:
Simonsson O, Carlbring P, Carhart-Harris R, Davis AK, Nutt DJ, Griffiths RR, Erritzoe D, Goldberg SB.

abstract:
We conducted a meta-analysis using individual participant data from three, two-dose psilocybin trials for depression (N = 102) with the aim of assessing the risk of symptom worsening. Clinically significant symptom worsening occurred for a minority of participants in the psilocybin and escitalopram conditions (∼10%) and for a majority of participants in the waitlist condition (63.6%). Using data from the two trials with control arms, the psilocybin arm showed a lower likelihood of symptom worsening versus waitlist, and no difference in the likelihood of symptom worsening versus escitalopram. The limitation of a relatively small sample size should be addressed in future studies.

raw_json:
{"europe_pmc_id":"37523886","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Natural psychedelics in the treatment of depression; a review focusing on neurotransmitters.
authors: Jahanabadi S, Amiri S, Karkeh-Abadi M, Razmi A.
publication_date: 2023-07-22
doi: 10.1016/j.fitote.2023.105620
pubmed_id: 37490982
source_url: https://doi.org/10.1016/j.fitote.2023.105620
keywords: N,N-Dimethyltryptamine, Neurotransmitter Agents, Hallucinogens, Depression, Molecular Structure
substance_tags: psilocybin,psilocin
topic_tags: Depression,Mechanism of Action,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Natural psychedelic compounds are emerging as potential novel therapeutics in psychiatry. This review will discuss how natural psychedelics exert their neurobiological therapeutic effects, and how different neurotransmission systems mediate the effects of these compounds. Further, current therapeutic strategies for depression, and novel mechanism of action of natural psychedelics in the treatment of depression will be discussed. In this review, our focus will be on N, N-dimethyltryptamine (DMT), reversible type A monoamine oxidase inhibitors, mescaline-containing cacti, psilocybin/psilocin-containing mushrooms, ibogaine, muscimol extracted from Amanita spp. mushrooms and ibotenic acid.

raw_json:
{"europe_pmc_id":"37490982","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Szigeti B, Phillips LD, Nutt D
journal: British journal of clinical pharmacology
publication_date: 2023-08-31
doi: 10.1111/bcp.15841
pubmed_id: 37455605
source_url: https://pubmed.ncbi.nlm.nih.gov/37455605/
keywords: Bayesian analysis, RCTs, Sir Michal Rawlins, depression, medical cannabis, psilocybin
substance_tags: psilocybin
topic_tags: Depression,Randomized Controlled Trial
study_type: Randomized Controlled Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"37455605"}
title:
Bayesian analysis of real-world data as evidence for drug approval: Remembering Sir Michael Rawlins.


title: Psilocybin for treatment resistant depression in patients taking a concomitant SSRI medication.
publication_date: 2023-07-12
doi: 10.1038/s41386-023-01648-7
pubmed_id: 37443386
source_url: https://doi.org/10.1038/s41386-023-01648-7
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
authors:
Goodwin GM, Croal M, Feifel D, Kelly JR, Marwood L, Mistry S, O'Keane V, Peck SK, Simmons H, Sisa C, Stansfield SC, Tsai J, Williams S, Malievskaia E.

abstract:
Psilocybin is being investigated as a treatment in adults with treatment-resistant depression (TRD). Withdrawal from serotonergic antidepressant drugs is a common prerequisite for taking part in trials of psilocybin due to the possibility of ongoing antidepressant drugs altering the psychedelic effect. This phase II, exploratory, international, fixed-dose, open-label study explored the safety, tolerability, and efficacy of a synthetic form of psilocybin (investigational drug COMP360) adjunct to a selective serotonin reuptake inhibitor in participants with TRD. Participants received a single 25 mg dose of psilocybin alongside psychological support and were followed-up for 3 weeks. The primary efficacy end point was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score from Baseline at Week 3. Secondary end points were safety, including treatment-emergent adverse events (TEAEs), the proportion of responders and remitters at Week 3, and the change from Baseline to Week 3 in Clinical Global Impression-Severity (CGI-S) score. Nineteen participants were dosed and the mean Baseline MADRS total score was 31.7 (SD = 5.77). Twelve (63.2%) participants had a TEAE, most of which were mild and resolved on the day of onset. There were no serious TEAEs or indication of increased suicidal ideation or behavior. At Week 3, mean change from Baseline in MADRS total score was -14.9 (95% CI, -20.7 to -9.2), and -1.3 (SD = 1.29) in the CGI-S. Both response and remission were evident in 8 (42.1%) participants. Larger, comparator-controlled trials are necessary to understand if this paradigm can optimize treatment-outcome where antidepressant drug withdrawal would be problematic.

keywords:
Humans, Antidepressive Agents, Treatment Outcome, Double-Blind Method, Adult, Depressive Disorder, Treatment-Resistant, Psilocybin, Major Depressive Disorder

topic_tags:
Depression,Receptor Pharmacology,Clinical Trial,Treatment-Resistant Depression,Safety,Adverse Events

raw_json:
{"europe_pmc_id":"37443386","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Clinical specificity profile for novel rapid acting antidepressant drugs.
authors: Scala M, Fanelli G, De Ronchi D, Serretti A, Fabbri C.
publication_date: 2023-06-29
doi: 10.1097/yic.0000000000000488
pubmed_id: 37381161
source_url: https://doi.org/10.1097/yic.0000000000000488
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
Mood disorders are recurrent/chronic diseases with variable clinical remission rates. Available antidepressants are not effective in all patients and often show a relevant response latency, with a range of adverse events, including weight gain and sexual dysfunction. Novel rapid agents were developed with the aim of overcoming at least in part these issues. Novel drugs target glutamate, gamma-aminobutyric acid, orexin, and other receptors, providing a broader range of pharmacodynamic mechanisms, that is, expected to increase the possibility of personalizing treatments on the individual clinical profile. These new drugs were developed with the aim of combining a rapid action, a tolerable profile, and higher effectiveness on specific symptoms, which were relatively poorly targeted by standard antidepressants, such as anhedonia and response to reward, suicidal ideation/behaviours, insomnia, cognitive deficits, and irritability. This review discusses the clinical specificity profile of new antidepressants, namely 4-chlorokynurenine (AV-101), dextromethorphan-bupropion, pregn-4-en-20-yn-3-one (PH-10), pimavanserin, PRAX-114, psilocybin, esmethadone (REL-1017/dextromethadone), seltorexant (JNJ-42847922/MIN-202), and zuranolone (SAGE-217). The main aim is to provide an overview of the efficacy/tolerability of these compounds in patients with mood disorders having different symptom/comorbidity patterns, to help clinicians in the optimization of the risk/benefit ratio when prescribing these drugs.

keywords:
Humans, Sleep Initiation and Maintenance Disorders, Bupropion, Antidepressive Agents, Comorbidity, Major Depressive Disorder

topic_tags:
Depression,Pharmacology,Mechanism of Action,Receptor Pharmacology,Review Article,Healthcare Workers,Safety,Adverse Events

raw_json:
{"europe_pmc_id":"37381161","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin: The most effective moral bio-enhancer?
authors: Rakić V.
publication_date: 2023-06-27
doi: 10.1111/bioe.13196
pubmed_id: 37376901
source_url: https://doi.org/10.1111/bioe.13196
keywords: Humans, Hallucinogens, Morals, Psilocybin
substance_tags: psilocybin
topic_tags: Receptor Pharmacology
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
This paper addresses the possible effects of psychedelic drugs, notably psilocybin, on moral bio-enhancement (MBE). It will be argued that non-psychedelic substances, such as oxytocin, serotonin/serotonin reuptake inhibitors, or vasopressin, have indirect effects on M(B)E, whereas psilocybin has direct effects. Additionally, morality and happiness have been shown to operate in a circularly supportive relationship. It will be argued that psilocybin also has more direct effects on the augmentation of human happiness than non-psychedelic substances. Hence, psilocybin multiplies its effects on morality and on moral enhancement (as well as on happiness) if compared with non-psychedelic substances. Still, caution is advised if psilocybin is being used, and the correct dosage should be prescribed by an appropriate physician. Furthermore, the use of psilocybin has additional effects on moral enhancement and happiness if combined with meditation, preferably under the guidance of an experienced meditation specialist.

raw_json:
{"europe_pmc_id":"37376901","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2023-06-16
doi: 10.1016/j.euroneuro.2023.04.019
pubmed_id: 37336163
source_url: https://doi.org/10.1016/j.euroneuro.2023.04.019
keywords: Humans, Hallucinogens, Cross-Over Studies, Memory, Sleep, Memory Consolidation, Psilocybin
substance_tags: psilocybin
topic_tags: Healthy Volunteers,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Psilocybin intoxication did not affect daytime or sleep-related declarative memory consolidation in a small sample exploratory analysis.

authors:
Nikolič M, Viktorin V, Zach P, Tylš F, Dudysová D, Janků K, Kopřivová J, Kuchař M, Brunovský M, Horáček J, Páleníček T.

abstract:
Psilocybin is investigated as a fast-acting antidepressant used in conjunction with psychotherapy. Intact cognitive functions, including memory, are one of the basic conditions of effective psychedelic-assisted therapy. While cognitive and memory processing is attenuated on various domains during psilocybin intoxication, the effect of psilocybin on the consolidation of memories learned outside of acute intoxication is not known. Thus the main aim of the current study was to test the effects of psilocybin on (A) memory consolidation of previously learned material just after the psilocybin session and (B) on overnight memory consolidation the night just after the psilocybin session. 20 healthy volunteers (10 M/10F) were enrolled in a placebo-controlled, double-blind, cross-over design. Effects on declarative memory consolidation in condition (A) The Groton Maze Learning Task and Rey Auditory Verbal Learning Test were used, and for (B) the Pair Associative Learning Test was used. We did not find psilocybin to improve memory consolidation. At the same time, we did not find psilocybin to negatively affect memory consolidation in any of the tests used. This evidence adds to the safety profile for the use of psilocybin.

raw_json:
{"europe_pmc_id":"37336163","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: HOPE: A Pilot Study of Psilocybin Enhanced Group Psychotherapy in Patients With Cancer.
authors: Lewis BR, Garland EL, Byrne K, Durns T, Hendrick J, Beck A, Thielking P.
publication_date: 2023-06-09
doi: 10.1016/j.jpainsymman.2023.06.006
pubmed_id: 37302533
source_url: https://doi.org/10.1016/j.jpainsymman.2023.06.006
keywords: Humans, Neoplasms, Pilot Projects, Psychotherapy, Group, Psilocybin, Major Depressive Disorder
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Context/objectivesPsilocybin-assisted psychotherapy shows promise in treating depression and existential distress in people with serious medical illness. However, its individual-based methodology poses challenges for scaling and resource availability. The HOPE trial (A Pilot Study of Psilocybin Enhanced Group Psychotherapy in Patients with Cancer) is an Institutional Review Boards-approved open-label feasibility and safety pilot study examining psilocybin-assisted group therapy in cancer patients with a DSM-5 depressive disorder (including major depressive disorder as well as adjustment disorder with depressed mood). We report here the safety and clinical outcome measures including six-months follow up data.MethodsOutcome measures were collected at baseline, two-weeks and 26-weeks postintervention. The study involved three group preparatory sessions, one high-dose (25 mg) group psilocybin session, and three group integration sessions with cohorts of four participants over a three-week intervention.ResultsTwelve participants completed the trial. no serious adverse events attributed to psilocybin occurred. The primary clinical outcome measures of change in symptoms of depression on the clinician administered 17-item-HAM-D showed clinically substantial decrease in HAM-D scores from baseline to the two-week timepoint (21.5-10.09, P < 0.001) and the 26-week timepoint (21.5-14.83, P = 0.006). Six out of 12 participants met criteria for remission at two weeks, as defined by HAM-D < 7, three out 12 demonstrated a clinically significant change (4-6 points), and eight out of twelve demonstrated a clinically substantial change (7-12 points).ConclusionThis pilot study demonstrated the safety, feasibility, and possible efficacy of psilocybin-assisted group therapy for cancer patients dealing with depressive symptoms. Based on demonstrated efficacy and significant reductions in therapist time, future investigations with the group therapy model are warranted.

topic_tags:
Depression,Review Article,Observational Study,Cancer Patients,Healthcare Workers,Safety,Adverse Events

raw_json:
{"europe_pmc_id":"37302533","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelics for Patients With Cancer: A Comprehensive Literature Review.
authors: White CM, Weisman N, Dalo J.
publication_date: 2023-01-11
doi: 10.1177/10600280221144055
pubmed_id: 36635883
source_url: https://doi.org/10.1177/10600280221144055
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Mechanism of Action,Randomized Controlled Trial,Review Article
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:06
abstract:
ObjectiveTo assess the role of psychedelics in the treatment of anxiety or depression among patients with cancer.Data sourcesPubMed search from inception to March 11, 2022, using the terms anxiety, depression, psychedelics, psilocybin, lysergic acid, methylenedioxymethamphetamine, or ayahuasca.Study selection and data extractionStudies assessing patients with cancer receiving psychedelics for the treatment of anxiety or depression.Data synthesisFive unique randomized, double-blind, placebo-controlled trials were conducted. Significant reductions were found in 2 trials with 2 anxiety scales (State-Trait Anxiety Inventory-State, State-Trait Anxiety Inventory-Trait) and in 1 trial with 2 additional anxiety scales (Hamilton Rating Scale-Anxiety, Hospital Anxiety and Depression Scale-Anxiety). Significant reductions were found in 2 trials in 2 depression scales (Hospital Anxiety and Depression Scale-Depression, Beck Depression Inventory) and in 1 trial with an additional depression scale (Hamilton Rating Scale-Depression). Two studies assessed for clinically relevant reductions in anxiety and depression scores, and they occurred much more commonly in psychedelic-treated patients than those given placebo.Relevance to patient care and clinical practiceThere is a new potential option for treating patients with anxiety and depression along with cancer, which is important given the generally lackluster benefits with traditional antidepressants. Only a few sessions may also provide benefits extending out for 6 to 12 months and possibly beyond that. However, the studies were small, had many methodological limitations, and there were increases in blood pressure and heart rate.ConclusionsPsychedelics have a unique mechanism of action that might be well suited for treating anxiety and depression associated with cancer. This offers new promise for patients who are not being sufficiently treated with current antianxiety or antidepressant medications.

keywords:
Humans, Neoplasms, N-Methyl-3,4-methylenedioxyamphetamine, Hallucinogens, Antidepressive Agents, Anxiety, Randomized Controlled Trials as Topic, Psilocybin

raw_json:
{"europe_pmc_id":"36635883","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: An Assessment of Psychedelic Knowledge Among People Using Psychedelics Naturalistically.
authors: Kruger DJ, Glynos NG, Fields CW, Herberholz M, Boehnke KF
journal: Journal of psychoactive drugs
publication_date: 2022-12-31
doi: 10.1080/02791072.2022.2142709
pubmed_id: 36328419
source_url: https://pubmed.ncbi.nlm.nih.gov/36328419/
keywords: DMT, LSD, Psychedelics, knowledge, psilocybin, therapeutic use
substance_tags: psilocybin
topic_tags: Microdosing,Clinical Trial,Observational Study,Adverse Events
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"36328419"}
abstract:
Identifying gaps and strengths in psychedelic-related knowledge is key to developing effective, evidence-based education to inform appropriate use of and harm reduction practices for psychedelics in the naturalistic use landscape. The current study piloted an assessment instrument with questions on legal status, therapeutic potential, and side effects of psychedelics among people reporting current psychedelic use. We recruited participants ( = 1435) at a psychedelic advocacy event and through psychedelic interest groups on social media. Respondents completed a brief survey of psychedelic use and psychedelic knowledge. Items assessed basic knowledge of various topics surrounding psychedelics, such as legal status, active compounds, and known therapeutic efficacy based on the clinical trial literature. Respondents who had used greater numbers of different psychedelics, with higher levels of education, lower age, greater frequency of psychedelic use, identifying as male, used high doses (vs. microdosing only), identifying as Caucasian/White, and with greater annual household income answered more questions correctly. Most respondents exhibited high knowledge of psychedelics, though there is also a demonstrated need for education and outreach, especially in under-represented communities.


authors: Weleff J, Akiki TJ, Barnett BS.
publication_date: 2022-10-10
doi: 10.1080/02791072.2022.2133757
pubmed_id: 36218281
source_url: https://doi.org/10.1080/02791072.2022.2133757
substance_tags: psilocybin
topic_tags: Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Bibliometric Analysis of Academic Journal Articles Reporting Results of Psychedelic Clinical Studies.

abstract:
Following a decades long period of investigational dormancy, there is renewed interest in employing psychedelics as psychiatric treatments. The academic journals, institutions, and countries that have helped sustain clinical psychedelic research and the evolution of the literature on clinical studies of psychedelics have only recently begun to be investigated. To expand upon this work, we conducted a bibliometric analysis of clinical studies of 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT), ayahuasca, dimethyltryptamine (DMT), lysergic acid diethylamide (LSD), ibogaine, mescaline, 3,4-methylenedioxymethamphetamine (MDMA), and psilocybin published from 1965-2021. Our search revealed 394 relevant articles. After a lull from the 1970s-1990s, publications in this area have resurged. Studies most frequently focused on MDMA (49%), LSD (19%), psilocybin (18%), and ayahuasca (7%). A subanalysis of studies from 1965 to 2009 ("Older cohort") compared to 2010-2021 ("Recent cohort") revealed that the Recent cohort had a higher proportion of studies investigating psychedelics' therapeutic applications and a lower proportion of studies investigating the effects of psychedelics on people using them in non-research settings. Compared to the Older cohort, psilocybin studies increased proportionally in the Recent cohort, while DMT and mescaline studies decreased. Network analyses of inter-country collaborations suggested that psychedelic researchers in the United Kingdom have the most diverse international collaborations.

raw_json:
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title: Predictors of Psychedelic Experience: A Thematic Analysis
journal: PsyArXiv
publication_date: 2021-12-20
source_url: https://osf.io/preprints/psyarxiv/5d7fc_v1
keywords: context, experience, psychedelics, qualitative, setting, Psychiatry
substance_tags: psilocybin
topic_tags: Mechanism of Action
study_type: Qualitative Study
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"5d7fc_v1","version":1,"reviews_state":"accepted"}
abstract:
Research on the therapeutic potential of psychedelic substances is rapidly expanding. A major limitation within this field is the unpredictability of individual responses to psychedelic substances. A better understanding of factors that can predict psychedelic experience is essential to both clinical progress and wider harm reduction frameworks. Ketamine, MDMA, LSD and psilocybin were selected for comparison due to their promising therapeutic effects and different mechanisms of action. The current study aimed to (a) identify factors that predict both positive and adverse psychedelic experience, and (b) compare these predictors across the four psychedelic substances. A thematic analysis was conducted on twenty-four subjective, first-person reports of psychedelic use (six per substance), sourced from the Erowid online database. The analysis revealed three external predictors (nature, music and preparation) and three internal predictors (understanding, mindset and motivation). Each predictor contained two sub-themes that further elucidated their meaning and impact. Nature and music emerged as potential tools for de-escalating adverse reactions to psychedelics, which was a novel finding. A comparison between substances further revealed that these predictors actually had different impacts, depending on the substance being taken. Finally, the importance of, and interrelationship between, preparation, mindset, understanding and motivation was made clear. The broader clinical and sociological implications of this were discussed, with particular reference to developing harm reduction frameworks. As psychedelic therapy and research continues to gain momentum, these findings constitute an early step in developing a more nuanced understanding of the factors shaping psychedelic experience.


title: Scoping Review of Experiential Measures from Psychedelic Research and Clinical Trials.
authors: Herrmann Z, Earleywine M, De Leo J, Slabaugh S, Kenny T, Rush AJ
journal: Journal of psychoactive drugs
publication_date: 2022-12-31
doi: 10.1080/02791072.2022.2125467
pubmed_id: 36127639
source_url: https://pubmed.ncbi.nlm.nih.gov/36127639/
substance_tags: psilocybin
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"36127639"}
abstract:
Subjective responses to psychoactive drugs have served as intriguing windows into consciousness as well as useful predictors. Subjective reactions to psychedelic molecules are particularly interesting given how they covary with subsequent improvements associated with psychedelic-assisted treatments. Although links between subjective reactions and decreases in treatment-resistant clinical depression, end-of-life anxiety, and maladaptive consumption of alcohol and nicotine appear in the empirical literature, the measurement of these subjective responses has proven difficult. Several scales developed over many decades show reasonable internal consistency. Studies suggest that many have a replicable factor structure and other good psychometric properties, but samples are often small and self-selected. We review the psychometric properties of some of the most widely used scales and detail their links to improvement in response to psychedelic-assisted treatments. Generally, assessments of mystical experiences or oceanic boundlessness correlate with improvements. Challenging subjective experiences, psychological insight, and emotional breakthroughs also show considerable promise, though replication would strengthen conclusions. We suggest a collaborative approach where investigators can focus on key responses to ensure that the field will eventually have data from many participants who report their subjective reactions to psychedelic molecules in a therapeutic setting. This may aid in predicting improvement amongst targeted conditions and wellbeing.

keywords:
Mystical experience questionnaire, hallucinogens, oceanic boundlessness, psilocybin, psychedelic-assisted psychotherapy, psychedelics

topic_tags:
Depression,Anxiety,End-of-Life Distress,Consciousness,Wellbeing,Emotional Processing,Mystical Experience,Clinical Trial,Review Article


authors: Longo MSC, Bienemann B, Multedo M, Negreiros MA, Schenberg E, Mograbi DC
journal: Journal of psychoactive drugs
publication_date: 2022-12-31
doi: 10.1080/02791072.2022.2112788
pubmed_id: 35984245
source_url: https://pubmed.ncbi.nlm.nih.gov/35984245/
keywords: DMT, LSD, Nature relatedness, ayahuasca, psilocybin, psychedelics
substance_tags: psilocybin
topic_tags: Addiction,Observational Study
study_type: Observational Study
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:38
raw_json: {"pubmed_id":"35984245"}
title:
The Association of Classic Serotonergic Psychedelic Use and Intention of Future Use with Nature Relatedness.

abstract:
This study sought to investigate the effects of different substances on nature relatedness (NR) in the general population. An online cross-sectional survey done in Brazil investigated use of ayahuasca/DMT, mushrooms, LSD, MDMA/ecstasy, cocaine, cannabis, and alcohol. NR was assessed using the short-form version of the nature related scale (NR-6). One-way analysis of variance (ANOVA) was used to assess group differences between substance naïve-individuals, past users, and current users of each substance. Regression models were used including all the substances and subsequently, sociodemographic variables. ANOVAs with substances which showed significantly higher NR-6 scores in the regression model were used in order to assess the effect of intention of future use on NR. ANOVAs indicated higher NR in users of classic serotonergic psychedelics (ayahuasca/DMT, mushrooms, LSD), cannabis, and MDMA/ecstasy. Regression models showed that current use of ayahuasca/DMT and mushrooms, and past use of LSD had a positive association with NR. When sociodemographic variables were added, only ayahuasca/DMT past and current use were positively associated with NR. Intention of future use was only significantly associated with NR in individuals who reported intention of future use of mushrooms.


