# publications

authors: Lewis BR, Hendrick J, Byrne K, Odette M, Wu C, Garland EL.
publication_date: 2025-09-18
doi: 10.1371/journal.pmed.1004519
pubmed_id: 40972137
source_url: https://doi.org/10.1371/journal.pmed.1004519
substance_tags: psilocybin
topic_tags: Depression,Randomized Controlled Trial,Observational Study,Healthcare Workers,Safety,Adverse Events
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Psilocybin-assisted group psychotherapy and mindfulness-based stress reduction for frontline healthcare provider COVID-19-related depression and burnout: A randomized controlled trial.

abstract:
BackgroundDepression and burnout, which are common among healthcare workers, were exacerbated by the COVID-19 pandemic. Mindfulness-Based Stress Reduction (MBSR) and psilocybin have been reported to reduce depressive symptoms, but the efficacy of the combination requires comparison to an active treatment control. We sought to evaluate the safety and preliminary efficacy of psilocybin and MBSR versus MBSR alone for frontline healthcare providers with symptoms of depression and burnout related to the COVID-19 pandemic. We hypothesized that psilocybin would augment the antidepressant effects of MBSR in this population.Methods and findingsWe conducted a randomized controlled trial that enrolled physicians and nurses with frontline clinical work during the COVID-19 pandemic and symptoms of depression and burnout. (ClinicalTrials.gov Identifier: NCT05557643) Participants were enrolled between January 2nd, 2023 and January 16th, 2024, and randomized in a 1:1 ratio to either an 8-week MBSR curriculum alone or an 8-week MBSR curriculum plus group psilocybin-assisted psychotherapy (PAP) with 25 mg psilocybin. Evaluation of safety and feasibility of enrollment and retention was a primary objective of the study. The primary efficacy endpoint was change in depressive symptoms, as measured by the Quick Inventory of Depressive Symptoms (QIDS-SR-16) at 2 weeks post-intervention. Symptoms of depression and burnout were assessed at baseline, and 2 weeks and 6 months post-intervention utilizing the Quick Inventory of Depressive Symptoms (QIDS-SR-16) and Maslach Burnout Inventory Human Services Survey for Medical Professionals (MBI-HSS-MP), respectively. Secondary outcome measures included the Demoralization Scale (DS-II) and the Watt's Connectedness Scale (WCS). Adverse events (AEs) and suicidality were assessed through a 6-month follow-up. Twenty-five participants were enrolled and randomized. Safety was a study outcome and assessed by rate and severity of AEs and any incident suicidality or significant mental health symptoms. Baseline and outcome data were summarized using descriptive statistics, with continuous variables reported as means and standard deviations. We recorded 12 study-related, Grade 1-2 AEs and no serious AEs. In a linear mixed model analysis (LMM), the MBSR + PAP arm evidenced a significantly larger decrease in QIDS-SR-16 score than the MBSR-only arm from baseline to 2-weeks post-intervention (between-groups effect = 4.6, 95% CI [1.51, 7.70]; p = 0.008). This effect waned at the 6-month follow-up. Secondary outcome measures for burnout (subscales of the MBI-HSS-MP), demoralization (DS II), and connectedness (WCS) favored the MBSR + PAP arm; however, these effects did not survive correction for multiple comparisons. A mixed RM-ANCOVA was conducted to control for baseline differences in outcome measures. Sensitivity analyses were conducted, adjusting for baseline differences in gender and clustering within group cohorts. Study limitations that affect the generalizability of results include a small sample size, homogenous study population, and significant differences in intervention intensity.ConclusionsThis trial met its primary endpoint: group psilocybin-assisted therapy plus MBSR was associated with clinically significant improvement in depressive symptoms without serious AEs and with greater reduction in symptoms than MBSR alone. Our findings suggest that integrating psilocybin with mindfulness training may represent a promising treatment for depression and burnout among physicians and nurses. Larger trials are needed to establish efficacy, generalizability, and durability of these effects.

keywords:
Humans, Treatment Outcome, Depression, Burnout, Professional, Psychotherapy, Group, Adult, Middle Aged, Health Personnel, Female, Male, Mindfulness, Psilocybin, COVID-19, SARS-CoV-2

raw_json:
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title: Reappraisal of the hype and hope offered by psilocybin treatment of depression.
authors: Beaglehole B, Manuel J.
publication_date: 2025-09-18
doi: 10.26635/6965.7138
pubmed_id: 40966702
source_url: https://doi.org/10.26635/6965.7138
substance_tags: psilocybin
topic_tags: Depression,Review Article,Treatment-Resistant Depression,Safety,Adverse Events
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
AimTo provide a balanced account of psilocybin treatment of depression for expectations to be appropriately set.MethodReview and discussion of key psilocybin efficacy studies. Reporting of side effects and risk of harm with psychedelic treatments. Comparisons and contrasts with ketamine studies of treatment-resistant depression (TRD).ResultEarly psilocybin studies offer promise but expectation bias and functional unblinding are factors in the treatment response. Psilocybin is generally well tolerated but side effects are often not systematically reported, and some recipients may experience harm. The ketamine research has similar methodological considerations, but the weight of positive evidence is stronger for a treatment-resistant group.ConclusionThe evidence for psilocybin treatment of depression is insufficient to press for wider availability and use.

keywords:
Humans, Ketamine, Hallucinogens, Treatment Outcome, Depression, Depressive Disorder, Treatment-Resistant, Hope, Psilocybin

raw_json:
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authors: Kermanshah A, Stapleton M, Mauriello CM, Cobas M, Cordoba Torres IT.
publication_date: 2025-09-16
doi: 10.7759/cureus.92568
pubmed_id: 41111708
source_url: https://doi.org/10.7759/cureus.92568
substance_tags: psilocybin
topic_tags: Receptor Pharmacology,Case Report,Toxicity
study_type: Case Report
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Severe Rhabdomyolysis With Stage 3 Acute Kidney Injury After Ayahuasca Use Managed Without Renal Replacement Therapy: A Case Report.

abstract:
Ayahuasca, a brew containing N,N-dimethyltryptamine (DMT) with monoamine oxidase-inhibiting β-carbolines, has expanded from traditional use to global retreats. Reported adverse effects include vomiting, agitation, serotonin toxicity-like syndromes, and cardiovascular events. Rhabdomyolysis has been described with other classic hallucinogens (e.g., lysergic acid diethylamide and psilocybin), but, to our knowledge, an ayahuasca-associated rhabdomyolysis case has not been previously reported. Our case is of a previously healthy man who ingested ayahuasca and undertook prolonged travel before presenting with diffuse myalgias and dark urine. Initial laboratory results showed creatine kinase (CK) at 110,659 IU/L, serum creatinine (Cr) at 6.8 mg/dL, and blood urea nitrogen (BUN) at approximately 95 mg/dL. Comprehensive hospital toxicology screens were negative for non-prescribed substances. Despite early treatment, Cr rose to 13.6 mg/dL (hospital day 7), with BUN peaking at approximately 130 mg/dL, consistent with severe acute kidney injury (AKI). CK declined rapidly with care, reaching

raw_json:
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title: Preliminary validation and refinement of the psychedelic aesthetic experience questionnaire.
authors: Hooper JF, Ellingson JM, Hutchison KE.
publication_date: 2025-09-14
doi: 10.3389/fpsyg.2025.1648968
pubmed_id: 41030347
source_url: https://doi.org/10.3389/fpsyg.2025.1648968
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Addiction,Chronic Pain,Consciousness,Emotional Processing,Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
abstract:
IntroductionAesthetic experiences under psychedelics are often described as vivid, emotionally powerful, and meaningful, yet they remain under-measured in psychometric research. This study aimed to refine and validate the Psychedelic Aesthetic Experience Questionnaire (PAEQ), a novel instrument designed to assess the aesthetic dimensions of acute psychedelic experiences.MethodsA total of 365 past-year psilocybin users completed an anonymous online survey assessing their most typical psychedelic experience. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted on split samples to examine the latent structure of the PAEQ. Reliability, convergent validity, and regression models predicting self-reported psychological outcomes were evaluated.ResultsEFA and CFA supported a four-factor structure reflecting sensory, affective, semantic, and flow dimensions. Internal consistency was high for the total scale (α = 0.90) and acceptable across subscales. Convergent validity was supported by strong correlations with MEQ (r = 0.69), EBI (r = 0.54), and PIS (r = 0.56). PAEQ scores modestly predicted improvements in sleep, pain, substance use, anxiety, depression, and quality of life following psychedelic use.DiscussionDespite some weaknesses, the PAEQ provides a psychometrically sound measure of aesthetic engagement during psychedelic experiences, a domain not fully captured by existing instruments. Its multidimensional structure grounded in the aesthetic triad and flow theory offers new avenues for assessing altered states of consciousness and their therapeutic relevance.ConclusionThe refined PAEQ is a valid tool for quantifying aesthetic aspects of psychedelic experiences and contributes to advancing empirical approaches for characterizing altered states of consciousness.

raw_json:
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title: Microdosing Psychedelics to Restore Synaptic Density in Schizophrenia.
authors: Sapienza J, Spangaro M, Comai S, Sabé M, La Torre J, Buonarroti M, Cavallaro R, Bosia M
journal: International journal of molecular sciences
publication_date: 2025-09-13
doi: 10.3390/ijms26188949
pubmed_id: 41009515
source_url: https://pubmed.ncbi.nlm.nih.gov/41009515/
substance_tags: psilocybin
topic_tags: Neuroplasticity,Aging,Microdosing,Animal Study,In Vitro Study
study_type: Animal Study
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"41009515"}
abstract:
Schizophrenia is a highly polygenic disease, and several genetic variants associated with the disease converge on altered synaptic homeostasis. In particular, the gene encoding complement component 4 (C4) showed the strongest association with schizophrenia, and this protein is involved in complement-dependent and microglia-mediated synaptic pruning. As a matter of fact, microglia are overactive in schizophrenia, and reduced synaptic arborization, especially in the prefrontal cortex (PFC), is an established hallmark of schizophrenia, likely associated with gray matter loss, cortical thinning, hypofrontality, and deficit syndrome. The recent development of a new radioligand targeting the synaptic vesicle glycoprotein 2A (SV2A) demonstrated in vivo lower synaptic density at the PFC level in individuals with schizophrenia, corroborating the synaptic hypothesis of thedisease first proposed by Feinberg in 1982. Interestingly, robust preclinical evidence (in vitro and animal models) showed the ability of psychedelics to promote neuroplasticity and synaptogenesis, potentially counteracting the excessive synaptic loss, restoring volume loss, and possibly explaining improvements in negative and cognitive symptoms described by old clinical studies. Overall, microdoses should be explored first as a possible treatment in a selected sample of patients affected by deficit schizophrenia, followed by low and full doses if encouraging results were to emerge.

keywords:
LSD, SV2A, cognition, complement 4, microglia, negative symptoms, neuroplasticity, psilocybin, psychosis, synaptogenesis


publication_date: 2025-09-11
doi: 10.3390/healthcare13182290
pubmed_id: 41008422
source_url: https://doi.org/10.3390/healthcare13182290
substance_tags: psilocybin
topic_tags: End-of-Life Distress,Review Article,Safety
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Supporting Meaningful Choices: A Decision Aid for Individuals Facing Existential Distress and Considering Psilocybin-Assisted Therapy.

authors:
Bélanger A, Chang SL, Stephan JF, Moureaux F, Tapp D, Foxman R, Gagnon P, Hébert J, Farzin H, Dorval M.

abstract:
Background/Objectives: Given the limitations of traditional approaches to treating existential distress in seriously ill patients, psilocybin-assisted therapy (PAT) has emerged as a promising treatment option. However, weighing up the potential risks and benefits of this approach can be challenging for both healthcare professionals and patients. Decision aids can play a key role in supporting shared decision making by clarifying options, improving knowledge, and enhancing decision quality. To date, there is no decision aid specific to PAT. This descriptive study aimed to develop a decision aid for individuals considering this therapy. Methods: A paper-based/electronic decision aid was developed with a multidisciplinary steering committee following the International Patient Decision Aids Standards Collaboration (IPDAS). Development included conducting a literature review and prototype design, evaluating acceptability and usability by potential users (i.e., patients and healthcare professionals), and producing a final version. Questionnaires, direct feedback, and semi-structured interviews with potential users allowed for evaluation and refinement of design and content. Results: The final version of the decision aid is presented as a booklet, covering areas such as PAT education, comparison of treatment options, and personal reflection. Feedback from patients (n = 5) and healthcare professionals (n = 5) guided improvements, helping clarify content, ensuring balanced information, optimizing its length for usability, and providing decision-making support. Conclusions: The decision aid developed in this study demonstrated satisfactory acceptability and usability, meeting IPDAS criteria. By providing balanced and accessible information, it may facilitate shared decision-making for individuals considering PAT, representing a significant step forward in this emerging area of palliative care.

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title: Correction: Therapeutic and legal aspects of psilocybin in cancer-related depression.
authors: Wierzbicka M, Kopczyk R, Gerlach A, Rymaszewska J.
abstract: [This corrects the article DOI: 10.3389/fpsyt.2025.1591864.].
publication_date: 2025-09-10
doi: 10.3389/fpsyt.2025.1698185
pubmed_id: 41019591
source_url: https://doi.org/10.3389/fpsyt.2025.1698185
substance_tags: psilocybin
topic_tags: Depression,Cancer Patients
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
raw_json:
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authors: Kargbo RB.
publication_date: 2025-08-14
doi: 10.1021/acsmedchemlett.5c00475
pubmed_id: 40959252
source_url: https://doi.org/10.1021/acsmedchemlett.5c00475
substance_tags: psilocybin
topic_tags: Depression,Receptor Pharmacology,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Therapeutic Divergence in 5-HT2A Agonism: Psilocybin and Phenalkylamines for Demoralization Syndrome.

abstract:
Novel phenalkylamines and tryptamines such as psilocybin demonstrate promising nontraditional pharmacological profiles for treating psychiatric syndromes. Structural modifications yield functional selectivity at 5-HT receptors, mitigating hallucinogenic risk while preserving therapeutic efficacy. This study integrates receptor and behavioral data to support phenalkylamines and psilocybin as rational therapeutics for demoralization syndrome and depression-related conditions.

raw_json:
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authors: Gushken F, Fidalgo TM, Tardelli VS.
publication_date: 2025-09-07
doi: 10.1097/adm.0000000000001580
pubmed_id: 40919756
source_url: https://doi.org/10.1097/adm.0000000000001580
substance_tags: psilocybin
topic_tags: Addiction,Clinical Trial,Review Article
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Characteristics of Ongoing Clinical Trials for Cocaine Use Disorder Registered on Global Clinical Trial Databases.

abstract:
ObjectivesCocaine use disorder (CUD) affects 1.4 million people in the United States, yet no FDA-approved treatments exist. In 2023, the Food and Drug Administration (FDA) released a draft guideline on treatments for stimulant use disorders, providing direction for trial design, outcomes, and population selection. In this study, we aimed to review ongoing clinical trials for CUD and assess their alignment with the FDA's recommendations.MethodsWe conducted a systematic search of the 6 major clinical trial databases (United States, Australia, Canada, Iran, Netherlands, and Switzerland) to identify ongoing interventional studies for CUD. We included trials evaluating pharmacological, behavioral, device-based, and mixed treatments. We extracted data on intervention type, target population, study design, duration, and primary outcomes. Trials were assessed for alignment with 5 key FDA recommendations, including trial duration, use of both self-reported and biological outcome measures, randomization, placebo control, and double blinding.ResultsIn total, 38 trials were identified, primarily from the United States (32). Most trials were randomized: 36 (94.7%), while 21 (55.3%) trials had combined endpoints or a 3-month minimum duration. Only 7 trials (18.4%) met all 5 key FDA recommendations. New treatment approaches were identified, including psilocybin and the dAd5GNE vaccine, as well as digital platforms for behavioral therapies.ConclusionsA variety of promising treatments for CUD are under investigation. However, many trials fall short of current FDA design recommendations. Improved adherence to regulatory guidance and stronger collaboration between researchers and regulators will be essential to advance effective, scalable treatments for CUD.

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publication_date: 2025-09-06
doi: 10.1177/20451253251372449
pubmed_id: 40933784
source_url: https://doi.org/10.1177/20451253251372449
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Effect of psilocybin therapy on suicidal ideation, attempts, and deaths in people with psychiatric diagnoses: a systematic review and meta-analysis.

authors:
Wong S, Meckling G, Fabiano N, Lee S, Jones BDM, Shorr R, Dargel A, Davis AK, Fiedorowicz JG, Solmi M, Rosenblat JD, Mulsant BH, Blumberger DM, Husain MI.

abstract:
BackgroundSuicidal ideation, attempts, and deaths present a major and tragic public health concern. Recent trials of psilocybin therapy (PT) have shown promise in treating treatment-resistant depression and have found a reduction in suicidal ideation. Given the growth of PT research, there is a need to further understand its effect on suicidal ideation, attempts, and deaths.ObjectiveTo assess and synthesize evidence on the effects of PT on suicidal ideation, attempts, and deaths in psychiatric patients.DesignPRISMA-compliant systematic review and meta-analysis.Data sourceMEDLINE, EMBASE, Cochrane, and PsychINFO.MethodDatabases were searched for randomized controlled trials of PT in adults with psychiatric diagnoses that reported suicide outcomes (ideation, attempts, and deaths). Abstract and full-text screening were conducted, and suicide outcomes were extracted. Meta-analysis was performed with a random effects model to assess changes in suicide outcomes compared to control through the standardized mean difference (SMD). Assessment of heterogeneity, risk of bias, and subgroup analysis was completed.ResultsNine studies were included (N = 593; 335 psilocybin & 258 control). Two studies were excluded from meta-analysis because suicide-related outcomes data were not available. Participants with PT experienced a small and significant decrease in suicidal ideation compared to control (k = 7, SMD = -0.24, 95% CI -0.42 to -0.06, p = 0.008, I2 = 0%). There was no publication bias found. Subgroup analysis found no significant differences between groups. No study reported suicide attempts or suicide deaths. Two studies had a high risk of bias.ConclusionPsilocybin therapy may reduce suicidal ideation in adults with psychiatric diagnoses. Current studies are limited by small sample size, lack of follow-up data, and assessment of blinding.Trial registrationCRD42023445706.

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

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authors: Mesquita Garcia AC, Teixeira F, Maia LO.
publication_date: 2025-09-02
doi: 10.1177/08980101251374371
pubmed_id: 40900021
source_url: https://doi.org/10.1177/08980101251374371
substance_tags: psilocybin
topic_tags: Anxiety,End-of-Life Distress,Emotional Processing,Spirituality
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Integrating Holistic Communication into Psychedelic-Assisted Therapies in Hospice and Palliative Care: An Approach Based on Peplau's Theory.

abstract:
Psychedelic-assisted therapy (PAT) has shown promising results in alleviating psychological and existential suffering among individuals with serious illnesses. In parallel, nursing offers a robust theoretical framework to guide therapeutic communication in this context. This article explores the application of Peplau's Theory of Interpersonal Relations (PTIR) as a foundation for holistic communication in PAT, particularly in hospice and palliative care. We examine how PTIR's core concepts (person, health, environment, and nursing) along with its articulation of therapeutic roles, phases of the nurse-patient relationship, and the concept of anxiety as a signal of unmet needs, can be integrated into PAT's preparation, dosing, and integration phases. Drawing on a fictional case study involving a patient with advanced cancer, we illustrate how nurses can use PTIR to support emotional processing, foster insight, and promote personal growth during psilocybin-assisted therapy. By aligning Peplau's theory with the emerging field of PAT, this article highlights nursing's vital contribution to the development of safe, ethical, and compassionate psychedelic care practices. The integration of PTIR into PAT provides a valuable model for holistic nursing, offering structured yet flexible guidance for therapeutic communication with patients facing the complex emotional, spiritual, and existential dimensions of life-limiting illness.

raw_json:
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title: Therapeutic Use of Psilocybin in Depression: a Systematic Review of Clinical Evidence.
authors: Andrade FRT, Buchborn T, Thalheimer G, Meinhardt MW, Joca S, de Almeida RMM.
publication_date: 2025-09-02
doi: 10.1017/neu.2025.10039
pubmed_id: 40899152
source_url: https://doi.org/10.1017/neu.2025.10039
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
BackgroundMajor depressive disorder (MDD) is a significant public health concern, and current treatments often have limitations in effectiveness and adherence. Psilocybin, a psychedelic compound found in certain mushrooms, is being explored as a potential treatment for depression. It primarily acts through the serotonin 5-HT2A receptor but interacts with 5-HT1A and 5-HT2C receptors. Its precise mechanisms remain under investigation.Objectives(1) To consolidate evidence on psilocybin’s efficacy and safety for depression and the role of 5HT2a, (2) to identify limitations in the literature, and (3) to highlight areas needing further research.MethodsThis systematic review follows PRISMA guidelines and analyses 22 studies, including randomised controlled trials (RCTs) and open-label studies. The studies cover various populations, including individuals with treatment-resistant depression, different dosing regimens, and adjunctive therapies.ResultsPsilocybin therapy shows substantial and rapid antidepressant effects, often after one or two sessions with psychological support. Improvements are sustained for weeks or months in many cases. Psilocybin is generally well-tolerated, with mild adverse effects such as anxiety during administration and transient headaches, which are manageable in controlled settings.ConclusionsPsilocybin demonstrates promise as a novel treatment for depression, especially for individuals unresponsive to conventional antidepressants. Further research is needed to refine dosing, explore long-term effects, and understand its mechanisms of action.

keywords:
Humans, Hallucinogens, Antidepressive Agents, Treatment Outcome, Randomized Controlled Trials as Topic, Depressive Disorder, Treatment-Resistant, Psilocybin, Major Depressive Disorder

topic_tags:
Depression,Anxiety,Headache / Migraine,Mechanism of Action,Receptor Pharmacology,Randomized Controlled Trial,Systematic Review,Review Article,Treatment-Resistant Depression,Safety

raw_json:
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publication_date: 2025-08-31
doi: 10.1093/aje/kwae443
pubmed_id: 39673252
source_url: https://doi.org/10.1093/aje/kwae443
substance_tags: psilocybin
topic_tags: Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Sample composition and HIV prevention indicator differences using physical vs virtual venue recruitment of men who have sex with men in San Francisco.

authors:
Chiu I, Tate M, Trujillo D, Suprasert B, Marr A, Arayasirikul S, Wilson EC, Raymond HF, McFarland W.

abstract:
During the COVID-19 pandemic, the sampling method for the National HIV Behavioral Surveillance (NHBS) in San Francisco changed from physical venue time-location sampling (TLS) to online or virtual venue TLS for men who have sex with men (MSM). We present differences in the samples of MSM recruited using physical venue TLS in 2017 and virtual venue TLS in 2021. We further assess changes in preventive and risk behaviors from 2017 to 2021 after controlling for differences in the sample compositions with multivariable Poisson models using generalized linear models with robust standard errors. Both sampling methods exceeded their targeted sample size of 500 (physical venue TLS n = 502, virtual venue TLS n = 505). Compared to physical venue TLS, the virtual venue TLS sample had fewer persons experiencing homelessness and incarceration, and more persons with health insurance and postgraduate degrees. After adjusting for these differences and age, race, and employment status, pre-exposure prophylaxis use increased from 2017 to 2021. The use of several noninjection drugs also increased, namely marijuana, poppers, ketamine, psilocybin, and LSD. We found virtual venue recruitment of MSM to be a viable approach for tracking trends in HIV-related behaviors, with notable appeal given possible future pandemic lockdowns of physical venues and changing socialization patterns.

keywords:
Humans, HIV Infections, Risk-Taking, Homosexuality, Male, Adult, Middle Aged, San Francisco, Male, Young Adult, Pre-Exposure Prophylaxis, COVID-19, SARS-CoV-2

raw_json:
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title: Active Constituents of Psilocybin Mushroom Edibles.
authors: van Breemen RB, Simchuk D, Fritzsche B, Huson D, Kuzdzal SA, Ferguson J.
publication_date: 2025-09-01
doi: 10.1001/jamanetworkopen.2025.31345
pubmed_id: 40932719
source_url: https://doi.org/10.1001/jamanetworkopen.2025.31345
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
raw_json:
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title: Do undergraduates’ views of psychedelics relate to the context for psychedelic use?
journal: PsyArXiv
publication_date: 2024-04-23
source_url: https://osf.io/preprints/psyarxiv/xnu5c_v1
substance_tags: psilocybin
topic_tags: Addiction,Microdosing,Observational Study,Safety
study_type: Observational Study
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"xnu5c_v1","version":1,"reviews_state":"accepted"}
abstract:
Background. Psychedelic drug policy is beginning to change, both in the U.S. and internationally. However, psychedelic use is not homogeneous, as there are multiple unique contexts for use, including clinical therapies, naturalistic use, and microdosing. There are notable differences between these contexts regarding emerging evidence for therapeutic efficacy, user safety, likely future legality, and other important characteristics. We compared psychedelic-naïve undergraduates’ views (expectancies, perceptions of benefits, and perceptions of harms) of psilocybin and lysergic acid diethylamide (LSD) across each context, assessed via multiple item pools. Methods. Item-level data were analyzed using non-parametric methods, correcting for multiple comparisons. Participants were 277 psychedelic-naïve undergraduates (75.81% female; 81.95% White; 76.17% non-Hispanic), with a mean age of approximately 19.50 years (SD = 2.01). Results. Only 19 out of 79 omnibus tests assessing views of psychedelics across contexts were statistically significant; when participants’ views of psychedelics were context dependent, they generally had the most positive views of clinical contexts, then microdosing, and, lastly, naturalistic contexts. Conclusion. This indicates that psychedelic-naïve undergraduates make limited distinctions between contexts for psychedelic use, suggesting that a) researchers should define the type of use they intend to study as explicitly as possible when surveying psychedelic-naïve populations and b) in the U.S., psychedelic-naïve undergraduates may benefit from education about differences between contexts, especially considering their potential to impact public policy. Future work should extend these findings to undergraduates (i.e., potential voters) from different U.S. states and international countries to better understand emerging policy phenomena surrounding psychedelics.

keywords:
expectancies, microdosing, naturalistic psychedelic use, perceptions of benefits, psychedelic-assisted therapy, risk perceptions, Social and Behavioral Sciences, Clinical Psychology, Substance Abuse and Addiction


title: Psychedelic use in Poland: prevalence, correlates and social attitudes.
authors: Holas P, Kamińska J.
publication_date: 2025-08-20
doi: 10.5114/ppn.2025.153566
pubmed_id: 40959683
source_url: https://doi.org/10.5114/ppn.2025.153566
substance_tags: psilocybin
topic_tags: Addiction,Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
abstract:
PurposeRecent years have witnessed a renewed interest in research exploring the therapeutic potential of classic psychedelics, such as psilocybin and lysergic acid diethylamide (LSD) in the treatment of mental disorders. However, our knowledge of the epidemiology of their use, factors associated with their recreational consumption, and attitudes toward these substances remains limited.MethodsA representative sample of Polish adults (N = 1051) completed an internet-based survey that included demographic questions, assessments of psychedelic substance use, including motivations and contexts, subjective evaluations of psychedelics experience, and attitudes towards psychedelics and psychedelic-assisted therapy (PAT).ResultsBetween 4% and 8% of Polish adults, equivalent to approximately 2 million people, have experimented with psychedelic substances at least once in their lives. Men were more likely to use psychedelics than women, with the largest group of users being individuals aged 25-34, primarily residing in urban areas. Curiosity emerged as the most common motivation for use, and home was typically reported as the context. The psychedelic experience was often described as a mixture of pleasant and unpleasant sensations. A substantial proportion of participants expressed indifferent or negative attitudes towards both PAT and psychedelics. However, prior psychedelic use, younger age, and a history of lifetime meditation practice were associated with more positive attitudes.ConclusionsApproximately 6% of Polish adults, mostly young men living in urban areas, reported using classic psychedelics, particularly LSD and psilocybin mushrooms. Further research and educational efforts are needed to support the scientific exploration of PAT, and to help shift public perceptions of its therapeutic potential.

raw_json:
{"europe_pmc_id":"40959683","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin Use in the Autism Spectrum Disorder: A Scoping Review.
authors: Moreno-Chaparro J, Castañeda-Millán G, Eslava Schmalbach J.
publication_date: 2025-09-03
doi: 10.1097/wnf.0000000000000653
pubmed_id: 40939192
source_url: https://doi.org/10.1097/wnf.0000000000000653
keywords: Humans, Hallucinogens, Autism Spectrum Disorder, Psilocybin
substance_tags: psilocybin
topic_tags: Microdosing,Emotional Processing,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
ObjectiveDue to the boom in the use of certain psychedelics in different neuropsychiatric conditions, the objective was to synthesize the available information on the use of psilocybin (a psychedelic) in the population with autism spectrum disorder (ASD; a developmental neuropsychiatric condition).MethodsScoping review. Question framework: Population: people with ASD-Concept: Psilocybin-Context: use, prescription, outcomes and pharmacological variables. The databases Medline (Pubmed), EMBASE, SCOPUS, LILACS, Web of Science and additional resources were searched until June 2024. Controlled and free terms combined with Boolean operators were used to find documents in English, Spanish and Portuguese. Screening was performed by title and abstract, full text and extraction independently by two reviewers. The analysis was descriptive and with emphasis on drug use. Protocol was registered in OSF (DOI code: 10.17605/OSF.IO/GPBVZ).ResultsFour studies were included. Indications for psilocybin prescription in ASD patients were related to cognitive rigidity, exacerbated fear, behavioral/social difficulties, and inability to generate mental imagery. Two studies mentioned specific psilocybin administration, identifying microdoses and dosing intervals. Results were grouped into increased empathy and emotionality/sociability, reduction of symptoms associated with their condition or comorbidity and changes compared with other populations. All the studies were of acceptable quality with low evidence level.ConclusionsDescriptive findings of a therapeutic signal were observed in some subjects with ASD at low doses, not associated with toxic or disruptive effects. As restrictions on psilocybin use are lifted, studies with a higher level of evidence should be conducted.

raw_json:
{"europe_pmc_id":"40939192","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Ross ML, Iyer R, Williams ML, Boughey M, O'Callaghan C, Hiscock R, Dwyer J.
publication_date: 2025-08-11
doi: 10.1016/j.genhosppsych.2025.08.001
pubmed_id: 40858059
source_url: https://doi.org/10.1016/j.genhosppsych.2025.08.001
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Psilocybin-assisted psychotherapy for depression and anxiety associated with life threatening illness: A phase 2b randomized controlled trial.

abstract:
ImportancePsilocybin-assisted psychotherapy may offer a novel approach to treating depression, anxiety, and existential distress in individuals with life threatening illnesses, where current treatments show limited efficacy.ObjectiveTo evaluate the efficacy and safety of psilocybin-assisted psychotherapy versus active placebo and psychotherapy in adults with life-threatening illnesses.DesignDouble-blind, randomized controlled phase 2b trial (RCT) with an open-label extension and 6-month follow-up (January 2020 - October 2023).SettingSingle-site study at a tertiary hospital's palliative care department (St. Vincent's Hospital Melbourne affiliated with the University of Melbourne).ParticipantsAdults aged 18-80 with a life-threatening illness and clinically significant depression and/or anxiety.InterventionsParticipants were randomized to receive 25 mg psilocybin or 100 mg niacin (active placebo), alongside three preparatory psychotherapy and six post-dose integration psychotherapy sessions. After 6-7 weeks post double blind dose, all participants received 25 mg psilocybin in an open-label extension, enabling a two dose versus one dose group comparator. Participants were followed up to 26 weeks post open label dose.Main outcomes and measuresPrimary outcome was change in depression and anxiety symptoms, assessed using the Hospital Anxiety and Depression Scale (HADS), from baseline to 6-7 weeks post-dose. Key secondary outcomes included the Beck Depression Inventory-II (BDI-II) and the State-Trait Anxiety Inventory - State version (STAI-S), which provided complementary, dimensional measures of depression and anxiety over the same time period. Additional secondary outcomes included Death Attitudes Profile, WHOQOL-BREF, State-Trait Anxiety Inventory (STAI-Trait scale), Mystical Experiences Questionnaire, and Persisting Effects Questionnaire. Exploratory outcomes included spiritual well-being, hopelessness, demoralization, and HADS-Trait scores.ResultsThirty-five participants (mean age 56.0; 54.3 % female) were randomized (psilocybin: n = 17; placebo: n = 18). At 6-7 weeks, psilocybin produced significantly greater reductions in HADS depression (B = -2.49; P =.02; d = 1.12), BDI-II (B = -7.56; P =.004; d = 2.97), and STAI-State anxiety (B = -12.59; P =.005; d = 4.51) compared to placebo. Benefits were sustained at 26 weeks. Exploratory outcomes demonstrated enhanced spiritual well-being, quality of life, and significant reductions in demoralization, death anxiety and hopelessness. No serious treatment-emergent adverse events occurred. Psilocybin was associated with more mild-to-moderate adverse events. One participant withdrew due to anxiety during dosing.Conclusions and relevancePsilocybin-assisted psychotherapy appears safe and may offer durable relief from depression and anxiety in individuals with a life-threatening illness.

keywords:
Humans, Critical Illness, Hallucinogens, Double-Blind Method, Depression, Anxiety, Psychotherapy, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Young Adult, Psilocybin, Outcome Assessment, Health Care

topic_tags:
Depression,Anxiety,End-of-Life Distress,Wellbeing,Spirituality,Mystical Experience,Clinical Trial,Randomized Controlled Trial,Adolescents,Safety,Adverse Events

raw_json:
{"europe_pmc_id":"40858059","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Hultgren J, Hafsteinsson MH, Brulin JG.
publication_date: 2025-08-04
doi: 10.1016/j.genhosppsych.2025.07.020
pubmed_id: 40782561
source_url: https://doi.org/10.1016/j.genhosppsych.2025.07.020
substance_tags: psilocybin
topic_tags: Depression,Meta-Analysis
study_type: Meta-Analysis
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
A dose of therapy with psilocybin - A meta-analysis of the relationship between the amount of therapy hours and treatment outcomes in psychedelic-assisted therapy.

abstract:
BackgroundPsilocybin-assisted therapy (PAT) has shown promising effects in treating depressive symptoms, but the role of the therapeutic component remains unclear. While most research has focused on the pharmacological effects of psilocybin, the contribution of therapy has been largely overlooked.ObjectiveThis meta-analysis investigated whether the amount of therapy hours provided is associated with treatment outcomes in psilocybin-assisted therapy for depression.MethodsA systematic search of PubMed and PsycINFO yielded 1095 records. Sixteen studies met inclusion criteria, providing sufficient data for analysis. A meta-regression was conducted to assess the relationship between therapy hours and treatment outcomes.ResultsThe overall treatment effect was large both in the short-term (Cohen's d = 1.69) and long-term follow-up (Cohen's d = 2.10). However, no significant association was found between the number of therapy hours and outcome in either the short-term (b = -0.05, p =.327) or long-term (b = -0.07, p =.340) analyses. All of the included studies provided some degree of therapy (4.5-18 h).ConclusionsOur findings did not support that the amount of therapy hours influence depressive outcomes in PAT. However, this interpretation should be made with caution due to small sample sizes, heterogeneity, and poor reporting of the therapeutic component across studies. Future research should apply greater methodological rigor and standardized reporting of therapy to clarify its role in PAT.

keywords:
Humans, Hallucinogens, Depression, Depressive Disorder, Psychotherapy, Psilocybin, Duration of Therapy, Outcome Assessment, Health Care

raw_json:
{"europe_pmc_id":"40782561","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: PsyArXiv
publication_date: 2025-02-24
source_url: https://osf.io/preprints/psyarxiv/48yg7_v2
substance_tags: psilocybin
topic_tags: Longevity,Personality Change,Observational Study,Safety
study_type: Observational Study
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"48yg7_v2","version":2,"reviews_state":"accepted"}
title:
The Impact of Communicating the Benefits and Safety of Psilocybin on Policy Support: A Survey Based Experiment.

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

keywords:
Acceptability, Acceptance, Attitudes, Policy Support, Psilocybin, Psychedelics, Social and Behavioral Sciences, Social and Personality Psychology, Attitudes and Persuasion, Health Psychology, Mental Health


title: Psilocybin as a psychophysical adaptogen in chronic pain rehabilitation.
authors: Cherup NP, Finan PH.
publication_date: 2025-07-20
doi: 10.1016/j.jpain.2025.105507
pubmed_id: 40701207
source_url: https://doi.org/10.1016/j.jpain.2025.105507
keywords: Humans, Hallucinogens, Adaptation, Psychological, Chronic Pain, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Chronic Pain,Consciousness,Emotional Processing
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
Those living with chronic pain and comorbid functional disabilities are often confronted by a physically and emotionally transformative experience, impacting their identity and ability to derive meaning in life. Despite the use of various pharmacological and non-pharmacological treatments to moderate symptoms, the degree of analgesia and functional recovery are far from optimal. Psychological disorders including depression and anxiety, and maladaptive cognitive-affective states such as pain catastrophizing and fear of movement collectively impact participant engagement with rehabilitation services, leading to further deteriorations in functional status while perpetuating pain symptoms into a continuous and distressing cycle of avoidance and sedentary behavior. Psilocybin is known to produce altered states of consciousness through altered functional connectivity among key brain regions responsible for self-referential and sensorimotor processing. While preliminary evidence suggests drastic and favorable therapeutic effects among those with psychiatric disorders and unhelpful coping skills, there is limited research examining its analgesic potential and ability to foster participation in structured rehabilitation programs through changes in self-perception and meaning-making processes. The current focus article examines the application of psilocybin as a psychophysical adaptogen among those suffering from chronic pain. We propose psilocybin may be used to simultaneously improve illness identity and neuromotor outcomes through a reframing of perceived barriers to exercise engagement. PERSPECTIVE: This focus article examines the potential of psilocybin to enhance patient engagement in chronic pain rehabilitation by modulating self-perception and meaning-making processes-two underexplored yet critical barriers to successful pain management. We also propose a novel integrative framework embedding targeted movement therapy sessions into psilocybin study protocols.

raw_json:
{"europe_pmc_id":"40701207","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-07-20
doi: 10.1097/jcp.0000000000002047
pubmed_id: 40685873
source_url: https://doi.org/10.1097/jcp.0000000000002047
substance_tags: psilocybin
topic_tags: Pharmacology,Mystical Experience,Clinical Trial,Observational Study,Safety,Adverse Events
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneous RE104: A Double-Blind, Randomized, Single Ascending Dose Placebo-Controlled Study.

authors:
Ludbrook G, Bryson N, Taylor B, Hocevar-Trnka J, Johnson MW, Hirman J, Morrish G, Alexander R, Pollack M.

abstract:
BackgroundThis study is the first to formally evaluate in humans the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of RE104, a prodrug of the synthetic psychedelic known as 4-hydroxy-N,N-diisopropyltryptamine or 4-OH-DiPT.MethodsThis double-blind, randomized, placebo-controlled, phase 1 study of single subcutaneous (SC) doses of RE104 (5 to 40 mg) included 6 cohorts and a total of 48 healthy adult participants with prior experiences with hallucinogenic or psychedelic compounds.ResultsSC doses of RE104 were generally safe up to 40 mg with no serious adverse events (AEs) or deaths. Most AEs occurred acutely under supervision and were mild to moderate. The Columbia-Suicide Severity Rating Scale score did not increase during the study, and the Assessment of Alertness and Sedation Scale was largely normal at all timepoints regardless of dose. RE104 exposure, based on Cmax, AUC0-t, and AUC0-inf, increased with dose from 5 to 40 mg RE104. 4-OH-DiPT appeared rapidly in plasma (median T max ranged from 1.0 to 1.25 hours across dose groups). Mean plasma 4-OH-DiPT t ½ ranged from 2.72 hours to 4.12 hours. PKs appeared linear at the doses examined. Plasma levels of 4-OH-DiPT correlated with the Drug Effect Questionnaire and Mystical Experience Questionnaire (MEQ). Dose-related increases were observed in frequency of the MEQ30 "complete mystical experience" responders.ConclusionsSingle SC doses of RE104 resulted in a psychoactive experience and a favorable safety profile similar to psilocybin but with a shorter duration of psychoactive effect (3 to 4 hours). Results suggest a potential for therapeutic effect, warranting further study.

keywords:
Humans, Hallucinogens, Prodrugs, Injections, Subcutaneous, Double-Blind Method, Dose-Response Relationship, Drug, Adult, Middle Aged, Female, Male, Young Adult

raw_json:
{"europe_pmc_id":"40685873","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Nadeem Z, Parker S, McGovern H, Sebben B, Oestreich LK.
publication_date: 2025-07-14
doi: 10.1177/00048674251346679
pubmed_id: 40660894
source_url: https://doi.org/10.1177/00048674251346679
substance_tags: psilocybin
topic_tags: Depression,PTSD,Observational Study,Treatment-Resistant Depression,Healthcare Workers,Safety
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Attitudes toward psychedelics and psychedelic-assisted psychotherapy among Australian mental healthcare providers.

abstract:
BackgroundRecent regulatory changes in Australia have approved 3,4-methylenedioxymethamphetamine for treating post-traumatic stress disorder and psilocybin for treatment-resistant depression. However, limited data exists on Australian mental healthcare providers' attitudes, knowledge and readiness to implement with psychedelic-assisted psychotherapy.MethodsA cross-sectional survey was conducted between December 2023 and March 2024, targeting Australian general practitioners, psychiatrists and psychologists. Participants completed online questionnaires developed based on the Knowledge, Attitude and Practices framework to explore mental healthcare providers' knowledge, attitudes and practices toward psychedelics.ResultsThe survey was completed by 109 clinicians (21% psychiatrists, 56% psychologists, 23% general practitioners). Attitudes toward psychedelic-assisted therapy were positive. However, safety and efficacy concerns persisted, particularly among psychiatrists, who were significantly more likely than psychologists to perceive psychedelic use as unsafe under medical supervision and question the scientific rigor of current research. Self-rated knowledge positively predicted actual knowledge, though many clinicians relied on informal sources such as podcasts and Internet-based media, highlighting gaps in evidence-based education. Clinicians with personal experience of psychedelic use expressed higher levels of agreement with statements relating to psychedelics improving outcomes in conjunction with psychotherapy and showing promise in treating psychiatric disorders.ConclusionWhile Australian mental healthcare providers generally support psychedelic-assisted psychotherapy, significant safety and efficacy concerns remain, particularly among psychiatrists. Targeted educational initiatives from professional bodies, emphasizing evidence-based training and accessible resources, are essential to support informed clinical decision-making and safe therapeutic practices in this emerging field.

keywords:
Humans, Hallucinogens, Cross-Sectional Studies, Attitude of Health Personnel, Health Knowledge, Attitudes, Practice, Stress Disorders, Post-Traumatic, Psychiatry, Psychology, Psychotherapy, Adult, Middle Aged, Health Personnel, Australia, Female, Male, General Practitioners

raw_json:
{"europe_pmc_id":"40660894","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Glenn DL, Choi SH, Zimmerman RS.
publication_date: 2025-07-10
doi: 10.1177/02698811251353251
pubmed_id: 40643107
source_url: https://doi.org/10.1177/02698811251353251
keywords: Humans, Hallucinogens, Smoking, Smoking Cessation, Serotonin 5-HT2 Receptor Agonists
substance_tags: psilocybin
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
A systematic review and narrative summary of the therapeutic potential of classic serotonergic psychedelics for smoking cessation and reduction.

abstract:
BackgroundClassic serotonergic psychedelics are 5-HT2A partial agonists that induce non-ordinary states of consciousness. Many have demonstrated anti-addictive properties; however, their impact on smoking behaviors remains under-researched. This review provides a synthesis of the therapeutic potential of these compounds in promoting smoking cessation and reduction.MethodsA systematic review of peer-reviewed studies on psychedelics and smoking outcomes, published in English, was conducted. Database searches of PubMed, CINAHL, PsycINFO, and EMBASE resulted in 3547 records. ASReview, an open-source machine-learning tool, was used to improve the screening process. Abstract and initial review screening excluded 2336 articles, leaving 29 full-text articles for review. After further exclusion based on the inclusion of psychedelics and reported outcomes, eight studies were included in the analysis. All studies were assessed for risk of bias using the risk of bias in non-randomized studies of interventions (ROBINS-I) tool.ResultsHeterogeneity in the data was observed. All studies showed a serious risk of bias. Psilocybin was the most frequently reported compound (n = 7), followed by lysergic acid diethylamide (LSD; n = 5), mescaline (n = 4), ayahuasca (n = 4), peyote (n = 2), and N,N-dimethyltryptamine (n = 1). Psilocybin, LSD, and ayahuasca revealed preliminary therapeutic potential for facilitating smoking cessation.ConclusionsCurrent literature on psychedelics' anti-addictive effects on smoking behaviors is promising but limited by weak study designs and low generalizability. Future research should allow for stronger sampling methods to improve statistical power and include comparative groups within experimental or quasi-experimental designs to strengthen inference for causal mechanisms between drug and nondrug influences on smoking outcomes.

topic_tags:
Addiction,Mechanism of Action,Receptor Pharmacology,Consciousness,Systematic Review,Review Article,Safety

raw_json:
{"europe_pmc_id":"40643107","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Swieczkowski D, Kwaśny A, Ciurkowska P, Pruc M, Szarpak L, Cubała WJ.
publication_date: 2025-07-10
doi: 10.1177/02698811251353250
pubmed_id: 40643096
source_url: https://doi.org/10.1177/02698811251353250
substance_tags: psilocybin,psilocin
topic_tags: Aging,Clinical Trial,Review Article,Healthy Volunteers,Older Adults,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Unequal representation? A cross-sectional analysis of age, sex, race, and ethnicity in clinical trials of classic psychedelics.

abstract:
BackgroundAlthough classic psychedelic trials show therapeutic potential, the limited diversity of participants raises concerns about generalizability and safety.AimsThis study assesses the representation of race, ethnicity, and sex in interventional clinical trials of psilocybin and lysergic acid diethylamide (LSD) to evaluate disparities in participant diversity.MethodsWe conducted a cross-sectional analysis of interventional trials registered on ClinicalTrials.gov up to 12 January 2025 that focused on classic psychedelics (psilocybin, psilocin, LSD, DMT, 5-MeO-DMT, and mescaline). Eligible trials were phases 2-4 and targeted psychiatric disorders or symptoms. Trials involving only healthy participants were excluded. Two reviewers extracted trial-level data independently; discrepancies were resolved by consensus.ResultsNine eligible trials included eight with psilocybin and one with LSD. In the psilocybin trials (n = 501), the age of participants ranged from 34.3 to 56.3 years; 47.7% were women. White participants accounted for 87.2%, while Black participants accounted for 3.0%, and Asian individuals accounted for 5.0%. Ethnicity was reported in 4 of 8 psilocybin trials (n = 134), with 13.4% identifying as Hispanic or Latino. In four U.S.-only trials(n = 139), participation-to-population ratios (PPRs) confirmed the underrepresentation of Black (PPR = 0.317) and Asian participants (PPR = 0.799). The LSD trial (n = 11) included older adults (average age: 51.7 years) who did not provide any information on race or origin.ConclusionsThe limited diversity in psychedelic trials demonstrates the need for broader recruitment. Without better representation, the safety and efficacy of these therapies remain uncertain. Standardized reporting and targeted strategies are essential to ensure equity.

keywords:
Humans, Lysergic Acid Diethylamide, Hallucinogens, Cross-Sectional Studies, Age Factors, Sex Factors, Patient Selection, Adult, Middle Aged, Female, Male, Clinical Trials as Topic, Psilocybin, Ethnicity, Racial Groups

raw_json:
{"europe_pmc_id":"40643096","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelics for Alcohol Use Disorder: A Narrative Review with Candidate Mechanisms of Action.
authors: Miller EA, Capone C, Eaton E, Swift RM, Haass-Koffler CL.
publication_date: 2025-07-09
doi: 10.1007/s40263-025-01199-z
pubmed_id: 40640527
source_url: https://doi.org/10.1007/s40263-025-01199-z
keywords: Animals, Humans, Alcoholism, Hallucinogens
substance_tags: psilocybin
topic_tags: Addiction,Neuroplasticity,Mechanism of Action,Clinical Trial,Review Article,Observational Study
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
Psychedelics have been studied since the 1950s as a potential treatment for alcohol use disorder (AUD), with over a dozen clinical trials of lysergic acid diethylamide (LSD), and several contemporary trials of psilocybin and ayahuasca for this indication. Herein, we characterize foundational studies from the 1950s to the present, with emphasis on key design factors that varied considerably between published studies. Critically, those design factors include pharmacological factors, such as presence or absence of a placebo control and the nature of the placebo (e.g., ephedrine, dextroamphetamine, diphenhydramine, or low-dose LSD), and non-pharmacological factors, such as the treatment setting and the presence or absence of psychotherapy. We found that observational studies nearly uniformly show promising results, but trials in which psychedelics were tested against placebo or standard of care control groups have been more inconsistent in both outcomes and methodologies. Given the inconsistency in published results, we review candidate mechanisms of action for psychedelics in the context of AUD. We take a biopsychosocial approach, reviewing mechanisms spanning several different hierarchical levels of analysis, including cellular neuroplasticity, cognitive neuroscience, subjective experience, and social connection. Taken together, this review highlights key findings on both the efficacy and potential mechanisms of psychedelics for the treatment of AUD, which could motivate future studies in this rapidly developing field.

raw_json:
{"europe_pmc_id":"40640527","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-05-01
doi: 10.1016/j.bpsgos.2025.100524
pubmed_id: 40599633
source_url: https://doi.org/10.1016/j.bpsgos.2025.100524
substance_tags: psilocin
topic_tags: Mechanism of Action,Consciousness
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Cross-Species Evidence for Psilocin-Induced Visual Distortions: Apparent Motion Is Perceived by Both Humans and Rats.

authors:
Vejmola Č, Šíchová K, Syrová K, Janečková L, Koudelka V, Tesař M, Nikolič M, Viktorinová M, Tylš F, Korčák J, Viktorin V, Kelemen E, Nekovářová T, Brunovský M, Horáček J, Kuchař M, Páleníček T.

abstract:
BackgroundPsychedelics, particularly psilocin, are increasingly being studied for their mind-altering effects and potential therapeutic applications in psychiatry. Visual hallucinations, especially the illusion of motion in static images, are a hallmark of their action. Despite growing interest, the underlying mechanisms remain poorly understood, as their systematic evaluation in both humans and animals is challenging.MethodsTo investigate psilocin-induced visual distortions, we designed a 2-choice visual discrimination task. Human participants and male rats indicated whether an image appeared static or moving while the image either actually moved or did not. In humans, performance was compared with self-reported hallucination intensity, Altered States of Consciousness scale scores, and psilocin plasma levels. Rats were tested in 2 distinct tasks, a luminance-based task and a motion-based task. Their performance was evaluated alongside decision time.ResultsBoth species exhibited significant impairment in distinguishing static from dynamic visual stimuli while under psilocin's influence. In humans, this impairment followed the time course of psilocin plasma levels and hallucination intensity. In rats, psilocin selectively impaired performance in the motion-based task, while performance in the luminance-based task remained intact, indicating a specific effect on visual perception. Decision time was linked to discrimination impairment.ConclusionsPsilocin impaired static-dynamic discrimination in both species, providing the first evidence that rats experience visual distortions similar to those reported by humans. The correlations between discrimination impairment, psilocin levels, and hallucination intensity in humans reinforce psilocin's effects on visual perception. This approach provides a valuable tool for investigating the neurobiology of altered visual perception in drug-induced states and psychiatric conditions.

raw_json:
{"europe_pmc_id":"40599633","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-06-30
doi: 10.1177/02698811251346697
pubmed_id: 40590216
source_url: https://doi.org/10.1177/02698811251346697
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Mystical Experience,Treatment-Resistant Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Examining mystical experiences as a predictor of psilocybin-assisted psychotherapy for treatment-resistant depression.

authors:
Brudner RM, Kaczmarek E, Blainey MG, Schulz-Quach C, Meshkat S, Doyle Z, Lipsitz O, Offman H, Sethi R, Weiglein G, McIntyre RS, Rosenblat JD.

abstract:
BackgroundPsilocybin-assisted psychotherapy (PAP) is a promising treatment for various psychiatric disorders. However, the exact biological and psychological mechanisms of action of PAP remain to be determined. Examining predictors of PAP outcomes may help identify necessary processes for positive treatment outcomes. Mystical experiences are considered a key aspect of the subjective effects of ingesting psilocybin. Mystical experiences have been observed to be possibly predictive of positive outcomes in psilocybin treatments. Therefore, some argue that mystical-type experiences are necessary to achieve therapeutic benefits.AimsThe current study examines mystical experiences as a predictor of antidepressant treatment outcomes in PAP, in a complex clinical sample.MethodsParticipants included 31 individuals with a primary diagnosis of major depressive disorder (MDD) or Bipolar II Disorder (BDII), with treatment resistance to symptoms of their disorder. Participants had one, two, or three PAP treatments with a fixed dose of 25 mg of psilocybin. Depressive symptoms were measured at baseline, at a pre-dose visit and at 2 weeks post-dosing. The presence of mystical experiences was measured on the dosing day after the acute effects had resolved.ResultsFor the first psilocybin dose, participants with greater levels of mystical experiences exhibited a greater antidepressant effect from PAP. This effect was not found at the second or third doses.ConclusionThese results provide preliminary support for the hypothesis that mystical experiences have therapeutic importance in PAP and extend the literature to include a clinical sample of individuals with treatment-resistant depression in the context of MDD or BDII.

keywords:
Humans, Hallucinogens, Antidepressive Agents, Treatment Outcome, Bipolar Disorder, Psychotherapy, Mysticism, Adult, Middle Aged, Female, Male, Depressive Disorder, Treatment-Resistant, Psilocybin, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"40590216","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Blanton AM, Parikh P, Zhou S, Mohamed M, Ufret-Vincenty RL, Mancini R.
publication_date: 2025-06-01
doi: 10.1016/j.ajoc.2025.102359
pubmed_id: 40535325
source_url: https://doi.org/10.1016/j.ajoc.2025.102359
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Case Report,Safety
study_type: Case Report
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Self-inflicted transorbital intracranial foreign body following ingestion of hallucinogenic psilocybin mushrooms.

abstract:
PurposeSelf-inflicted penetrating orbital trauma is a rare ophthalmologic emergency requiring timely intervention and neurological monitoring to identify and treat any possible intracranial complications and to prevent irreversible vision loss. This case report aims to describe a fatal case of self-inflicted ocular trauma following the consumption of psilocybin mushrooms, necessitating urgent multidisciplinary care by the ophthalmology and neurosurgery services.ObservationsA 21-year-old Hispanic male presented urgently to the emergency department (ED) after self-inflicted ocular trauma with a wood-cased pencil, which was embedded in the upper eyelid and transversed the left orbit, extending to the pons, as depicted on computed tomography (CT). Physical examination of the left eye was difficult due to the risk of displacement of the pencil within the brainstem and concern for further damage. The pencil was successfully removed via fluoroscopy-guided neuro-interventional catheterization and stenting. Following the removal of the foreign body, there was no apparent damage to the globe, and a canthotomy/cantholysis was performed due to increased retro-orbital pressure. The neurovascular damage sustained by the trauma led to a progressive neurological decline in the following days and, ultimately, a fatal outcome.Conclusions and importanceWith growing support in the literature for psilocybin and its therapeutic medicinal benefits for conditions such as depression and anxiety, this report details a case of self-inflicted trans-orbital trauma with brainstem injury following ingestion of this psychoactive hallucinogen along with the proper medical and surgical management.

raw_json:
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authors: Beck SA, Barlow C, Engel L, Barratt MJ.
publication_date: 2025-08-31
source_url: https://europepmc.org/article/AGR/IND609301091
substance_tags: psilocybin
topic_tags: Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
title:
“Wood-lover paralysis”: Describing a toxidrome with symptoms of weakness caused by some lignicolous “wood-loving” Psilocybe mushrooms

abstract:
Psilocybin-containing mushrooms have long been used for their psychoactive effects, but emerging evidence suggests that certain lignicolous (“wood-loving”) species may also induce a distinct toxidrome known as “wood-lover paralysis” (WLP). WLP is characterised by transient weakness following mushroom ingestion, but its aetiology and prevalence remain poorly understood. In this paper, we present an investigation of WLP, based on a retrospective online survey conducted in 2020 (N = 392: 71.8 % male; 34.1 % aged 26-35 years; mainly from Australia and New Zealand). We found that 42.1 % of respondents reported experiencing WLP, with onset typically occurring within 4 h of ingestion. Weakness primarily impaired mobility (80.4 %), with some reporting difficulties swallowing (26.7 %) and breathing (16.6 %). Symptoms persisted into the following day for nearly half of those affected (48.1 %), and 21.5 % experienced a fall or accident. WLP was reported across different methods of mushroom preparation and environmental growth conditions, with no significant associations observed between WLP occurrence and age, gender, health status, or allergies. While the true prevalence of WLP remains unclear, our results suggest it is an under-recognised potential adverse outcome that can occur with ingestion of certain lignicolous Psilocybe species. Given the increasing medical and recreational use of psilocybin-containing mushrooms following policy shifts toward decriminalisation and legalisation, further research is needed to elucidate the currently unknown mechanism of WLP and inform harm reduction strategies and healthcare responses. Awareness among consumers, service providers and regulators will be crucial in improving recognition, reporting, and appropriate responses to this toxidrome.

raw_json:
{"europe_pmc_id":"IND609301091","source":"AGR","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Andersen KAA, Holmøy B, Kvam TM, Johnson MW.
publication_date: 2025-05-25
doi: 10.1016/j.jpsychires.2025.05.062
pubmed_id: 40466556
source_url: https://doi.org/10.1016/j.jpsychires.2025.05.062
substance_tags: psilocybin
topic_tags: Observational Study,Adolescents
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Adverse reactions among psychedelic users: Norwegian validation of the Challenging Experience Questionnaire.

abstract:
Psychedelic drugs, known for their potent psychoactive effects, have gained attention for their potential therapeutic benefits in treating mental disorders. However, distressing experiences induced by psychedelics can lead to adverse long-term effects. To better assess these experiences, we aimed to provide a Norwegian translation and psychometric validation of the Challenging Experience Questionnaire (CEQ), a key tool for evaluating adverse psychedelic experiences. Our study employed an anonymous online survey targeting Norwegian recreational psychedelic users, focusing on their most memorable psychedelic encounter. A sample of 729 participants, predominantly male (73 %) and aged between 26 and 35 years (41 %), with 90 % having used LSD or psilocybin, was analyzed. Half of the participants had completed a university degree, and 48 % reported a diagnosed mental disorder. The CEQ underwent a rigorous seven-stage translation process and was included in the survey to validate the original 7-factor structure. Our findings revealed excellent internal consistency (alpha = 0.94) and robust overall model fit (χ2[278] = 1451.80, RMSEA = 0.076, SRMR = 0.051, CFI = 0.913) for the 7-factor model, with evidence of factorial invariance across gender and psychiatric status. Further, the relationship between reported difficulty and CEQ factors such as fear, grief, insanity, and death underscored its convergent validity. In conclusion, our study confirms the 7-factor structure of the CEQ while demonstrating its reliability and validity. This provides Norwegian researchers with a culturally adapted, psychometrically valid tool for assessing complex adverse reactions to psychedelic use.

keywords:
Humans, Lysergic Acid Diethylamide, Hallucinogens, Reproducibility of Results, Psychometrics, Adolescent, Adult, Middle Aged, Norway, Female, Male, Young Adult, Surveys and Questionnaires, Psilocybin

raw_json:
{"europe_pmc_id":"40466556","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-05-27
doi: 10.1177/02698811251338232
pubmed_id: 40437853
source_url: https://doi.org/10.1177/02698811251338232
substance_tags: psilocybin,psilocin
topic_tags: Neuroplasticity,Mechanism of Action,Biomarkers,Animal Study,In Vitro Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Effects of serotonergic psychedelics on synaptogenesis and immediate early genes expression - comparison with ketamine, fluoxetine and lithium.

authors:
Vella Y, Syrová K, Petrušková A, Koutrouli I, Kútna V, Pala J, Šíchová K, Nikolič M, Mazoch V, Jurok R, Kuchař M, Bendová Z, Páleníček T.

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

keywords:
Cerebral Cortex, Animals, Rats, Rats, Wistar, Lithium, N,N-Dimethyltryptamine, Fluoxetine, Ketamine, Lysergic Acid Diethylamide, Cytoskeletal Proteins, Nerve Tissue Proteins, Hallucinogens, Organ Culture Techniques, Gene Expression Regulation, Neuronal Plasticity, Genes, Immediate-Early, Female, Early Growth Response Protein 1, Psilocybin, Basic Helix-Loop-Helix Proteins

raw_json:
{"europe_pmc_id":"40437853","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: McCoy K, Reed F, Conn K, Foldi CJ.
publication_date: 2025-08-31
source_url: https://europepmc.org/article/AGR/IND609297819
substance_tags: psilocybin
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Separate or inseparable? Serotonin and dopamine system interactions may underlie the therapeutic potential of psilocybin for anorexia nervosa

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

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

raw_json:
{"europe_pmc_id":"IND609297819","source":"AGR","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Set and setting of psychedelics for therapeutic use in psychiatry: A systematic review.
authors: Estric C, Duron T, Kabani S, Lopez-Castroman J.
publication_date: 2025-05-11
doi: 10.1177/02698811251338214
pubmed_id: 40353492
source_url: https://doi.org/10.1177/02698811251338214
keywords: Humans, Hallucinogens, Mental Disorders, Randomized Controlled Trials as Topic
substance_tags: psilocybin
topic_tags: Clinical Trial,Randomized Controlled Trial,Systematic Review,Review Article
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
abstract:
Psychedelics offer promising outcomes in psychiatry. However, the preparation of participants (set) and the environmental conditions of taking a psychedelic (setting) are not standardized. We describe the set and setting for therapeutic use of psychedelic drugs in people with psychiatric disorders. In this systematic review, articles were identified in the PubMed and Web of Science databases until 12 December 2023. Only clinical trials published in English or French were eligible, and studies using psychedelics for withdrawal were excluded. Sixteen domains of set and setting were assessed covering participant selection, pre- and post-session interventions, monitor presence, environmental management, and end-of-session procedure. Of 4912 articles screened, 27 articles were retained reporting on 25 studies. Thirteen of the included studies reported randomized trials, while 12 were open-label studies, on a total of 763 participants. Studies considered features of set and setting to different extents. Participant selection and the creation of a safe environment were consistently present, but articles were more heterogeneous about reporting monitor training (52%), controlling visual distractors (64%) and creating a pleasant environment (68%). Psilocybin was over-represented (47%). Many key elements were described in each study, but differences in set and setting limit comparability and reproducibility. Harmonizing these aspects would aid the interpretation of future studies and help understand the effect of psychedelics in psychiatry.

raw_json:
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title: Psilocybin biosynthesis enhancement through gene source optimization.
publication_date: 2025-04-15
doi: 10.1016/j.ymben.2025.04.003
pubmed_id: 40250599
source_url: https://doi.org/10.1016/j.ymben.2025.04.003
keywords: Escherichia coli, Fungal Proteins, Psilocybe, Metabolic Engineering, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Pharmacology,Mechanism of Action,Clinical Trial,Proteomics
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
authors:
Keller MR, McKinney MG, Sen AK, Guagliardo FG, Hellwarth EB, Islam KN, Kaplan NA, Gibbons WJ, Kemmerly GE, Meers C, Wang X, Jones JA.

abstract:
Psilocybin, the prodrug to the psychoactive compound in 'magic' mushrooms, is currently being studied in clinical trials as a treatment for severe mental health conditions, such as depression and anxiety. Previous reports of psilocybin biosynthesis as reconstituted in E. coli reported maximum titers of 1.16 g/L, exclusively using genes from the most common recreationally used mushroom, Psilocybe cubensis. This study explores the effect of gene species variation on psilocybin and baeocystin production using various exogenous genes sourced from psilocybin-producing mushrooms Psilocybe cubensis, Psilocybe cyanescens, Panaeolus cyanescens, and Gymnopilus dilepis. The psiD and psiK genes sourced from P. cubensis demonstrated unequivocally superior performance, while psiM showed varied production levels of psilocybin and the pathway intermediate baeocystin with changes in gene source. Strains containing a psiM gene sourced from Psilocybe cyanescens demonstrated a higher degree of baeocystin selectivity as compared to other psiM genes, demonstrating a key difference between species. Most notably, the strain Gymdi30, containing psiM sourced from G. dilepis, achieved a psilocybin titer of 1.46 ± 0.13 g/L, the highest reported to date. Comparative proteomic analysis of Gymdi30 during periods of high and low productivity was also performed to investigate bottlenecks in cellular metabolism, which could be limiting strain performance. This work represents a significant improvement in psilocybin biosynthesis, a key step towards the development of a biosynthetic manufacturing route for psilocybin.

raw_json:
{"europe_pmc_id":"40250599","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Lifetime classic psychedelic use and headaches: A cross-sectional study.
authors: Bjurenfalk Z, Cosmo A, Simonsson O, Ran C.
publication_date: 2025-03-11
doi: 10.1177/02698811251324372
pubmed_id: 40071875
source_url: https://doi.org/10.1177/02698811251324372
substance_tags: psilocybin
topic_tags: Headache / Migraine,Observational Study,Adolescents
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
abstract:
BackgroundMigraine and cluster headache are two primary headache disorders for which conventional treatments are limited. Classic psychedelic substances such as lysergic acid diethylamide (LSD) and psilocybin are potentially promising new treatment candidates for these conditions.AimsThe aim of the present study was to investigate the possible relationship between the lifetime use of classic psychedelics and frequent bad headaches in a large British cohort sample.MethodsUsing data (N = 11,419) collected in 1999-2000 as part of the 1958 British National Child Development Study, this cross-sectional study used multiple logistic regression, controlling for a range of potential confounders, to test the hypothesis that lifetime use of classic psychedelics would be associated with lower odds of having frequent bad headaches.ResultsLifetime use of classic psychedelics was associated with 25% lower odds of having frequent bad headaches (adjusted odds ratio = 0.75, 95% CI: 0.59-0.95, p = 0.016).ConclusionsThe results of the present study add to the literature suggesting classic psychedelics as a possible future prophylactic treatment option for primary headache disorders.

keywords:
Humans, Cluster Headache, Headache, Lysergic Acid Diethylamide, Hallucinogens, Cohort Studies, Cross-Sectional Studies, Adolescent, Adult, Child, Female, Male, Migraine Disorders, Young Adult, United Kingdom, Psilocybin

raw_json:
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authors: Ahuja S, Zaher F, Palaniyappan L.
publication_date: 2025-02-15
doi: 10.1177/02698811251319455
pubmed_id: 39956789
source_url: https://doi.org/10.1177/02698811251319455
keywords: Humans, Ketamine, Hallucinogens, Psychotropic Drugs, Natural Language Processing, Machine Learning
substance_tags: psilocybin
study_type: Meta-Analysis
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Quantitative natural language processing markers of psychoactive drug effects: A pre-registered systematic review.

abstract:
Psychoactive substances used for recreational purposes have mind-altering effects, but systematic evaluation of these effects is largely limited to self-reports. Automated analysis of expressed language (speech and written text) using natural language processing (NLP) tools can provide objective readouts of mental states. In this pre-registered systematic review, we investigate findings from applying the emerging field of computational linguistics to substance use with specific focus on identifying short-term effects of psychoactive drugs. From the literature identified to date, we note that all the studied drugs - stimulants, 3,4-methylenedioxymethamphetamine (MDMA), cannabis, ketamine and psychedelics - affect language production. Based on two or more studies per substance, we note some emerging patterns: stimulants increase verbosity; lysergic acid diethylamide reduces the lexicon; MDMA increases semantic proximity to emotional words; psilocybin increases positive sentiment and cannabis affects speech stream acoustics. Ketamine and other drugs are understudied regarding NLP features (one or no studies). One study provided externally validated support for NLP and machine learning-based identification of MDMA intoxication. We could not undertake a meta-analysis due to the high degree of heterogeneity among outcome measures and the lack of sufficient number of studies. We identify a need for harmonised speech tasks to improve replicability and comparability, standardisation of methods for curating and analysing speech and text data, theory-driven inquiries and the need for developing a shared 'substance use language corpus' for data mining. The growing field of computational linguistics can be utilized to advance human behavioral pharmacology of psychoactive substances. Achieving this will require concerted efforts towards consistency in research methods.

topic_tags:
Addiction,Pharmacology,Biomarkers,Emotional Processing,Meta-Analysis,Systematic Review,Review Article

raw_json:
{"europe_pmc_id":"39956789","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-01-12
doi: 10.1037/pst0000551
pubmed_id: 39804360
source_url: https://doi.org/10.1037/pst0000551
substance_tags: psilocybin
topic_tags: Chronic Pain,Spirituality,Clinical Trial,Cancer Patients,Healthcare Workers
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
A critical evaluation of psilocybin-assisted therapy protocol components from clinical trial patients, facilitators, and caregivers.

authors:
Palitsky R, Maples-Keller JL, Peacock C, Dunlop BW, Mletzko T, Grant GH, Raison CL, Chao S, Shub I, Mendelbaum-Kweller M, Smolyar L, Kaplan DM, Rothbaum BO, Zarrabi AJ.

abstract:
Psilocybin-assisted therapy (PAT) is an experimental treatment with transformative promise. Developing standards for PAT psychotherapy protocols is a priority, but psychotherapeutic protocol components of PAT have been subjected to little rigorous research. This study was designed to assess protocol components in a trial of PAT. The Enhanced Critical Incident Technique (E-CIT) was used to identify critical incidents in the treatment, wish list items comprising components or modifications that would have improved the treatment experience, and contributing factors that influenced the treatment. Participants included patients (n = 10), facilitators (n = 7 licensed mental health clinicians and certified spiritual health clinicians), and caregivers (n = 7) in an open-label trial investigating PAT for cancer-related demoralization and chronic pain. Patients and caregivers were interviewed after their last treatment session in the trial; facilitators were interviewed at the end of the entire trial. Rapid qualitative analysis identified specific domains for improvement in the treatment protocol based on the E-CIT. Critical incidents, wish list items, and contributing factors pertained to aspects of the therapy (e.g., importance of intention-setting) and the overall protocol (e.g., navigating transitions in the treatment). Findings indicate the importance of tailoring PAT to accommodate the medical history and needs of this population, support common factors, and ensure collaborative care. Recommendations across nine topic areas were derived from the data and presented in the Discussion. The E-CIT shows promise for advancing early stage research on PAT components. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

keywords:
Humans, Neoplasms, Hallucinogens, Treatment Outcome, Clinical Protocols, Psychotherapy, Adult, Middle Aged, Caregivers, Female, Male, Chronic Pain, Psilocybin

raw_json:
{"europe_pmc_id":"39804360","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: PsyArXiv
publication_date: 2024-10-30
source_url: https://osf.io/preprints/psyarxiv/dwhcu_v1
keywords: experts, personal experience, psychedelics, qualitative, Psychiatry, Social and Behavioral Sciences
substance_tags: psilocybin
topic_tags: Wellbeing,Clinical Trial,Safety
study_type: Clinical Trial
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"dwhcu_v1","version":1,"reviews_state":"accepted"}
title:
Personal Psychedelic Experience as a Training Qualification for Facilitators: A Thematic Analysis of Qualitative Interviews with Psilocybin Experts

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


title: The Epidemiology of Psychedelic Use Among United States Military Veterans.
authors: Davis AK, Bates M, Lund EM, Sepeda ND, Levin AW, Armstrong SB, Koffman R, Hooyer K, Yehuda R
journal: Journal of psychoactive drugs
publication_date: 2024-12-31
doi: 10.1080/02791072.2024.2401977
pubmed_id: 39263894
source_url: https://pubmed.ncbi.nlm.nih.gov/39263894/
keywords: Epidemiology, adverse outcomes, mental health, psychedelic, veterans
substance_tags: psilocybin
topic_tags: Spirituality,Observational Study,Veterans
study_type: Observational Study
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 06:54:12
raw_json: {"pubmed_id":"39263894"}
abstract:
We sought to identify patterns of psychedelic use among United States military veterans, compare demographic variables and perspectives of those who did and did not report use, and characterize benefits and adverse outcomes associated with use. Respondents ( = 426) were recruited to complete an online cross-sectional survey. Approximately one-half (51%) reported using psychedelics. Most did so for healing/treatment (70%) and/or spiritual purposes (48%), and most (85%) reported benefiting from use. Those who used psychedelics reported they would be more likely to use VA services ( < .001, d = 0.64) and to return to the VA for care ( < .001, d = 0.79) if psychedelic therapy was offered. Almost two-thirds (59%) reported adverse outcomes associated with use. Equivalent proportions rated their psychedelic experiences as beneficial among those who did (89%) and did not (81%) report adverse outcomes. Fewer adverse outcomes were associated with being older, using psilocybin, feeling prepared and confident in the reasons for use, being in a comfortable setting, and being able to "trust, let go, and be open" (R = 0.77;  < .001). Psychedelics may offer benefits but may also lead to adverse outcomes without proper preparation and support. Future research should examine the utility of psychedelic-based approaches for veteran mental health care.


authors: Thaoboonruang N, Lohitnavy M, Lohitnavy O.
publication_date: 2024-09-09
doi: 10.1080/02791072.2024.2399128
pubmed_id: 39257234
source_url: https://doi.org/10.1080/02791072.2024.2399128
keywords: Animals, Humans, Hallucinogens, Dose-Response Relationship, Drug, Psilocybe, Psilocybin
substance_tags: psilocybin,psilocin
topic_tags: Depression,Pharmacology,Clinical Trial,Systematic Review,Review Article,In Vitro Study
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Pharmacokinetics of Psilocybin, a Tryptamine Alkaloid in Magic Mushroom (Psilocybe cubensis): A Systematic Review.

abstract:
Psilocybin, a major indole alkaloid found in magic mushrooms (Psilocybe cubensis), has recently drawn attention as a breakthrough therapy to treat major depressive disorder. This review aimed to summarize and identify knowledge gaps concerning their pharmacokinetic characteristics of psilocybin and its active metabolite, psilocin. Original studies related to pharmacokinetics of psilocybin conducted in vitro, animals, and humans were systematically collected from PubMed, Scopus, and ScienceDirect, from their inceptions to November 2023. Twenty articles were included in this work and assessed for study quality. A comprehensive review of the pharmacokinetics of psilocybin and psilocin in both animals and humans was performed. Psilocybin is considered a prodrug that is dephosphorylated to psilocin by alkaline phosphatase. Following ingestion, the peak psilocin plasma and brain levels were rapidly achieved in a dose-dependent manner. Psilocin is metabolized primarily through both Phase I and Phase II processes with the half-life of 2-3 hours. This review also identified lack of some pharmacokinetic related information and limitations of available research that may help direct future investigations to better understand the pharmacokinetics and improve study design including dose selection and dosage optimization.

raw_json:
{"europe_pmc_id":"39257234","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Magic of the Mushrooms: Effects of Psilocybin Decriminalization.
authors: Bhave A.
publication_date: 2024-07-09
doi: 10.1080/02791072.2024.2376755
pubmed_id: 38984875
source_url: https://doi.org/10.1080/02791072.2024.2376755
substance_tags: psilocybin
topic_tags: Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
In the past few years, psilocybin, a psychedelic compound found in "magic mushrooms" (psilocybin mushrooms), has undergone decriminalization in numerous cities across the US and has been legalized in Oregon and Colorado. Proponents of psilocybin decriminalization have emphasized its therapeutic potential in treating mental health disorders. Furthermore, psilocybin mushrooms are considered the safest psychedelic option, with lower potency and a reduced risk of overdoses and emergency hospitalizations compared to other prevalent psychedelics, such as LSD (lysergic acid diethylamide) and MDMA (3,4-methylenedioxymethamphetamine). We analyzed the impact of psilocybin reforms on public interest in psilocybin, as well as their cross-commodity effects on LSD and MDMA, utilizing extensive web-based search data. We observe a significant increase in psilocybin search volume and a notable reduction in search volume associated with LSD and MDMA. Our results are consistent nationwide across states, irrespective of their stance on psilocybin reforms. The shift in public interest toward psilocybin, which is considered the safest psychedelic, away from LSD and MDMA, carries positive implications for public health.

keywords:
Humans, Agaricales, N-Methyl-3,4-methylenedioxyamphetamine, Lysergic Acid Diethylamide, Hallucinogens, United States, Psilocybin

raw_json:
{"europe_pmc_id":"38984875","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Askariyan K, Joghataei MT, Dehghan S, Nohesara S, Riahi Pour L, Mohammadi MH, Ahmadirad N.
publication_date: 2025-07-24
doi: 10.1016/j.pnpbp.2025.111461
pubmed_id: 40716639
source_url: https://doi.org/10.1016/j.pnpbp.2025.111461
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
An overview of psilocybin, LSD, MDMA, and ketamine in revitalizing psychedelic-assisted therapy: Insights, limitations and future directions.

abstract:
The resurgence of psychedelic-assisted psychotherapy marks a pivotal evolution in mental health treatment, challenging traditional paradigms by integrating compounds such as psilocybin, LSD, MDMA, and ketamine into clinical practice. Historically marginalized due to regulatory and societal concerns, these agents are now gaining recognition for their unique neurobiological mechanisms and therapeutic potential in addressing complex conditions like depression, PTSD, and addiction. Unlike conventional treatments, psychedelics exert their effects primarily through modulation of serotonin receptors and brain network connectivity, with each substance demonstrating distinct pharmacological profiles and clinical applications. Notably, psilocybin and LSD share serotonergic pathways but differ in receptor specificity and subjective effects, while MDMA's empathogenic properties and ketamine's rapid antidepressant action offer alternative therapeutic avenues. Recent FDA breakthrough therapy designations for psilocybin and MDMA underscore a shift toward evidence-based acceptance, yet the field remains challenged by methodological limitations, regulatory barriers, and ethical considerations. This narrative review synthesizes historical developments, mechanistic insights, and clinical outcomes, emphasizing the need for rigorous research, diverse patient cohorts, and thoughtful integration of psychedelics with psychotherapeutic modalities to realize their full therapeutic promise.

keywords:
Animals, Humans, N-Methyl-3,4-methylenedioxyamphetamine, Ketamine, Lysergic Acid Diethylamide, Hallucinogens, Psychotherapy, Psilocybin

topic_tags:
Depression,PTSD,Addiction,Mechanism of Action,Receptor Pharmacology,Review Article,Observational Study

raw_json:
{"europe_pmc_id":"40716639","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Examining the potential of psilocybin and 5-MeO-DMT as therapeutics for traumatic brain injury.
authors: Plummer Z, Allen J, Brand J, Mayo LM, Shultz SR, Christie BR.
publication_date: 2025-07-13
doi: 10.1016/j.pnpbp.2025.111448
pubmed_id: 40669813
source_url: https://doi.org/10.1016/j.pnpbp.2025.111448
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
Traumatic brain injury (TBI) is a significant global health challenge, with limited effective treatments for its acute and chronic consequences. TBI is characterized by neuroinflammation, oxidative stress, impaired neuroplasticity, imbalances in neurotransmission, and cell death - factors that contribute to the development of neurological and psychiatric disorders. Emerging evidence suggests that serotonergic psychedelics psilocybin and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) may hold promise as treatments for TBI. These compounds promote neuroplasticity, exert anti-inflammatory and neuroprotective effects, and have shown efficacy in treating psychiatric conditions that share pathophysiological features with TBI. 5-HT1A and 5-HT2A receptors are implicated in their effects, but psilocybin also targets neurotrophic TrkB receptors, whereas 5-MeO-DMT targets sigma-1 receptors, known to have neuroprotective properties. This review integrates current preclinical and clinical research, highlighting both the shared and distinct mechanistic pathways through which psilocybin and 5-MeO-DMT may alleviate TBI-related impairments, such as cognitive and affective dysfunction and neuroinflammation. Additionally, the safety profiles, dosing paradigms, and clinical challenges of these psychedelics are critically examined. By bridging insights from psychedelic science and neurotrauma research, this review underscores the innovative potential of psilocybin and 5-MeO-DMT as adjunctive treatments for TBI, paving the way for novel interventions in neurorehabilitation.

keywords:
Animals, Humans, N,N-Dimethyltryptamine, Hallucinogens, Neuroprotective Agents, Psilocybin, Brain Injuries, Traumatic

topic_tags:
Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Oxidative Stress,Review Article,Animal Study,Safety,Inflammation

raw_json:
{"europe_pmc_id":"40669813","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Avanceña ALV, Vuong L, Kahn JG, Marseille E.
publication_date: 2025-08-28
doi: 10.1038/s41398-025-03556-4
pubmed_id: 40883271
source_url: https://doi.org/10.1038/s41398-025-03556-4
substance_tags: psilocybin
topic_tags: Depression,Treatment-Resistant Depression,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Psilocybin-assisted therapy for treatment-resistant depression in the US: a model-based cost-effectiveness analysis.

abstract:
Psilocybin-assisted therapy (PAT) has been shown in early trials to reduce the symptoms of treatment-resistant depression (TRD). This study evaluated the cost-effectiveness of PAT as a third-line treatment for major depressive disorder compared to standard of care (SOC). We used an individual-level, probabilistic simulation model that portrays representative US adults with TRD who receive SOC (pharmacotherapy, psychotherapy, electroconvulsive therapy, and esketamine nasal spray) and PAT over 12 months. We assumed the total cost of PAT was $5000, which we varied in sensitivity analyses ($3000-20,000). We calculated total costs, health effects (in terms of quality-adjusted life years [QALYs] gained), and incremental cost-effectiveness ratio (ICER) from limited healthcare and societal perspectives. PAT leads to an additional 0.031 QALYs and $3639 costs compared to SOC over 12 months, giving an ICER of $117,517 per QALY gained from a limited healthcare perspective. Using a $150,000 cost-effectiveness threshold, PAT had a 75% probability of being the cost-effective choice, and it was associated with a lower expected loss than SOC ($301 vs. $1307). Results were sensitive to uncertainty in model parameters, particularly the cost of PAT. PAT had a 1% probability of being cost-effective when its overall costs were $10,000 and 95% when its costs were $3000. This cost-effectiveness analysis found that when its costs are $5000 or less, PAT may offer economic value compared to available TRD treatments. Future studies can explore ways to reduce the cost of PAT and to understand its long-term effectiveness in maintaining remission and reducing the risk of relapse.

keywords:
Humans, Electroconvulsive Therapy, Quality-Adjusted Life Years, Adult, Middle Aged, Cost-Benefit Analysis, United States, Female, Male, Depressive Disorder, Treatment-Resistant, Psilocybin, Cost-Effectiveness Analysis, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"40883271","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Fernandes-Nascimento MH, Viana-Ferreira K, Negrão AB.
publication_date: 2025-08-27
doi: 10.1089/psymed.2024.0031
pubmed_id: 40933206
source_url: https://doi.org/10.1089/psymed.2024.0031
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Addiction,Clinical Trial
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Overview and Specificity of Psilocybin Use in the Treatment of Mental Disorders: A Scientometric Analysis.

abstract:
BackgroundPsilocybin is a natural alkaloid with therapeutic potential in the treatment of different mental disorders. Bibliometric information on its use is still scattered in the literature.ObjectiveTo investigate the temporal and bibliometric patterns of publications and the specificity of psilocybin in the treatment of mental disorders.MethodPerformed a bibliometric analysis using VOSviewer software. Documents from the period 1963 to 2023 were retrieved from the Scopus database. The search string comprised terms related to psilocybin and mental disorders. An exponential regression was performed to investigate the number of publications over time. The specificity was evaluated based on a manual analysis of the clinical trials' findings carried out with individuals diagnosed with mental disorders.ResultsWe identified 853 eligible publications. An exponential regression analysis revealed an increase in the number of publications over time, with significant growth between 2016 and 2023 (52%). Publications cover countries on five continents, but are predominantly from nations with a high Human Development Index, such as the United States and the United Kingdom. Depression was the most prominent term in keyword analysis. Meta-analyses have indicated the efficacy of psilocybin in the treatment of different mental disorders (depression, anxiety, and substance use disorders).ConclusionThe global academic panorama shows the growing recognition of psilocybin as a promising alternative in psychiatric treatment, highlighting the need for randomized clinical trials to ensure its safe and effective use.

raw_json:
{"europe_pmc_id":"40933206","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Is There More to Magic Mushrooms than Psilocybin?
authors: Johnson-Groh M.
publication_date: 2025-07-02
doi: 10.1021/acscentsci.5c01146
pubmed_id: 40893965
source_url: https://doi.org/10.1021/acscentsci.5c01146
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
abstract:
Some scientists think that including secondary compounds from psychedelic mushrooms can make for better drugs. With scarce data, others remain skeptical.

raw_json:
{"europe_pmc_id":"40893965","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelic Therapy, Positive Emotional Experiences, and the Central Role of Self-Compassion
journal: Research Square
publication_date: 2025-08-21
doi: 10.21203/rs.3.rs-7420529/v1
source_url: https://doi.org/10.21203/rs.3.rs-7420529/v1
substance_tags: psilocybin
topic_tags: Depression,Emotional Processing,Mystical Experience,Clinical Trial,Observational Study
study_type: Clinical Trial
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
authors:
Zeifman R, Danias G, Agin-Liebes G, Pagni B, Kettner H, Bhat V, Ross S, Erritzoe D, Carhart-Harris R.

abstract:
Abstract Background: Psychedelics can acutely induce mystical experiences and elevated positive mood, which may contribute to the potential benefits of psychedelic therapy. However, there remains limited understanding of the occurrence and importance of specific positive emotional experiences within psychedelic therapy. Therefore, we examined the effects of psychedelics on positive emotional experiences and their association with improvements in mental health. Methods: Study 1 was an observational study of naturalistic psychedelic use. Study 2 used data from a clinical trial that compared psilocybin with escitalopram in individuals with major depressive disorder. In this trial, participants completed two dosing sessions, where they received either 25mg or 1mg of psilocybin. In both studies, following their psychedelic experience or psilocybin dosing sessions, participants rated their acute experiences of seven specific positive emotional experiences (self-compassion, compassion toward others, gratitude, love, awe, ecstasy, and peace). Results: Relative to low-dose psychedelic, medium and high-dose psychedelic use were associated with greater positive emotional experiences. Relative to 1mg psilocybin, 25mg psilocybin was associated with greater positive emotional experiences. Several positive emotional experiences predicted improvements in mental health and mediated treatment outcomes, with the strongest evidence for the effect of self-compassion (over and above mystical experience and positive mood). Discussion: Positive emotional experiences, especially self-compassion, appear to play an important role within psychedelic therapy. Based on these findings, we highlight key considerations surrounding psychotherapeutic approaches to, and optimization of, psychedelic therapy. Future research should move beyond retrospective, self-reports of emotional experiences to fully capture their role within psychedelic therapy.

raw_json:
{"europe_pmc_id":"PPR1071953","source":"PPR","pub_type":null,"publisher":"Research Square","importer":"Europe PMC"}


title: Psychedelics and the Serotonin Hypothesis of Eating Disorders.
authors: Bilenker D, Avena NM.
publication_date: 2025-08-20
doi: 10.3390/brainsci15080893
pubmed_id: 40867224
source_url: https://doi.org/10.3390/brainsci15080893
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
abstract:
Recent advances in psychedelic research have renewed interest in their therapeutic potential for psychiatric disorders characterized by cognitive and behavioral rigidity. This review examines the rationale for using serotonergic psychedelics-particularly 5-HT2A receptor agonists such as psilocybin-in the treatment of eating disorders (EDs), including anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). The paper contextualizes these interventions within the broader serotonin hypothesis of EDs, emphasizing serotonergic dysregulation and impaired cognitive flexibility as central features of these conditions. Drawing from animal models, human neuroimaging studies, and emerging clinical trials, the authors outline how psychedelics may promote neuroplasticity and psychological insight through modulation of 5-HT2A signaling. Preliminary evidence from open-label studies suggests psilocybin may improve ED symptoms and quality of life, though findings are early and methodologically limited. The paper also reviews data on ayahuasca, MDMA, and non-psychedelic serotonergic agents, highlighting both the promise and complexity of psychedelic-assisted therapy in EDs. The authors conclude that while further controlled trials are needed to clarify efficacy, safety, and optimal treatment parameters, psychedelics offer a novel, mechanistically distinct avenue for addressing entrenched ED psychopathology.

topic_tags:
Eating Disorders,Neuroplasticity,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Aging,Clinical Trial,Review Article,Animal Study,Safety

raw_json:
{"europe_pmc_id":"40867224","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Madden MB, Schaefgen C, Vedak B, Kwon J, Pedra KSD, Sheats SH, Puche AC, Wolff SBE, Mathur BN.
publication_date: 2025-08-18
doi: 10.1038/s41467-025-62980-8
pubmed_id: 40830107
source_url: https://doi.org/10.1038/s41467-025-62980-8
substance_tags: psilocybin,psilocin
topic_tags: Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Serotonin and psilocybin activate 5-HT1B receptors to suppress cortical signaling through the claustrum.

abstract:
Through its widespread reciprocal connections with the cerebral cortex, the claustrum is implicated in sleep and waking cortical network states. Yet, basic knowledge of neuromodulation in this structure is lacking. The claustrum is richly innervated by serotonergic fibers, expresses serotonin receptors, and is suggested to play a role in the ability of psilocybin, which is metabolized to the non-specific serotonin receptor agonist psilocin, to disrupt cortex-wide network states. We therefore addressed the possible role of serotonin, and the classic psychedelic psilocybin, in modulating cortical signaling through the claustrum. We show that serotonin activates 5-HT1B receptors on anterior cingulate cortex inputs - a primary driver of claustrum activity - to suppress signaling to parietal association cortex-projecting claustrum neurons. Additionally, we demonstrate that psilocybin injection also activates anterior cingulate cortex presynaptic 5-HT1B receptors to suppress cortical signaling through the claustrum. Thus, serotonin, via 5-HT1B, may provide gain-control of cortical input to the claustrum, a mechanism that may be directly targeted by psilocybin to modulate downstream cortical network states.

keywords:
Gyrus Cinguli, Cerebral Cortex, Neurons, Animals, Mice, Inbred C57BL, Mice, Serotonin, Receptor, Serotonin, 5-HT1B, Hallucinogens, Signal Transduction, Male, Serotonin 5-HT1 Receptor Agonists, Psilocybin, Claustrum

raw_json:
{"europe_pmc_id":"40830107","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Hughes B, Mirza S, Ponamala M, Sagaser J, Paredes R, Hematillake N, Tailor C, Khan R, Pemminati S.
publication_date: 2025-08-17
doi: 10.7759/cureus.90425
pubmed_id: 40970030
source_url: https://doi.org/10.7759/cureus.90425
substance_tags: psilocybin
study_type: Meta-Analysis
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Exploring the Therapeutic Potential of Ketamine and Psilocybin in Comparison to Current Treatment Regimens for Treatment-Resistant Depression, Mood Disorders, and Post-traumatic Stress Disorder in the Pediatric Population: A Narrative Review.

abstract:
The stresses of the Coronavirus Disease of 2019 (COVID-19) pandemic highlighted the burden of psychiatric disorders within the pediatric population, revealing a pre-existing need for rapid-onset therapies that have since driven efforts to expand effective therapeutic interventions. In this narrative review, we utilized the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines to direct our report and study selection. We explored the current-state efficacy and therapeutic potential of ketamine and psilocybin in comparison to current treatment regimens for pediatric non-psychotic disorders, including Treatment-Resistant Depression (TRD), mood disorders like anxiety and bipolar disorder, and Post-Traumatic Stress Disorder (PTSD). We chose these pediatric disorders to eliminate concerns regarding reality orientation and the use of dissociative and/or psychedelic medicines in patients who are experiencing symptoms of psychosis. Also, we briefly discuss ketamine's more widely accepted utilization by medical providers as a pediatric anesthetic, and how this gives credence to further evaluation of ketamine's multifaceted indications in pediatric psychiatry. Recent studies have shed light on the involvement of glutamate pathways in the pathophysiology of TRD, mood disorders, and PTSD, and both ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, and psilocybin, a 5-hydroxytryptamine receptor 2A (5-HT2A) agonist, have emerged as promising options due to their ability to augment glutamate release. Ketamine's use for pediatric TRD demonstrated rapid-onset relief for signs and symptoms of depression in children and adolescents, and psilocybin also decreased symptoms in patients with longstanding or refractory depression. Ketamine has been well tolerated and exhibited symptom improvements for youth with mood disorders such as anxiety and bipolar depression, while psilocybin showed promise in fostering emotional processing. In youth suffering from PTSD, ketamine-assisted psychotherapy (KAP) brought about decreases in PTSD symptom severity, though outcomes varied across populations. Psilocybin enhanced neural plasticity, allowing patients to revisit and reframe memories under therapeutic guidance, especially for those with complex or treatment-resistant PTSD. Ethical considerations are involved in the use of dissociative and hallucinogenic therapies like ketamine and psilocybin in the pediatric population, and we explore some ethical issues regarding their use. Further research exploring specific brain locations and mechanisms of action underlying glutamate modulation by ketamine and psilocybin, and the subsequent rapid-acting relief of psychiatric symptoms offered by these substances, could pave the way for innovative treatments targeting pediatric mental health disorders.

topic_tags:
Depression,Anxiety,PTSD,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Emotional Processing,Meta-Analysis,Systematic Review,Review Article,Adolescents,Treatment-Resistant Depression

raw_json:
{"europe_pmc_id":"40970030","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Selective Phosphorylation of Phenols and Benzenediols by the Kinase PsiK and Variants Thereof.
authors: Kim A, Morato NM, Saha P, Eyimegwu PN, Niyaz AA, Huang R, Cooks RG, Phelan RM, Lewis JC.
publication_date: 2025-06-24
doi: 10.1002/anie.202503538
pubmed_id: 40526241
source_url: https://doi.org/10.1002/anie.202503538
keywords: Phenols, Protein Kinases, Substrate Specificity, Phosphorylation, Biocatalysis
substance_tags: psilocin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
Phosphorylation plays important roles in biology by modulating the structure, reactivity, and biological function of a broad range of molecules. Biocatalytic phosphorylation has attracted attention from synthetic chemists due to its selectivity and mild reaction conditions using ATP as a phosphate donor. Given the potential synthetic utility of kinases with activity on small molecule substrates, we explored the activity of PsiK, the enzyme responsible for selective 4-O-phosphorylation of 4-hydroxytryptamine or psilocin in psylocybin biosynthesis by Psilocybe cubensis. We find that PsiK has good activity on a range of substituted phenols and benzenediols beyond its native substrate, enabling preparative phosphorylation of different substrates, and substantially expands the substrate scope of biocatalytic phosphorylation. We also show that active site mutations can further expand substrate scope and improve site-selectivity. This engineering effort was greatly expedited using DESI-MS screening, which enabled analysis of 2688 reactions in only 40 min. Finally, gram-scale phosphorylation of a representative substrate was achieved with a turnover number over 10 000. Together, these results highlight the biocatalytic utility of PsiK and derivatives thereof for selective phosphorylation of phenols and benzenediols under mild conditions.

raw_json:
{"europe_pmc_id":"40526241","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Repple J, Bayas M, Möser C, Kobayashi NF, Reif A.
publication_date: 2025-03-07
doi: 10.1016/j.biopsych.2025.02.903
pubmed_id: 40064389
source_url: https://doi.org/10.1016/j.biopsych.2025.02.903
keywords: Humans, Antidepressive Agents, Bipolar Disorder
substance_tags: psilocybin
topic_tags: Depression,Addiction,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 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Current Evidence for the Role of Rapid-Acting Antidepressants in Bipolar Depression: A Perspective and Plan for Action.

abstract:
After decades of limited progress in depression treatment, recent advancements have sparked renewed interest in developing novel antidepressants, particularly rapid-acting antidepressants (RAADs). Despite these promising developments, there remains a significant gap in research on bipolar depression. While several antipsychotics have been investigated for their efficacy in bipolar depression due to the reduced risk of mania induction, research on RAADs, such as (es)ketamine, remains scarce despite their demonstrated safety and effectiveness. In this review, we give an overview of current developments in RAADs in the context of bipolar disorder. Both published studies as well as phase II, III, and IV studies on bipolar depression (based on ClinicalTrials.gov) are reviewed in this work. The following RAAD substance classes have been or are currently being investigated as possible treatments for bipolar depression: NMDA antagonists and indirect AMPA agonists (ketamine, esketamine, riluzole, felbamate), GABAA (gamma-aminobutyric acid A) activators or positive allosteric modulators (zuranolone, pregnenolone, PEA), psychedelics (psilocybin, 5-MeO-DMT), muscarine receptor antagonists (scopolamine), and kappa opioid receptor antagonists (navacaprant). Other than the well-established efficacy and safety of (es)ketamine in treating bipolar depression, there has been little research effort in the treatment of bipolar depression. Recent research into RAADs demonstrates the growing field of novel mechanisms of action in the pharmacological treatment of bipolar depression. However, there is an urgent need for well-controlled clinical studies on RAADs in bipolar depression to expand treatment options and improve outcomes for millions of affected individuals worldwide.

raw_json:
{"europe_pmc_id":"40064389","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelics and Headache Disorders: an Update.
authors: Im JJH, Sandoe CH
journal: Current neurology and neuroscience reports
publication_date: 2025-08-08
doi: 10.1007/s11910-025-01446-2
pubmed_id: 40782223
source_url: https://pubmed.ncbi.nlm.nih.gov/40782223/
keywords: Cluster headache, DMT, Headache, LSD, Migraine, Psilocybin, Psychedelics
substance_tags: psilocybin
topic_tags: Chronic Pain,Headache / Migraine,Review Article,Case Report,Observational Study,Safety
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"40782223"}
abstract:
Psychedelics are often queried as a potential therapeutic option in a multitude of conditions, including pain and mental health disorders, with a growing body of patient reports and scientific publications describing potential benefit. This article reviews recent research on psychedelic compounds for treatment of headache disorders.
Observational data, case reports, and a few recent small, controlled trials suggest symptom benefit at sub-hallucinogenic doses for both migraine and cluster headache. There have not been new completed studies of psychedelics in other headache disorders. Safety signals also tend to be favorable, although there are continuing concerns for systemic and psychiatric effects in varying doses, preparations and clinical contexts. While available studies on psychedelics suggest potential benefit in cluster headache and migraine, access remains complex due to legal considerations, and additional studies are needed to confirm their effectiveness and to ensure safety before they can be recommended for use.


title: Psychedelic-Assisted Therapy: Potential Benefits and Challenges in Mental Health Treatment.
authors: Silczuk A, Madejek RJ, Koweszko T, Mularczyk-Tomczewska P, Adamska E, Gujski M, Szulc A.
publication_date: 2025-08-08
doi: 10.12659/msm.948302
pubmed_id: 40781763
source_url: https://doi.org/10.12659/msm.948302
keywords: Humans, Lysergic Acid Diethylamide, Hallucinogens, Mental Health, Mental Disorders, Psychotherapy
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
abstract:
Psychedelics, derived from the Greek words "psyche" (soul) and "deloun" (revealing), are substances historically and currently considered "soul-revealing". Also termed hallucinogens due to their impact on sensory perception, they are further categorized into hallucinogens, such as lysergic acid diethylamide (LSD), psilocybin, and mescaline; entactogens or empathogens, such as 3,4-methylenedioxymethamphetamine (MDMA); and dissociatives, such as phencyclidine (PCP) and ketamine. The concept of using these substances to enhance psychotherapy emerged in the 1940s, leading to the first wave of psychedelic research, which yielded promising initial results. Following a period of restricted research, modern investigations began anew around 20 years ago. In this review, we analyze the last 10 years of research, exploring the potential of psychedelics in psychotherapy. Current evidence reveals that psychedelic-assisted psychotherapy remains an experimental approach. While preliminary studies suggest potential therapeutic benefits in treating various conditions, including depression, post-traumatic stress disorder, obsessive-compulsive disorder, and substance use disorders, a definitive assessment of efficacy and safety is hampered by the scarcity of large-scale, rigorous clinical trials. Psychedilics should rather be viewed as integral components of broader therapeutic frameworks than as standalone treatment. The unique mechanisms of psychedelics, notably their effect on neuroplasticity, hint at the potential to address treatment gaps in patients unresponsive to conventional methods. However, this potential requires validation through larger, more rigorously designed studies. Future research must prioritize high-quality, randomized, double-blind, placebo-controlled trials encompassing diverse populations to produce reliable, generalizable findings and ensure responsible clinical implementation. The aim of this article is to review the current status of psychedelic-assisted psychotherapy.

topic_tags:
Depression,PTSD,Addiction,OCD,Neuroplasticity,Mechanism of Action,Clinical Trial,Review Article,Safety

raw_json:
{"europe_pmc_id":"40781763","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-07-15
doi: 10.1021/acsptsci.5c00445
pubmed_id: 40894333
source_url: https://doi.org/10.1021/acsptsci.5c00445
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
The Causal Role of Consciousness in Psychedelic Therapy for Treatment-Resistant Depression: Hypothesis and Proposal.

authors:
Fernández-Borkel T, Borkel LF, Rojas-Hernández J, Hernández-Álvarez E, Quintana-Hernández DJ, Ponti LG, Henríquez-Hernández LA.

abstract:
The therapeutic potential of psychedelic substances, particularly psilocybin, for treatment-resistant depression (TRD) has garnered considerable attention. However, the necessity of subjective psychedelic experiences for therapeutic efficacy remains unclear, creating a critical gap in the field. To determine whether subjective psychedelic experiences induced by psilocybin are required for its antidepressant effects or whether these effects are mediated solely by neurobiological actions independent of consciousness. We propose a randomized controlled trial with three groups: (P) Psilocybin (25 mg oral dose with guided therapeutic integration), (P+A) Psilocybin under propofol-induced general anesthesia (eliminating subjective experiences), and (X+A) Propofol-induced anesthesia with placebo (with no psilocybin). Clinical assessments of depression and anxiety, combined with fMRI-based brain connectivity analysis (including fractal complexity, brain entropy, and network dynamics), will be conducted at baseline, postintervention, and during follow-ups. The proposed study protocol expects distinct therapeutic outcomes across groups. Superior improvements in depression and anxiety symptoms are anticipated in the conscious psilocybin group (P) compared to both anesthetized groups (P+A) and (X+A). Additionally, increased brain connectivity measures in fractal complexity and entropy are hypothesized to correlate positively with therapeutic improvements, particularly pronounced in the conscious condition. Isolating subjective experiences through anesthesia, aims to determine whether conscious psychedelic experiences play a causal role in therapeutic outcomes. Results have significant implications for clinical protocols, treatment guidelines, and the broader theoretical understanding of consciousness and its relationship to mental health.

topic_tags:
Depression,Anxiety,Brain Imaging,Consciousness,Randomized Controlled Trial,Treatment-Resistant Depression

raw_json:
{"europe_pmc_id":"40894333","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The Medial Prefrontal Cortex Modulates Psychedelic-like Effects of Psilocin.
authors: Zhang M, Zhai H, Yang L, Li H, Wang X, Wang X.
publication_date: 2025-07-07
doi: 10.1021/acsptsci.5c00324
pubmed_id: 40810162
source_url: https://doi.org/10.1021/acsptsci.5c00324
substance_tags: psilocybin,psilocin
topic_tags: Depression,Mechanism of Action,Animal Study,Safety
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
Recent advancements in the study of psilocybin and its active metabolite psilocin have highlighted their unique psychedelic properties and potential therapeutic applications, particularly in the rapid and sustained treatment of depression. However, the potent acute psychedelic effects of psilocybin necessitate a deeper understanding of the neural mechanisms underlying its action. In this study, we investigated the psilocin-induced neural activity in male mice using c-Fos immunofluorescent labeling and identified brain regions associated with psychedelic-like activity. Among the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), interstitial nucleus of the posterior limb of the anterior commissure (IPAC), and dorsomedial striatum (DMS), only the mPFC was specifically associated with the head twitch response (HTR), a hallmark of psychedelic-like behavior. A picomolar dose of psilocin in the mPFC was sufficient to induce significant HTR, suggesting that c-Fos-positive neurons in this region modulate psychedelic-like activity. To validate this hypothesis, optogenetic activation of these neurons significantly increased spontaneous HTR in TRAP2 mice, whereas acute inhibition suppressed drug-induced HTR. These findings establish the mPFC as a critical regulator of psilocin-induced psychedelic-like activity and provide valuable insights for enhancing the clinical safety and therapeutic application of psychedelics.

raw_json:
{"europe_pmc_id":"40810162","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Substance Abuse and Cognitive Decline: The Critical Role of Tau Protein as a Potential Biomarker.
publication_date: 2025-08-06
doi: 10.3390/ijms26157638
pubmed_id: 40806766
source_url: https://doi.org/10.3390/ijms26157638
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
authors:
Rebolledo-Pérez L, Hernández-Bello J, Martínez-Ramos A, Castañeda-Arellano R, Fernández-Quezada D, Sandoval-García F, Aguilar-García IG.

abstract:
Tau protein is essential for the structural stability of neurons, particularly through its role in microtubule assembly and axonal transport. However, when abnormally hyperphosphorylated or cleaved, Tau can aggregate into insoluble forms that disrupt neuronal function, contributing to the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD). Emerging evidence suggests that similar Tau-related alterations may occur in individuals with chronic exposure to psychoactive substances. This review compiles experimental, clinical, and postmortem findings that collectively indicate a substance-specific influence on Tau dynamics. Alcohol and opioids, for instance, promote Tau hyperphosphorylation and fragmentation through the activation of kinases such as GSK-3β and CDK5, as well as proteases like caspase-3, leading to neuroinflammation and microglial activation. Stimulants and dissociatives disrupt insulin signaling, increase oxidative stress, and impair endosomal trafficking, all of which can exacerbate Tau pathology. In contrast, cannabinoids and psychedelics may exert protective effects by modulating kinase activity, reducing inflammation, or enhancing neuroplasticity. Psychedelic compounds such as psilocybin and harmine have been demonstrated to decrease Tau phosphorylation and facilitate cognitive restoration in animal models. Although the molecular mechanisms differ across substances, Tau consistently emerges as a convergent target altered in substance-related cognitive disorders. Understanding these pathways may provide not only mechanistic insights into drug-induced neurotoxicity but also identify Tau as a valuable biomarker and potential therapeutic target for the prevention or treatment of cognitive decline associated with substance use.

keywords:
Animals, Humans, Alzheimer Disease, Substance-Related Disorders, tau Proteins, Phosphorylation, Biomarkers, Cognitive Dysfunction

topic_tags:
Addiction,Neuroplasticity,Mechanism of Action,Biomarkers,Oxidative Stress,Review Article,Animal Study,Toxicity,Inflammation

raw_json:
{"europe_pmc_id":"40806766","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-08-05
doi: 10.3389/fpsyt.2025.1594307
pubmed_id: 40842948
source_url: https://doi.org/10.3389/fpsyt.2025.1594307
substance_tags: psilocybin
topic_tags: Depression,PTSD,Neuroplasticity,Brain Imaging,Emotional Processing,Veterans
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Improved mental health outcomes and normalised spontaneous EEG activity in veterans reporting a history of traumatic brain injuries following participation in a psilocybin retreat.

authors:
Blest-Hopley G, Pasculli G, Ruffell SGD, Tsang W, Emmanuel O, Pate KM, Kettner H, Roseman L, Erritzoe D, Carhart-Harris R.

abstract:
IntroductionPsilocybin, a serotonergic psychedelic, has shown therapeutic potential in treating mental health disorders by, amongst the many effects, promoting neuroplasticity and reorganising functional connectivity across cortical and subcortical networks involved in emotion and cognition. Veterans with traumatic brain injuries (TBI) often experience chronic neurological and psychological symptoms such as post-traumatic stress disorder (PTSD) and depression. This study investigates the effects of psilocybin administered in retreat settings on veterans with a history of TBI, focusing on mental health outcomes and changes in brain connectivity as measured by EEG.MethodsA total of 21 participants were recruited through the Heroic Hearts Project, which facilitated access to two six-day psilocybin retreats in Jamaica. Before the retreat, participants underwent three individual and three group coaching sessions to prepare for the experience. During the retreat, two psilocybin ceremonies were held, spaced 48 hours apart. Participants received an initial dose of 1.5g to 3.5g of dried psilocybin mushrooms, with the option to increase the second dose up to 5g. Psilocybin was administered in a tea format, under the supervision of experienced facilitators. Psychological outcomes were assessed using validated questionnaires (PCL-5, PHQ-9, STAI) at baseline (four weeks pre-retreat) and four weeks post-retreat. Electroencephalography (EEG) was used to measure brainwave activity pre- and post-treatment. Paired t-tests were used to analyze changes in psychological scores, while EEG frequency band analysis assessed changes in brain function and connectivity.ResultsImprovements were observed across several mental health measures: PTSD (PCL-5 scores decreased by 50%, p=0.010), depression (PHQ-9 scores decreased by 65%, p

raw_json:
{"europe_pmc_id":"40842948","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Yang A, Lv X, Wang H, Wang X.
publication_date: 2025-07-22
doi: 10.1021/acschemneuro.5c00509
pubmed_id: 40702747
source_url: https://doi.org/10.1021/acschemneuro.5c00509
keywords: Brain, Humans, Hallucinogens, Cognition, Spirituality, Mysticism, Psilocybin, Cognitive Flexibility
substance_tags: psilocybin
topic_tags: Spirituality,Mystical Experience
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
title:
Psychedelics, Spirituality, and Fundamentalism: A Brain Network Approach to Cognitive Flexibility and Rigidity.

abstract:
This viewpoint reconceptualizes mysticism and fundamentalism as brain network disorders, with psychedelics like psilocybin, lysergic acid diethylamide, and N,N-dimethyltryptamine offering potential to modulate these states. By disrupting rigid neural patterns, psychedelics may foster cognitive flexibility, challenge inflexible belief systems, and offer therapeutic value for extremism and mental health disorders.

raw_json:
{"europe_pmc_id":"40702747","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelics and the Gut Microbiome: Unraveling the Interplay and Therapeutic Implications.
authors: Wang X, Jun F, Lin C, Wang X
journal: ACS chemical neuroscience
publication_date: 2025-08-05
doi: 10.1021/acschemneuro.5c00418
pubmed_id: 40631920
source_url: https://pubmed.ncbi.nlm.nih.gov/40631920/
keywords: Gut Microbiome, Gut−Brain Axis, Inflammation, Neuropsychiatric Disorders, Psilocybin, Psychedelics
substance_tags: psilocybin
topic_tags: Neuroplasticity,Pharmacology,Mechanism of Action,Receptor Pharmacology,Microbiome,Inflammation
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"40631920"}
abstract:
Classic psychedelics and the gut microbiome interact bidirectionally through mechanisms involving 5-HT receptor signaling, neuroplasticity, and microbial metabolism. This viewpoint highlights how psychedelics may reshape microbiota and how microbes influence psychedelic efficacy, proposing microbiome-informed strategies─such as probiotics or dietary interventions─to personalize and enhance psychedelic-based mental health therapies.


authors: Adeyinka D, Forsyth D, Currie S, Faraone N.
publication_date: 2025-08-04
doi: 10.3389/fnsys.2025.1585367
pubmed_id: 40894380
source_url: https://doi.org/10.3389/fnsys.2025.1585367
substance_tags: psilocybin
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Neurobiology of psilocybin: a comprehensive overview and comparative analysis of experimental models.

abstract:
Psilocybin, a compound found in Psilocybe mushrooms, is emerging as a promising treatment for neurodegenerative and psychiatric disorders, including major depressive disorder. Its potential therapeutic effects stem from promoting neuroprotection, neurogenesis, and neuroplasticity, key factors in brain health. Psilocybin could help combat mild neurodegeneration by increasing synaptic density and supporting neuronal growth. With low risk for addiction and adverse effects, it presents a safe option for long-term use, setting it apart from traditional treatments. Despite their relatively simpler neuronal networks, studies using animal models, such as Drosophila and fish, have provided essential insights on the efficacy and mechanism of action of psilocybin. These models provide foundational information that guides more focused investigations, facilitating high-throughput screening, enabling researchers to quickly explore the compound's effects on neural development, behavior, and underlying genetic pathways. While mammalian models are indispensable for comprehensive studies on psilocybin's pharmacokinetics and its nuanced interactions within the complex nervous systems, small non-mammalian models remain valuable for identifying promising targets and mechanisms at early research stages. Together, these animal systems offer a complementary approach to drive rapid hypothesis generation to refine our understanding of psilocybin as a candidate for not only halting but potentially reversing neurodegenerative processes. This integrative strategy highlights the transformative potential of psilocybin in addressing neurodegenerative disorders, leveraging both small and mammalian models to achieve translational research success.

topic_tags:
Depression,Addiction,Neuroplasticity,Neurogenesis,Pharmacology,Mechanism of Action,Aging,Animal Study,Safety,Drug Interactions

raw_json:
{"europe_pmc_id":"40894380","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Therapeutic and legal aspects of psilocybin in cancer-related depression.
authors: Małgorzata W, Kopczyk R, Gerlach A, Rymaszewska J.
publication_date: 2025-08-03
doi: 10.3389/fpsyt.2025.1591864
pubmed_id: 40831528
source_url: https://doi.org/10.3389/fpsyt.2025.1591864
substance_tags: psilocybin,psilocin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
Depression prevalence is markedly elevated in oncological patients, particularly among head and neck cancer (HNC) cohorts, who face twice the prevalence of major depressive disorder (MDD) compared to other cancer populations. MDD in this context independently predicts poorer clinical outcomes and increased morbidity. HNC management often involves acute surgical interventions with disfiguring effects, creating a narrow therapeutic window for conventional antidepressants requiring weeks to achieve efficacy. Psychological interventions face similar time constraints, complicating perioperative mental health support. Psilocybin - metabolized to psilocin - modulates serotonin (5-HT2A) and dopamine receptors, demonstrating rapid antidepressant effects within hours rather than weeks. Clinical trials validate its superiority over escitalopram in MDD treatment and efficacy in PTSD and treatment-resistant depression. Despite these benefits, no studies explore perioperative applications in HNC patients. Psilocybin lacks international scheduling under UN conventions, permitting variable national policies: Australia - MDMA/psilocybin prescriptions (2023), USA - Insurance billing codes (2024), Portugal - Decriminalized, South Africa - Prescription medicine. In Polish Context psilocybin remains restricted to research settings, classified as a Group I-P substance under the 1971 Psychotropic Convention. This legal framework complicates clinical implementation despite emerging evidence of therapeutic potential. The critical challenge lies in reconciling psilocybin's rapid antidepressant properties with regulatory barriers, particularly for HNC patients requiring immediate psychiatric support post-surgery. Interdisciplinary collaboration between oncologists, psychiatrists, and policymakers is essential to design ethical clinical pathways under current legislative constraints.

topic_tags:
Depression,PTSD,Mechanism of Action,Receptor Pharmacology,Clinical Trial,Observational Study,Cancer Patients,Treatment-Resistant Depression

raw_json:
{"europe_pmc_id":"40831528","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Latent Classes of Lifetime Use of Seven Hallucinogens in the United States.
authors: Meacham MC, Mian MN, Wang RC, Coker AR, Anderson BT, Montoy JCC.
publication_date: 2025-08-03
doi: 10.1080/02791072.2025.2537040
pubmed_id: 40760833
source_url: https://doi.org/10.1080/02791072.2025.2537040
substance_tags: psilocybin
topic_tags: Clinical Trial,Observational Study
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
abstract:
Interest in and use of hallucinogens appears to be growing in the United States, yet less is known about the use of multiple hallucinogens. The aims of this study are to characterize subgroups of lifetime hallucinogen use and to identify sociodemographic correlates of these subgroups. Latent class models were fit using 2021-2022 National Survey on Drug Use and Health (NSDUH) data on a sub-sample of individuals who reported having ever used any hallucinogen (n = 17,977). A four-class model identified the following subgroup classes: Psilocybin (16%), LSD/Psilocybin (46%), Ecstasy (23%), and a fourth class (15%) labeled Multiple substances, with high probabilities of use of psilocybin, LCD, and ecstasy, in addition to moderate probabilities of use of other hallucinogens. In survey-weighted multinomial logistic regression analyses, compared to the Psilocybin class, the adjusted odds of being in the LSD/Psilocybin class increased with age-group level (AORs = 1.5-6.4, 95% CIs:1.3-8.7), and non-White participants had higher odds of being in the Ecstasy class (AORs = 1.7-3.2, 95% CIs:1.1-4.4). As policies regulating and clinical practice with hallucinogens continue to evolve, these patterns of lifetime hallucinogen use demonstrate the overlapping nature of hallucinogen experiences in the U.S. population, which has implications for expanding clinical trial inclusion criteria and establishing a baseline for future trends.

raw_json:
{"europe_pmc_id":"40760833","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Interventions to support spirituality among adults with cancer: a scoping review.
authors: Miller M, Meyers M, Krainak K, Lewis SP.
publication_date: 2025-08-01
doi: 10.1007/s00520-025-09787-x
pubmed_id: 40751754
source_url: https://doi.org/10.1007/s00520-025-09787-x
keywords: Humans, Neoplasms, Spiritual Therapies, Palliative Care, Spirituality, Adult, Mindfulness
substance_tags: psilocybin
topic_tags: End-of-Life Distress,Wellbeing,Spirituality,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
abstract:
PurposeSpirituality is a core component of holistic cancer care, yet additional support is needed to understand and implement spirituality-focused interventions in practice. The aim of this review was to identify available interventions to address spirituality among people with cancer, to explore common components, and to examine efficacy across interventions.MethodsA scoping review was conducted. Research questions and criteria were formulated at the outset, followed by identifying relevant publications, charting data, and collating results. Upon identification of available interventions, each was examined for its components and efficacy.ResultsN = 26 publications were included, representing N = 21 unique interventions. While each intervention varied, they often included key components of prayer, mindfulness/meditation practices, and facilitated sessions with trained spiritual and/or palliative care providers. The effects of interventions varied, with some studies reporting positive outcomes and others reporting mixed effects or no significant changes. Notably, individually focused spiritual support interventions were found to increase hope, spiritual well-being, meaning, self-transcendence, and faith; spiritual group therapy interventions were found to increase spiritual health and spiritual well-being (meaning, peace, and faith); mindfulness-based cancer recovery groups were found to increase spiritual well-being; and psilocybin-assisted therapy yielded improvements in spiritual well-being, faith, and connection.ConclusionsThis review offers a novel examination of interventions focused on enhancing spirituality in cancer care. Given spirituality's central role among many patients and the well-documented desire for spiritual support, future research should clarify which interventions are most effective and under what conditions, to support translation of high-quality spiritual care interventions into practice.

raw_json:
{"europe_pmc_id":"40751754","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-07-20
doi: 10.1111/nyas.15391
pubmed_id: 40689865
source_url: https://doi.org/10.1111/nyas.15391
substance_tags: psilocybin
topic_tags: Depression,Neuroplasticity
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
title:
Perturbing whole-brain models of brain hierarchy: An application for depression following pharmacological treatment.

authors:
Socoró-Garrigosa M, Perl YS, Kringelbach ML, Erritzoe D, Nutt DJ, Carhart-Harris R, Vohryzek J, Deco G.

abstract:
Determining the scale of neural representations is a central challenge in neuroscience. While localized representations have traditionally dominated, evidence suggests information is also encoded in distributed, hierarchical networks. Recent research indicates that the hierarchy of causal influences shaping functional patterns serves as a signature of distinct brain states, with implications for neuropsychiatric disorders. Here, we first explore how whole-brain models, guided by the thermodynamics of mind framework, estimate brain hierarchy and how perturbing such models enables the study of in-silico transitions represented by static functional connectivity. We then apply this to major depressive disorder, where different brain hierarchical reconfigurations emerge following psilocybin and escitalopram treatments. We build resting-state whole-brain models of depressed patients before and after interventions and conduct a dynamic sensitivity analysis to explore brain states' susceptibility-measuring their capacity to change-and their drivability to healthier states. We show that susceptibility is on average reduced by escitalopram and increased by psilocybin, and that both treatments promote healthier transitions. These results align with the post-treatment window of plasticity opened by serotonergic psychedelics and the similar clinical efficacy of both drugs in trials. Overall, this work demonstrates how whole-brain models of brain hierarchy can inform in-silico neurostimulation protocols for neuropsychiatric disorders.

keywords:
Brain, Humans, Citalopram, Hallucinogens, Depression, Models, Neurological, Psilocybin, Escitalopram, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"40689865","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-07-31
doi: 10.1002/cncr.70003
pubmed_id: 40679122
source_url: https://doi.org/10.1002/cncr.70003
substance_tags: psilocybin
topic_tags: Depression
study_type: Qualitative Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Correction to "Acceptability of psilocybin-assisted group therapy in patients with cancer and major depressive disorder: Qualitative analysis".

raw_json:
{"europe_pmc_id":"40679122","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-07-31
doi: 10.1111/fcp.70038
pubmed_id: 40670864
source_url: https://doi.org/10.1111/fcp.70038
substance_tags: psilocybin,psilocin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Psilocybin as Transformative Fast-Acting Antidepressant: Pharmacological Properties and Molecular Mechanisms.

authors:
Adebo M, Bonnet M, Laouej O, Defaix C, McGowan JC, Butlen-Ducuing F, David DJ, Poupon E, Tritschler L, Gardier AM.

abstract:
In the 1950s-60s, serotonergic psychedelic drugs were studied as potential adjuvants to psychotherapy to treat addiction and alcoholism. However, starting in the 70s, preclinical and clinical studies on psychedelics stopped for decades because legislation controlled its recreational use, citing their hallucinogenic and psychotomimetic effects, as well as their abuse potential. Amazingly, we are witnessing an impressive return of these drugs due to recent clinical trials suggesting a therapeutic potential of psychedelics, among them psilocybin, for treating patients with depression resistant to conventional antidepressant drugs. Yet, their underlying mechanisms of action remain incompletely elucidated. This review provides an update on seminal clinical trials using psilocybin, as well as preclinical work uncovering the pharmacological properties and experimental pharmacology of psilocybin and its active metabolite psilocin. These drugs are primarily serotonin 5-HT2A receptor (5-HT2AR) agonists. Although there is a consensus that 5-HT2AR activation mediates its psychedelic effects in human and rodent models of anxiety/depression, its role in psilocin's antidepressant effects remains controversial. This review also provides an overview of neurotransmitter systems, neuroplasticity, and neural circuits activated by psilocin. Further research in developing effective antidepressants for depression is prescient now more than ever, as according to the World Health Organization (WHO), depression will be the main cause of disability in 2030. Understanding the mechanisms through which psilocybin/psilocin would be an effective antidepressant is crucial to ultimately validate its therapeutic potential when combined with SSRIs/SNRIs in mood disorders.

keywords:
Animals, Humans, Hallucinogens, Antidepressive Agents, Depression, Serotonin 5-HT2 Receptor Agonists, Psilocybin

topic_tags:
Depression,Anxiety,Addiction,Neuroplasticity,Pharmacology,Mechanism of Action,Receptor Pharmacology,Clinical Trial,Review Article,Animal Study

raw_json:
{"europe_pmc_id":"40670864","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: PsyArXiv
publication_date: 2025-06-05
source_url: https://osf.io/preprints/psyarxiv/ugr69_v2
substance_tags: psilocybin
topic_tags: Wellbeing,Mystical Experience
study_type: Qualitative Study
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"ugr69_v2","version":2,"reviews_state":"accepted"}
title:
Meditation and psychedelics facilitate similar types of mystical, psychological, and philosophical-existential insights predictive of wellbeing: A qualitative-quantitative approach

abstract:
Both psychedelic substances and meditation have been proposed to facilitate personally meaningful and transformative experiences, with insights playing a central role. However, previous research has mainly relied on questionnaires, limiting the range of insights that can be identified. In this study, we recruited participants who provided narrative reports of insights in personally meaningful psychedelic (n = 147) or meditation (n = 66) experiences. Psychedelic experiences were facilitated both by classic (e.g., LSD, psilocybin, DMT) as well as non-classic (e.g., MDMA, ketamine, cannabis) psychedelics. Qualitative analysis revealed three main insight themes: Mystical-type (subclasses Unity, Metaphysical, and Other), Psychological (subclasses Metacognitive, Value, and Compassion), and Philosophical-existential (subclasses Purpose, Value, and Other). Mystical-type insights were more frequent in reports of meditation experiences, while value insights were more common in psychedelic reports. Otherwise, the reported insights were highly similar across the two types of reports, and only minor differences were observed between classic and non-classic psychedelics. Regression analyses indicated that metacognitive and value insights were positively associated with perceived improvements in positive affect, while mystical-type insights predicted increased meaning in life. These findings suggest that both psychedelic substances and meditation can facilitate a broad range of insights that are not fully captured by existing questionnaires. The results highlight similarities between psychedelic and meditation experiences supporting the notion that transformative experiences are not exclusive to classic psychedelics but can be facilitated through various means.

keywords:
insight, meditation, psychedelics, qualitative analysis, quantitative analysis, wellbeing, Social and Behavioral Sciences


title: Treatment approaches and efficacy in psychedelic-induced psychosis: A systematic review.
journal: Asian journal of psychiatry
publication_date: 2025-07-31
doi: 10.1016/j.ajp.2025.104604
pubmed_id: 40614615
source_url: https://pubmed.ncbi.nlm.nih.gov/40614615/
keywords: Antipsychotics, Hallucinogens, Haloperidol, LSD, Psilocybin, Psychosis, Risperidone
substance_tags: psilocybin
topic_tags: Systematic Review,Review Article,Safety
study_type: Systematic Review
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"40614615"}
authors:
Sulstarova A, Scheuerlein L, Monari S, Seragnoli F, Gabriel T, Preller K, Böge K, Sentissi O, Kaiser S, Solmi M, Kirschner M, Sabé M

abstract:
Psychedelics are increasingly used in the general population, yet they are associated with increased risk of psychosis in a minority of users that can experience psychedelic-induced psychosis (


title: Australia's psychedelic experiment: reflections from a psychiatrist clinical researcher.
authors: Bayes A.
publication_date: 2025-06-25
doi: 10.1177/10398562251347890
pubmed_id: 40574457
source_url: https://doi.org/10.1177/10398562251347890
substance_tags: psilocybin
topic_tags: Depression,PTSD,Treatment-Resistant Depression,Healthcare Workers,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
BackgroundDespite a limited evidence base to inform clinicians, Australia has adopted a national approach in rescheduling psilocybin and MDMA as clinical therapies for treatment-resistant depression (TRD) and post-traumatic stress disorder (PTSD), respectively.PurposeThis paper explores clinical research domains warranting further investigation through outlining the reflections of a clinical-academic psychiatrist involved in psychedelic trial work.ResultsEight domains were found to warrant further research investigation including: efficacy, safety (including combining with psychotropics), psychotherapy models, psychological support, therapeutic touch, set/setting and examination of naturalistic data.ConclusionsThe clinical availability of psychedelic-assisted therapy (PAT) gives greater impetus for careful research studies, informing treatment and improving patient outcomes.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Hallucinogens, Stress Disorders, Post-Traumatic, Psychiatry, Biomedical Research, Research Personnel, Australia, Depressive Disorder, Treatment-Resistant, Psilocybin, Psychiatrists

raw_json:
{"europe_pmc_id":"40574457","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Henry J, Giribaldi B, Nutt DJ, Erritzoe D, Carhart-Harris R, Lyons T.
publication_date: 2025-06-22
doi: 10.1016/j.euroneuro.2025.06.003
pubmed_id: 40554997
source_url: https://doi.org/10.1016/j.euroneuro.2025.06.003
substance_tags: psilocybin
topic_tags: Depression,Receptor Pharmacology,Randomized Controlled Trial
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
The effects of psilocybin therapy versus escitalopram on cognitive bias: A secondary analysis of a randomized controlled trial.

abstract:
BackgroundPatients with Major Depressive Disorder (MDD) have more dysfunctional attitudes than healthy individuals and these pessimistic biases are correlated with depression severity. Psilocybin has demonstrated sustained remission in depression.MethodsSecondary analysis of a two-arm randomized controlled trial assessing the effect of psilocybin therapy versus escitalopram on 'maladaptive' cognitive biases relevant to the construct of depression. Primary outcomes were post-treatment changes in biases at six weeks compared with baseline, as measured using three validated psychological scales.FindingsFifty-nine MDD patients were randomly allocated to the psilocybin (n = 30) or escitalopram (n = 29) groups. Self-reported optimism showed a large increase six-weeks after psilocybin treatment (Mdiff=6·63 p < 0·0001; 95 % CI [4·06, 9·20], d = 1·1), whereas there was no change following escitalopram (Mdiff=1·52, p = 0·205; 95 % CI [-0·59, 3·62], d = 0·4). Behavioral results found that patients were more optimistic about desirable life events after psilocybin treatment (Mdiff=0·16, p = 0·0002; 95 % CI [0·08, 0·23], d = 1·1), but they were also less pessimistic about negative life events after escitalopram treatment (Mdiff=0·07, p = 0·018; 95 % CI [0·01, 0·13], d = 0·5). We found improvements in all three domains of dysfunctional attitudes following psilocybin treatment: achievement (Mdiff=10·37, p < 0·0001; 95 % CI [6·38, 14·53], d = 1·0); dependency (Mdiff=7·97, p < 0·0001; 95 % CI [4·00, 11·93], d = 0·9) and self-control (Mdiff=6·40, p = 0·0006; 95 % CI [2·60, 10·20], d = 0·8)), whereas only the achievement domain improved after escitalopram (Mdiff=4·10, p = 0·005; 95 % CI [1·35, 6·86], d = 0·6).InterpretationThese results suggest that two high-dose sessions with psilocybin therapy are superior to a six-week daily course of a selective serotonin-reuptake inhibitor antidepressant, in remediating negative cognitive biases in depression.

keywords:
Humans, Citalopram, Hallucinogens, Treatment Outcome, Cognition, Psychiatric Status Rating Scales, Adult, Middle Aged, Female, Male, Psilocybin, Escitalopram, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"40554997","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Vinarcsik L, Smoller C, Grossberg G.
publication_date: 2025-06-23
doi: 10.1007/s40266-025-01221-5
pubmed_id: 40553322
source_url: https://doi.org/10.1007/s40266-025-01221-5
keywords: Humans, Hallucinogens, Aged, Depressive Disorder, Treatment-Resistant, Major Depressive Disorder
substance_tags: psilocybin
topic_tags: Depression,Receptor Pharmacology,Aging,Review Article,Older Adults,Safety
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Use of Psychedelic Agents in Older Adults with Treatment-Resistant Major Depressive Disorder: What the Evidence Shows.

abstract:
The use of drugs with psychedelic and dissociative effects for the treatment of psychiatric illnesses has become increasingly popular in recent years. However, few trials have been conducted to determine the efficacy of these agents in the specific setting of treatment-resistant major depressive disorder (MDD) in older adults. In this paper, we review notable aspects of treatment-resistant MDD in older adults, review classical and nonclassical psychedelic agents and dissociative agents presently being trialed mostly in younger populations for the treatment of depression, and review what is known about trialing these agents in older adults with treatment-resistant MDD. Given the limitations to extant standard treatment and the potential risks associated with first-line pharmacological agents such as selective serotonin reuptake inhibitors (SSRIs) in this population, psychedelic-assisted psychotherapy may offer an important alternative for managing treatment-resistant MDD in older adults. This subset of patients is understudied and stands to benefit significantly from improved treatment regimens. The limited research available that details psychedelic-assisted treatment in this specific group is promising. Here we focus on reviewing those agents with the most controlled data available, beginning with the dissociative anesthetic ketamine/esketamine, and the hallucinogenic agent psilocybin, and concluding with a brief review of related substances including lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), ayahuasca, ibogaine, 3,4-methylenedioxymethamphetamine (MDMA), and mescaline. Treatment-resistant MDD is highly prevalent among older adults, and while preliminary findings seem promising regarding the safety and tolerability of psychedelics, concerns remain owing to insufficient data, and therefore further research is crucial to establish the safety, efficacy, and applications of psychedelic therapy in this population.

raw_json:
{"europe_pmc_id":"40553322","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-06-15
doi: 10.1007/s43440-025-00742-5
pubmed_id: 40522607
source_url: https://doi.org/10.1007/s43440-025-00742-5
substance_tags: psilocybin
topic_tags: Brain Imaging,Consciousness,Aging,Emotional Processing,Clinical Trial,Healthy Volunteers,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
title:
The phenomenology of psilocybin's experience mediates subsequent persistent psychological effects independently of sex, previous experience, or setting.

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

abstract:
BackgroundRecent studies intensively explore psilocybin's antidepressant potential, but variables like previous experience, repeated use, setting, and sex remain underexplored. This study examines acute and long-term effects of psilocybin in healthy individuals.MethodsA double-blind, placebo-controlled, cross-over study included 40 healthy participants (20 females, mean age 38). Each received two doses of psilocybin (0.26 mg/kg) at least 56 days apart (mean 488) in two neuroimaging study arms. Nearly half had previous psychedelic experience. Acute effects were measured using the Altered States of Consciousness Scales (ASCs) and a Visual Analogue Scale (VAS) for emotional valence. The Persisting Effects Questionnaire (PEQ) assessed long-term effects.ResultsAll results were independent of observed variables such as previous psychedelic experience, repeated use, setting, sex and occupation. Acute effects were moderate on the ASCs, with VAS ratings showing mostly pleasant or fluctuating experiences and only one unpleasant session. All experiences resolved in a positive or neutral state by the session's end. Psilocybin produced lasting positive effects across all PEQ domains, with negligible negative effects. Oceanic Boundlessness (OBN) and Visionary Restructuralization (VRS) correlated with positive outcomes, while Dread of Ego Dissolution (DED), typically associated with fear, did not predict negative effects. The nature of the acute experience (pleasant or mixed) was not linked to the direction or intensity of long-term outcomes. Peak experiences ending in a positive mood were strongly associated with favourable long-term effects.ConclusionRepeated psilocybin administration in healthy individuals induces positive, lasting effects, with challenging experiences in controlled settings not causing adverse outcomes. These findings support psilocybin's psychological safety and its repeated use in clinical trials.

keywords:
Humans, Hallucinogens, Cross-Over Studies, Double-Blind Method, Emotions, Consciousness, Sex Factors, Adult, Middle Aged, Female, Male, Young Adult, Psilocybin

raw_json:
{"europe_pmc_id":"40522607","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Berkovitch L, Fauvel B, Preller KH, Gaillard R.
publication_date: 2025-05-30
doi: 10.1016/j.neubiorev.2025.106239
pubmed_id: 40456393
source_url: https://doi.org/10.1016/j.neubiorev.2025.106239
keywords: Brain, Nerve Net, Humans, Hallucinogens, Cognition, Neuroimaging, Psilocybin
substance_tags: psilocybin
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Neurocognitive effects of psilocybin: A systematic and comprehensive review of neuroimaging studies in humans.

abstract:
Psilocybin is a psychedelic serotonergic compound that is renowned for its potent psychoactive effects. Over the past 15 years, an increasing number of controlled clinical trials showed that it has a fast-acting and sustainable efficacy in treating various psychiatric disorders. Neuroimaging studies have been conducted with the objective of elucidating the neurobiological mechanisms underlying the subjective and therapeutic effects of psilocybin. However, the diversity of neuroimaging techniques, tasks, and analytical approaches makes it difficult to gain a comprehensive overview of psilocybin's effects on the brain. To address this gap in the literature, we conducted a systematic review in the Medline, Psychinfo and Cochrane databases between January 1, 1990, and May 9, 2025, following PRISMA recommendations. A total of 81 articles met the inclusion criteria. A variety of neuroimaging techniques were employed in small samples of healthy volunteers and patients with medical conditions. The studies investigated the effects of psilocybin on brain activity and connectivity, both at rest and during cognitive tasks. They revealed that psilocybin reproducibly impacted neuronal networks such as the default mode network. However, other findings were more inconsistent. Psilocybin effects on the brain were associated with acute alterations in self-experience, sensory and emotional processing, and sustained effects on mood, personality, and social functioning. In patients with depression, clinical outcomes correlated with brain changes. This review indicates that psilocybin induces acute and long-lasting functional brain changes. While these neuroimaging data require confirmation and further expansion, they shed light on the mechanisms of psilocybin's acute subjective and therapeutic effects in humans.

topic_tags:
Depression,Brain Imaging,Mechanism of Action,Default Mode Network,Aging,Personality Change,Emotional Processing,Clinical Trial,Systematic Review,Review Article,Healthy Volunteers

raw_json:
{"europe_pmc_id":"40456393","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Swieczkowski D, Kwaśny A, Sadko K, Pruc M, Gaca Z, Szarpak L, Cubała WJ.
publication_date: 2025-05-21
doi: 10.1016/j.psychres.2025.116559
pubmed_id: 40440859
source_url: https://doi.org/10.1016/j.psychres.2025.116559
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,Treatment-Resistant Depression,Safety,Adverse Events
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Lessons learned from the regulatory alignment in ketamine, esketamine and arketamine clinical trials: A cross-sectional analysis of protocols from ClinicalTrials.gov.

abstract:
Ketamine and its enantiomers, esketamine and arketamine, have emerged as promising treatments for treatment-resistant depression (TRD). This cross-sectional study evaluates the regulatory alignment of 40 clinical trials listed on ClinicalTrials.gov, focusing on the methodological challenges. The study highlights methodological inconsistencies, particularly around the challenges of functional unblinding caused by ketamine's dissociative effects, addressing expectancy bias, and the inadequate safety monitoring practices in many trials. A notable concern is the variability in blinding techniques, with many trials failing to adequately mask the perceptual effects of ketamine, potentially compromising outcome assessments. Furthermore, the placebo response, which accounts for a significant portion of treatment effects, was not consistently managed across trials, and safety strategies, particularly for monitoring adverse events such as dissociation and abuse potential, were not uniformly robust. Another critical issue is the lack of long-term follow-up in most trials, limiting the understanding of ketamine's safety profile over extended periods. The findings emphasize the need for harmonized and rigorous methodological frameworks to support the effective use of ketamine and its enantiomers in clinical practice. The potential lessons learned from these trials could be instrumental in guiding future research on other psychedelics currently under investigation for mental health disorders, such as psilocybin and DMT, ensuring both efficacy and safety in future therapeutic approaches. Such harmonization will be crucial to improve regulatory approval and achieve therapeutic success in real-world applications, making these treatments more accessible and reliable for patients with TRD.

keywords:
Humans, Ketamine, Antidepressive Agents, Cross-Sectional Studies, Clinical Trials as Topic, Depressive Disorder, Treatment-Resistant, Outcome Assessment, Health Care

raw_json:
{"europe_pmc_id":"40440859","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Paracha N.
publication_date: 2025-05-27
doi: 10.1089/jicm.2024.0713
pubmed_id: 40425035
source_url: https://doi.org/10.1089/jicm.2024.0713
substance_tags: psilocybin
topic_tags: Mechanism of Action,Wellbeing
study_type: Qualitative Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Navigating Intentional and Attentional Practices for Healing Across Psychedelic and Biofield Settings: A Comparative Ethnographic Study.

abstract:
Objectives: This study was conducted to bring psychedelic and biofield science into interdisciplinary dialogue and encourage scientific investigations of psychedelic therapy as a form of energy medicine. In thinking these two sites together, important resonances between both forms of therapy were highlighted which can help elucidate clearer therapeutic mechanisms across both therapies. Methods/Design: Comparative ethnographic methods and a repeated measures design were used to conduct this research over a period of 2 years. A total of 150 qualitative interviews with 135 participants present at psychedelic-assisted therapy retreats and 15 at biofield settings were conducted. All the participants belonged to different ethnic, racial, and religious backgrounds; age groups; and reported differing levels of illness and health. The data (ethnographer's field notes, audio and video archives, as well as background research conducted on each of the field sites) was then transcribed and collated, and resonant themes were highlighted. Interventions: The research was conducted at wellness retreat spaces in the Netherlands and in Mexico; across entheogenic substances such as ayahuasca/yage, psilocybin-containing mushrooms, as well as psilocybin-containing truffles; and in biofield settings in the United States and Europe that included practices such as Reiki. Results/Findings: Based on 2 years of ethnographic research at psychedelic-assisted therapy retreats and in biofield settings, this article proffers that interdisciplinary dialogue between both forms of therapy is vital in understanding intention and attention as temporally and conceptually distinct categories with divergent healing effects. The research also demonstrates intention and attention as embodied phenomenon as opposed to mental acts. Conclusions: Intention and attention are conceptually and temporally distinct embodied phenomenon, and these differences can be best understood through an interdisciplinary study across psychedelic and biofield therapies. Scientists studying these topics should take these distinctions into account to be able to more accurately understand healing mechanisms across both forms of therapy.

keywords:
Humans, Hallucinogens, Anthropology, Cultural, Adult, Middle Aged, Mexico, Netherlands, Female, Male, Mind-Body Therapies, Young Adult, Psilocybin

raw_json:
{"europe_pmc_id":"40425035","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Pathway engineering for the biosynthesis of psychedelics.
authors: Abrahms ZN, Sen AK, Jones JA.
publication_date: 2025-05-14
doi: 10.1016/j.copbio.2025.103314
pubmed_id: 40381450
source_url: https://doi.org/10.1016/j.copbio.2025.103314
keywords: Humans, Hallucinogens, Biosynthetic Pathways, Synthetic Biology, Metabolic Engineering
substance_tags: psilocybin
topic_tags: Mechanism of Action
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
Naturally occurring psychoactive compounds have been used for cultural and ethnomedical purposes for centuries. Several more such molecules continue to be chemically synthesized, exhibiting a wide range of potency, therapeutic, and hallucinogenic effects. Promising clinical data and a renewed interest in understanding the cellular mechanisms of action have inspired synthetic biology efforts to develop alternative production routes for psychedelic compounds. Here, we highlight the latest biosynthetic accomplishments for indolamines (psilocybin, N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, and bufotenine), ergolines (lysergic acid), and phenethylamines (mescaline) in both eukaryotic and prokaryotic production hosts. We further curate a list of relevant biosynthetic enzymes that have reports of successful in vivo heterologous activity.

raw_json:
{"europe_pmc_id":"40381450","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Gattuso JJ, Wilson C, Hannan AJ, Renoir T.
publication_date: 2025-04-05
doi: 10.1038/s41380-025-03005-0
pubmed_id: 40189698
source_url: https://doi.org/10.1038/s41380-025-03005-0
substance_tags: psilocybin
topic_tags: OCD
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:05
title:
Letter to the editor: Comments on 'Striking long-term beneficial effects of single-dose psilocybin and psychedelic mushroom extract in the SAPAP3 rodent model of OCD-like excessive self-grooming' by Brownstien et al. (2024).

raw_json:
{"europe_pmc_id":"40189698","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Ley L, Liechti ME, Becker AM, Straumann I, Klaiber A, Holze F, Vogt SB, Arikci D, Schmid Y
journal: Psychopharmacology
publication_date: 2025-07-31
doi: 10.1007/s00213-025-06772-4
pubmed_id: 40140019
source_url: https://pubmed.ncbi.nlm.nih.gov/40140019/
substance_tags: psilocybin
topic_tags: Healthy Volunteers
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"40140019"}
title:
Motivation and retrospective appraisal of psychedelic study participation: a qualitative study in healthy volunteers.

abstract:
Little is known about motives of healthy volunteers to participate in psychedelic trials and how they appraise their study experience retrospectively.
This paper explored reasons why healthy people register for psychedelic trials, factors that they considered to contribute to either positive or negative study experiences, and under which circumstances they would seek a psychedelic experience again.
This study used the data of 151 healthy volunteers who had ingested serotonergic psychedelics in one of six randomized, double-blind, placebo-controlled crossover trials at the same research site under similar conditions. The data were analyzed through qualitative content analysis.
The predominant motivations to participate in a trial were interest in psychedelics and an appealing setting. Expectations involved personal development and the occurrence of typical psychedelic effects. Hopes included transformative processes. The setting factors that promoted a positive experience were music and access to nature, whereas the sterile hospital environment was considered bothersome. Most participants valued the trusting relationship with their investigator. The most commonly criticized investigator characteristics were a perceived lack of support and investigator-induced psychological discomfort. Most participants considered their expectations exceeded and would take the study substances again, preferably in a setting in nature with friends.
This paper identified four pivotal factors to be considered for psychedelic study experiences: (1) a secure interpersonal relationship, (2) an aesthetically pleasing environment, (3) access to nature, and (4) the use of music. This analysis reveals subjective views of volunteers in psychedelic Phase-I trials and may improve research standards.

keywords:
Appraisal, Dimethyltryptamine, Healthy volunteers, Lysergic acid diethylamide, Mescaline, Motivation, Psilocybin, Psychedelics


authors: Yasmo Perez JP, Chegwin Angarita C, Saldarriaga Ochoa OD, Urrego Restrepo SA.
publication_date: 2025-02-20
doi: 10.1016/j.talanta.2025.127777
pubmed_id: 40020610
source_url: https://doi.org/10.1016/j.talanta.2025.127777
substance_tags: psilocin
topic_tags: General
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Development and validation of a HPLC-DAD method for determining the content of tryptamines in methanolic extracts of fruiting bodies of mushrooms belonging to species of the Psilocybe genus.

abstract:
This study presents the development and validation of a high-performance liquid chromatography method with diode array detection (HPLC-DAD) for determining the content of tryptamines in methanolic extracts of dried fruiting bodies of mushrooms belonging to species of the Psilocybe genus. The objective is to initiate the assessment of tryptamine content in fungi marketed as Psilocybes in Colombia, using a standard chromatographic method that can be replicated. The separation was conducted in reverse phase using a Synergi 4 μm Hydro-RP C18 column (150 × 4.6 mm), eluted in a gradient mode with water-trifluoroacetic acid (100:0.1 v/v) and acetonitrile-trifluoroacetic acid (100:0.1 v/v) as the mobile phase. The gradient started at 5 % B at 0 min, reaching 30 % B at 15 min, with a flow rate of 0.20-0.22 mL/min, a column temperature of 35 ± 2 °C, and an injection volume of 10 μL. After establishing chromatographic conditions, the method was validated in terms of selectivity, linearity, system suitability, precision, robustness, and limits of detection and quantification, following the guidelines recommended by the International Conference on Harmonization (ICH) and the U.S. Food and Drug Administration (FDA). Once the mentioned parameters were evaluated, it was concluded that the method is suitable for the analysis of tryptamines in mushrooms. These conditions enabled the comparison of tryptamine content in 19 fungal samples from the Antioquia region (near Medellín city, Colombia), revealing a total content ranging from 0.01 % to 0.73 % of tryptamines in psilocin equivalents per fungal biomass.

keywords:
Agaricales, Fruiting Bodies, Fungal, Methanol, Tryptamines, Chromatography, High Pressure Liquid, Psilocybe, Limit of Detection

raw_json:
{"europe_pmc_id":"40020610","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Hashimoto K.
publication_date: 2024-02-26
doi: 10.1007/s00406-024-01770-7
pubmed_id: 38411629
source_url: https://doi.org/10.1007/s00406-024-01770-7
substance_tags: psilocybin
topic_tags: Depression,Receptor Pharmacology,Mystical Experience,Clinical Trial,Adverse Events
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Are "mystical experiences" essential for antidepressant actions of ketamine and the classic psychedelics?

abstract:
The growing interest in the rapid and sustained antidepressant effects of the dissociative anesthetic ketamine and classic psychedelics, such as psilocybin, is remarkable. However, both ketamine and psychedelics are known to induce acute mystical experiences; ketamine can cause dissociative symptoms such as out-of-body experience, while psychedelics typically bring about hallucinogenic experiences, like a profound sense of unity with the universe or nature. The role of these mystical experiences in enhancing the antidepressant outcomes for patients with depression is currently an area of ongoing investigation and debate. Clinical studies have shown that the dissociative symptoms following the administration of ketamine or (S)-ketamine (esketamine) are not directly linked to their antidepressant properties. In contrast, the antidepressant potential of (R)-ketamine (arketamine), thought to lack dissociative side effects, has yet to be conclusively proven in large-scale clinical trials. Moreover, although the activation of the serotonin 5-HT2A receptor is crucial for the hallucinogenic effects of psychedelics in humans, its precise role in their antidepressant action is still under discussion. This article explores the importance of mystical experiences in enhancing the antidepressant efficacy of both ketamine and classic psychedelics.

keywords:
Humans, Ketamine, Hallucinogens, Antidepressive Agents, Depression, Dissociative Disorders, Mysticism

raw_json:
{"europe_pmc_id":"38411629","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Ciszowski K, Ziaja A, Niedzielska-Andres E, Pomierny-Chamioło L.
publication_date: 2025-06-30
doi: 10.24425/fmc.2025.156119
pubmed_id: 41329968
source_url: https://doi.org/10.24425/fmc.2025.156119
keywords: Animals, Humans, Fungi, Hallucinogens, Psilocybin
substance_tags: psilocybin
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Natural hallucinogens of fungal and animal origin: action and potentialapplications - a narrative review.

abstract:
IntroductionNatural hallucinogens derived from fungi and animals have been used for centuries in shamanic, ritualistic, and medicinal practices across diverse cultures. These compounds exhibit a widerange of structures and mechanisms of action, affecting various neurotransmitter systems pathways. Fungal hallucinogens, primarily indole alkaloids like psilocybin and ergot alkaloids, as well as animal-derived toxins, such as bufotenine, ciguatoxins, or semiochemicals from insects, can induce profound alterations in perception, cognition, and mood. Despite their traditional use and psychoactive effects, many of these substances remain underexplored in terms of pharmacology and therapeutic potential. Recent studies suggest their possible roles in treating neuropsychiatric disorders, inflammatory conditions, and chronic pain, highlighting the need for a systematic review of their biological activity and medical applications.Aim of the studyThis review aims to provide an overview of hallucinogenic compounds of fungal and animal origin, focusing on their chemical nature, pharmacodynamic properties, and current evidence for potential therapeutic use.MethodologyThe review was based on publications retrieved from databases such as PubMed, Google Scholar, and ScienceDirect, covering the period from 1983 to 2025. Search terms included: fungal hallucinogens, animal-derived psychedelics, natural psychoactive compounds, toxicity, therapeutic application of hallucinogens, and psychedelic drug research.ResultsThe analyzed hallucinogens differ markedly in terms of chemical structure, receptor activity, intensity of hallucinogenic effects, and potential for clinical use. Preclinical and limited clinical data suggest beneficial effects in mood and anxiety disorders, treatment-resistant depression, pain syndromes, and potentially neurodegenerative diseases. Some compounds show promise as leads for the synthesis of novel bioactive molecules.ConclusionsHallucinogens of fungal and animal origin represent a biologically diverse and pharmacologically rich group of natural substances. Further interdisciplinary research is required to explore their mechanisms of action, safety profiles, and therapeutic potential. Their continued investigation may lead to the development of innovative treatments in neuropsychiatry and beyond.

topic_tags:
Depression,Anxiety,Chronic Pain,Pharmacology,Mechanism of Action,Receptor Pharmacology,Systematic Review,Review Article,Animal Study,Treatment-Resistant Depression,Safety,Toxicity,Inflammation

raw_json:
{"europe_pmc_id":"41329968","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Liechti ME, Gasser P, Aicher HD, Mueller F, Hawrot T, Schmid Y.
publication_date: 2025-07-30
doi: 10.1016/j.nsa.2025.105525
pubmed_id: 40800003
source_url: https://doi.org/10.1016/j.nsa.2025.105525
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Implementing psychedelic-assisted therapy: History and characteristics of the Swiss limited medical use program.

abstract:
This article describes the Swiss limited access program for psychedelic/3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy. The Swiss Federal Office of Public Health can issue authorizations for the limited medical use of otherwise prohibited substances. To be eligible, patients suffer from a mostly incurable disease, the prohibited substance can alleviate the suffering, and there are no alternative treatments, or such treatments have already extensively been used with insufficient outcome. The current program started in 2014 with two physicians. In 2024, there were approximately 100 physicians who held authorizations to treat 723 patients with MDMA (245 patients), lysergic acid diethylamide (130 patients), or psilocybin (348 patients). There were approximately 1660 psychedelic/MDMA-assisted treatments in 2024, with patients typically being treated 2-4 times with the respective substance within 12 months. Various aspects of the program, including its history, provider characteristics and setting, legal requirements, treatment cost, the role of professional societies, education and continuous formation, personal experience, patient characteristics, outcome, and adverse effects, are described and discussed relative to other recently established programs in Canada and Australia. Such information could be of interest to psychedelic-assisted therapy stakeholders, including professionals, patients, and regulatory bodies that are considering setting up similar restricted access programs.

raw_json:
{"europe_pmc_id":"40800003","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-07-30
doi: 10.1017/jme.2025.10109
pubmed_id: 40739983
source_url: https://doi.org/10.1017/jme.2025.10109
substance_tags: psilocybin
topic_tags: Depression,Anxiety,End-of-Life Distress,Clinical Trial,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Psychedelic Treatment with Psilocybin: Addressing Medical Malpractice Risk and Physicians' Concerns.

authors:
Cheung K, Brodie M, Chang SL, Deschamps P, Fallu JS, Farzin H, Hébert J, Stephan JF, Dorval M, Joly Y, P3A Study Group.

abstract:
Psychedelic treatment with psilocybin is receiving increased attention following clinical trials showing it may help treat end-of-life anxiety, depression, and several other conditions. Despite this, physicians may be reluctant to prescribe psilocybin and carry out psilocybin treatment because of the stigma surrounding psychedelics and the potential for medical malpractice liability. This paper explores whether psilocybin treatment gives rise to a risk of medical malpractice liability for physicians. Following an overview of psilocybin treatment and its regulatory regime in Canada, exploratory vignettes are used to highlight the relevance and limits of malpractice claims. This paper argues that the lack of established medical standards, standardized training, and credentialing contribute to liability risks surrounding psilocybin treatment. More clinical trials, meta-studies of research analyses, and knowledge sharing will help to develop training programs and medical standards of practice to better realize psilocybin's potential.

raw_json:
{"europe_pmc_id":"40739983","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-06-30
doi: 10.5152/pcp.2025.24934
pubmed_id: 40864832
source_url: https://doi.org/10.5152/pcp.2025.24934
substance_tags: psilocybin
topic_tags: PTSD,Clinical Trial,Observational Study,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
title:
Perspectives on Trauma Treatment, Self-Management Strategies, and Attitudes Toward Psychedelic Therapies in Individuals with Psychological Trauma Symptoms.

authors:
Modlin NL, Jessica L MK, Sarang M, Siebenaler L, Maggio C, Pick S, Williamson V, Cleare A, Rucker J.

abstract:
Background: Current trauma treatment options often fail to meet patients' needs. Despite the availability of established interventions, many trauma treatments fail to adequately meet patients' needs. In parallel, there has been renewed scientific and public interest in the therapeutic potential of psychedelics and related compounds, accompanied by increasing unsupervised use. This underscores the need to examine patients' willingness to engage with these therapies should they receive regulatory approval and to better characterize patterns of self-administration in order to inform patient-centered care and harm reduction strategies. Methods: An online survey recruited individuals with self-reported trauma symptoms or a formal diagnosis of post-traumatic stress disorder (PTSD)/complex post-traumatic stress disorder (CPTSD). Participants were asked about their treatment history, satisfaction with current treatments, and use of illicit substances for symptom management. Further, after receiving psychoeducation on 3,4-methylenedioxymethamphetamine (MDMA) and psilocybin therapies, participants' perceptions and willingness to participate in these treatments were assessed. Results: Of the 873 respondents, 94.8% reported experiencing psychological trauma, with 73.4% diagnosed with PTSD or CPTSD. Many had attempted multiple treatments, predominantly medications and various psychotherapies, but reported high dissatisfaction. Significant rates of marijuana, psychedelics, and MDMA use for self-management of trauma symptoms were reported, with minimal physical and psychological complications. Willingness to try MDMA and psilocybin therapies was high (0.81 and 0.83, respectively). Notably, women and heterosexual individuals showed lower willingness, while younger respondents and those with higher education levels showed greater willingness to try these treatments. Conclusion: High willingness to try MDMA and psilocybin therapies among trauma-exposed individuals highlights the need for further research and clinical trials. Understanding demographic variations in willingness can guide the development of accessible and effective treatment options for PTSD and CPTSD. Public education about potential risks and harm reduction strategies is crucial to promote safe and informed use of these emerging therapies.

raw_json:
{"europe_pmc_id":"40864832","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Bevione F, Lacidogna MC, Lavalle R, Abbate Daga G, Preti A.
publication_date: 2025-07-28
doi: 10.1007/s40519-025-01771-y
pubmed_id: 40730892
source_url: https://doi.org/10.1007/s40519-025-01771-y
keywords: Humans, Hallucinogens, Clinical Trials as Topic, Feeding and Eating Disorders, Psilocybin
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Psilocybin in the treatment of eating disorders: a systematic review of the literature and registered clinical trials.

abstract:
BackgroundFluoxetine remains the only pharmacological treatment approved for Bulimia Nervosa, and no other drugs have been approved for eating disorders (EDs). The rationale for exploring psilocybin as a treatment for EDs is compelling, both from biological and psychological perspectives. Moreover, its safety profile in healthy individuals appears favorable. This systematic review aims to examine original research articles and registered clinical trials to assess the current psilocybin's therapeutic potential in EDs.MethodsSystematic review following the indications of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed, Excerpta Medica Database (EMBASE), and the Cochrane Library from inception until 29 July 2024, with key terms: "psilocybin" and "eating disorders". Quality was assessed through the Quality Assessment Tool for Before-After (Pre-Post) Studies With No Control Group released by the National Heart, Lung, and Blood Institute (NHLBI). We performed an additional search on the registry of clinical trials available at the website https://clinicaltrials.gov.ResultsTwo studies met the inclusion criteria for our analysis. The first was an open-label feasibility study involving 10 individuals with Anorexia Nervosa (AN), without a control group. The second was a single case report describing the use of psilocybin in a person with AN. In addition, six registered clinical trials of psilocybin in individuals with EDs were identified.ConclusionsThe initial evidence shows that psilocybin might be safe and well-tolerated in AN. The promising results and the need for tests in enlarged samples encourage further research on psilocybin in EDs.Level of evidence viiiEvidence from nonrandomized controlled clinical trials, nonrandomized clinical trials, cohort studies, case series, case reports, and individual qualitative studies.

topic_tags:
Eating Disorders,Clinical Trial,Randomized Controlled Trial,Systematic Review,Review Article,Case Report,Observational Study,Safety

raw_json:
{"europe_pmc_id":"40730892","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Rudy LM, Godlewski MM.
publication_date: 2025-07-25
doi: 10.3390/ijms26157233
pubmed_id: 40806366
source_url: https://doi.org/10.3390/ijms26157233
substance_tags: psilocybin
topic_tags: Mechanism of Action,Receptor Pharmacology,Consciousness,Review Article,Drug Interactions
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Molecular Pathways Potentially Involved in Hallucinatory Experiences During Sleep Paralysis: The Emerging Role of β-Arrestin-2.

abstract:
Sleep paralysis (SP), an REM parasomnia, can be characterized as one of the symptoms of narcolepsy. The SP phenomenon involves regaining meta-consciousness by the dreamer during REM, when the physiological atonia of skeletal muscles is accompanied by visual and auditory hallucinations that are perceived as vivid and distressing nightmares. Sensory impressions include personification of an unknown presence, strong chest pressure sensation, and intense fear resulting from subjective interaction with the unfolding nightmare. While the mechanism underlying skeletal muscle atonia is known, the physiology of hallucinations remains unclear. Their complex etiology involves interactions among various membrane receptor systems and neurotransmitters, which leads to altered neuronal functionality and disruptions in sensory perception. According to current knowledge, serotonergic activation of 5-hydroxytryptamine-receptor-2A (5-HT2A)-associated pathways plays a critical role in promoting hallucinogenesis during SP. Furthermore, they share similarities with psychedelic-substance-induced ones (i.e., LSD, psilocybin, and 2,5-dimethoxy-4-iodoamphetamine). These compounds also target the 5-HT2A receptor; however, their molecular mechanism varies from serotonin-induced ones. The current review discusses the intracellular signaling pathways responsible for promoting hallucinations in SP, highlighting the critical role of β-arrestin-2. We propose that the β-arrestin-2 signaling pathway does not directly induce hallucinations but creates a state of network susceptibility that facilitates their abrupt emergence in sensory areas. Understanding the molecular basis of serotonergic hallucinations and gaining better insight into 5-HT2A-receptor-dependent pathways may prove crucial in the treatment of multifactorial neuropsychiatric disorders associated with the dysfunctional activity of serotonin receptors.

keywords:
Animals, Humans, Hallucinations, Sleep Paralysis, Serotonin, Receptor, Serotonin, 5-HT2A, Signal Transduction, beta-Arrestin 2

raw_json:
{"europe_pmc_id":"40806366","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-07-23
doi: 10.1186/s40337-025-01328-5
pubmed_id: 40708053
source_url: https://doi.org/10.1186/s40337-025-01328-5
substance_tags: psilocybin
topic_tags: PTSD,Eating Disorders,Microdosing,Clinical Trial,Observational Study,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Psychedelic use in individuals living with eating disorders or disordered eating: findings from the international MED-FED survey.

authors:
Rodan SC, Meez N, Lloyd-Hurwitz S, Bedoya-Pérez MA, Suraev A, Sommer N, Greenstien K, Maguire S, McGregor IS.

abstract:
BackgroundThere are few effective treatments for eating disorders (EDs), and new interventions are urgently needed. The MEDication and other drugs For Eating Disorders ("MED-FED") survey investigated the lived experience of adults with EDs regarding their prescription and non-prescription drugs use. Psychedelic drugs were highly rated in this survey for their impact on ED symptoms and general mental health. Here, we provide a more granular analysis of a subset of the data pertaining to psychedelic drug use from this survey.MethodsThe MED-FED survey recruited adults who self-reported either a clinically diagnosed ED or disordered eating that was currently undiagnosed but causing significant distress. The demographics of recent and lifetime psychedelic users relative to non-users were examined, as well as their use of other prescription and non-prescription drugs, and co-morbid conditions. Qualitative analysis was used to examine themes emerging from open-ended comments around use of psychedelic drugs.ResultsOf the 5247 participants who completed the survey, 1699/5247 (32.4%) reported lifetime psychedelic use, with 1019/5247 (19.4%) having used in the last 12 months. Typical use involved infrequent consumption, once or twice per year, of psilocybin, LSD, 2-CB, or DMT. Those who reported recent psychedelic use were younger and less likely to currently use prescription drugs or to have been recently hospitalised for their ED. They were more likely to use other non-prescription drugs (e.g. cannabis, ketamine, stimulants) and to report co-morbid ADHD, PTSD, ASD, and substance misuse. Participants with a diagnosis of anorexia nervosa were less likely to report psychedelic use, while those with an undiagnosed ED were more likely. Qualitative analysis of responses (n = 200) revealed themes of profound transformation, increased connectedness, and new insights into illness following psychedelic experiences. A handful of respondents reported benefits from microdosing. A few respondents reported adverse outcomes in their open-ended comments, including "bad trips" (n = 15) and worsened ED symptoms (n = 8) after psychedelic use.ConclusionsThese findings provide a unique insight into psychedelic use among individuals with EDs. The results align with emerging evidence suggesting that psychedelics may be beneficial in this population, highlighting the need for further research, including clinical trials, to explore their efficacy and safety.

raw_json:
{"europe_pmc_id":"40708053","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Luquiens A, Belahda D, Graux C, Igounenc N, Serrand C, Rochefort P, Mura T, Sergent F.
publication_date: 2025-07-23
doi: 10.1111/add.70152
pubmed_id: 40702912
source_url: https://doi.org/10.1111/add.70152
substance_tags: psilocybin
topic_tags: Depression,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 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Psilocybin in alcohol use disorder and comorbid depressive symptoms: Results from a feasibility randomized clinical trial.

abstract:
Background and aimsPsilocybin has emerged as a potential treatment for alcohol use disorder (AUD), but early efficacy data are inconsistent. Depression following alcohol detoxification significantly increases the risk of relapse. This pilot study aimed to evaluate the feasibility, acceptability, and preliminary efficacy of psilocybin-assisted psychotherapy for patients with comorbid AUD and depression.DesignA prospective, single-center, double-blind, parallel (2:1), randomized controlled pilot study.SettingThe study was conducted in a French inpatient addiction treatment program offering intensive relapse prevention interventions.ParticipantsOf 350 screened patients, 30 adults (mean age 49 ± 10 years; 43% female) with severe AUD (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [DSM-5] criteria) and a Beck Depression Inventory-II (BDI-II) score ≥14 were included. Participants had completed detoxification between 14 and 60 days prior to inclusion.InterventionsParticipants received either two oral sessions of 25 mg (n = 20) or 1 mg (n = 10) psilocybin-assisted psychotherapy spaced three weeks apart, as an add-on to standard care. Patients, investigators and outcome assessors were all blinded to patient group.MeasurementsThe primary outcome was feasibility, according to participation in both dosing sessions and recruitment/inclusion rates. Secondary outcomes included alcohol use (Alcohol Timeline Followback), time to relapse, craving (Craving Experience Questionnaire), depression (BDI-II), safety and blinding integrity.FindingsOne participant in the 25 mg group could not receive the second dose due to myocardial infarction occurring three days earlier, unrelated to the treatment. Four participants in the control group refused the second session after guessing their group assignment (p-value = 0.019), with one participant self-administering 3,4-Methylenedioxymethamphetamine (MDMA). At 12 weeks, the 25 mg group showed significantly greater abstinent rate (11/20 (55%) vs 1/9 (11%) (one lost of follow up) (difference = -44%, [95% confidence interval [CI]: -82% to -5.9%]), p = 0.043), reductions in % drinking days -100 (-100 to -49) vs - 93 (-96 to 0), p = 0.038 and craving frequency -8 (-23 to -1) vs + 7 (-2 to 11), p = 0.045, respectively in the 25 vs 1 mg groups (median [25;75]). Relapse rates were 35% in the 25 mg group and 50% in the control group (HR = 0.52 [0.16 to1.65]). No efficacy differences were observed based on antidepressant use in terms of drinking and depression. Blinding was imperfect (correct guess by patients: 93.3%; investigators: 86.7%). Twenty-five adverse events were reported in 10 patients (50%) in the 25 mg group versus 6 patients (60%) in the control group.ConclusionsPsilocybin-assisted psychotherapy appears feasible, acceptable, and safe in recently detoxified patients with comorbid alcohol use disorder and depression.

raw_json:
{"europe_pmc_id":"40702912","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-07-09
doi: 10.1021/acsomega.5c02751
pubmed_id: 40727727
source_url: https://doi.org/10.1021/acsomega.5c02751
substance_tags: psilocybin,psilocin
topic_tags: Depression,Anxiety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Exploring the Frontiers of Psychedelics: A New Chromatographic Method for Detection and Quantification of Psilocybin and Psilocin in Psilocybe cubensis Mushrooms.

authors:
Pereira Galdino T, Oliveira LC, Luz MA, Costa Barbosa R, Torres MCM, Sivieri K, Fernandes PA, Santos ML, Lima AGB, Silva SML, Fook MVL.

abstract:
Innovative therapies, such as psilocybin-assisted psychotherapies, hold great promises for treating anxiety, depression, and various other mental health disorders, addressing some of the challenges faced by conventional psychiatric medicine. This study focuses on developing and validating an HPLC-DAD methodology for detecting psilocybin and psilocin in extracts from psychedelic mushrooms intended for medicinal use. The methodology to has been validated following the guidelines of RDC No. 166/2017 from the Brazilian National Health Surveillance Agency (ANVISA). Utilizing a PerkinElmer C18 column (150.0 mm length × 4.6 mm internal diameter × 5 μm particle size), the gradient method employed ultrapure Milli-Q water (mobile phase A) and acetonitrile (mobile phase B), both acidified to 0.3% with formic acid (starting at a ratio of 95:5 v/v), with a flow rate of 0.8 mL/min over 18 min and an injection volume of 15 μL. The column temperature was maintained at 30 °C, and the analysis was conducted at a wavelength of 266 nm. The limit of detection (LOD) and limit od quantification (LOQ) values for psilocybin were 1.58 and 4.78 mg/L, respectively, while for psilocin, they were 1.70 and 5.17 mg/L. The method's accuracy showed recovery intervals for psilocybin ranging from 80 to 120% and for psilocin from 98 to 116%. Accurately determining the content of psilocybin (2.57%) and psilocin (0.16%) is essential for their application as pharmaceutical compounds. This methodological rigor ensures that these substances can be reliably used in therapeutic contexts, underscoring the importance of precise quantification in developing safe and effective medical treatments.

raw_json:
{"europe_pmc_id":"40727727","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Cioe PA, Stang GS, Azam D, Dugal S.
publication_date: 2025-07-20
doi: 10.1186/s13722-025-00563-0
pubmed_id: 40691651
source_url: https://doi.org/10.1186/s13722-025-00563-0
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Addiction,Safety,Adverse Events
study_type: Qualitative Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
"I've learned that I'm open-minded to this possibility": A qualitative study to evaluate the acceptability of a psilocybin-aided smoking cessation treatment for people with HIV who smoke.

abstract:
BackgroundPeople with HIV (PWH) are disproportionately affected by cigarette use, with a 40 - 70% prevalence rate. Although many express a strong interest in quitting, many PWH who smoke experience lower cessation rates with traditional treatments, in part due to their comorbid anxiety and depressive symptoms. Psilocybin, a classic psychedelic referred to as "breakthrough therapy" by the U.S. Food & Drug Administration (FDA), has been shown to have potential as a therapeutic treatment for psychiatric symptoms, (e.g., anxiety and depression) and substance use disorders, including tobacco dependence. Preliminary evidence has shown that administering psilocybin to people who smoke and have been previously unable to quit with traditional treatments resulted in impressive smoking abstinence rates (80%) at 6-months in a smoking cessation pilot study.ObjectiveExplore, using qualitative methods, the perceptions and acceptability of a psilocybin-assisted treatment for smoking cessation among PWH who smoke.MethodsSemi-structured, in-depth qualitative interviews were conducted with PWH who smoke. Interviews were audio-recorded, transcribed verbatim, and analyzed using rapid thematic analysis.ResultsTwenty-five participants were enrolled: 15 cis male, 9 cis female, and 1 transgender female. Five main themes emerged: varying previous experiences with psilocybin; uncertainty about psilocybin's effects and concern over potential side effects; need for trusted sources of information and testimonials; ultimately willing to try psilocybin-aided therapy for tobacco treatment; and, set and setting of psilocybin use matters.ConclusionsPsilocybin-assisted smoking cessation treatment appears to be acceptable among PWH who smoke. Participants highlighted the importance of addressing key concerns related to an emerging therapy to increase acceptability and willingness to try it. Further research is needed to evaluate the safety and effectiveness of psilocybin prior to incorporating this emerging therapy for smoking cessation into tobacco treatment clinical services for PWH.

keywords:
Humans, HIV Infections, Hallucinogens, Smoking Cessation, Qualitative Research, Adult, Middle Aged, Patient Acceptance of Health Care, Female, Male, Psilocybin

raw_json:
{"europe_pmc_id":"40691651","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Islam S, Liden T, Goff R, Schug KA.
publication_date: 2025-06-30
source_url: https://europepmc.org/article/AGR/IND609270047
substance_tags: psilocybin,psilocin
topic_tags: General
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Untargeted analysis of psilocybin and non-psilocybin mushrooms using liquid chromatography quadrupole time of flight mass spectrometry

abstract:
Psilocybin mushrooms, particularly those containing the psychoactive compounds psilocybin and psilocin, have attracted recent attention due to their potential therapeutic use for the treatment of psychological disorders. To use psilocybin mushrooms in a clinical context, it is important to understand their chemical composition more fully. An untargeted analysis using liquid chromatography (LC) quadrupole time-of-flight mass spectrometry was performed to explore the chemical diversity of various species of psilocybin mushrooms (PM) relative to edible non-psilocybin mushrooms (NPM). The analysis was performed using reversed phase LC with electrospray ionization in data independent acquisition mode. The study revealed the presence of several classes of compounds and their derivatives. The data was analyzed using multiple statistical methods. Principal component analysis showed that the psilocybin mushrooms and non-psilocybin mushrooms are compositionally very different from each other. These findings contribute to a deeper understanding of the chemical complexity of psilocybin mushrooms and lay groundwork for future research into their potential applications in medicine and psychology.

raw_json:
{"europe_pmc_id":"IND609270047","source":"AGR","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-08-31
source_url: https://europepmc.org/article/AGR/IND609227368
substance_tags: psilocybin,psilocin
topic_tags: Depression,Anxiety,PTSD,Addiction,Headache / Migraine,Mechanism of Action,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Biochemical Insights into Diverse Psilocybe Mushrooms and Their Metabolites as Sources of Neuroactive Agents: A Review

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

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

raw_json:
{"europe_pmc_id":"IND609227368","source":"AGR","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Behavioural and pharmacological evaluation of the psilocybin analogue baeocystin in Wistar rats.
publication_date: 2025-07-04
doi: 10.1016/j.pnpbp.2025.111439
pubmed_id: 40619050
source_url: https://doi.org/10.1016/j.pnpbp.2025.111439
substance_tags: psilocybin
topic_tags: Anxiety,Pharmacology
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
authors:
Danda H, Mazochová K, Šíchová K, Mazoch V, Olejníková-Ladislavová L, Syrová K, Jurásek B, Cihlářová P, Jurok R, Páleníček T, Kuchař M.

abstract:
Baeocystin is a naturally occurring tryptamine-based compound found in various psychoactive mushrooms, including in several species of Psilocybe genus. Due to its structural similarity to psilocybin, which has shown a therapeutic potential in treatment of psychiatric disorders, there is a growing interest in investigating whether baeocystin exhibits comparable effects. This study investigated the pharmacokinetic profile and acute behavioural effects of baeocystin in Wistar rats. Behavioural assessments including locomotor activity and its spatial characteristics (in the open field test) and sensorimotor gating measured by prepulse inhibition were evaluated after subcutaneous administration of 1.25 or 5 mg/kg baeocystin. Pharmacokinetics and brain-serum ratios were analysed after the 5 mg/kg sc. dose. Pharmacokinetics demonstrated that both baeocystin and its metabolite, norpsilocin, have a very limited ability to cross the blood-brain barrier. Consistent with the pharmacokinetic profile, baeocystin had no significant effects on locomotor activity, exploratory behaviour, anxiety-like responses, or sensorimotor gating at doses of either 1.25 or 5 mg/kg. In conclusion, our results suggest that baeocystin has minimal to no behavioural effects in rats, probably due to its poor permeability across the blood-brain barrier. This limited penetration may account for its negligible neurobiological and psychedelic activity.

keywords:
Animals, Rats, Rats, Wistar, Hallucinogens, Behavior, Animal, Exploratory Behavior, Motor Activity, Locomotion, Dose-Response Relationship, Drug, Male, Sensory Gating, Prepulse Inhibition, Psilocybin

raw_json:
{"europe_pmc_id":"40619050","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Females in Psychedelic Research: A Perspective for Advancing Research and Practice.
authors: Cohen ZZ, Blest-Hopley G
journal: ACS pharmacology & translational science
publication_date: 2025-07-10
doi: 10.1021/acsptsci.5c00255
pubmed_id: 40672681
source_url: https://pubmed.ncbi.nlm.nih.gov/40672681/
keywords: estrogen, menstrual Cycle, progesterone, psilocybin, psychedelics
substance_tags: psilocybin
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"40672681"}
abstract:
The influence of ovarian hormone fluctuations on neurochemistry, cognition, and psychological responses remains insufficiently examined in current psychedelic research and clinical protocols. Traditional practices and case studies underscore the importance of accounting for these factors in investigations of psychedelic effects. This opinion paper explores the critical intersections between female hormones and psychedelic experiences, informing improved research and practice. Estradiol (E2) and progesterone (P4), the primary ovarian hormones, modulate neurotransmitter systems central to psychedelic pharmacology, including serotonin (5-HT), dopamine, GABA, and glutamate. These hormonal interactions affect interhemispheric communication, synaptic plasticity, mood, cognition, and behavior. Fluctuations across the menstrual cycle influence 5-HT2A receptor expression and functional connectivity, potentially modulating both the subjective intensity and therapeutic efficacy of psychedelics. Additionally, oscillations in female hormones across the menstrual and life cycles affect mindset, a significant factor in safe and effective psychedelic use. These findings suggest that female hormonal variability may play a pivotal role in psychedelic experiences. Incorporating menstrual phase tracking and hormonal assays in both clinical trials and observational studies can reduce data variability, support individualized care, and improve informed consent practices. This would improve data integrity and ensure that women are fully informed about the potential influence of their hormonal state on their psychedelic experience, supporting truly informed consent. This paper emphasizes the need for an improved understanding of the complex interplay between female-specific biology and psychedelic pharmacodynamics to advance safe, ethical, and effective psychedelic research and therapies for women.

topic_tags:
Neuroplasticity,Pharmacology,Receptor Pharmacology,Clinical Trial,Observational Study,Drug Interactions


title: Equitable access to psilocybin-assisted psychotherapy in New Zealand.
authors: Lacey C.
publication_date: 2025-07-10
doi: 10.26635/6965.e1618
pubmed_id: 40638925
source_url: https://doi.org/10.26635/6965.e1618
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
raw_json:
{"europe_pmc_id":"40638925","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Clade III Synthases Add Cyclic and Linear Terpenoids to the Psilocybe Metabolome.
authors: Zschoche N, Schober S, Walther K, Chadeayne AR, Gressler M, Bartram S, O'Connor SE, Hoffmeister D.
publication_date: 2025-06-03
doi: 10.1002/cbic.202500167
pubmed_id: 40318115
source_url: https://doi.org/10.1002/cbic.202500167
keywords: Terpenes, Sesquiterpenes, Psilocybe, Metabolome
substance_tags: psilocybin
topic_tags: In Vitro Study,Metabolomics
study_type: In Vitro Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
Psilocybe "magic mushrooms" are best known for their indolethylamine psilocybin, yet they encode enzymes for a much more diverse arsenal of small and potentially bioactive molecules. Herein, four Psilocybe cubensis clade III sesquiterpene synthases, CubB-CubE, whose genes are differently expressed in fruiting bodies compared to vegetative mycelium are reported. CubB-CubE were functionally characterized in vitro by product formation assays with heterologously produced enzymes and in vivo by transgene expression in Aspergillus niger, followed by extensive gas chromatography-mass spectrometry analyzes. CubB was identified as a single product (3R,6E)-(-)-nerolidol synthase. CubC is a multiproduct enzyme producing β-caryophyllene, β-elemene, α-humulene, and β-farnesene. CubD and CubE catalyze (near-)exclusively sterpurene formation. P. cubensis young fruiting bodies and vegetative mycelium were analyzed for sesquiterpenes, which verified the presence of the CubB product α-(3R,6E)-(-)-nerolidol. As various Psilocybe species encode highly similar enzymes, this study contributes generally to the as-yet little-understood secondary metabolome of the genus.

raw_json:
{"europe_pmc_id":"40318115","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Acute effects of psilocybin on the dynamics of gaze fixations during visual aesthetic perception.
authors: Muller S, Cavanna F, de la Fuente L, Bruno N, D'Amelio TA, Pallavicini C, Tagliazucchi E.
publication_date: 2025-07-08
doi: 10.1038/s41598-025-10206-8
pubmed_id: 40634541
source_url: https://doi.org/10.1038/s41598-025-10206-8
substance_tags: psilocybin
topic_tags: Chronic Pain,Consciousness,Emotional Processing
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
Serotonergic psychedelics are remarkable for their capacity to induce variable yet reproducible modifications to human consciousness. The acute effects of these compounds include perceptual alterations, predominantly in the visual domain, yet these alterations have been mostly documented only by subjective reports. We used eye-tracking to quantify the effects of low vs. high doses of psilocybin mushrooms on eye movements during the exploration of complex visual stimuli under semi-naturalistic conditions, focusing on the case of aesthetic perception. The experimental condition (high vs. low dose) was a priori unknown to participants and experimenters. High doses resulted in a more local visual exploration of paintings, and a less entropic distribution of fixations. While psilocybin altered gaze behavior and increased subjective emotional intensity and feelings of flow, it did not affect the aesthetic ratings of the stimuli, suggesting a dissociation between perceptual and evaluative aspects of aesthetic experience. These findings suggest that psilocybin may influence gaze fixation by altering the perception of low-level visual features, including textures, shapes, and colors. Our work highlights the possibility of investigating psychedelics by addressing their effect on behavior under complex naturalistic conditions, contributing to maintaining subject engagement while also increasing the ecological validity of the findings.

keywords:
Humans, Hallucinogens, Eye Movements, Photic Stimulation, Visual Perception, Esthetics, Fixation, Ocular, Adult, Female, Male, Young Adult, Psilocybin

raw_json:
{"europe_pmc_id":"40634541","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin treatment extends cellular lifespan and improves survival of aged mice.
authors: Kato K, Kleinhenz JM, Shin YJ, Coarfa C, Zarrabi AJ, Hecker L.
publication_date: 2025-07-07
doi: 10.1038/s41514-025-00244-x
pubmed_id: 40628762
source_url: https://doi.org/10.1038/s41514-025-00244-x
substance_tags: psilocybin,psilocin
topic_tags: Mechanism of Action,Longevity,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
Psilocybin, the naturally occurring psychedelic compound produced by hallucinogenic mushrooms, has received attention due to considerable clinical evidence for its therapeutic potential to treat various psychiatric and neurodegenerative indications. However, the underlying molecular mechanisms remain enigmatic, and few studies have explored its systemic impacts. We provide the first experimental evidence that psilocin (the active metabolite of psilocybin) treatment extends cellular lifespan and psilocybin treatment promotes increased longevity in aged mice, suggesting that psilocybin may be a potent geroprotective agent.

raw_json:
{"europe_pmc_id":"40628762","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin has no immediate or persistent analgesic effect in acute and chronic mouse pain models
authors: Gregory NS, Girard TE, Ram A, Casey AB, Malenka RC, Tawfik VL, Heifets BD.
journal: bioRxiv
publication_date: 2025-07-06
doi: 10.1101/2025.07.06.663398
source_url: https://doi.org/10.1101/2025.07.06.663398
substance_tags: psilocybin
topic_tags: Chronic Pain,Animal Study,Inflammation
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
The psychedelic psilocybin may have lasting therapeutic effects for patients with chronic pain syndromes. Some clinical and preclinical data suggest these putative benefits derive from direct analgesic effects. However, this possibility has not been comprehensively tested in preclinical models. Here, we show that psilocybin is not analgesic over a range of doses across multiple pain assays and models of acute and chronic inflammatory, neuropathic, or musculoskeletal pain in mice.

raw_json:
{"europe_pmc_id":"PPR1047940","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


authors: Braekow P, Neumann J, Kirchhefer U, Gergs U.
publication_date: 2025-07-05
doi: 10.3390/ph18071009
pubmed_id: 40732298
source_url: https://doi.org/10.3390/ph18071009
substance_tags: psilocybin,psilocin
topic_tags: Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Effects of Psilocin and Psilocybin on Human 5-HT4 Serotonin and H2 Histamine Receptors in Perfused Hearts of Transgenic Mice.

abstract:
Background/Objectives: Hallucinogenic substances such as psilocybin, psilocin, ergometrine, ergotamine, and lysergic acid diethylamide (LSD) have been demonstrated to enhance the force of contraction (FOC), in part due to the phosphorylation of phospholamban in human atrial preparations via 5-HT4 serotonin receptors and/or H2 histamine receptors. However, whether psilocybin or psilocin acts at isolated mammalian ventricular preparations and whether they increase protein phosphorylation in the mammalian ventricle remains to be elucidated. Methods: To this end, the FOC and phospholamban phosphorylation in isolated perfused hearts from transgenic mice with cardiomyocyte-specific overexpression of either human 5-HT4 receptors (5-HT4-TG) or human H2 receptors (H2-TG) and their wild-type littermates (WT) were examined. Furthermore, the ergot alkaloids ergometrine, ergotamine, and LSD were used as references. Results: Psilocybin and psilocin enhanced the FOC to 137% and to 152%, respectively, and elevated the phospholamban phosphorylation in isolated perfused hearts from 5-HT4-TG. In H2-TG hearts, psilocybin and psilocin increased the FOC to a much lesser extent but had no effect on the phospholamban phosphorylation. In contrast, LSD increased the FOC and phosphorylation state of phospholamban in isolated hearts of both 5-HT4-TG and H2-TG. On the other hand, ergometrine and ergotamine increased the FOC only in H2-TG. Ergometrine increased the phosphorylation state of phospholamban in perfused hearts from H2-TG, but not from 5-HT4-TG. Ergotamine failed to increase the phospholamban phosphorylation in both H2-TG and 5-HT4-TG. Psilocybin, psilocin, ergotamine, ergometrine, and LSD were unable to increase FOC and phospholamban phosphorylation in perfused hearts from WT. Conclusions: The increase in the phosphorylation state of phospholamban could provide a partial explanation for the positive inotropic effects and the relaxant effects of not only psilocybin and psilocin but also ergometrine and LSD in the isolated hearts of the animals used in this study.

raw_json:
{"europe_pmc_id":"40732298","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-07-05
doi: 10.1080/02791072.2025.2526403
pubmed_id: 40619866
source_url: https://doi.org/10.1080/02791072.2025.2526403
substance_tags: psilocybin
topic_tags: Depression,PTSD,Addiction,Observational Study,Safety
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Exploring Jordanian Physicians' and Medical Students' Perspectives on Ketamine and Psychedelic-Assisted Therapies: An Insight from the Middle East.

authors:
Ahmed KE, Abu Nasrieh D, Banihani HA, Obaidat MF, Mazzawi T, Al-Tarawneh AK, Bani Mustafa R, Al Kayed Z.

abstract:
Psychedelic-assisted therapies and ketamine are two modalities gaining attention in psychiatry for treating conditions such as depression, PTSD, and substance use disorders. However, perceptions of these treatments vary globally. This study explores the familiarity, attitudes, and perceptions of Jordanian physicians and medical students toward psychedelic substances, addressing a gap in Middle Eastern research. A cross-sectional study conducted from July to August 2024 utilized a validated online survey among medical students and physicians in Jordan. The survey covered demographics, familiarity to psychedelics and ketamine, attitudes toward their medical use, and concerns about risks and legality. Statistical analyses, including multivariate regression and factor analysis, assessed the influence of demographics on participant perspectives. Of the 1,985 respondents, most had limited familiarity to psychedelics. LSD was the most recognized substance, while fewer participants identified psilocybin or MDMA. familiarity and attitudes varied significantly by age, gender, and prior familiarity, with professional status showing no impact. Three attitude clusters emerged: opposers (n = 1000), cautious (n = 677), and supporters (n = 308), each influenced by different demographics. This study reveals a notable familiarity gap and mixed attitudes toward psychedelic therapies among Jordanian healthcare professionals, highlighting the need for targeted education to enhance understanding of these treatments in Jordan's medical community.

raw_json:
{"europe_pmc_id":"40619866","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Christen SE, Bekka E, Schmid Y, Benowitz NL, Liakoni E.
publication_date: 2025-06-30
doi: 10.57187/s.4346
pubmed_id: 40811135
source_url: https://doi.org/10.57187/s.4346
keywords: Humans, Cannabis, Nicotine, Caffeine, Psychotropic Drugs, Psilocybin
substance_tags: psilocybin
topic_tags: Pharmacology,Consciousness,Emotional Processing,Review Article,Safety,Toxicity
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Caffeine, nicotine, cannabis, and psilocybin: Pharmacology, toxicology, and potential therapeutic uses of four naturally occurring psychoactive substances.

abstract:
Psychoactive substances are compounds that can influence perception, consciousness, cognition, and emotions. The psychoactive substances caffeine, nicotine, cannabis, and psilocybin all originate from natural sources and can be used without complex processing or synthesis. Their natural availability has contributed to a long-standing history of human use and cultural significance. Caffeine and nicotine are freely available and commonly used as everyday stimulants, whereas psilocybin is more strictly regulated and cannabis has been legalised in some countries and regions. Some of these substances have been intensively studied, and their pharmacological and toxicological properties are well known, but ongoing research continues to investigate their therapeutic use for specific diseases and disorders. This narrative review aims to provide an overview of the pharmacology and toxicology of these four naturally occurring psychoactive substances, including a summary of the currently available evidence on their therapeutic potential, health benefits, and associated risks.

raw_json:
{"europe_pmc_id":"40811135","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Brown R, Hamilton NM, Mallon C, Stevenson J, Faley MT, Kargbo RB, Sherwood AM, Upeandran B.
publication_date: 2025-06-30
doi: 10.1002/jlcr.4155
pubmed_id: 40743107
source_url: https://doi.org/10.1002/jlcr.4155
substance_tags: psilocybin,psilocin
topic_tags: Depression,Anxiety,PTSD,Pharmacology
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Synthesis of Psilocin, Psilocybin and 5-MeO-DMT Succinate, All Labelled With Carbon-14 at the Indole 2-Position.

abstract:
Three novel 14C-labelled isotopologues of the psychoactive agents psilocin, psilocybin and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) were synthesised, all labelled at the 2-position of the indole. The syntheses involved incorporating the 3-dimethylaminoethyl substituent common to all three substances onto a 4- or 5-substituted indole intermediate via successive treatments with oxalyl chloride, dimethylamine and reduction with lithium aluminium hydride. Psilocybin-2-14C with a specific activity of 234 μCi/mg exhibited limited stability, but a 5.5-fold radio dilution with unlabelled psilocybin afforded material that maintained a radiochemical purity exceeding 97.5% after 1-month storage at ≤ -70°C. The stability of 5-MeO-DMT-2-14C succinate salt with a specific activity of 173 μCi/mg was assessed over a more extended storage period, and after 6 months at ≤ -70°C the radiochemical purity was 98.0%, supporting its use in long-term studies. The radiolabelled psilocybin-2-14C and 5-MeO-DMT-2-14C succinate represent new tools for in vivo pharmacokinetic and metabolic studies with psychedelic tryptamines. These novel derivatives may offer enhanced metabolic stability and facilitate more precise ADME and mass balance studies. Future research will explore their behaviour in biological systems to support necessary studies toward regulatory approval of both psilocybin and 5-MeO-DMT for treating mental health disorders such as depression, anxiety and post-traumatic stress disorder.

keywords:
Carbon Radioisotopes, N,N-Dimethyltryptamine, Indoles, Hallucinogens, Isotope Labeling, Radiochemistry, Chemistry Techniques, Synthetic, Psilocybin

raw_json:
{"europe_pmc_id":"40743107","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Hieronymus F, López E, Werin Sjögren H, Lundberg J.
publication_date: 2025-06-30
doi: 10.1001/jamanetworkopen.2025.24119
pubmed_id: 40736734
source_url: https://doi.org/10.1001/jamanetworkopen.2025.24119
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Control Group Outcomes in Trials of Psilocybin, SSRIs, or Esketamine for Depression: A Meta-Analysis.

abstract:
ImportancePsilocybin has demonstrated rapid and sustained antidepressant efficacy, with acute-phase effect sizes often more than double those for conventional antidepressants. However, concerns have been raised that high rates of functional unblinding in combination with trial participants with positive expectations of psychedelic use might bias treatment outcomes.ObjectiveTo compare outcomes for patients receiving control treatments in randomized clinical trials of psilocybin for depression with control treatment outcomes from trials of selective serotonin reuptake inhibitors (SSRIs) and esketamine.Data sourcesTwo previous meta-analyses and 1 US Food and Drug Administration review published between March 2019 and December 2024 were used to identify double-blind trials on adult major depressive disorder (MDD) or treatment-resistant depression (TRD) that had a relevant control treatment arm and used the Montgomery-Åsberg Depression Rating Scale (MADRS) for symptom rating.Study selectionFollowing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline, trials of psilocybin for MDD and TRD, esketamine for TRD, and a selective serotonin reuptake inhibitor (SSRI) for MDD were selected. Studies that included only individuals aged younger than 18 years or older than 65 years, used a crossover design, or had a duration less than 2 weeks were excluded.Data extraction and synthesisAll authors assessed the 3 reviews for includable trials. Three authors independently extracted data for all trials, with disagreements resolved by consensus discussion. Data were pooled using random-effects models.Main outcomes and measuresStandardized mean change (SMC) in MADRS scores from baseline to up to 6 weeks after randomization was used to assess within-group effect sizes, and standardized mean difference (SMD) was used to assess between-group effect sizes. Omnibus Test of Moderators (QM) was used to test whether the study population significantly moderated effect sizes.ResultsThe study included 17 trials: 4 of psilocybin (n = 373), 2 of esketamine (n = 573), and 11 of SSRIs (n = 4014). Pretreatment to posttreatment SMCs (SEMs) were 1.21 (0.15) for psilocybin, 1.28 (0.06) for SSRIs, and 1.43 (0.15) for esketamine and were 0.50 (0.15), 1.00 (0.08), and 1.12 (0.17) for their respective control treatments. Study population was a significant moderator of between-group SMDs (QM, 10.7; df, 2; P =.005) and pre- to post-control treatment SMCs (QM, 10.4; df, 2; P =.005) but not of pre- to post-active treatment SMCs (QM, 1.21; df, 2; P =.55). MADRS response rates for control treatments in SSRI trials were 14 percentage points higher than in psilocybin trials and in esketamine trials were 23 percentage points higher than in psilocybin trials. Dropout rates for psilocybin (active treatment: 10 of 186 [5%]; control: 20 of 187 [11%]) and esketamine (active treatment: 43 of 349 [12%]; control: 18 of 224 [8%]) were similar and considerably lower than for SSRIs (active treatment: 866 of 2694 [32%]; control: 467 of 1320 [35%]).Conclusions and relevanceIn this meta-analysis of control treatment outcomes in trials of psilocybin, SSRIs, or esketamine for depression, participants receiving control treatment in psilocybin trials had significantly less improvement in depression ratings than participants receiving control treatment in trials of SSRIs or esketamine. This might indicate that psilocybin's antidepressant efficacy is overestimated compared with that of SSRIs and esketamine.

keywords:
Humans, Ketamine, Hallucinogens, Antidepressive Agents, Treatment Outcome, Randomized Controlled Trials as Topic, Depressive Disorder, Treatment-Resistant, Psilocybin, Selective Serotonin Reuptake Inhibitors, Major Depressive Disorder

topic_tags:
Depression,Receptor Pharmacology,Clinical Trial,Randomized Controlled Trial,Meta-Analysis,Systematic Review,Review Article,Treatment-Resistant Depression

raw_json:
{"europe_pmc_id":"40736734","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Chemical Composition and Biological Activities of Psilocybe Mushrooms: Gaps and Perspectives.
publication_date: 2025-06-30
doi: 10.3390/ph18070989
pubmed_id: 40732278
source_url: https://doi.org/10.3390/ph18070989
substance_tags: psilocybin,psilocin
topic_tags: Review Article,Observational Study
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
authors:
Luz MA, Guedes HVS, Bisneto ABM, Jesus RA, Galdino TP, Oliveira LC, Afonso VI, Fook MVL, Lima AGB, Silva SML, Torres MCM.

abstract:
The Psilocybe genus is known for producing tryptamine alkaloids, specifically the compounds psilocybin and psilocin, which have shown antidepressant and anxiolytic potential. The presence of these alkaloids makes Psilocybe mushrooms promising sources of molecules with potential applications in the treatment of mental disorders. To explore this, a bibliographic study was conducted with the aim of synthesizing published data regarding the biological properties and chemical composition of Psilocybe mushrooms. Searches were performed on indexing platforms, and the articles found were processed using StArt software. These articles were then classified by score and selected based on inclusion and exclusion criteria. This survey yielded a total of 74 articles, and among them, 66 works showed the presence of psilocybin and/or psilocin alkaloids, indicating the psychoactivity of the mushrooms, and 4 works demonstrated the antimicrobial and antioxidant activities of the extract from certain species of the genus. Additionally, 37 chemical compounds were identified across the genus, 23 of which are alkaloids. Data regarding the temporal and chemical stability of these compounds were also observed, which could help optimize the handling of materials that contain indole alkaloids. Therefore, it is evident that species of this genus remain underexplored in terms of chemical diversity; only compounds classified as alkaloids, terpenoids and phenolic compounds were found, and, in total, only 36 compounds in a study range time of 67 years. Furthermore, most studies focused primarily on evaluating the tryptamine alkaloids responsible for the psychoactivity of the mushrooms, without any study focusing on demonstrating the biological activity of isolated compounds against any pathological factor, except for studies relating the whole extract to larvicidal, antimicrobial and antioxidant potential. So, this review provides a general overview of the molecules isolated from the genus and their biological activities and also suggests that researchers working with these mushroom species could focus their efforts on isolating new compounds and evaluating other types of biological activities that can improve the knowledge of mushrooms' alternative applications.

raw_json:
{"europe_pmc_id":"40732278","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelic drugs for the treatment of substance use disorders.
authors: Sofuoglu M, De Aquino JP, MacLean RR
journal: Expert review of clinical pharmacology
publication_date: 2025-06-30
doi: 10.1080/17512433.2025.2541103
pubmed_id: 40726066
source_url: https://pubmed.ncbi.nlm.nih.gov/40726066/
substance_tags: psilocybin
topic_tags: Addiction
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"40726066"}
keywords:
Psychedelic-assisted therapy, addiction, alcohol use disorder, ketamine, opioid use disorder, psilocybin


authors: Stirn J, Klein CD.
publication_date: 2025-06-30
doi: 10.1002/ardp.70022
pubmed_id: 40702794
source_url: https://doi.org/10.1002/ardp.70022
substance_tags: psilocybin,psilocin
topic_tags: Headache / Migraine,Epigenetics,In Vitro Study
study_type: In Vitro Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Efficient Acyloxymethylation of Psilocin and Other Tryptamines Yielding ACOM Prodrugs for Psychedelic-Assisted Therapy.

abstract:
Acyloxymethyl (ACOM) derivatives of tryptamines such as the psychedelic drug psilocin and the anti-migraine drug sumatriptan bear potential as prodrugs. Previous synthetic approaches suffer from insufficient chemoselectivity between the desired functionalization of the phenolic (psilocin) or sulfonamide (sumatriptan) groups versus other reactive groups in the parent drugs. We report a novel synthetic route toward ACOM prodrugs of tryptamines via the chemoselective installation of a carbamate protecting group at the indole nitrogen by means of a Heller-Sarpong reagent and final deprotection under extremely mild conditions. This enables delicate transformations such as the O-acyloxymethylation of psilocin or the N2-acyloxymethylation of sumatriptan. Several novel O-ACOM ethers of hydroxytryptamines were obtained and evaluated in vitro for their potential as novel prodrugs for psychedelic therapy. The rate of bioactivation in human plasma may be adjusted to rapid (t1/2 240 min) kinetics by varying the acyl residue in the ACOM promoiety. Irrespective of the acyl residue, short half-lives in human saliva will likely preclude the sublingual or buccal application of ACOM ether prodrugs of hydroxytryptamines, while other routes such as peroral, transdermal, nasal, or intravenous administration may be pursued.

keywords:
Humans, Sumatriptan, Tryptamines, Carbamates, Indoles, Prodrugs, Drug Administration Routes, Molecular Structure, Psilocybin

raw_json:
{"europe_pmc_id":"40702794","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: What fMRI studies say about the nature of the psychedelic effect: a scoping review.
authors: Beneš M, Páleníček T, Horáček J.
publication_date: 2025-06-30
doi: 10.3389/fnins.2025.1606798
pubmed_id: 40666257
source_url: https://doi.org/10.3389/fnins.2025.1606798
substance_tags: psilocybin
topic_tags: Brain Imaging,Mechanism of Action,Default Mode Network,Biomarkers,Aging,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
Research on psychedelic drugs, such as psilocybin, LSD or DMT, is a burgeoning field, with an increasing number of studies showing their promise in treatment of mental disorders as well as examining their mechanism of action. Determining their effect on the brain is crucial from clinical standpoint, but also offers highly promising avenues of advancement in basic neuroscience-functional magnetic resonance imaging (fMRI) is one of the most useful techniques to do so, with a number of newly published studies increasing every year. Here we present a scoping review of existing fMRI studies of serotonergic psychedelics to date, with a focus on finding unifying themes among them, in order to comprehensively grasp current directions within this field. We cluster the existing studies by fMRI modality and find several lines of developing concepts complementing the established models of psychedelic actions on the brain: namely, we describe a general picture of de-differentiation with the default mode network at its core captured by a diverse array of different techniques, complex changes to the thalamus, amygdala and medial temporal lobe structures, and the importance of the phenomenon of ego dissolution. Finally, contrasts to phenomenologically similar states and the successful process of anchoring fMRI findings to other markers are discussed.

raw_json:
{"europe_pmc_id":"40666257","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-06-30
doi: 10.1002/brb3.70660
pubmed_id: 40619953
source_url: https://doi.org/10.1002/brb3.70660
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Wellbeing,Observational Study,Veterans,Safety
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
title:
Exploring the Therapeutic Effects of Psychedelics Administered to Military Veterans in Naturalistic Retreat Settings.

authors:
Calnan M, Blest-Hopley G, Busch C, Adams M, Ruffell SGD, Piper T, Roseman L, Kettner H, Carhart-Harris R.

abstract:
BackgroundMilitary veterans are at risk of various mental health conditions, with profound implications for post-deployment quality of life. Current treatment options encounter high dropout rates and non-responsiveness, and overlook the importance of community building in veterans' holistic recovery. Preliminary research suggests psychedelics offer therapeutic benefits for depression and post-traumatic stress disorder (PTSD) in veterans. Integrating psychedelic therapies with a communal retreat setting could provide a more holistic framework for improving veterans' well-being.ObjectivesTo evaluate the effects of psychedelic retreats on mental health and community reintegration in veterans.MethodsFifty-eight veterans attended psilocybin or ayahuasca retreats. Participants completed eight mental health questionnaires (e.g. PTSD Checklist, PCL-5; Patient Health Questionnaire, PHQ-9), and the Military to Civilian Questionnaire (M2C-Q) up to 4 weeks both pre- and post-retreat. Paired t-tests analyzed changes in outcome responses between time points, and gender and substance-specific analysis was conducted. Baseline scores were correlated with improvements in PCL-5 and PHQ-9 to investigate the relationship between initial symptom severity and percentage improvement following the retreat.ResultsSignificant improvements were found for all eight outcomes post-retreat, with the greatest percentage improvements found for depression (PHQ-9; 29.1%) and PTSD (PCL-5; 26.1%). Veterans attending psilocybin retreats showed greater improvements in seven out of eight outcomes, whereas ayahuasca retreats demonstrated greater improvements in PCL-5 scores for PTSD (ayahuasca: 26.4%; Psilocybin 24.8%). Male participants experienced greater improvements across all outcomes apart from the PCL-5 for PTSD (Male: 24.1%; Female: 32.1%). Higher baseline scores on the PCL-5 (PTSD) and PHQ-9 (depression), indicating worse initial mental health, correlated with greater outcome improvements.ConclusionsThis is the first study to investigate psychedelic retreats as a holistic therapy for veterans' mental health alongside community reintegration. Psilocybin and ayahuasca retreats significantly improved veterans' mental well-being, quality of life, PTSD, anxiety, depression, sleep, concussion, and post-deployment reintegration. Participants with more severe symptoms have the potential to benefit most from this intervention, with nuanced insight into improved outcomes based on gender and type of substance. Psychedelic retreats could provide a treatment framework to aid veterans' recovery by addressing psychological well-being, communal factors, and reintegration into civilian life.

keywords:
Humans, Banisteriopsis, Hallucinogens, Treatment Outcome, Depression, Stress Disorders, Post-Traumatic, Quality of Life, Adult, Middle Aged, Veterans, Female, Male, Surveys and Questionnaires, Psilocybin

raw_json:
{"europe_pmc_id":"40619953","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Wu Y, Ran J, Mo J, Wang J.
publication_date: 2025-06-30
doi: 10.1111/adb.70063
pubmed_id: 40590377
source_url: https://doi.org/10.1111/adb.70063
substance_tags: psilocin
topic_tags: Mechanism of Action,Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
title:
4-HIAA Blocks Methamphetamine-Induced Conditioned Place Preference in Mice Through Modulation of the 5-HT Pathway in the Nucleus Accumbens.

abstract:
4-hydroxyindole-3-acetic acid (4-HIAA) is a metabolite of psilocin. Here, we explored the ability of 4-HIAA to cross the blood-brain barrier and its potential effects on methamphetamine (METH)-induced conditioned place preference (CPP) in mice. Treatment with 1-mg/kg 4-HIAA inhibited CPP formation during the acquisition phase, promoted METH extinction and inhibited METH relapse. Furthermore, the regulatory effect of 4-HIAA on METH was underscored by altered 5-HT expression in the nucleus accumbens. Collectively, our findings provide novel insights into the molecular mechanisms of the 4-HIAA-induced blockade of the acquisition, extinction and reinstatement of METH-induced CPP.

keywords:
Nucleus Accumbens, Animals, Mice, Inbred C57BL, Mice, Serotonin, Methamphetamine, Hydroxyindoleacetic Acid, Central Nervous System Stimulants, Male, Extinction, Psychological, Conditioning, Psychological

raw_json:
{"europe_pmc_id":"40590377","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Harding R, Singer N, Wall MB, Hendler T, Erritzoe D, Nutt D, Carhart-Harris R, Roseman L.
publication_date: 2025-06-30
doi: 10.1038/s41380-025-03066-1
pubmed_id: 40481249
source_url: https://doi.org/10.1038/s41380-025-03066-1
substance_tags: psilocybin
topic_tags: Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Correction: Dissociable effects of psilocybin and escitalopram for depression on processing of musical surprises.

raw_json:
{"europe_pmc_id":"40481249","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: 5-HT2A receptors: Pharmacology and functional selectivity.
authors: Cummins BR, Billac GB, Nichols DE, Nichols CD.
publication_date: 2025-04-22
doi: 10.1016/j.pharmr.2025.100059
pubmed_id: 40418878
source_url: https://doi.org/10.1016/j.pharmr.2025.100059
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
abstract:
Serotonin 5-HT2A receptors were one of the first serotonin receptors to be pharmacologically characterized. In mammals, they are expressed throughout the body in nearly every cell and tissue type, with the highest density in cortical layer V of the brain. They are involved in several aspects of normal physiological processes and behaviors and have been implicated in the etiology of neuropsychiatric diseases such as schizophrenia. Atypical antipsychotics have targeted blockade of 5-HT2A receptors as part of their therapeutic mechanism. More recently, 5-HT2A receptors have come to prominence for their role as the primary target for psychedelic drugs, which activate this receptor subtype to produce their characteristic behavioral effects. 5-HT2A receptor agonists like psilocybin, dimethyltryptamine, and lysergic acid diethylamide have each demonstrated long-lasting therapeutic efficacy in clinical trials for psychiatric disorders such as major depression and substance use disorders. There is a significant effort in both academia and industry to develop new agonists of 5-HT2A receptors with therapeutic efficacy. There are 3 primary scaffolds for agonists: tryptamines, ergolines, and phenylalkylamines, each engaging different subsets of amino acid residues in the receptor binding pocket. Differences can lead to differential responses between ligands for functionally selective outcomes. Here, we provide a historical perspective on 5-HT2A receptors, their key structural features and motifs involved in ligand-receptor interactions, and how these interactions can affect signaling pathways downstream of the receptor. Understanding how ligands interact with the 5-HT2A receptor will fundamentally inform future drug discovery to optimize therapeutics for a variety of disorders. SIGNIFICANCE STATEMENT: Psychedelic drugs have demonstrated long-lasting therapeutic efficacy for several conditions in multiple clinical trials. Their target, serotonin 5-HT2A receptors, are GPCRs with complex pharmacology. Having knowledge of how ligands interact with 5-HT2A receptors in the orthosteric binding pocket at the structural level to induce specific signal transduction pathways will inform on efforts to design and develop functionally selective drugs to potentially treat a variety of diseases.

keywords:
Animals, Humans, Receptor, Serotonin, 5-HT2A, Hallucinogens, Mental Disorders, Serotonin 5-HT2 Receptor Agonists, Serotonin 5-HT2 Receptor Antagonists

topic_tags:
Depression,Addiction,Pharmacology,Mechanism of Action,Receptor Pharmacology,Aging,Clinical Trial,Drug Interactions

raw_json:
{"europe_pmc_id":"40418878","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-06-30
doi: 10.1093/jat/bkaf045
pubmed_id: 40418247
source_url: https://doi.org/10.1093/jat/bkaf045
substance_tags: psilocybin,psilocin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Development and validation of an analytical method for the determination of select 4-position ring-substituted tryptamines in plasma by liquid chromatography-tandem mass spectrometry.

authors:
Pego AMF, Schoffner M, Sammeta VR, Naeem M, Manke DR, Chadeayne A, Glatfelter GC, Baumann MH, Concheiro-Guisán M.

abstract:
4-Phosporyloxy-N, N-dimethyltryptamine (psilocybin) is a psychedelic tryptamine found in certain mushroom species that has shown efficacy in the treatment of various psychiatric disorders. In conjunction with the renewed interest in therapeutic effects of psychedelics, there has been an increase in psilocybin-like designer tryptamines appearing in non-medical drug markets. The present study aimed to develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for detecting and quantifying 4-position ring-substituted tryptamines and their 4-hydroxy metabolites in plasma. Specifically, we investigated 4-phosphoryloxy-N, N-dimethyltryptamine (psilocybin), 4-acetoxy-N, N-dimethyltryptamine (psilacetin), 4-propionoxy-N, N-dimethyltryptamine (4-Pro-DMT) and their shared metabolite 4-hydroxy-N, N-dimethyltryptamine (psilocin), along with 4-methyl carbonato-N, N-di-n-propyltryptamine (4-MeCO3-DPT) and its metabolite 4-hydroxy-N, N-di-n-propyltryptamine (4-HO-DPT). Mass spectrometry analysis employed electrospray ionization (ESI) in positive mode, with two multiple reaction monitoring (MRM) transitions per analyte. Plasma samples were acidified with ascorbic acid, followed by protein precipitation with acetonitrile. Linearity was achieved across a concentration range of 0.5-100 ng/mL for all analytes, except psilocybin, which displayed linearity from 5 to 100 ng/mL. Validation results demonstrated acceptable bias (±20%) and imprecision (

keywords:
Animals, Rats, Tryptamines, Hallucinogens, Chromatography, Liquid, Reproducibility of Results, Substance Abuse Detection, Male, Tandem Mass Spectrometry, Limit of Detection, Psilocybin

raw_json:
{"europe_pmc_id":"40418247","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin and Obsessive-Compulsive Disorder: Exploring New Therapeutic Horizons.
authors: Yang L, Li H, Wang X, Wang X.
publication_date: 2025-05-13
doi: 10.1007/s12264-025-01415-2
pubmed_id: 40366622
source_url: https://doi.org/10.1007/s12264-025-01415-2
substance_tags: psilocybin
topic_tags: OCD
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
raw_json:
{"europe_pmc_id":"40366622","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Non-hallucinogenic psychedelics for mood and anxiety disorders: A systematic review.
publication_date: 2025-05-07
doi: 10.1016/j.psychres.2025.116532
pubmed_id: 40354769
source_url: https://doi.org/10.1016/j.psychres.2025.116532
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Consciousness,Clinical Trial,Systematic Review,Review Article,Case Report
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
authors:
Chen MJQ, Chen-Li D, Chisamore N, Husain MI, Di Vincenzo JD, Mansur RB, Phan L, Johnson D, McIntyre RS, Rosenblat JD.

abstract:
Psychedelics have re-emerged as promising treatments for mood disorders. The current model provides a moderate-to-high dose of a psychedelic agent (e.g., psilocybin) to reliably induce an altered state of consciousness. Unfortunately, the hallucinatory effects limit the treatment's potential scalability given patients' vulnerability and extensive monitoring costs, leading to growing interest in non-hallucinatory psychedelics (NHPs). This review's objective was to identify, summarize and synthesize all published pre-clinical and clinical studies evaluating NHPs for mood and anxiety disorders. We included five animal studies demonstrating antidepressant-like effects through assessments like forced swim test (FST) and open field test (OFT) without observing head-twitch response (HTR), and one case report that identified a patient who inadvertently combined trazodone and psilocybin and experienced potent antidepressant effects without psychedelic effects. These preliminary findings provide a strong impetus for further investigation in human samples with rigorously designed clinical trials that may delineate the potential antidepressant effects of psychedelics without hallucinatory effects.

keywords:
Animals, Humans, Hallucinogens, Antidepressive Agents, Anxiety Disorders, Mood Disorders, Psilocybin

raw_json:
{"europe_pmc_id":"40354769","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Syed OA, Petranker R, Tsang B.
publication_date: 2025-05-08
doi: 10.1016/j.neubiorev.2025.106204
pubmed_id: 40348309
source_url: https://doi.org/10.1016/j.neubiorev.2025.106204
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,OCD,Microdosing,Wellbeing,Review Article,Animal Study,Safety
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
The effect of psychedelic microdosing on animal behavior: A review with recommendations for the field.

abstract:
Microdosing, the repeated use of psychedelic substances at low doses, is growing in popularity among recreational consumers. While this practice is associated with many benefits to mood, well-being and health, research in this area is in its early stages and predominantly centered on human applications. In this narrative review, we synthesize the findings from studies investigating the effects of microdosing on the behaviors of three animal species: rats, mice, and zebrafish. A total of 12 studies were identified that implemented a microdosing regimen of LSD, psilocybin, or DMT in these animal models. Overall, microdosing caused little changes in behaviors associated with anxiety- and depressive-like states. Moreover, while microdosing was well-tolerated across species, further research is needed to capture specific safety concerns. Finally, we critically appraise the studies included in this review based on their methodologies and discuss further avenues of research to advance the preclinical literature on psychedelic microdosing. Specifically, we recommend that future research prioritize the replication of existing findings to inform the development of robust study designs and dosing protocols, as well as establish standardized methodologies to enable effective comparisons across different animal models. Furthermore, future investigations should explore the therapeutic potential of mescaline microdosing, examine sex-dependent effects, and extend research to additional models of psychiatric conditions, including those related to obsessive-compulsive disorder and post-traumatic stress disorder.

keywords:
Animals, Mice, Rats, N,N-Dimethyltryptamine, Lysergic Acid Diethylamide, Hallucinogens, Behavior, Animal, Psilocybin

raw_json:
{"europe_pmc_id":"40348309","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Harding R, Singer N, Wall MB, Hendler T, Erritzoe D, Nutt D, Carhart-Harris R, Roseman L.
publication_date: 2025-04-25
doi: 10.1038/s41380-025-03035-8
pubmed_id: 40281226
source_url: https://doi.org/10.1038/s41380-025-03035-8
substance_tags: psilocybin
topic_tags: Depression,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Aging,Emotional Processing
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Dissociable effects of psilocybin and escitalopram for depression on processing of musical surprises.

abstract:
Psilocybin therapy (PT) is emerging as an effective intervention for Major Depressive Disorder (MDD), offering comparable efficacy to conventional treatments like selective serotonin reuptake inhibitors (SSRIs). Music, an emotionally evocative stimulus, provides a valuable tool to explore changes in hedonic and predictive processing mechanisms via expectancy violations, or 'surprises'. This study sought to compare behavioural and functional magnetic resonance imaging (fMRI) responses to musical surprises in MDD patients treated with either PT or the SSRI, escitalopram. In this secondary analysis of a trial, 41 MDD patients (with usable fMRI data) were randomly assigned to either PT (n = 22) or escitalopram (n = 19) treatment groups. Participants listened to music during fMRI and tracked their emotional experience, both before and after a 6-week intervention. Surprise-related valence and arousal indices were calculated. Musical surprises were entered as regressors for whole-brain and region of interest fMRI analyses. PT caused a greater decrease in anhedonia scores compared with escitalopram. While escitalopram led to reductions in surprise-related affective responses, PT showed no significant change. Escitalopram was associated with increased activation in memory and emotional processing areas during musical surprises (versus control events) when compared with PT. Following PT, there was decreased activation in the ventromedial prefrontal cortex and angular gyrus, and greater activation in sensory regions. PT may allow for the subjective response to musical surprises to be maintained through a lasting reduction in the salience of prediction errors, or, alternatively, by increasing hedonic priors. Contrastingly, escitalopram may diminish hedonic priors, highlighting fundamental differences in treatment mechanisms.

keywords:
Brain, Humans, Citalopram, Magnetic Resonance Imaging, Emotions, Auditory Perception, Music, Adult, Middle Aged, Female, Male, Psilocybin, Escitalopram, Selective Serotonin Reuptake Inhibitors, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"40281226","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The Rise of Psilocybin Use in the United States: A Multisource Observational Study.
publication_date: 2025-04-21
doi: 10.7326/annals-24-03145
pubmed_id: 40258279
source_url: https://doi.org/10.7326/annals-24-03145
substance_tags: psilocybin
topic_tags: Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
authors:
Rockhill KM, Black JC, Ladka MS, Sumbundu KB, Olsen HA, Jewell JS, Hunt J, Wolf RC, Nerurkar K, Dart RC, Monte AA.

raw_json:
{"europe_pmc_id":"40258279","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Swieczkowski D, Kwaśny A, Pruc M, Gaca Z, Szarpak L, Cubała WJ.
publication_date: 2025-04-16
doi: 10.1055/a-2529-7029
pubmed_id: 40245934
source_url: https://doi.org/10.1055/a-2529-7029
substance_tags: psilocybin,psilocin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Regulatory Alignment of Psilocybin Clinical Trials in Major Depressive Disorder on ClinicalTrials.gov: A Cross-Sectional Analysis.

abstract:
Regulatory compliance is crucial in the clinical development of psychedelic substances, including psilocybin. This study aimed to examine the alignment of clinical trial protocols for psilocybin in the treatment of major depressive disorder (MDD) and treatment-resistant depression (TRD) with established regulatory requirements.A cross-sectional investigation was conducted on ClinicalTrials.gov using the keywords: "Psilocybin" and "Psilocin" to identify interventional studies with posted trial protocols. Only protocols for MDD and TRD were included. Data extraction focused on key regulatory aspects, including safety, functional unblinding, expectancy bias, and the distribution of investigational medical products.Eleven psilocybin trial protocols were identified, with four meeting the inclusion criteria. The most commonly studied psilocybin dose was 25 mg. Two trials were double-blind. Although the analyzed protocols superficially adhered to regulatory requirements, there were gaps in addressing potential drug interactions, the acute and chronic concurrent use of antidepressants, and prohibited medications. Certain aspects, such as functional unblinding or expectancy bias, did not share all pathways. Risk mitigation strategies were primarily based on external criteria. Patients with bipolar spectrum disorders or schizoaffective disorders were excluded.This study underscores the importance of conducting clinical trials on psychedelics in strict adherence to regulatory standards. Future research should focus on improving regulatory compliance and exploring the efficacy of psychedelics in broader patient populations.

keywords:
Humans, Hallucinogens, Cross-Sectional Studies, Clinical Trials as Topic, Depressive Disorder, Treatment-Resistant, Psilocybin, Major Depressive Disorder

topic_tags:
Depression,Mechanism of Action,Clinical Trial,Treatment-Resistant Depression,Safety,Drug Interactions

raw_json:
{"europe_pmc_id":"40245934","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin therapy for mood dysfunction in Parkinson's disease: an open-label pilot trial.
publication_date: 2025-04-08
doi: 10.1038/s41386-025-02097-0
pubmed_id: 40205013
source_url: https://doi.org/10.1038/s41386-025-02097-0
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Safety,Adverse Events
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
authors:
Bradley ER, Sakai K, Fernandes-Osterhold G, Szigeti B, Ludwig C, Ostrem JL, Tanner CM, Bock MA, Llerena K, Finley PR, O'Donovan A, Zuzuarregui JRP, Busby Z, McKernan A, Penn AD, Wang ACC, Rosen RC, Woolley JD.

abstract:
Mood dysfunction is highly prevalent in Parkinson's disease (PD), a main predictor of functional decline, and difficult to treat-novel interventions are critically needed. Psilocybin shows early promise for treating depression and anxiety, but its potential in PD is unknown, as safety concerns have excluded people with neurodegenerative disease from previous trials. In this open-label pilot (NCT04932434), we examined the feasibility of psilocybin therapy among people with mild to moderate stage PD plus depression and/or anxiety. 12 participants (mean age 63.2 ± 8.2 years, 5 women) received psilocybin (one 10 mg followed by one 25 mg dose) with psychotherapy. There were no serious adverse events, no medical interventions required to manage effects of psilocybin, and no exacerbation of psychosis. Ten participants experienced treatment-emergent adverse events; the most frequent were anxiety, nausea, and increased blood pressure. We observed no worsening of PD symptomology measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). On the contrary, non-motor (MDS-UPDRS Part I: -13.8 ± 1.3, p

keywords:
Humans, Parkinson Disease, Hallucinogens, Treatment Outcome, Pilot Projects, Depression, Anxiety, Mood Disorders, Aged, Middle Aged, Female, Male, Psilocybin

raw_json:
{"europe_pmc_id":"40205013","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Exploring serotonergic psychedelics as a treatment for personality disorders.
journal: Neuropharmacology
publication_date: 2025-06-30
doi: 10.1016/j.neuropharm.2025.110413
pubmed_id: 40081794
source_url: https://pubmed.ncbi.nlm.nih.gov/40081794/
substance_tags: psilocybin
topic_tags: Pharmacology,Mechanism of Action,Personality Change,Review Article,Observational Study,Safety
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"40081794"}
authors:
Carrithers BM, Roberts DE, Weiss BM, King JD, Carhart-Harris RL, Gordon AR, Pagni BA, Moreau M, Ross S, Zeifman RJ

abstract:
Both psychotherapeutic interventions and pharmacological agents have demonstrated limited efficacy in the treatment of personality disorders (PDs). Emerging evidence suggests that psychedelic therapy, already showing promise in treating various psychiatric conditions commonly comorbid with PDs, may exert therapeutic effects by promoting adaptive changes in personality. Thus, psychedelic therapy could hold potential for addressing core features of PDs through shared mechanisms of personality modulation. Although historical literature and observational studies suggest the potential clinical utility of psychedelics in treating PDs, rigorous research is lacking, and individuals with PDs are often excluded from modern psychedelic therapy trials. In the present review, we first discuss research on the effects of psychedelics in individuals with a PD through the conventional lens of the Diagnostic and Statistical Manual of Mental Disorders (5th ed., text rev.; DSM-5-TR) categorical model. Next, using the dimensional DSM Alternative Model of Personality Disorders (DSM-AMPD) as a framework, we examine how psychedelics may affect self-functioning, interpersonal functioning, and pathological personality traits. We conclude by discussing the clinical relevance of psychedelic therapy as a treatment for personality pathology, including safety considerations, gaps and limitations, and recommendations for approaching psychedelic therapy within these more complex clinical populations.

keywords:
Personality disorders, Personality traits, Psilocybin-assisted therapy, Psychedelics, Psychopharmacology, Psychotherapy


publication_date: 2025-02-25
doi: 10.1177/0271678x251323364
pubmed_id: 40007438
source_url: https://doi.org/10.1177/0271678x251323364
substance_tags: psilocybin,psilocin
topic_tags: Depression,Brain Imaging,Receptor Pharmacology,Aging,Healthy Volunteers
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Acute psilocybin and ketanserin effects on cerebral blood flow: 5-HT2AR neuromodulation in healthy humans.

authors:
Larsen K, Lindberg U, Ozenne B, McCulloch DE, Armand S, Madsen MK, Johansen A, Stenbæk DS, Knudsen GM, Fisher PM.

abstract:
Psilocin, the active metabolite of psilocybin, is a psychedelic and agonist at the serotonin 2A receptor (5-HT2AR) that has shown positive therapeutic effects for brain disorders such as depression. To elucidate the brain effects of psilocybin, we directly compared the acute effects of 5-HT2AR agonist (psilocybin) and antagonist (ketanserin) on cerebral blood flow (CBF) using pseudo-continuous arterial spin labeling magnetic resonance imaging (MRI) in a single-blind, cross-over study in 28 healthy participants. We evaluated associations between plasma psilocin level (PPL) or subjective drug intensity (SDI) and CBF. We also evaluated drug effects on internal carotid artery (ICA) diameter using time-of-flight MRI angiography. PPL and SDI were significantly negatively associated with regional and global CBF (∼11.6% at peak drug effect, p

keywords:
Carotid Artery, Internal, Humans, Ketanserin, Receptor, Serotonin, 5-HT2A, Hallucinogens, Magnetic Resonance Imaging, Cross-Over Studies, Single-Blind Method, Cerebrovascular Circulation, Adult, Female, Male, Young Adult, Serotonin 5-HT2 Receptor Agonists, Serotonin 5-HT2 Receptor Antagonists, Psilocybin

raw_json:
{"europe_pmc_id":"40007438","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelic Therapeutics for Adolescents: Ethics, Safety, Opportunities, and Equipoise.
authors: Croarkin PE, Sutherland I, Ho MF.
publication_date: 2024-12-18
doi: 10.1016/j.jaac.2024.12.003
pubmed_id: 39709009
source_url: https://doi.org/10.1016/j.jaac.2024.12.003
substance_tags: psilocybin
topic_tags: Adolescents,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
We read with great interest the commentary by Jeffrey et al. entitled "Clinical Research Trials of Psychedelic-Assisted Therapy in Adolescents Aged 16 to 17 Years: Rationale Balanced With Caution."1 We appreciate the efforts of the authors, the scholarship of this commentary, and the advocacy for research initiatives with psychedelic therapeutics such as psilocybin, lysergic acid diethylamide, and 3,4-methylenedioxymethamphetamine. We agree that there is a compelling rationale for timely, rigorous studies with adolescents as it is likely that these compounds have been and will be used in adolescents with therapeutic intent. We are writing to catalyze further collegial dialogue and advocacy in our field. We do have some considerations for the authors.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Lysergic Acid Diethylamide, Hallucinogens, Adolescent, Psilocybin

raw_json:
{"europe_pmc_id":"39709009","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-07-03
doi: 10.1007/s00213-024-06644-3
pubmed_id: 38963553
source_url: https://doi.org/10.1007/s00213-024-06644-3
substance_tags: psilocybin
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:05
title:
Unraveling psilocybin's therapeutic potential: behavioral and neuroplasticity insights in Wistar-Kyoto and Wistar male rat models of treatment-resistant depression.

authors:
Kolasa M, Nikiforuk A, Korlatowicz A, Solich J, Potasiewicz A, Dziedzicka-Wasylewska M, Bugno R, Hogendorf A, Bojarski A, Faron-Górecka A.

abstract:
RationaleOur study aimed to unravel the unknown mechanisms behind the exceptional efficacy of Psilocybin (PSI) in treating treatment-resistant depression (TRD). Focusing on Wistar-Kyoto (WKY) rats with a TRD phenotype and Wistar (WIS) rats as a normative comparison, we investigated behavioral and neuroplasticity-related responses to PSI, striving to shed light on the distinctive features of its antidepressant effects.ObjectivesWe set out to assess the behavioral impact of acute and prolonged PSI administration on WKY and WIS rats, employing Novel Object Recognition (NORT), Social Interaction (SI), and Forced Swimming Test (FST). Our secondary objectives involved exploring strain-specific alterations in neuroplasticity-related parameters, including brain-derived neurotrophic factor (BDNF) and activity-regulated cytoskeleton-associated protein (Arc).MethodsConducting post-acute and extended assessments after a single PSI administration, we applied behavioral tests and biochemical analyses to measure serum BDNF levels and neuroplasticity-related parameters in the prefrontal cortex. Statistical analyses were deployed to discern significant differences between the rat strains and assess the impact of PSI on behavioral and biochemical outcomes.ResultsOur findings uncovered significant behavioral disparities between WKY and WIS rats, indicating passive behavior and social withdrawal in the former. PSI demonstrated pronounced pro-social and antidepressant effects in both strains, each with its distinctive temporal trajectory. Notably, we identified strain-specific variations in BDNF-related signaling and observed the modulation of Arc expression in WKY rats.ConclusionsOur study delineated mood-related behavioral nuances between WKY and WIS rat strains, underscoring the antidepressant and pro-social properties of PSI in both groups. The distinct temporal patterns of observed changes and the identified strain-specific neuroplasticity alterations provide valuable insights into the TRD phenotype and the mechanisms underpinning the efficacy of PSI.

keywords:
Prefrontal Cortex, Animals, Rats, Inbred WKY, Rats, Rats, Wistar, Disease Models, Animal, Brain-Derived Neurotrophic Factor, Cytoskeletal Proteins, Nerve Tissue Proteins, Antidepressive Agents, Behavior, Animal, Species Specificity, Neuronal Plasticity, Male, Depressive Disorder, Treatment-Resistant, Psilocybin

topic_tags:
Depression,Neuroplasticity,Mechanism of Action,Animal Study,Treatment-Resistant Depression,Drug Interactions

raw_json:
{"europe_pmc_id":"38963553","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Barnett BS, Koons CJ, Van den Eynde V, Gillman PK, Bodkin JA.
publication_date: 2024-06-20
doi: 10.1080/02791072.2024.2368617
pubmed_id: 38903003
source_url: https://doi.org/10.1080/02791072.2024.2368617
substance_tags: psilocybin
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Hypertensive Emergency Secondary to Combining Psilocybin Mushrooms, Extended Release Dextroamphetamine-Amphetamine, and Tranylcypromine.

abstract:
Data on medication interactions with psychedelics are limited. Here we present what may be the first published report of a hypertensive emergency following the combination of psilocybin mushrooms with a monoamine oxidase inhibitor (MAOI). A42-year-old man with treatment-resistant major depressive disorder took 1 g of Psilocybe cubensis mushrooms, while prescribed tranylcypromine, extended-release dextroamphetamine-amphetamine, and other medications. Approximately half an hour later, he developed severe hypertension with chest pain, palpitations, and headache. Upon hospital presentation, the electrocardiogram demonstrated ST-elevation. The patient was diagnosed with a myocardial infarction and treated with lorazepam, nitroglycerin, and aspirin. He subsequently underwent emergency cardiac catheterization, which revealed no significant cardiac abnormalities. Following overnight hospitalization, he was discharged home with no lasting physical sequelae. Though data are few, past studies suggest that classic serotonergic psychedelics (5HT-2A receptor agonists) such as dimethyltryptamine (DMT), lysergic acid (LSD), and synthetic psilocybin should not produce hypertensive emergency when combined with MAOIs. We suspect phenylethylamine, found in Psilocybe cubensis and other species of psilocybin mushrooms, interacted with tranylcypromine and dextroamphetamine-amphetamine to produce this hypertensive emergency. Patients prescribed MAOIs should be warned of the potential for hypertensive emergency when consuming psilocybin mushrooms, particularly when also prescribed norepinephrine releasers such as dextroamphetamine-amphetamine.

keywords:
Humans, Hypertension, Dextroamphetamine, Tranylcypromine, Hallucinogens, Delayed-Action Preparations, Drug Combinations, Monoamine Oxidase Inhibitors, Drug Interactions, Adult, Male, Psilocybe, Depressive Disorder, Treatment-Resistant, Psilocybin, Hypertensive Crisis, Major Depressive Disorder

topic_tags:
Depression,Chronic Pain,Headache / Migraine,Receptor Pharmacology,Randomized Controlled Trial,Drug Interactions

raw_json:
{"europe_pmc_id":"38903003","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Atiq MA, Baker MR, Voort JLV, Vargas MV, Choi DS
journal: Psychopharmacology
publication_date: 2025-06-30
doi: 10.1007/s00213-024-06599-5
pubmed_id: 38743110
source_url: https://pubmed.ncbi.nlm.nih.gov/38743110/
substance_tags: psilocybin
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"38743110"}
title:
Disentangling the acute subjective effects of classic psychedelics from their enduring therapeutic properties.

abstract:
Recent research with classic psychedelics suggests significant therapeutic potential, particularly for neuropsychiatric disorders. A mediating influence behind symptom resolution is thought to be the personal insight - at times, bordering on the mystical - one acquires during the acute phase of a psychedelic session. Indeed, current clinical trials have found strong correlations between the acute subjective effects (ASE) under the influence of psychedelics and their enduring therapeutic properties. However, with potential barriers to widespread clinical implementation, including the healthcare resource-intensive nature of psychedelic sessions and the exclusion of certain at-risk patient groups, there is an active search to determine whether ASE elimination can be accompanied by the retention of persisting therapeutic benefits of these class of compounds. Recognizing the aberrant underlying neural circuitry that characterizes a range of neuropsychiatric disorders, and that classic psychedelics promote neuroplastic changes that may correct abnormal circuitry, investigators are rushing to design and discover compounds with psychoplastogenic, but not hallucinogenic (i.e., ASE), therapeutic potential. These efforts have paved the discovery of 'non-psychedelic/subjective psychedelics', or compounds that lack hallucinogenic activity but with therapeutic efficacy in preclinical models. This review aims to distill the current evidence - both clinical and preclinical - surrounding the question: can the ASE of classic psychedelics be dissociated from their sustained therapeutic properties? Several plausible clinical scenarios are then proposed to offer clarity on and potentially answer this question.

keywords:
5-HT2A, Acute subjective effects, Addiction, Classic psychedelics, Major depressive disorder, Neuropsychiatry, Psilocybin, Psychedelics, Substance use disorder

topic_tags:
Depression,Addiction,Receptor Pharmacology,Mystical Experience,Clinical Trial,Review Article,Animal Study,Safety


authors: Nayak SM, White SH, Hilbert SN, Lowe MX, Jackson H, Griffiths RR, Garcia-Romeu A, Yaden DB.
publication_date: 2024-05-06
doi: 10.1080/02791072.2024.2346130
pubmed_id: 38715376
source_url: https://doi.org/10.1080/02791072.2024.2346130
substance_tags: psilocybin
topic_tags: Adolescents
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Psychedelic Experiences Increase Mind Perception but do not Change Atheist-Believer Status: A Prospective Longitudinal Study.

abstract:
Recent studies suggest psychedelic use may be associated with changes in a variety of beliefs or belief-like states, including increased 1) mind perception, 2) non-naturalistic beliefs, and 3) Atheist-Believer status (e.g. believer, agnostic, or nonbeliever). We conducted a prospective longitudinal study among participants (N = 657) who planned to have a psilocybin experience outside a laboratory setting. We asked participants about their beliefs concerning mind perception of various entities, specific metaphysical positions, and Atheist-Believer status both before (and after their experience. Replicating previous findings, we observed increases in mind perception across a variety of living and non-living targets (e.g. plants, rocks). However, we found little to no change in metaphysical beliefs (e.g. dualism) or Atheist-Believer status. Taken together, these findings contrast with those from cross-sectional studies that psilocybin experiences result in changes to Atheist-Believer status and non-naturalistic beliefs but support the relevance of mind perception and mentalization.

keywords:
Humans, Hallucinogens, Longitudinal Studies, Prospective Studies, Perception, Adolescent, Adult, Middle Aged, Female, Male, Young Adult, Psilocybin

raw_json:
{"europe_pmc_id":"38715376","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Rahbarnia A, Li Z, Fletcher PJ.
publication_date: 2023-10-18
doi: 10.1007/s00213-023-06474-9
pubmed_id: 37855864
source_url: https://doi.org/10.1007/s00213-023-06474-9
substance_tags: psilocybin
topic_tags: Depression,Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
title:
Effects of psilocybin, the 5-HT2A receptor agonist TCB-2, and the 5-HT2A receptor antagonist M100907 on visual attention in male mice in the continuous performance test.

abstract:
RationaleNeuropsychiatric disorders such as depression are characterized in part by attention deficits. Attention is modulated by the serotonin (5-HT) neurotransmitter system. The 5-HT2A agonist and hallucinogen psilocybin (PSI) is a promising treatment for disorders characterized by attention changes. However, few studies have investigated PSI's direct effect on attention.ObjectiveUsing the rodent continuous performance task (CPT), we assessed PSI's effect on attention. We also evaluated the impact of 5-HT2A receptor agonist TCB-2 and antagonist M100907 for comparative purposes.MethodsIn the CPT, mice learned to distinguish visual targets from non-targets for milkshake reward. Performance was then tested following injections of PSI (0.3, 1, and 3 mg/kg), TCB-2 (0.3, 1, and 3 mg/kg), or M100907 (0.1, 0.3, and 1 mg/kg). Subsequently, drug effects were then evaluated using a more difficult CPT with variable stimulus durations. Mice were then tested on the CPT following repeated PSI injections. Drug effects on locomotor activity were also measured.ResultsIn the CPT, all three drugs reduced hit and false alarm rate and induced conservative responding. PSI also reduced target discrimination. These effects were seen primarily at doses that also significantly reduced locomotor activity. No drug effects were seen on the more difficult CPT or following repeated PSI injections.ConclusionsPsilocybin, TCB-2, and M100907 impaired performance of the CPT. However, this may be in part due to drug-induced locomotor changes. The results provide little support for the idea that psilocybin alters visual attention, or that 5-HT2A receptors modulate this process.

keywords:
Animals, Mice, Methylamines, Fluorobenzenes, Piperidines, Receptor, Serotonin, 5-HT2A, Hallucinogens, Psychomotor Performance, Attention, Dose-Response Relationship, Drug, Male, Serotonin 5-HT2 Receptor Agonists, Serotonin 5-HT2 Receptor Antagonists, Bridged Bicyclo Compounds, Heterocyclic, Bridged Bicyclo Compounds, Psilocybin

raw_json:
{"europe_pmc_id":"37855864","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: PsyArXiv
publication_date: 2022-09-29
source_url: https://osf.io/preprints/psyarxiv/kh3cx_v1
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Emotional Processing,Clinical Trial,Safety
study_type: Clinical Trial
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"kh3cx_v1","version":1,"reviews_state":"accepted"}
title:
Psilocybin Therapy for Treatment Resistant Depression: Prediction of Clinical Outcome by Natural Language Processing

abstract:
Background: Therapeutic administration of psychedelic drugs has shown significant potential in historical accounts and in recent clinical trials in the treatment of depression and other mood disorders. A recent randomized double-blind phase-IIb study demonstrated the safety and efficacy of COMP360, COMPASS Pathways’ proprietary synthetic formulation of psilocybin, in participants with treatment resistant depression. While promising, the treatment works for a portion of the population and early prediction of outcome is a key objective. Methods: Transcripts were made from audio recordings of the psychological support session between participant and therapist one day post COMP360 administration. A zero-shot machine learning classifier based on the BART large language model was used to compute two-dimensional sentiment (valence and arousal) for the participant and therapist from the transcript. These scores, combined with the Emotional Breakthrough Index (EBI) and treatment arm were used to predict treatment outcome as measured by MADRS scores. Code and data are available at https://github.com/compasspathways/Sentiment2D Results: Two multinomial logistic regression models were fit to predict responder status at week 3 and through week 12. Cross-validation of these models resulted in 85% and 88% accuracy and AUC values of 88% and 85%. Conclusions: A machine learning algorithm using NLP and EBI accurately predicts long term patient response, allowing rapid prognostication of personalized response to psilocybin treatment and insight into therapeutic model optimization. Further research is required to understand if language data from earlier stages in the therapeutic process hold similar predictive power.

keywords:
Depression, Emotional Breakthrough Index, Machine Learning, Natural Language Processing, Sentiment, Psychiatry, Social and Behavioral Sciences, Clinical Psychology, Quantitative Methods, Statistical Methods


authors: Schuman HDM, Savard C, Mina R, Barkova S, Conradi HSW, Deleemans JM, Carlson LE.
publication_date: 2025-06-29
doi: 10.3390/curroncol32070380
pubmed_id: 40710191
source_url: https://doi.org/10.3390/curroncol32070380
keywords: Humans, Neoplasms, Ketamine, Hallucinogens, Depression, Anxiety, Psilocybin
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
title:
Psychedelic-Assisted Therapies for Psychosocial Symptoms in Cancer: A Systematic Review and Meta-Analysis.

abstract:
This systematic review and meta-analysis evaluates (1) the effectiveness of psychedelic-assisted therapy (PAT) using psilocybin and ketamine for psychosocial symptoms in adults with cancer, (2) contextualizes findings with non-randomized and exploratory studies of other psychedelics, and (3) examines the role of therapeutic frameworks in shaping outcomes. We searched PubMed, Cochrane Library, PsycINFO, and EMBASE (2000-2024) for randomized controlled trials (RCTs) and non-randomized studies investigating psychedelic agents in cancer populations. Meta-analyses pooled RCTs of psilocybin or ketamine using random-effects models. Non-randomized studies were synthesized narratively. Risk of bias and evidence certainty were assessed via Cochrane ROB2.0, NIH Before-After tool, and GRADE. Eleven placebo-controlled RCTs and four single open-label studies were included. Meta-analysis of four ketamine RCTs (n = 354) showed large, rapid effects on depression/anxiety (Hedges' g = -1.37, 95% CI: -2.66 to -0.08; I2 = 92%). Three psilocybin RCTs (n = 101) showed a large effect of psilocybin on alleviating depression (Hedges' g = -3.13, 95% CI: -10.04 to 3.77; I2 = 95%). MDMA and LSD trials suggested promise but lacked rigor. PAT may offer meaningful relief for cancer-related distress, though effects vary by therapeutic model and context. Oncology-specific trials are needed to standardize and scale for implementation.

topic_tags:
Depression,Anxiety,Randomized Controlled Trial,Meta-Analysis,Systematic Review,Review Article,Cancer Patients,Safety

raw_json:
{"europe_pmc_id":"40710191","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: A Scoping Review of Research in Naturalistic Studies with Psychedelics.
authors: Carvalho LC, Encantado J, Kettner H, Timmermann C, Veiga D, Teixeira PJ.
publication_date: 2025-06-27
doi: 10.1080/02791072.2025.2520221
pubmed_id: 40581772
source_url: https://doi.org/10.1080/02791072.2025.2520221
substance_tags: psilocybin
topic_tags: Clinical Trial,Review Article,Observational Study
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
Psychedelic research has traditionally focused on controlled, clinical settings to evaluate the therapeutic potential of substances such as psilocybin. However, in recent years, there has been growing interest in naturalistic research, which explores psychedelic use in real-world settings. This review aims to critically analyze trends in naturalistic psychedelic research, focusing on sample demographics and the diversity of contextual factors across different settings. A systematic search in PubMed, PsycINFO, and Web of Science was conducted, including studies that involved the use of classic psychedelics in real-world settings. Two reviewers independently screened articles and extracted data on both sample and setting characteristics. A total of 103 studies were included, most of which employed a cross-sectional survey-based design (n = 54), with sample characteristics being widely reported, albeit with considerable variability across studies. Ayahuasca was the most frequently studied substance (66%), and ceremonial settings were the most commonly reported (35.9%). While sample characteristics were widely reported, there was significant variability. Specific contextual components, such as music, were often underreported, with longitudinal studies providing the most comprehensive details. This review highlights the need for systematic reporting standards in naturalistic psychedelic research to maximize its complementary value alongside clinical trials.

raw_json:
{"europe_pmc_id":"40581772","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Marek J, Domek-Gumprecht M, Macionga A, Szafoni S, Więckiewicz G
journal: Frontiers in psychiatry
publication_date: 2024-12-31
doi: 10.3389/fpsyt.2025.1591658
pubmed_id: 40656049
source_url: https://pubmed.ncbi.nlm.nih.gov/40656049/
keywords: DMT, MDMA, PolDrugs, drugs, marijuana, psilocybin, psychiatry, psychoactive substances
substance_tags: psilocybin
topic_tags: Depression,Addiction,Observational Study
study_type: Observational Study
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"40656049"}
title:
PolDrugs 2025: results of the third edition of the nationwide study on psychoactive substance use in the context of psychiatry and harm reduction.

abstract:
PolDrugs is a biennial epidemiological study aimed at analyzing patterns of mostly illicit psychoactive substance use in Poland in the context of psychiatry and harm reduction. This survey was held for the third time, and its results were compared to the last two editions.
The survey was conducted as an online survey with 37 closed-ended single-choice questions and 3 multiple-choice questions. Respondents were recruited through outreach on social media platforms, primarily Facebook and Instagram, in drug-related groups. Recruitment efforts were supported by activists and advocacy groups who promoted the questionnaire through their own social media networks. The sample consisted of 2,447 people between the ages of 13 and 63 years. Statistical analysis included descriptive statistics only.
The study population (mean age 27 years) was predominantly male and urban. Marijuana was the most common substance used after alcohol, caffeine, and nicotine, though overall consumption was infrequent (35.6% reporting use once every few months or less) and mainly occurred in social settings (50.2%) or at home (52.3%). Notably, 83.6% never tested substance composition, and 51.4% relied on visual estimation for dosing. Sixty percent had neglected daily responsibilities, while 16.8% faced legal issues. Although 70.7% had not sought medical help, nearly half had seen a psychiatrist (primarily for depression), with 41.1% of these having attempted suicide and 70.5% using illicit substances before their initial consultation. Only 40% consistently disclosed their substance use to a physician.
Stimulant use and subsequent medical consultations-particularly for mephedrone derivatives-are rising warranting further investigation. The proportion of respondents who use psychoactive substances alone is increasing, now exceeding 25%. Psychedelic use is declining possibly due to reduced mainstream media attention. The observation also shows a growing acceptance of psychiatric care in Polish society.


authors: Laabi S, LeMmon C, Vogel C, Chacon M, Jimenez VM.
publication_date: 2025-05-25
doi: 10.1016/j.intimp.2025.114940
pubmed_id: 40424654
source_url: https://doi.org/10.1016/j.intimp.2025.114940
substance_tags: psilocybin,psilocin
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Psilocybin and psilocin regulate microglial immunomodulation and support neuroplasticity via serotonergic and AhR signaling.

abstract:
BackgroundPsilocybin, a serotonergic psychedelic, has demonstrated therapeutic potential in neuropsychiatric disorders. While its neuroplastic and immunomodulatory effects are recognized, the underlying mechanisms remain unclear. This study investigates how psilocybin and its active metabolite, psilocin, influence microglial inflammatory responses and neurotrophic factor expression through serotonergic and AhR signaling.MethodsUsing in vitro models of resting and LPS-activated microglia, we evaluated the effects of psilocybin and psilocin on the expression of pro-inflammatory cytokines (TNF-α), anti-inflammatory cytokines (IL-10), and neuroplasticity-related markers (BDNF). Receptor-specific contributions were assessed using selective antagonists for 5-HT2A, 5-HT2B, 5-HT7, TrkB, and AhR.ResultsPsilocybin and psilocin significantly suppressed TNF-α expression and increased BDNF levels in LPS-activated microglia. These effects were mediated by 5-HT2A, 5-HT2B, 5-HT7, and TrkB signaling, while AhR activation was required for psilocin-induced BDNF upregulation but not TNF-α suppression. IL-10 levels remained unchanged under normal conditions but increased significantly when serotonergic, TrkB, or AhR signaling was blocked, suggesting a compensatory shift in anti-inflammatory pathways.ConclusionPsilocybin and psilocin promote a microglial phenotype that reduces inflammation and supports neuroplasticity via receptor-specific mechanisms. Their effects on TNF-α and BDNF depend on distinct serotonergic and neurotrophic pathways, with AhR playing a selective role in psilocin's action. These findings clarify the receptor-mediated dynamics of psilocybin's therapeutic effects and highlight alternative anti-inflammatory pathways that may be relevant for clinical applications.

keywords:
Microglia, Cells, Cultured, Animals, Mice, Lipopolysaccharides, Brain-Derived Neurotrophic Factor, Tumor Necrosis Factor-alpha, Receptors, Serotonin, Receptors, Aryl Hydrocarbon, Hallucinogens, Interleukin-10, Cytokines, Signal Transduction, Neuronal Plasticity, Immunomodulation, Psilocybin

topic_tags:
Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Biomarkers,Animal Study,In Vitro Study,Inflammation

raw_json:
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publication_date: 2025-06-24
doi: 10.3389/fneur.2025.1594335
pubmed_id: 40635716
source_url: https://doi.org/10.3389/fneur.2025.1594335
substance_tags: psilocybin,psilocin
topic_tags: Depression,PTSD,Receptor Pharmacology,Observational Study,Veterans
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Serotonin 5-HT2A receptor expression is chronically decreased in the anterior cerebral cortex of male rats following repetitive low-level blast exposure.

authors:
De Gasperi R, Perez Garcia G, Gama Sosa MA, Perez GM, Abutarboush R, Kawoos U, Hof PR, Zhu CW, Ahlers ST, Elder GA.

abstract:
IntroductionMany Veterans who experienced blast-related traumatic brain injuries (TBIs) in Iraq and Afghanistan currently suffer from chronic cognitive and mental health problems that include depression and post-traumatic stress disorder (PTSD). Male rats exposed to repetitive low-level blast develop chronic cognitive and PTSD-related behavioral traits that are present for more than 1 year after exposure. Psychedelic agents alter cognition as well as mood and agents such as psilocybin have gained attention as possible treatments for the mental health disorders that affect Veterans. The best-known action of psilocybin's metabolite psilocin is to stimulate the serotonin 2A receptor (5-HT2AR). The aim of this study was to determine whether 5-HT2AR levels are altered by blast exposure.Methods5-HT2AR expression was examined by Western blot in 7 cohorts of rats exposed to low level repetitive blast collected from 2 weeks to 12 months after blast exposure. The analysis included three brain regions (anterior cerebral cortex, hippocampus and amygdala) that were chosen based on being relevant to fear learning and the biological basis of PTSD. Possible correlations between Western blot data and behavioral outcomes were evaluated.Results5-HT2AR was chronically decreased in anterior cortex of blast-exposed rats in all cohorts except the one studied at 2 weeks after blast exposure. 5-HT2AR levels were variably affected in the other regions. 5-HT2AR expression correlated differently in blast and control rats in some behavioral parameters.ConclusionThese findings have implications for understanding the neurochemical basis of blast-induced cognitive and behavioral changes. They also suggest 5-HT2AR as a potential therapeutic target for treatment of PTSD-related symptoms that follow blast injury.

raw_json:
{"europe_pmc_id":"40635716","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Mathew A, Dongre R, Kim SH, Turner J, Mathew A, Cherryholmes E, Mehrinfar M, Kamprath S.
publication_date: 2025-06-23
doi: 10.7759/cureus.86659
pubmed_id: 40718283
source_url: https://doi.org/10.7759/cureus.86659
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Wellbeing,Clinical Trial,Review Article,In Vitro Study
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
The Clinical Applications of Psilocybin Therapies and Post-COVID Syndrome: A Comprehensive Narrative Review.

abstract:
The coronavirus variant (causing the COVID-19 disease) that led to a pandemic sent global shockwaves, resulting in long-term effects on physical, mental, and social well-being and impacting both individuals and communities. With the pandemic's notable impact on mental health, one such potential treatment discussed in recent literature is psilocybin. Psilocybin is a naturally occurring prodrug compound found in select mushrooms shown to reduce clinical symptoms of certain mental health disorders. In this study, we review the status and usage of psilocybin in clinical practice preceding and following the COVID-19 pandemic. The search criteria for the study included psilocybin or psychedelics or psychedelic-therapy psychiatry and long-haul COVID. The search spanned English articles from January 2020 to April 2024, utilizing the PsychInfo, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, and PubMed databases. Two reviewers independently screened each record to decide if a study met the inclusion criteria and to account for bias. Each article researched different pathologies, including depression, anxiety, post-traumatic stress disorder, and COVID-19. The manuscripts collectively emphasize that there is evidence that psilocybin has a role in the treatment of said pathologies, with relatively safe outcomes if administered under proper medical supervision. Psilocybin use was followed up for a relatively long period after some trials, but further research is warranted to draw a more definitive conclusion regarding the therapeutic uses of psilocybin. Our review reflects that barriers to using psilocybin therapeutically for long-haul COVID-19 exist, which significantly impacts the scope of our research. While evidence suggests its efficacy in mental health conditions such as depression and mood disorders, more robust clinical trials are needed. Current literature supports the pharmacological basis that psilocybin may be effective in treating COVID-19 sequelae. Psilocybin's role in inhibiting SARS-Cov-2 protease shows promise, but ultimately, in vitro validation will be necessary before wider approval of the drug. Lastly, large clinical trials comparing psilocybin to standard care and assessing symptom relief in long-term COVID patients may help validate the findings seen in much of the current literature.

raw_json:
{"europe_pmc_id":"40718283","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Koolen M, Wirsching A, Krediet E, van Elk M.
publication_date: 2025-06-22
doi: 10.1080/02791072.2025.2508156
pubmed_id: 40551401
source_url: https://doi.org/10.1080/02791072.2025.2508156
substance_tags: psilocybin
topic_tags: Depression,PTSD,Consciousness,Observational Study,Healthcare Workers,Safety
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
title:
Assessing the Attitudes of Dutch Mental Health Care Professionals Toward Psychedelic-Assisted Psychotherapy: A Cross-Sectional Exploratory Study.

abstract:
Psychedelic-assisted psychotherapy (PAP) constitutes a novel treatment paradigm in mental health care practice that is currently being evaluated for its clinical efficacy and safety. Insight into the attitudes of clinicians toward PAP remains crucial for its successful integration into mental health care. This cross-sectional survey explores the attitudes of Dutch mental health care professionals toward PAP, specifically focusing on 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder and psilocybin-assisted psychotherapy for major depressive disorder. The study included 198 clinicians who completed a 40-item online survey, distributed between April and May 2022. The study examined clinicians' attitudes toward PAP, the relation between these attitudes and several demographic variables, and clinicians' perceived implementation barriers. Respondents generally exhibited positive attitudes toward PAP, which in turn were related to previous use of either MDMA or psilocybin. Participants believed that psychiatrists and licensed psychologists were the ideal professionals to administer PAP, expressed concerns about their ability to establish a connection with patients during psychedelic states of consciousness, and preferred administering PAP in specialized facilities within hospital settings. This study provides valuable insights into the implementation of PAP and helps informing educational and training programs for clinicians, as well as integrating PAP into mental health care.

raw_json:
{"europe_pmc_id":"40551401","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Correction: Psilocybin's acute and persistent brain effects: a precision imaging drug trials.
journal: Scientific data
publication_date: 2025-06-17
doi: 10.1038/s41597-025-05397-8
pubmed_id: 40533500
source_url: https://pubmed.ncbi.nlm.nih.gov/40533500/
substance_tags: psilocybin
topic_tags: Brain Imaging,Aging
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"40533500"}
authors:
Subramanian S, Reneau TR, Perry D, Chacko R, Laumann TO, Flavin K, Horan C, Schweiger J, Metcalf N, Lenze EJ, Snyder AZ, Dosenbach NUF, Nicol G, Siegel JS


title: Classic Psychedelics in Pain Modulation: Mechanisms, Clinical Evidence, and Future Perspectives.
authors: Czopek A, Jończyk J, Fryc M, Kluzik D, Zagórska A.
publication_date: 2025-06-05
doi: 10.1021/acschemneuro.5c00152
pubmed_id: 40474592
source_url: https://doi.org/10.1021/acschemneuro.5c00152
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
Millions worldwide suffer from chronic pain, a complex condition often accompanied by depression and anxiety, highlighting the urgent need for innovative treatments. Classic psychedelics, including psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltryptamine (DMT), primarily act on serotonin 5-HT2A receptors and have emerged as potential modulators of pain perception and mood regulation. These substances may offer an alternative to conventional analgesics, such as opioids and nonsteroidal anti-inflammatory drugs (NSAIDs), by influencing neuroplasticity, descending pain modulation pathways, and inflammatory processes. Evidence from case studies, preclinical research, and early phase clinical trials suggests that psychedelics may alleviate pain in conditions such as cluster headaches, migraines, fibromyalgia, and chronic pain syndromes. However, the exact mechanisms underlying their analgesic properties are yet to be fully understood. While psychedelics show promise in reshaping pain management strategies, rigorous randomized controlled trials are needed to establish their safety, efficacy, and optimal dosing. This review highlights the therapeutic potential of psychedelics for chronic pain and emphasizes the necessity of further research to validate their role in modern pain medicine.

keywords:
Animals, Humans, Pain, Lysergic Acid Diethylamide, Analgesics, Hallucinogens, Pain Management, Chronic Pain

topic_tags:
Depression,Anxiety,Addiction,Chronic Pain,Headache / Migraine,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Clinical Trial,Randomized Controlled Trial,Review Article,Animal Study,Safety,Inflammation

raw_json:
{"europe_pmc_id":"40474592","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Zhang Y, Yang L, Zhang Q, Li C, Mao F, Zhuo C.
publication_date: 2025-06-15
doi: 10.1038/s41398-025-03410-7
pubmed_id: 40523911
source_url: https://doi.org/10.1038/s41398-025-03410-7
substance_tags: psilocybin
topic_tags: Pharmacology,Mechanism of Action,Drug Interactions
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
The molecular mechanisms through which psilocybin prevents suicide: evidence from network pharmacology and molecular docking analyses.

abstract:
Psilocybin is among the most extensively studied psychedelics, with previous research suggesting its potential therapeutic role in suicide prevention. However, the precise mechanisms through which psilocybin may aid in suicide prevention remain unclear. This study thus employed network pharmacology and molecular docking tools to explore the mechanisms by which psilocybin may contribute to suicide prevention. Relevant drug- and disease-related targets were identified. Overlapping drug- and disease-related targets were extracted from the bioinformatics platform and imported into the STRING database to construct a protein-protein interaction (PPI) network. Key targets were selected based on topological parameters derived from network analyses conducted using Cytoscape 3.10.1. These key targets were further analyzed using GO and KEGG enrichment approaches conducted with the DAVID tool. A drug-disease-target-pathway network was subsequently constructed in Cytoscape 3.10.1. Finally, molecular docking analyses were performed to assess psilocybin's potential to interact with key targets using AutoDock Vina and the PyMOL software. A total of 46 potential targets associated with psilocybin and relevant to suicide treatment were identified, of which 13 were imported into the DAVID tool for enrichment analyses. Network analyses identified four targets-HTR2A, HTR2C, HTR7, and PRKACA-that may serve as therapeutic targets for psilocybin in suicide prevention. Enrichment analysis outcomes suggested that psilocybin may prevent suicide by modulating the serotonergic synapse and calcium signaling pathways. Molecular docking analyses revealed that HTR2A, HTR2C, HTR7, and PRKACA strongly bind to psilocybin. This study provides insights into the molecular mechanisms underlying the potential role of psilocybin in suicide prevention, offering a novel basis for further research.

keywords:
Humans, Suicide, Computational Biology, Databases, Protein, Protein Interaction Maps, Molecular Docking Simulation, Psilocybin, Network Pharmacology, Suicide Prevention

raw_json:
{"europe_pmc_id":"40523911","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Long-term benefits of single-dose psilocybin in depressed patients with cancer.
authors: Agrawal M, Roddy K, Jenkins B, Leeks C, Emanuel E.
publication_date: 2025-05-31
doi: 10.1002/cncr.35889
pubmed_id: 40518804
source_url: https://doi.org/10.1002/cncr.35889
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Clinical Trial,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
BackgroundPatients with cancer often struggle with depression, which can negatively impact quality of life as well as be challenging to manage.MethodsA phase 2 trial was conducted that demonstrated safety, feasibility, and efficacy of a single dose of psilocybin combined with psychological support in a community cancer setting in 30 patients with cancer and a major depressive disorder. Here, efficacy outcomes at 2 years' follow-up are reported.ResultsOf 28 patients, 15 (53.6%) demonstrated significant reduction in depression as measured by the Montgomery Asberg Depression Rating Scale (average, -15.0 points from baseline; p

keywords:
Humans, Neoplasms, Hallucinogens, Antidepressive Agents, Treatment Outcome, Combined Modality Therapy, Feasibility Studies, Anxiety, Psychotherapy, Quality of Life, Adult, Aged, Middle Aged, Female, Male, Psilocybin, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"40518804","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Modzelewski S, Stankiewicz A, Waszkiewicz N, Łukasiewicz K.
publication_date: 2025-03-06
doi: 10.1016/j.neuropharm.2025.110402
pubmed_id: 40058407
source_url: https://doi.org/10.1016/j.neuropharm.2025.110402
substance_tags: psilocybin
topic_tags: Anxiety,Microdosing,Systematic Review,Review Article,Adverse Events
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Side effects of microdosing lysergic acid diethylamide and psilocybin: A systematic review of potential physiological and psychiatric outcomes.

abstract:
ObjectivePsychedelics are gaining renewed attention, especially through the practice of microdosing, where low doses are taken regularly. Microdosing lysergic acid diethylamide (LSD) and psilocybin is used by both healthy individuals and those with mental health conditions to improve daily functioning, reduce anxiety, and enhance mood and cognition. However, there is limited information about the side effects of this practice. This review aimed to collect and characterize the side effects of psychedelic microdosing.MethodsWe conducted a systematic review of original papers from PubMed, Web of Science, and Scopus (accessed August 03, 2024) that reported side effects of microdosing LSD and psilocybin. Non-English papers, non-original studies, studies without typical microdosing doses, or those lacking descriptions of side effects were excluded. Our methodology has been developed in accordance with PRISMA guidelines. Because side effects were assessed heterogeneously in these papers, we did not perform a bias evaluation.ResultsWe included 31 studies, 15 of which we classified as laboratory studies with higher quality evidence, and 14 studies with lower quality evidence, as well as 2 clinical cases. Side effects were typically dose-dependent, mild, and short-lived. Common adverse effects included increased blood pressure, anxiety, and cognitive impairment.DiscussionThis review is limited by the heterogeneity in reporting side effects and the short duration of many studies. Future studies should transparently and systematically present a description of side effects.

keywords:
Animals, Humans, Lysergic Acid Diethylamide, Hallucinogens, Dose-Response Relationship, Drug, Psilocybin

raw_json:
{"europe_pmc_id":"40058407","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-06-13
doi: 10.1038/s41398-025-03421-4
pubmed_id: 40517150
source_url: https://doi.org/10.1038/s41398-025-03421-4
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Evaluation of behavioural and neurochemical effects of psilocybin in mice subjected to chronic unpredictable mild stress.

authors:
Erkizia-Santamaría I, Horrillo I, Martínez-Álvarez N, Pérez-Martínez D, Rivero G, Erdozain AM, Meana JJ, Ortega JE.

abstract:
Depression and anxiety are disabling and high incidence mental disorders characterized by phenotypic heterogeneity. Currently available treatments show severe limitations. Thus, there is an urgent need for effective treatments in this population. In the search for novel rapid-acting antidepressants, the psychedelic psilocybin has emerged as a promising therapy in several clinical trials. However, its antidepressant mechanism of action is still not well understood. The aim of the present study was to evaluate the therapeutic potential of psilocybin in ameliorating the adverse behavioural and neurochemical consequences of chronic stress. To this end, a chronic unpredictable mild stress (CUMS) animal model was used, and psilocybin treatment was administered (two doses of 1 mg/kg, i.p., administered 7 days apart). Psilocybin reversed impairments in anhedonia and behavioural despair dimensions of depressive phenotype but not in apathy-related behaviour. Psilocybin administration was also able to exert an anxiolytic-like effect on treated animals. Physiological alterations caused by stress, indicative of a hyperactive hypothalamic-pituitary-adrenal axis (HPA), were not reversed by psilocybin. When neuroplasticity-related proteins were assessed in cerebral cortex, brain-derived neurotrophic factor (BDNF) was found to be decreased in stressed animals, and treatment did not reverse such impairment. Psilocybin administration increased the expression and function of serotonin-2A-receptor (5HT2AR) in brain cortex of control and CUMS groups. Furthermore, psilocybin treatment caused a selective increase in the expression of glucocorticoid-receptor (GR) in brain cortex of CUMS mice. In conclusion, psilocybin was able to rescue impairments in the depressive phenotype, and to induce anxiolytic-like effects. Furthermore, an enhancement in sensitivity to psilocybin-induced HTR was observed following a booster dose. Altogether, this work provides new knowledge on the putative benefit/risk actions of psilocybin and contributes to the understanding of the therapeutic mechanism of action of psychedelics.

keywords:
Pituitary-Adrenal System, Hypothalamo-Hypophyseal System, Animals, Mice, Disease Models, Animal, Brain-Derived Neurotrophic Factor, Hallucinogens, Antidepressive Agents, Behavior, Animal, Depression, Stress, Psychological, Anxiety, Male, Anhedonia, Psilocybin

topic_tags:
Depression,Anxiety,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Clinical Trial,Animal Study,Safety

raw_json:
{"europe_pmc_id":"40517150","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Mycelium Growth and Development of Psilocybe spp. Mother Cultures on Agar-Based Media.
authors: Pepe M, Hesami M, Fleishmann L, Hsiang T, Jones AMP.
publication_date: 2025-06-12
doi: 10.3390/jof11060450
pubmed_id: 40558962
source_url: https://doi.org/10.3390/jof11060450
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
The resurgence of interest in the therapeutic potential of psilocybin-producing mushrooms has recently led to numerous research and commercialization efforts. Due to its ease of cultivation and high potency, Psilocybe is the primary genus of interest, and there is a growing need to standardize maintenance, proliferation, and cultivation techniques for efficient and consistent production. The investigation of mycelial growth and development on agar-based media is of principal importance to regulate and optimize mycelium growth and preservation protocols for subsequent fruiting body development. The current investigation is the first to examine the mycelial growth and morphology of four Psilocybe genotypes cultured on different agar-based media. The results from this simple set of experiments provides the foundation for future optimization studies. Ultimately, the information presented can be used to develop genotype-specific mycelial growth and development practices that will shape the future of psychedelic mushroom production for clinical and industrial applications.

raw_json:
{"europe_pmc_id":"40558962","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Zhai H, Wang H, Li H, Wang X.
publication_date: 2025-05-14
doi: 10.1021/acsptsci.5c00234
pubmed_id: 40534671
source_url: https://doi.org/10.1021/acsptsci.5c00234
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
title:
The Intersection of Psychedelics and Sleep: Exploring the Impacts on Sleep Architecture, Dream States, and Therapeutic Implications.

abstract:
The interplay between psychedelics, such as psilocybin, lysergic acid diethylamide (LSD) and dimethyltryptamine (DMT), and sleep is an emerging area, but their impact on sleep remains relatively underexplored. This viewpoint provides a perspective on how psychedelics may alter sleep phases, dreaming, and their potential therapeutic applications for sleep disorders.

raw_json:
{"europe_pmc_id":"40534671","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-05-28
doi: 10.1021/acsptsci.5c00208
pubmed_id: 40534669
source_url: https://doi.org/10.1021/acsptsci.5c00208
substance_tags: psilocybin
topic_tags: Receptor Pharmacology,Clinical Trial
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
The Selective Serotonin 5-HT2A Receptor Agonist (S)-3-(2,5-Dimethoxy-4-(trifluoromethyl)phenyl)piperidine (LPH-5) Induces Persistent and Robust Antidepressant-Like Effects in Rodents.

authors:
Jensen AA, Cecchi CR, Hibicke M, Bach AH, Kaadt E, Märcher-Rørsted E, Nichols CD, Elfving B, Kristensen JL.

abstract:
Psychedelics have emerged as a promising treatment for mental health disease, and the therapeutic potential of psilocybin and lysergic acid diethylamide (LSD) is presently being pursued in numerous clinical trials. This has prompted a search for novel agents with more specific pharmacological activities than the rather promiscuous classical psychedelics. Here we present the detailed pharmacological characterization of one such compound, LPH-5 [(S)-3-(2,5-dimethoxy-4-(trifluoromethyl)-phenyl)-piperidine]. LPH-5 was found to be a potent partial agonist at the 5-HT2A receptor (5-HT2AR) with pronounced selectivity for 5-HT2AR over the related 5-HT2BR and 5-HT2CR in a range of functional assays. LPH-5 dose-dependently induced head-twitch responses (HTR) as well as robust acute and persistent antidepressant-like effects in rats. These results suggest that selective 5-HT2AR activation holds antidepressant potential and indicate that this activity component is key for the therapeutics effects of classical psychedelics.

raw_json:
{"europe_pmc_id":"40534669","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Synergistic behavioral and neuroplastic effects of psilocybin-NMDAR modulator administration.
authors: Ben-Tal T, Pogodin I, Botvinnik A, Lifschytz T, Heresco-Levy U, Lerer B.
publication_date: 2025-06-12
doi: 10.1038/s41398-025-03428-x
pubmed_id: 40514369
source_url: https://doi.org/10.1038/s41398-025-03428-x
substance_tags: psilocybin
topic_tags: Depression,Neuroplasticity,Receptor Pharmacology,Animal Study,Safety
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
abstract:
The full therapeutic potential of serotonergic psychedelics (SP) in treating neuropsychiatric disorders, such as depression and schizophrenia, is limited by possible adverse effects, including perceptual disturbances and psychosis, which require administration in controlled clinical environments. This study investigates the synergistic benefits of combining psilocybin (PSIL) with N-methyl-D-aspartate receptor (NMDAR) modulators D-serine (DSER) and D-cycloserine (DCS) to enhance both efficacy and safety. Using ICR male mice, we examined head twitch response (HTR), MK-801-induced hyperlocomotion, and neuroplasticity related synaptic protein levels in the frontal cortex, hippocampus, amygdala, and striatum. Our results indicate that PSIL significantly increased HTR-a surrogate measure for hallucinogenic effects-which was reduced by the co-administration of DSER or DCS in a dose-dependent manner. Similarly, combining PSIL with DSER or DCS significantly decreased MK-801-induced hyperactivity, modeling antipsychotic effects. Neuroplasticity-related synaptic protein assays demonstrated that the PSIL-DSER combination enhanced GAP43 expression over all 4 brain examined and overall expression of the 4 assayed synaptic proteins in the hippocampus, while PSIL-DCS elevated PSD95 levels across all 4 brain regions, suggesting a synaptogenic synergy. These findings support the hypothesis that combinations of SP with NMDAR modulators could optimize the therapeutic potential of SP by mitigating adverse effects and enhancing neuroplasticity. Future studies should focus on refining administration protocols and evaluating translational applicability for broader clinical use.

keywords:
Brain, Hippocampus, Animals, Mice, Inbred ICR, Mice, Cycloserine, Dizocilpine Maleate, Receptors, N-Methyl-D-Aspartate, Hallucinogens, Behavior, Animal, Neuronal Plasticity, Drug Synergism, Male, Psilocybin

raw_json:
{"europe_pmc_id":"40514369","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelic fungi.
authors: Slot J, Hoffmeister D.
publication_date: 2025-05-31
doi: 10.1016/j.cub.2025.02.026
pubmed_id: 40494306
source_url: https://doi.org/10.1016/j.cub.2025.02.026
keywords: Animals, Humans, Fungi, Hallucinogens, Psilocybin
substance_tags: psilocybin
topic_tags: Receptor Pharmacology
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
Several species of fungi, collectively known as 'psychedelic fungi', produce a range of psychoactive substances, such as psilocybin, ibotenic acid, muscimol and lysergic acid amides. These substances interact with neurotransmitter receptors in the human brain to induce profound psychological effects. These substances are found across multiple fungal phyla, in the mushroom-forming genera Psilocybe, Amanita, and others, and also the ergot-producing Claviceps and insect-pathogenic Massospora. The ecological roles of these psychedelics may include deterring predators or facilitating spore dispersal. Enzymes for psychedelic compound biosynthesis are encoded in metabolic gene clusters that are sometimes dispersed by horizontal gene transfer, resulting in a patchy distribution of psychedelics among species. The (re-)emerging science of these strange substances creates new opportunities and challenges for science and humanity at large.

raw_json:
{"europe_pmc_id":"40494306","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin and hallucinogenic mushrooms - ERRATUM.
authors: Fradet M, Kelly CM, Donnelly AJ, Suppes T.
publication_date: 2025-06-08
doi: 10.1017/s1092852925100291
pubmed_id: 40485503
source_url: https://doi.org/10.1017/s1092852925100291
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
raw_json:
{"europe_pmc_id":"40485503","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Modlin NL, Williamson V, Maggio C, Stubley J, Kirlic N, Cleare A, Rucker J.
publication_date: 2025-06-07
doi: 10.1177/20451253251342319
pubmed_id: 40492108
source_url: https://doi.org/10.1177/20451253251342319
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Clinical conceptualisation of PTSD in psilocybin treatment: disrupting a pre-determined and over-determined maladaptive interpretive framework.

abstract:
Post-traumatic stress disorder (PTSD) and associated trauma and stressor-related disorders are common and debilitating, presenting significant treatment challenges due to their complex interplay of biological, cognitive, affective, somatic and social factors. Current treatments, while advancing and effective, yield limited efficacy for many individuals, underscoring the need for novel therapeutic approaches. This review explores the multifaceted nature of PTSD, emphasising its intricate predisposing and maintaining factors and explores the potential of psilocybin, a classical psychedelic, as a therapeutic agent. This review synthesises recent literature on the safety, efficacy and proposed mechanisms of action and change of psychedelic therapies for psychiatric conditions associated with traumatic stress, including treatment-resistant depression, end-of-life anxiety and anorexia nervosa. Correspondingly, it proposes a conceptual framework for psilocybin treatment in PTSD, framing the condition as a complex, maladaptive interpretive framework that is both predetermined and over-determined. A clinical narrative illustrates how psilocybin's unique psychopharmacological properties and catalysed subjective effects may facilitate therapeutic progress by disrupting this rigid and restricting framework. Finally, we offer recommendations for the safe administration of psilocybin for traumatised patients in medical research settings, emphasising the importance of rigorous and trauma-informed protocols and comprehensive patient care.

topic_tags:
Depression,Anxiety,PTSD,Eating Disorders,End-of-Life Distress,Mechanism of Action,Review Article,Treatment-Resistant Depression,Safety

raw_json:
{"europe_pmc_id":"40492108","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-06-05
doi: 10.3389/fpsyg.2025.1580663
pubmed_id: 40547590
source_url: https://doi.org/10.3389/fpsyg.2025.1580663
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
title:
Enhanced meaning in life following psychedelic use: converging evidence from controlled and naturalistic studies.

authors:
Roseby W, Kettner H, Roseman L, Spriggs MJ, Lyons T, Peill J, Giribaldi B, Erritzoe D, Nutt DJ, Carhart-Harris RL.

abstract:
IntroductionPsychedelics, such as psilocybin, are increasingly recognized for their propensity to elicit powerful subjective experiences that carry personal meaning. While research has demonstrated the capacity for these compounds to promote psychological wellbeing, it has yet to be shown to what extent they modulate "meaning in life", a specific contributor to mental and physical health.MethodsUsing the Meaning in Life Questionnaire (MLQ), we examined changes in meaning in life occurring across three different contexts of psychedelic use, including a randomized clinical trial of psilocybin for depression, controlled administration of psilocybin in a single-arm healthy volunteer study, and a naturalistic observational study following participants in psychedelic retreats. Meaning in life changes were analyzed with linear mixed models, and relationships to other predictors and outcomes were examined via Pearson correlations.ResultsAcross all contexts, the sub-factor "presence of meaning" was strongly increased after a psychedelic experience, while the sub-factor "search for meaning" was only weakly reduced. Enhancements of meaning in life were also moderately correlated with changes in measures of mental health, including mental wellbeing and depression severity. In line with previous research, we found that mystical, ego dissolution and emotional breakthrough experiences were correlated with an increase of meaning in life, with context-dependent differences in the strength of the association.DiscussionThe convergence of evidence from multiple studies shows that psychedelic use has a robust and long-lasting positive effect on meaning in life. We explore potential mechanisms of psychedelic-induced meaning enhancement and highlight the possible influences of psychosocial context on outcomes.

topic_tags:
Depression,Mechanism of Action,Wellbeing,Emotional Processing,Mystical Experience,Clinical Trial,Observational Study,Healthy Volunteers

raw_json:
{"europe_pmc_id":"40547590","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Role of endogenous serotonin in psychedelic-like effects of psilocybin in mice.
authors: Erkizia-Santamaría I, Martínez-Álvarez N, Salinas-Novoa L, Meana JJ, Ortega JE.
publication_date: 2025-05-31
doi: 10.1093/ijnp/pyaf035
pubmed_id: 40413648
source_url: https://doi.org/10.1093/ijnp/pyaf035
substance_tags: psilocybin
topic_tags: Depression,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Animal Study,Drug Interactions
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
BackgroundThe psychedelic psilocybin has been posited as efficacious for the treatment of depression. However, the potential link between the intensity of acute psychedelic effects and long-term therapeutic outcomes remains undiscovered. Moreover, the impact of classical antidepressant drugs that modulate serotonergic activity on psilocybin's effects is a clinically relevant concern. The aim of the present study was to assess serotonergic mechanisms implicated in the regulation of the intensity of the psilocybin-induced acute effects.MethodsThe head-twitch response (HTR), the most translational behavioral assay to characterize the psychedelic-like effect in rodents was performed. Moreover, the role of endogenous serotonin (5-HT) on psilocybin-induced HTR was studied by in vivo brain microdialysis technique.ResultsMaximally effective psilocybin dose (1 mg/kg) induced progressively lower HTR in heterozygous and homozygous knockout mice for serotonin 2A receptor (5HT2AR), compared to wild type. Synaptic increase of 5-HT by citalopram dose-dependently attenuated psilocybin-induced HTR after both acute and chronic dosing regimens. Conversely, depletion of 5-HT by p-chlorophenylalanine potentiated psilocybin-evoked HTR. Serotonin 1A receptor (5HT1AR) agonist 8-OH-DPAT dose-dependently decreased psilocybin-induced HTR, demonstrating functional interaction between 5HT2AR and 5HT1AR for psychedelic effects.ConclusionsThe present findings reveal an inverse correlation between cortical 5-HT levels and the acute psychedelic-like effects of psilocybin. Consequently, the enhancement of serotonergic activity induced by prior antidepressant treatment may underlie interindividual variability in the acute response to psychedelics. Investigating these mechanisms in relation to the sustained therapeutic outcomes of psilocybin could contribute to optimizing the efficacy of psychedelic-based therapies.

keywords:
Brain, Animals, Mice, Inbred C57BL, Mice, Knockout, Mice, Serotonin, Citalopram, Receptor, Serotonin, 5-HT2A, Hallucinogens, Microdialysis, Dose-Response Relationship, Drug, Male, Psilocybin

raw_json:
{"europe_pmc_id":"40413648","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin's acute and persistent brain effects: a precision imaging drug trial.
publication_date: 2025-06-04
doi: 10.1038/s41597-025-05189-0
pubmed_id: 40473634
source_url: https://doi.org/10.1038/s41597-025-05189-0
substance_tags: psilocybin
topic_tags: Brain Imaging,Aging,Healthy Volunteers
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
authors:
Subramanian S, Reneau TR, Perry D, Chacko R, Laumann TO, Flavin K, Horan C, Schweiger J, Metcalf N, Lenze EJ, Snyder AZ, Dosenbach NUF, Nicol G, Siegel JS.

abstract:
Psilocybin (PSIL) is a psychedelic drug and a promising experimental therapeutic for many psychiatric conditions. Precision functional mapping (PFM) combines densely repeated resting state fMRI sampling and individual-specific network mapping to improve signal-to-noise ratio (SNR) and effect size in brain imaging research. We present a randomized cross-over study in which PFM was used to characterize acute and persistent effects of psilocybin or methylphenidate (MTP) on brain networks. Seven healthy volunteers (mean age 34.1 years, SD = 9.8; n = 3 females, n = 6 Caucasians) underwent (1) extensive baseline imaging, (2) imaging beginning 60-90 minutes after drug exposure, and (3) longitudinal imaging for up to two weeks after drug exposure. Four individuals also participated in an open-label PSIL replication protocol over 6 months later. This dataset includes resting state (using advanced high-resolution multi-echo fMRI), task fMRI, structural, and diffusion basis spectral imaging as well as assessments of subjective experience. We are releasing this unique dataset as a resource for neuroscientists to study the acute and persistent effects of PSIL and MTP on brain networks.

keywords:
Brain, Humans, Methylphenidate, Hallucinogens, Magnetic Resonance Imaging, Brain Mapping, Cross-Over Studies, Adult, Female, Male, Psilocybin

raw_json:
{"europe_pmc_id":"40473634","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Leveraging psychedelic neuroscience to boost human creativity using artificial intelligence.
authors: Ross BM.
publication_date: 2025-06-03
doi: 10.3389/frai.2025.1589086
pubmed_id: 40535200
source_url: https://doi.org/10.3389/frai.2025.1589086
substance_tags: psilocybin
topic_tags: Mechanism of Action,Default Mode Network,Aging,Creativity,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
Psychedelics, such as LSD and psilocybin, disrupt entrenched cognitive patterns by facilitating novel insights and new associations. This paper considers how AI can potentially mimic these psychedelic-induced cognitive disruptions to augment and enhance human creativity. Psychedelics likely enhance creativity by altering brain function, notably the activity of the Default Mode Network, which leads to changes in cognition. Psychologically, they may reduce latent inhibition, increase divergent thinking, and promote implicit learning. Similarly, AI systems can replicate these creative enhancements by introducing novel associations, reframing familiar information, and facilitating unconscious cognitive shifts. The risks associated with AI use are also compared to psychedelics, including dependency, ethical concerns, and homogenization of outputs due to bias. Integrating the cognitive mechanisms activated by psychedelics into AI design provides promising pathways for creativity enhancement. Carefully designed AI could act as a cognitive catalyst, fostering innovative thought processes and adaptive problem-solving while addressing identified ethical and practical concerns.

raw_json:
{"europe_pmc_id":"40535200","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Effects of Psilocybin on Mouse Brain Microstructure.
authors: Frautschi PC, Singh AP, Stowe NA, Grady SM, Zahid Z, Banks MI, Yu JJ.
publication_date: 2025-06-02
doi: 10.3174/ajnr.a8634
pubmed_id: 39880687
source_url: https://doi.org/10.3174/ajnr.a8634
keywords: Brain, Animals, Mice, Inbred C57BL, Mice, Hallucinogens, Male, Diffusion Tensor Imaging, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Brain Imaging,Mechanism of Action,Aging,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
Background and purposeThere is surging interest in the therapeutic potential of psychedelic compounds like psilocybin in the treatment of psychiatric illnesses like major depressive disorder (MDD). Recent studies point to the rapid antidepressant effect of psilocybin; however, the biologic mechanisms underlying these differences remain unknown. This study determines the feasibility of using diffusion MRI to characterize and define the potential spatiotemporal microstructural differences in the brain following psilocybin treatment in C57BL/6J male mice.Materials and methodsEleven- to 15-week-old C57BL/6J male mice were randomly assigned to receive psilocybin, 6-fluoro-N, N-diethyltryptamine, or saline and ex vivo imaged 24 hours (n=18) and 72 hours (n=18) posttreatment. A1-way ANOVA with multiple comparison testing (Bonferroni correction) assessed diffusion metric differences (tractography, DTI, neurite orientation dispersion and density imaging) between the 3 groups and was performed in the following regions of interest: amygdala, striatum, hippocampus, thalamus, primary visual cortex area, frontal association cortex, and medial prefrontal cortex at 24 hours and 72 hours postdrug administration.ResultsPsilocybin-treated mice demonstrated structural connectivity differences at 72 hours in the frontal association cortex (compared with saline, mean tract length increases, P =.03). Psilocybin also induced microstructural differences at 24 hours postinjection in the primary visual cortex (compared with saline, mean diffusivity [MD] increases, P =.02) and 72 hours postinjection in the striatum (compared with saline; MD increases, P =.02, neurite density index [NDI] decreases, P =.02) and hippocampus (compared with saline; MD increases, P =.04, NDI decreases, P =.02).ConclusionsDiffusion microstructure imaging and white matter tractography are sensitive methods to detect and characterize the neural substrates and microstructural differences accompanying psilocybin treatment. These findings suggest the potential role for diffusion microstructure imaging to quantify the bioeffects of psychedelics like psilocybin on the brain, monitor treatment response, and identify salient clinical end points in an emerging therapeutic option for patients with MDD.

raw_json:
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authors: Karthiyayini B, Kalyani NN, Gowdhami B, Muthuselvam M, Dharumadurai D.
publication_date: 2024-10-12
doi: 10.1007/s12088-024-01396-2
pubmed_id: 40655360
source_url: https://doi.org/10.1007/s12088-024-01396-2
substance_tags: psilocybin
topic_tags: Depression,Toxicity
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Characterization and Identification of an Antimicrobial Compound Psilocybin from Psychedelic Mushroom.

abstract:
The antimicrobial compound psilocybin possesses psychoactive properties with therapeutic applications. Psilocybin is the main component naturally present in psychedelic mushrooms and has been utilized in the treatment of depression and neurological disorders. In this study, psychedelic mushrooms were collected from Kodaikanal, Tamil Nadu. They underwent solvent extraction using High Performance Thin Layer Chromatography (HPTLC) and Liquid Chromatography-Mass Spectrometry (LC-MS). Psilocybin, the primary compound, was extracted and evaluated. The extracted psilocybin was then assessed for antimicrobial activity against bacterial and fungal strains using the well diffusion method. Furthermore, HPTLC and LC-MS were employed for the identification of the psilocybin compound. The Rf values of psilocybin were found to be 0.73 and 0.77. Psilocybin inhibited the growth of bacterial and fungal pathogens including Staphylococcus epidermidis, Pseudomonas aeruginosa, Candida tropicalis, and Trichophyton rubrum. The bacterial culture was inhibited at a minimum inhibitory concentration of 12.5 µg/mL, whereas fungal pathogens were inhibited at 6.25 µg/mL. Thus, the findings conclude that in addition to its psychoactive properties, psilocybin could be utilized to develop antimicrobial drugs in future studies with in vivo efficacy and toxicity assays.Graphical abstract

raw_json:
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title: Race and Gender Differences in the Moderating Relationship of Psychedelics on Stigma and Distress.
authors: Viña SM.
publication_date: 2025-05-25
doi: 10.1089/psymed.2024.0021
pubmed_id: 40530404
source_url: https://doi.org/10.1089/psymed.2024.0021
substance_tags: psilocybin
topic_tags: Mechanism of Action,Observational Study,Drug Interactions
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
ObjectivePrior research has found an association between psychedelic use and reduced stigma attached to mental illness. However, whether psychedelics alleviate stigma-related distress remains unclear. Since stigma impacts different groups uniquely, any moderating effect of psychedelics on stigma-related distress is likely to vary across subpopulations. This study addresses two main questions: (1) Do psychedelics moderate the relationship between stigma and distress? and (2) does this relationship vary by gender and race/ethnicity? By exploring these questions, this research seeks to contribute to our understanding of psychedelic use and its impact on mental health across diverse populations.MethodsData from the National Survey of Drug Use (2008-2019) were analyzed, with a weighted sample of 458,372. The main analysis used regression models in Stata 18 to examine the associations between lifetime psychedelic use (LPU) (psilocybin, lysergic acid diethylamide [LSD], N,N-dimethyltryptamine, peyote/mescaline, ayahuasca, and 3,4-Methylenedioxymethamphetamine), stigma attached to seeking mental health care, and psychological distress. This analysis examines whether the association between stigma and distress differs by gender, race/ethnicity, and psychedelic use (i.e., White men, White women, Black men, Black women, Asian men, Asian women, Hispanic men, and Hispanic women).ResultsResults indicate that men report lower perceived stigma than women, while women report higher distress. White, Black, and Hispanic women report the highest stigma levels. Regression analysis suggests that among the total population, stigma is statistically associated with higher distress, and interaction terms indicate that MDMA, psilocybin, LSD, and LPU are linked to variations in this relationship. Regression models stratified by gender and race/ethnicity suggest that while LPU, LSD, and DMT were statistically associated with differences in the relationship between stigma and distress for White men, these associations appeared weaker for other groups.ConclusionPsychedelic use is associated with lower reported distress from internalized stigma, though the directionality and mechanisms underlying this association remain unclear. Further research should be conducted to investigate how psychedelics can be integrated into comprehensive health treatment programs outside of psychedelics-assisted therapy. However, it is worth noting that individuals from gender and racial/ethnic minority groups may not experience the same level of benefits, suggesting other strategies may be necessary to address the stigma experienced by different groups.

raw_json:
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authors: Fonzo GA, Doss MK, Nemeroff CB.
publication_date: 2025-05-31
doi: 10.1176/appi.ajp.20250247
pubmed_id: 40450555
source_url: https://doi.org/10.1176/appi.ajp.20250247
substance_tags: psilocybin
topic_tags: Depression,Emotional Processing
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
There's More Than One Way to Bring Health Back: Divergent Effects of Psilocybin and Escitalopram Treatment on Emotional Brain Function in Depression.

raw_json:
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title: Pharmacologic interventions for alcohol use disorder.
authors: Menge J, Evitt B.
publication_date: 2025-05-26
doi: 10.1097/01.jaa.0000000000000106
pubmed_id: 40421949
source_url: https://doi.org/10.1097/01.jaa.0000000000000106
substance_tags: psilocybin
topic_tags: Addiction,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
AbstractAlcohol use disorder (AUD) has devastating effects, and its prevalence in the US is growing. It is therefore important to examine multiple avenues for successful cessation and continued abstinence. Disulfiram, oral naltrexone, naltrexone IM, and acamprosate are currently the only four medications approved for the treatment of AUD by the FDA. This review aims to examine the efficacy of the approved medications as well as explore the use of off-label pharmacologic treatments used for AUD treatment (including gabapentin, baclofen, oxytocin, N-acetylcysteine, calcium carbonate, and psilocybin). Through this exploration, the most effective treatment for individuals with AUD can be determined to enable providers in ameliorating the prevalence of this disease.

keywords:
Humans, Alcoholism, Baclofen, Disulfiram, Taurine, Naltrexone, Acetylcysteine, Alcohol Deterrents, Off-Label Use, Gabapentin, Acamprosate

raw_json:
{"europe_pmc_id":"40421949","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin-enhanced fear extinction linked to bidirectional modulation of cortical ensembles
authors: Rogers SA, Heller EA, Corder G.
journal: bioRxiv
publication_date: 2024-02-03
doi: 10.1101/2024.02.04.578811
source_url: https://doi.org/10.1101/2024.02.04.578811
substance_tags: psilocybin
topic_tags: Brain Imaging,Receptor Pharmacology,Aging
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
abstract:
The serotonin 2 receptor (5HT2R) agonist psilocybin displays rapid and persistent therapeutic efficacy across neuropsychiatric disorders characterized by cognitive inflexibility. However, the impact of psilocybin on patterns of neural activity underlying sustained changes in behavioral flexibility has not been characterized. To test the hypothesis that psilocybin enhances behavioral flexibility by altering activity in cortical neural ensembles, we performed longitudinal single-cell calcium imaging in the retrosplenial cortex across a five-day trace fear learning and extinction assay. A single dose of psilocybin induced ensemble turnover between fear learning and extinction days while oppositely modulating activity in fearand extinctionactive neurons. The acute suppression of fear-active neurons and delayed recruitment of extinction-active neurons were predictive of psilocybin-enhanced fear extinction. A computational model revealed that acute inhibition of fear-active neurons by psilocybin is sufficient to explain its neural and behavioral effects days later. These results align with our hypothesis and introduce a new mechanism involving the suppression of fear-active populations in the retrosplenial cortex.

raw_json:
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title: The pharmacological treatment of anxiety in people with eating disorders: A systematic review.
authors: Morris R, Keeler J, Treasure J, Himmerich H.
publication_date: 2025-05-13
doi: 10.1016/j.phrs.2025.107782
pubmed_id: 40378942
source_url: https://doi.org/10.1016/j.phrs.2025.107782
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
abstract:
People with eating disorders experience high rates of psychiatric comorbidities, including anxiety disorders such as generalised anxiety disorder, social anxiety disorder and specific phobias. Anxiety can influence the prognosis of an eating disorder, by worsening symptoms, and acting as a barrier to treatment. Therefore, targeting treatment efforts towards anxiety may improve eating disorder outcomes. The primary aim of this systematic review was to summarise the evidence base for the pharmacological treatment of anxiety symptoms in people with eating disorders. An electronic search of three databases (PubMed, Medline, and PsycInfo) was conducted. Papers were included if they investigated pharmacotherapy (antidepressants, antipsychotics, antianxiety, psychedelics, etc.) in eating disorder samples, with primary or secondary outcomes of anxiety. A total of 51 studies were included, and results were mixed across drug classes documenting both favourable and non-significant anxiety outcomes. There was evidence for the use of fluoxetine for anxiety in anorexia and bulimia nervosa, but not for binge eating disorder. Evidence for the use of olanzapine was documented for anxiety in AN, and preliminary case reports suggested its use in ARFID for anxiety symptoms. Preliminary evidence for developing pharmacological agents, such as psilocybin and ketamine, reported favourable outcomes in AN patients. More RCTs are required to explore efficacy and safety of pharmacological agents in treating anxiety in people with eating disorders.

keywords:
Animals, Humans, Anti-Anxiety Agents, Antipsychotic Agents, Antidepressive Agents, Anxiety, Anxiety Disorders, Feeding and Eating Disorders

topic_tags:
Depression,Anxiety,Eating Disorders,Randomized Controlled Trial,Systematic Review,Review Article,Case Report,Safety

raw_json:
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authors: Wall MB, Demetriou L, Giribaldi B, Roseman L, Ertl N, Erritzoe D, Nutt DJ, Carhart-Harris RL.
publication_date: 2025-05-06
doi: 10.1176/appi.ajp.20230751
pubmed_id: 40329640
source_url: https://doi.org/10.1176/appi.ajp.20230751
substance_tags: psilocybin
topic_tags: Depression,Brain Imaging,Receptor Pharmacology,Aging,Emotional Processing
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Reduced Brain Responsiveness to Emotional Stimuli With Escitalopram But Not Psilocybin Therapy for Depression.

abstract:
ObjectivePsilocybin is an emerging intervention for depression that may be at least as effective as selective serotonin reuptake inhibitors (SSRIs), but effects of the two treatments on the neural correlates of emotional processing have never been directly compared.MethodsThe authors assessed neural responses to emotional faces using blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) in two groups with major depression. One group (N=25; 9 women and 16 men) received two dosing sessions with 25 mg psilocybin plus 6 weeks of daily inert placebo, and the second group (N=21; 6 women and 15 men) received 6 weeks of escitalopram plus two dosing sessions with a nonpsychoactive (placebo) dose of 1 mg psilocybin. Both groups had equal psychological support throughout: 3 hours of preparation, one in-person integration session following the psilocybin dosing sessions, and two further integration sessions conducted via video call or telephone. An emotional face fMRI paradigm was completed before treatment and at the 6-week posttreatment primary end point (3 weeks following psilocybin dosing sessions).ResultsPatient group (psilocybin versus escitalopram) interacted with time point (before versus after treatment) on a distributed set of cortical regions. Post hoc within-condition analyses showed that posttreatment BOLD responses to emotional faces of all types were significantly reduced in the escitalopram group, with no change or a slight increase in the psilocybin group. Analyses of amygdala responsivity showed a reduction of response to fearful faces in the escitalopram group, but lesser effects for the psilocybin group.ConclusionsDespite large improvements in depressive symptoms in the psilocybin group, psilocybin therapy had only a minor effect on brain responsiveness to emotional stimuli. These results are consistent with prior findings that the antidepressant action of SSRIs is often accompanied by a reduction in emotional responsiveness, but this effect may not occur in psychedelic therapy.

keywords:
Brain, Amygdala, Humans, Hallucinogens, Magnetic Resonance Imaging, Facial Expression, Treatment Outcome, Double-Blind Method, Emotions, Adult, Middle Aged, Female, Male, Psilocybin, Escitalopram, Selective Serotonin Reuptake Inhibitors, Major Depressive Disorder

raw_json:
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title: Innovation and inequity in psychedelic research at the Mayo Clinic.
authors: Klim C, VanDreese B, Meyerhoefer T, Breitinger S
journal: History of psychiatry
publication_date: 2025-05-31
doi: 10.1177/0957154x251318489
pubmed_id: 40293719
source_url: https://pubmed.ncbi.nlm.nih.gov/40293719/
keywords: Bioethics, LSD, psilocybin, psychedelics, schizophrenia
substance_tags: psilocybin
topic_tags: Safety
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"40293719"}
abstract:
This paper provides an overview of psychedelic research at the Mayo Clinic in the 1950s and 1960s, focusing on methods, objectives, findings, and ethical practices. We highlight instances where researchers prioritized scientific progress over the autonomy, safety, and equitable treatment of research subjects, and discuss this history in the context of ongoing challenges with informed consent and equity in contemporary psychedelic research.


publication_date: 2025-04-14
doi: 10.1016/j.neubiorev.2025.106163
pubmed_id: 40245969
source_url: https://doi.org/10.1016/j.neubiorev.2025.106163
keywords: Humans, Substance-Related Disorders, Hallucinogens, Psilocybin, Outcome Assessment, Health Care
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Efficacy and safety of psilocybin for the treatment of substance use disorders: A systematic review.

authors:
Meshkat S, Malik G, Zeifman RJ, Swainson J, Balachandra K, Reichelt AC, Zhang Y, Burback L, Winkler O, Greenshaw A, Vermetten E, Mayo LM, Tanguay R, Jetly R, Bhat V.

abstract:
Psilocybin, a serotonergic psychedelic, may have therapeutic benefits for Substance Use Disorders (SUDs), but its overall efficacy and safety remain uncertain. This systematic review assessed the safety and efficacy of psilocybin for SUDs through a systematic database search conducted via OVID on May 22, 2024, and summarized 26 ongoing clinical trials registered on clinicaltrials.gov. Among 16 published included studies, 7 (43.75 %) focused on Alcohol Use Disorder (AUD), 5 (31.25 %) on Tobacco Use Disorder (TUD), and the remainder on Cocaine Use Disorder (CUD) (1, 6.25 %), Opioid Use Disorder (1, 6.25 %), Nicotine Use Disorder (1, 6.25 %), and multiple SUDs (1, 6.25 %). Study designs included open-label trials (5, 31.25 %), cross-sectional observational studies (6, 37.5 %), qualitative analyses (2, 12.5 %), one double-blind RCT (6.25 %), one pilot fMRI study (6.25 %), and one long-term follow-up (6.25 %). Psilocybin-assisted psychotherapy (PAP) was used in 10 studies (62.5 %), with doses ranging from microdosing to 20-40 mg/70 kg. PAP was associated with significant reductions in alcohol consumption, smoking cessation, and related psychological improvements. AUD studies reported fewer heavy drinking days, increased abstinence rates, and neuroimaging data indicating normalization of brain activity. TUD studies demonstrated high smoking abstinence rates, with mystical experiences predicting long-term outcomes. Findings for other SUDs were mixed, though psilocybin showed potential in reducing opioid dependence and nicotine use. Preliminary evidence supports psilocybin's efficacy and safety for AUD and TUD, particularly with psychotherapy, but larger clinical trials are needed to confirm these findings.

topic_tags:
Addiction,Brain Imaging,Aging,Microdosing,Mystical Experience,Clinical Trial,Randomized Controlled Trial,Systematic Review,Review Article,Observational Study,Safety

raw_json:
{"europe_pmc_id":"40245969","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Umbacia MA, Leon MX, Quintero JM, Castro LM, Paez V, Dodd S, Bustos RH.
publication_date: 2025-04-09
doi: 10.1080/14728214.2025.2488786
pubmed_id: 40178229
source_url: https://doi.org/10.1080/14728214.2025.2488786
substance_tags: psilocybin
topic_tags: Depression,End-of-Life Distress,Mechanism of Action,Receptor Pharmacology,Wellbeing,Clinical Trial
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
title:
Exploring psilocybin's role in mental health and palliative medicine: a path to improved well-being.

abstract:
IntroductionAlthough long known for their psychoactive effects, psychedelic drugs have only recently been investigated for medicinal use. Psilocybin has attracted the greatest interest with studies suggesting that it may be a useful agent in psychiatry and in palliative care.Areas coveredClinical trials that included psilocybin were searched in PubMed, Embase, and ClinicalTrials.gov, demonstrating that adult psychiatry and palliative care are the medical fields that show the greatest interest in psilocybin treatment.Expert opinionPsilocybin is a powerful drug that needs to be used with caution but may benefit some patients, including when other options have failed. It is best evidenced in treatment resistant depression and in palliative care, where patients are usually treated in specialist care centers. It has a novel mechanism of action, targeting the 5HT2A receptor, and can show rapid onset of action. There are many questions regarding its use that remain to be clarified, including its efficacy for other indications and its role as adjunctive treatment in psychotherapy. The psychoactive, or psychedelic effects are well documented, but their clinical importance is disputed.

keywords:
Animals, Humans, Hallucinogens, Palliative Care, Mental Health, Mental Disorders, Psychotherapy, Adult, Depressive Disorder, Treatment-Resistant, Psilocybin

raw_json:
{"europe_pmc_id":"40178229","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin's lasting action requires pyramidal cell types and 5-HT2A receptors.
publication_date: 2025-04-01
doi: 10.1038/s41586-025-08813-6
pubmed_id: 40175553
source_url: https://doi.org/10.1038/s41586-025-08813-6
substance_tags: psilocybin
topic_tags: Neuroplasticity,Brain Imaging,Receptor Pharmacology,Aging,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
authors:
Shao LX, Liao C, Davoudian PA, Savalia NK, Jiang Q, Wojtasiewicz C, Tan D, Nothnagel JD, Liu RJ, Woodburn SC, Bilash OM, Kim H, Che A, Kwan AC.

abstract:
Psilocybin is a serotonergic psychedelic with therapeutic potential for treating mental illnesses1-4. At the cellular level, psychedelics induce structural neural plasticity5,6, exemplified by the drug-evoked growth and remodelling of dendritic spines in cortical pyramidal cells7-9. A key question is how these cellular modifications map onto cell-type-specific circuits to produce the psychedelics' behavioural actions10. Here we use in vivo optical imaging, chemogenetic perturbation and cell-type-specific electrophysiology to investigate the impact of psilocybin on the two main types of pyramidal cells in the mouse medial frontal cortex. We find that a single dose of psilocybin increases the density of dendritic spines in both the subcortical-projecting, pyramidal tract (PT) and intratelencephalic (IT) cell types. Behaviourally, silencing the PT neurons eliminates psilocybin's ability to ameliorate stress-related phenotypes, whereas silencing IT neurons has no detectable effect. In PT neurons only, psilocybin boosts synaptic calcium transients and elevates firing rates acutely after administration. Targeted knockout of 5-HT2A receptors abolishes psilocybin's effects on stress-related behaviour and structural plasticity. Collectively, these results identify that a pyramidal cell type and the 5-HT2A receptor in the medial frontal cortex have essential roles in psilocybin's long-term drug action.

keywords:
Pyramidal Cells, Frontal Lobe, Dendritic Spines, Animals, Mice, Inbred C57BL, Mice, Calcium, Receptor, Serotonin, 5-HT2A, Hallucinogens, Action Potentials, Neuronal Plasticity, Female, Male, Psilocybin

raw_json:
{"europe_pmc_id":"40175553","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: Psychiatry research
publication_date: 2025-05-31
doi: 10.1016/j.psychres.2025.116446
pubmed_id: 40147088
source_url: https://pubmed.ncbi.nlm.nih.gov/40147088/
keywords: Ayahuasca, Ibogaine, Ketamine, LSD, Noribogaine, Opioid use disorder, Psilocybin, Psychedelics
substance_tags: psilocybin
topic_tags: Addiction,Receptor Pharmacology,Systematic Review,Review Article,Animal Study,Safety
study_type: Systematic Review
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"40147088"}
title:
The therapeutic effects of psychedelics for opioid use disorder: A systematic review of clinical studies.

authors:
Weleff J, Pulido-Saavedra A, Aghaei AM, Ing K, Arakelian M, Fontenele R, Nero N, Barnett BS, Anand A, Bassir Nia A, Angarita GA

abstract:
Opioid-related overdose deaths have reached record high levels, and novel treatments for opioid use disorder (OUD) are needed. The three United States Food and Drug Administration (FDA)-approved medications for OUD function primarily at the mu-opioid receptor. While these remain the gold-standard treatment for OUD, they have shortcomings and treatment options separate from the opioid receptor system deserve attention. Preclinical, clinical, and naturalistic studies of psychedelics have shown some evidence that they may reduce opioid and other substance use. Here, we present the results of a systematic review of clinical studies investigating the therapeutic applications of psychedelics for OUD to describe the current state of the literature and guide future clinical study design in this area. Findings indicate few studies completed using serotonergic psychedelics, with most investigating ibogaine or ketamine. In addition, findings are limited by many studies of weak design focused on opioid withdrawal, and few double-blind or placebo-controlled trials with considerable methodological heterogeneity making comparisons difficult across compounds. Most studies were found to have a high risk of bias mostly related to lack of randomization, blinding, and blinding of assessment outcomes. We outline these limitations and steps towards improving the quality of future studies of psychedelics for OUD.


publication_date: 2025-02-27
doi: 10.1002/cpt.3618
pubmed_id: 40022427
source_url: https://doi.org/10.1002/cpt.3618
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Acute Effects and Pharmacokinetics of LSD after Paroxetine or Placebo Pre-Administration in a Randomized, Double-Blind, Cross-Over Phase I Trial.

authors:
Becker AM, Humbert-Droz M, Mueller L, Jelušić A, Tolev A, Straumann I, Avedisian I, Erne L, Thomann J, Luethi D, Grünblatt E, Meyer Zu Schwabedissen H, Liechti ME.

abstract:
Psychedelics, such as psilocybin and lysergic acid diethylamide (LSD), are being investigated for the treatment of depressive and anxiety disorders, for which concomitant treatment with selective serotonin reuptake inhibitors (SSRIs) is prevalent. The present study investigated the acute response to single doses of LSD (100 μg) after daily administration of paroxetine (10 mg for 7 days, followed by 20 mg for 35 days) or placebo (42 days) using a randomized, double-blind, cross-over design in 23 healthy participants. Paroxetine did not alter pleasant subjective effects of LSD but significantly reduced "bad drug effect," "anxiety," and "nausea." No differences in autonomic effects or QTc interval after LSD administration were found between both conditions. The strong cytochrome P450 2D6 (CYP2D6) inhibitor paroxetine led to higher maximal concentrations and total exposures of LSD (geometric mean ratios of 1.4 and 1.5, respectively) indicating relevant involvement of CYP2D6 in its metabolism. The extent of this inhibition was nominally highest in genetic CYP2D6 normal metabolizers and lowest in poor metabolizers. The present findings suggest that add-on treatment with LSD to an SSRI is well-tolerated. The pharmacokinetic and pharmacodynamic interactions indicate that no dose adjustment of LSD seems necessary in the presence of an SSRI that inhibits CYP2D6. For SSRIs that do not relevantly inhibit CYP2D6, a dose increase of LSD might be appropriate, but due to lacking data and potential other pharmacokinetic interactions with these compounds, no definitive dose recommendation can be made.

keywords:
Humans, Lysergic Acid Diethylamide, Paroxetine, Cytochrome P-450 CYP2D6, Hallucinogens, Cross-Over Studies, Double-Blind Method, Drug Interactions, Adult, Middle Aged, Female, Male, Young Adult, Cytochrome P-450 CYP2D6 Inhibitors, Selective Serotonin Reuptake Inhibitors

topic_tags:
Depression,Anxiety,Pharmacology,Receptor Pharmacology,Clinical Trial,Healthy Volunteers,Drug Interactions

raw_json:
{"europe_pmc_id":"40022427","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Glynos NG, Baker A, Aday JS, Kruger D, Boehnke KF, Lake S, Lucas P.
publication_date: 2025-02-10
doi: 10.1177/20494637251319497
pubmed_id: 39944237
source_url: https://doi.org/10.1177/20494637251319497
substance_tags: psilocybin
topic_tags: Addiction,Chronic Pain,Observational Study,Safety
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Psychedelics and chronic pain: self-reported outcomes on changed substance use patterns and health following naturalistic psychedelic use.

abstract:
Psychedelic substances have shown preliminary efficacy for several neuropsychiatric disorders and are currently being investigated for chronic pain conditions. However, few studies have investigated outcomes of naturalistic psychedelic use among individuals with chronic pain, and none have assessed psychedelic-related changes in substance use patterns in this population. In a cross-sectional survey of adults who reported using psychedelics to self-treat a chronic pain condition (n = 466; 46.1% women), we investigated changed substance use patterns and self-reported outcomes on physical and mental health following use of a psychedelic. Most (86.3%; n = 391/453) indicated that they ceased or decreased use of one or more non-psychedelic substances "as a result of" psychedelic use, and 21.2% (n = 83/391) indicated that the decrease in use persisted for more than 26 weeks after psychedelic use. Alcohol (71.1%; n = 226/318) and prescription opioids (64.1%; n = 100/156) had the highest proportions for ceased/decreased use. Illicit opioids (27.8%; n = 22/79) and cannabis (21.5%; n = 78/362) had the highest proportions for increased/initiated use. In multivariate regression modeling, having a motivation to reduce one's substance use was positively associated with ceasing/decreasing substance use (p <.001). Perceptions of health outcomes following psychedelic use were broadly positive, and psilocybin was reported to be the most effective substance for both physical and mental health symptoms. Although limited by a cross-sectional study design, findings from this large sample merit future investigation into the benefits and risks of naturalistic psychedelic use among individuals with chronic pain.

raw_json:
{"europe_pmc_id":"39944237","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Yousefi P, Lietz MP, O'Higgins FJ, Rippe RCA, Hasler G, van Elk M, Enriquez-Geppert S.
publication_date: 2025-01-22
doi: 10.1007/s00213-024-06742-2
pubmed_id: 39847068
source_url: https://doi.org/10.1007/s00213-024-06742-2
substance_tags: psilocybin
topic_tags: Mechanism of Action,Meta-Analysis,Systematic Review,Review Article,Healthy Volunteers
study_type: Meta-Analysis
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Acute effects of psilocybin on attention and executive functioning in healthy volunteers: a systematic review and multilevel meta-analysis.

abstract:
RationalePsilocybin shows promise for treating neuropsychiatric disorders. However, insight into its acute effects on cognition is lacking. Given the significant role of executive functions in daily life and treatment efficacy, it is crucial to evaluate how psilocybin influences these cognitive domains.ObjectivesThis meta-analysis aims to quantify the acute effects of psilocybin on executive functions and attention, while examining how dosage, timing of administration, cognitive domain, and task characteristics moderate these effects.MethodsA systematic review and multilevel meta-analysis were conducted on empirical studies assessing psilocybin's acute effects on working memory, conflict monitoring, response inhibition, cognitive flexibility, and attention. Effect sizes for reaction time (RT) and accuracy (ACC) were calculated, exploring the effects of timing (on-peak defined as 90-180 min post-administration), dosage, cognitive function categories, and task sensitivity to executive functions as potential moderators.ResultsThirteen studies (42 effect sizes) were included. In the acute phase, psilocybin increased RTs (Hedges' g = 1.13, 95% CI [0.57, 1.7]) and did not affect ACC (Hedges' g = -0.45, 95% CI [-0.93, 0.034]). Effects on RT were dose dependent. Significant between-study heterogeneity was found for both RT and ACC. Task sensitivity to executive functions moderated RT effects. Publication bias was evident, but the overall effect remained significant after adjustment for this.ConclusionsOur meta-analysis shows that psilocybin impairs executive functions and results in a slowing down of RT. We discuss potential neurochemical mechanisms underlying the observed effects as well as implications for the safe use of psilocybin in clinical and experimental contexts.

keywords:
Humans, Hallucinogens, Cognition, Memory, Short-Term, Attention, Reaction Time, Dose-Response Relationship, Drug, Executive Function, Healthy Volunteers, Psilocybin

raw_json:
{"europe_pmc_id":"39847068","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin increases emotional empathy in patients with major depression.
authors: Jungwirth J, von Rotz R, Dziobek I, Vollenweider FX, Preller KH.
publication_date: 2024-12-17
doi: 10.1038/s41380-024-02875-0
pubmed_id: 39695323
source_url: https://doi.org/10.1038/s41380-024-02875-0
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Emotional Processing,Healthy Volunteers,Drug Interactions
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
Empathy plays a crucial role in interpersonal relationships and mental health. It is decreased in a variety of psychiatric disorders including major depression. Psilocybin, a promising candidate for treating depression, has been shown to acutely increase emotional empathy in healthy volunteers. However, no study has investigated this effect and its relevance for symptom improvement in a clinical population. This study examines the enduring effects of psilocybin-assisted therapy on empathy in depressed patients using a randomized, placebo-controlled design. Fifty-one depressed patients were randomly assigned to receive a single dose of psilocybin (0215 mg/kg body weight) or a placebo embedded in a 4-week psychological support intervention. Empathy was measured using the Multifaceted Empathy Test at baseline and 2 days, 1 week, and 2 weeks after substance administration. Changes in empathy were compared between treatment conditions. Patients who received psilocybin showed significant improvements in explicit emotional empathy driven by an increase in empathy towards positive stimuli compared to the placebo group for at least two weeks. This study highlights the potential of psychedelics to enhance social cognition in individuals living with depression and contributes to a better understanding of the psychological mechanisms of action of psychedelics. Further studies are necessary to investigate the interaction between social cognition and clinical efficacy.The trial is registered on clinicaltrials.gov (Identifier: NCT03715127) and KOFAM (Identifier: SNCTP000003139).

keywords:
Humans, Hallucinogens, Treatment Outcome, Double-Blind Method, Emotions, Empathy, Adult, Middle Aged, Female, Male, Psilocybin, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"39695323","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: Psychopharmacology
publication_date: 2025-05-31
doi: 10.1007/s00213-024-06654-1
pubmed_id: 39030424
source_url: https://pubmed.ncbi.nlm.nih.gov/39030424/
substance_tags: psilocybin
topic_tags: Depression,Neuroplasticity,Animal Study,Treatment-Resistant Depression
study_type: Animal Study
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"39030424"}
title:
Correction to: Unraveling psilocybin's therapeutic potential: behavioral and neuroplasticity insights in Wistar-Kyoto and Wistar male rat models of treatment-resistant depression.

authors:
Kolasa M, Nikiforuk A, Korlatowicz A, Solich J, Potasiewicz A, Dziedzicka-Wasylewska M, Bugno R, Hogendorf A, Bojarski A, Faron-Górecka A


authors: Vina SM.
publication_date: 2024-05-15
doi: 10.1007/s40615-024-02023-y
pubmed_id: 38753105
source_url: https://doi.org/10.1007/s40615-024-02023-y
substance_tags: psilocybin
topic_tags: Observational Study,Adolescents
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:05
title:
Minorities' Diminished Psychedelic Returns: Income and Educations Impact on Whites, Blacks, Hispanics, and Asians.

abstract:
Growing evidence suggests that the race and ethnic minority population may experience fewer protective effects of psychedelics on mental health. The minority diminished psychedelic returns theory proposes that racism, manifested in socioeconomic inequality, could partially account for the smaller health gains observed. Therefore, it is important to investigate whether socioeconomic inequality reduces the impact of psychedelics on health outcomes for minority populations. Additionally, despite having higher socioeconomic status, it remains unclear whether psychedelic use among minorities is associated with the same level of health benefits as observed in non-Hispanic whites. This study utilizes data from the National Survey of Drug Use (N = 2008 to 2019), which involved 458,372 participants aged 18 and above. The objective is to examine the impact of various psychedelics (MDMA, psilocybin, DMT, ayahuasca, peyote/mescaline, and LSD), as well as lifetime classic psychedelics use (LCPU), on psychological distress in the past month, taking into account socioeconomic factors (education level and family income) and race/ethnic differences (White, Black, Hispanic, and Asian). The analysis employed a series of nested ordinary least-square regression models using Stata 18. The results indicate that, after controlling for socioeconomic status, there is no association between Black and Hispanic psychedelic use and distress. However, white psychedelic use remains associated with lower levels of distress. Additionally, despite having higher levels of education and income, psychedelic use among minority groups does not appear to be linked to reduced stress. In fact, for Asians with higher education and income, certain psychedelic use is associated with increased distress.

keywords:
Humans, Hallucinogens, Minority Groups, Socioeconomic Factors, Adolescent, Adult, Middle Aged, Educational Status, Income, United States, Female, Male, Young Adult, Psychological Distress, Ethnicity, Hispanic or Latino, Black or African American, Asian, White

raw_json:
{"europe_pmc_id":"38753105","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: PsyArXiv
publication_date: 2025-03-06
source_url: https://osf.io/preprints/psyarxiv/6xgu8_v2
substance_tags: psilocybin
topic_tags: Personality Change
study_type: Other
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"6xgu8_v2","version":2,"reviews_state":"accepted"}
title:
Exploring Public Sentiments of Psychedelics Versus Other Substances: A Reddit-Based Natural Language Processing Study

abstract:
New methods that capture the public's perception of controversial topics may be valuable. This study investigates public sentiments towards psychedelics and other substances through analyzes of Reddit discussions, using Google’s cloud-based Natural Language Processing (NLP) infrastructure. Our findings indicate that illicit substances such as heroin and methamphetamine are associated with highly negative general sentiments, whereas psychedelics like Psilocybin, LSD, and Ayahuasca generally evoke neutral to slightly positive sentiments. This study underscores the effectiveness and cost efficiency of NLP and machine learning models in understanding the public’s perception of sensitive topics. The findings indicate that online public sentiment towards psychedelics may be growing in acceptance of their therapeutic potential. However, limitations include potential selection bias from the Reddit sample and challenges in accurately interpreting nuanced language using NLP. Future research should aim to diversify data sources and enhance NLP models to capture the full spectrum of public sentiment towards psychedelics. Our findings support the importance of ongoing research and public education to inform policy decisions and therapeutic applications of psychedelics.

keywords:
Natural Language Processing (NLP), Psychedelics, Psychoactive Substances, Public Perception, Sentiment Analysis, Social Media Analysis, Social and Behavioral Sciences, Quantitative Methods, Computational Modeling, Social and Personality Psychology, Attitudes and Persuasion, Health Psychology, Mental Health


authors: Abboud A, Schiebrel C, Nahhas RW, Durkin S, Hua K, Redding H, Gainer D.
publication_date: 2025-05-28
doi: 10.1080/02791072.2025.2511752
pubmed_id: 40443112
source_url: https://doi.org/10.1080/02791072.2025.2511752
substance_tags: psilocybin
topic_tags: Depression,PTSD,Addiction,Personality Change,Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Patients' Attitudes Toward Hallucinogenic and Non-Hallucinogenic Psilocybin for Mental Health Treatment.

abstract:
This study examined patient perspectives on psilocybin therapy, specifically their acceptance and views on the therapeutic benefits of both hallucinogenic and non-hallucinogenic forms. A cross-sectional survey was conducted among psychiatric patients aged 18-65 at a community mental health center, assessing their attitudes, knowledge, and acceptance of psilocybin therapy. In total, 62.4% of the participants expressed openness to hallucinogenic psilocybin (p =.009), while 60.4% were open to non-hallucinogenic forms (p =.023). Patients with major depressive disorder preferred hallucinogenic therapy more (p =.010), while those with borderline personality disorder (BPD) (p =.030) and post-traumatic stress disorder (PTSD) (p =.035) favored non-hallucinogenic options, possibly due to concerns about the intensity of hallucinogenic experiences. Individuals with substance use disorder (SUD) demonstrated a greater acceptance of both hallucinogenic (p =.007) and non-hallucinogenic forms (p =.046) than individuals without SUD. These findings suggest that societal stigma is not a significant barrier to psilocybin therapy and that non-hallucinogenic forms may provide a more accessible option for certain patient groups. Understanding patient perspectives on psilocybin therapy, including vulnerability to adverse hallucinogenic experiences, can inform personalized and effective treatments for resistant conditions.

raw_json:
{"europe_pmc_id":"40443112","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


