Adverse Events in Studies of Classic Psychedelics: A Systematic Review and Meta-Analysis
JAMA Psychiatry meta-analysis of 114 studies and 3,504 people summarizing reported harms; the safety anchor a skeptic asks for.
Psilocybin research
75 peer-reviewed studies and reviews, 1958 to 2026. 37 are randomized trials or meta-analyses. Below, what the published studies actually found, one by one, each linked to its source.
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The most-cited results in the field, each with a line on why it matters. New to the evidence, start here; the full register is below.
Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial
JAMA multi-site randomized trial in 104 adults with major depression; extends the evidence beyond treatment-resistant cases.
Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression
NEJM phase 2b in 233 patients across 10 countries; the largest controlled psilocybin depression trial and the basis for phase 3.
Trial of Psilocybin versus Escitalopram for Depression
First head-to-head test against a standard antidepressant; NEJM, 59 patients, no significant difference on the main measure.
Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial
Johns Hopkins randomized double-blind trial in 51 people with cancer distress; a cornerstone of the modern psilocybin research era.
Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial
NYU randomized trial in 29 cancer patients, published the same day as the Johns Hopkins study; together they anchored the field.
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Topic
Study design
Years
75 studies
Depression & mood
Efficacy and Safety of Psilocybin in Treatment-Resistant Major Depression: The EPISODE Randomized Clinical Trial
This phase 2b, triple-blind randomized clinical trial at two German university hospitals tested psilocybin for treatment-resistant major depression in 144 participants.
Single-Dose Synthetic Psilocybin With Psychotherapy for Treatment-Resistant Bipolar Type II Major Depressive Episodes: A Nonrandomized Open-Label Trial
A 2024 nonrandomized, open-label trial (n=15) conducted at Sheppard Pratt gave adults with treatment-resistant bipolar II disorder, during a major depressive episode, a single 25 mg dose of...
Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial
This phase 2, double-blind randomized clinical trial enrolled 104 adults with moderate-to-severe major depressive disorder across 11 U.S.
Single-dose psilocybin-assisted therapy in major depressive disorder: a placebo-controlled, double-blind, randomised clinical trial
This randomized, double-blind, placebo-controlled trial (n=52), published in eClinicalMedicine, gave adults with major depressive disorder either a single moderate weight-adjusted dose of...
Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression
This 2022 phase 2b, double-blind, randomized trial (n=233) tested a single dose of a synthetic psilocybin formulation (COMP360) given with psychological support to adults with...
Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up
This 2022 paper reported a prospective 12-month follow-up (n=24) of a Johns Hopkins trial in which adults with major depression received two doses of psilocybin alongside supportive psychotherapy.
Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial
In this randomized, waiting-list-controlled trial at Johns Hopkins, 27 adults with major depressive disorder were assigned to receive psilocybin-assisted therapy either immediately or after an...
Trial of Psilocybin versus Escitalopram for Depression
A 2021 phase 2, double-blind, randomized controlled trial (n=59) compared two sessions of psilocybin with a six-week course of the antidepressant escitalopram in adults with long-standing moderate-to-severe depression.
Psilocybin with psychological support for treatment-resistant depression: six-month follow-up
This 2018 open-label study followed up the same 20 patients with severe, treatment-resistant unipolar depression who had received two oral doses of psilocybin (10 mg then 25 mg, seven days...
Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study
In this open-label feasibility study, researchers at Imperial College London gave 20 patients with treatment-resistant depression two oral doses of psilocybin (10 mg, then 25 mg a week later)...
Psilocybin for treatment resistant depression in patients taking a concomitant SSRI medication
This phase 2, open-label exploratory study examined whether an ongoing SSRI blunts the response to a single 25 mg dose of synthetic psilocybin (COMP360) given with psychological support.
End-of-life & cancer distress
Psilocybin-assisted psychotherapy for depression and anxiety associated with life threatening illness: A phase 2b randomized controlled trial
A 2025 double-blind, randomized phase 2b trial in Australia (n=35; 17 received psilocybin, 18 received placebo) tested a single 25 mg dose of psilocybin against 100 mg niacin as an active...
Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer
This 2020 study reports long-term follow-up of the NYU trial cohort, surveying surviving participants who had received a single psilocybin session for cancer-related psychiatric and existential...
Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial
In this randomized, double-blind crossover trial at Johns Hopkins, 51 people with life-threatening cancer and symptoms of depression and/or anxiety received a very low, placebo-like dose of...
Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial
In this double-blind, placebo-controlled crossover trial at New York University, 29 patients with cancer-related anxiety and depression were randomly assigned to a single dose of psilocybin...
Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer
A 2011 double-blind, placebo-controlled pilot study (n=12) gave adults with advanced-stage cancer and anxiety a moderate dose of psilocybin (0.2 mg/kg) and a placebo (niacin) in separate sessions.
Acute and Sustained Reductions in Loss of Meaning and Suicidal Ideation Following Psilocybin-Assisted Psychotherapy for Psychiatric and Existential Distress in Life-Threatening Cancer
This 2021 paper is a secondary analysis of the NYU randomized cancer trial (n=29) focused on existential outcomes.
Psilocybin-assisted group therapy for demoralized older long-term AIDS survivor men: An open-label safety and feasibility pilot study
This 2020 open-label pilot study tested the safety and feasibility of psilocybin-assisted group therapy in 18 older gay-identified men who had survived an HIV/AIDS diagnosis from before 1996...
Substance use
Psilocybin-assisted therapy for relapse prevention in alcohol use disorder: a phase 2 randomized clinical trial
A 2025 single-center, double-blind, randomized phase 2 trial in Switzerland (37 completers; 18 psilocybin, 19 placebo) tested a single 25 mg dose of psilocybin against placebo (mannitol), each...
Psilocybin in alcohol use disorder and comorbid depressive symptoms: Results from a feasibility randomized clinical trial
A 2025 single-center, double-blind, randomized pilot trial (n=30 adults with severe alcohol use disorder and depression, allocated 2:1) compared a single 25 mg psilocybin session plus...
Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder: A Randomized Clinical Trial
A 2022 double-blind randomized clinical trial (95 adults randomized, 93 treated) compared two psilocybin-assisted psychotherapy sessions (25-40 mg per 70 kg) against an active placebo...
Long-term follow-up of psilocybin-facilitated smoking cessation
A 2017 long-term follow-up of the 15-participant open-label smoking-cessation pilot reported that 10 participants (67%) were confirmed abstinent at 12 months, and 9 (60%) remained abstinent at...
Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction
A 2014 open-label pilot study (n=15 nicotine-dependent smokers) tested psilocybin delivered within a structured cognitive behavioral therapy program for smoking cessation.
Cessation and reduction in alcohol consumption and misuse after psychedelic use
A 2019 retrospective online survey (n=343 adults who had previously met criteria for alcohol use disorder and later had a psychedelic experience outside of treatment) reported changes in self-described drinking afterward.
Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study
A 2015 open-label proof-of-concept study (n=10) gave adults diagnosed with alcohol dependence oral psilocybin in one or two supervised sessions alongside Motivational Enhancement Therapy.
Psilocybin-Occasioned Mystical Experiences in the Treatment of Tobacco Addiction
A 2014 secondary analysis of the 15-participant open-label smoking-cessation pilot examined how the subjective quality of the psilocybin sessions related to outcomes.
Other indications
A randomized clinical trial of repeated doses of psilocybin for the treatment of obsessive-compulsive disorder
A 2026 randomized controlled trial (n=15 participants with obsessive-compulsive disorder) compared psilocybin with an active placebo (lorazepam).
Psilocybin therapy for females with anorexia nervosa: a phase 1, open-label feasibility study
A 2023 phase 1, open-label feasibility study (n=10 adult females with anorexia nervosa) reported on a single 25 mg dose of psilocybin given alongside psychological support.
Psilocybin pulse regimen reduces cluster headache attack frequency in the blinded extension phase of a randomized controlled trial
This 2024 paper reports the blinded extension phase (n=10) of a controlled cluster-headache study, in which participants could return for an open repeat of the three-dose psilocybin pulse...
Pilot study of single-dose psilocybin for serotonin reuptake inhibitor-resistant body dysmorphic disorder
A 2023 open-label pilot trial (n=12 adults with body dysmorphic disorder unresponsive to serotonin reuptake inhibitors) tested a single 25 mg oral dose of psilocybin given with psychological support.
Exploratory investigation of a patient-informed low-dose psilocybin pulse regimen in the suppression of cluster headache: Results from a randomized, double-blind, placebo-controlled trial
A 2022 randomized, double-blind, placebo-controlled exploratory trial (n=14 analyzed) tested a patient-informed regimen of three low doses of psilocybin (0.143 mg/kg), given about five days...
Exploratory Controlled Study of the Migraine-Suppressing Effects of Psilocybin
A 2021 double-blind, placebo-controlled cross-over study (n=10) tested a single oral dose of psilocybin (0.143 mg/kg) against placebo in people with migraine, tracking headaches for two weeks after each session.
Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder
A 2006 modified double-blind study (n=9 patients with obsessive-compulsive disorder) reported on up to four single doses of psilocybin per participant, ranging from sub-hallucinogenic to...
Hallucinogen-induced relief of obsessions and compulsions
A 1997 single-patient case report in the American Journal of Psychiatry (filed as a letter) describing a person with obsessive-compulsive disorder who, the authors report, experienced temporary...
Mechanism & neuroimaging
Psilocybin desynchronizes the human brain
This 2024 study used dense, repeated brain scanning (precision functional mapping, roughly 18 MRI sessions per person) in a small group of healthy adults who received a 25 mg dose of psilocybin...
Increased global integration in the brain after psilocybin therapy for depression
This 2022 study reanalyzed brain-scan (fMRI) data from two earlier trials of psilocybin for depression, including one open-label trial and one randomized trial comparing psilocybin with the antidepressant escitalopram.
Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo
This 2021 mouse study used two-photon microscopy to watch individual brain-cell connections over time.
Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function
This 2019 review from the Johns Hopkins group draws together four strands of classic-psychedelic research: population surveys on use and outcomes, early-phase clinical trials across several...
Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels
In this 2019 study, researchers gave healthy volunteers single oral doses of psilocybin (ranging from about 3 to 30 mg) and used PET brain scans plus blood samples to track what was happening in the body.
REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics
A 2019 theoretical review in Pharmacological Reviews (vol 71, issue 3, pp 316-344) proposing the 'REBUS' model, Relaxed Beliefs Under pSychedelics, which combines the entropic-brain hypothesis...
Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression
This 2018 Imperial College London analysis (Frontiers in Pharmacology, 8:974) drew on an open-label study in which 19 people with treatment-resistant depression received two doses of psilocybin with psychological support.
Psychedelics Promote Structural and Functional Neural Plasticity
This 2018 laboratory study tested several psychedelic compounds in rodent and fruit-fly models and in cultured neurons.
Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms
In this 2017 open-label study, researchers used fMRI to scan the brains of patients with treatment-resistant depression before and one day after two doses of psilocybin (usable imaging data from 16 of 19 participants).
Patients' Accounts of Increased "Connectedness" and "Acceptance" After Psilocybin for Treatment-Resistant Depression
A 2017 qualitative study (Journal of Humanistic Psychology, vol 57, pp 520-564) drawn from the Imperial College open-label trial of psilocybin for treatment-resistant depression.
Psychedelics
This 2016 review by pharmacologist David E. Nichols is a widely cited, book-length survey of the serotonergic psychedelics, including psilocybin, LSD, mescaline and DMT. It covers their...
The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs
This 2014 'Hypothesis and Theory' paper by Carhart-Harris and colleagues draws on psilocybin neuroimaging data to propose the 'entropic brain' hypothesis: that the richness of a conscious state...
Prediction of psilocybin response in healthy volunteers
A pooled analysis of data from 23 controlled laboratory studies, covering 409 psilocybin administrations to 261 healthy volunteers, examining which factors predict the acute response.
Factor Analysis of the Mystical Experience Questionnaire: A Study of Experiences Occasioned by the Hallucinogen Psilocybin
A 2012 psychometric study that analyzed questionnaire data from 1,602 people who had taken psilocybin and reported a 4-factor structure underlying classic mystical-type experiences:...
Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin
In this 2012 fMRI study, researchers led by Carhart-Harris scanned two groups of healthy volunteers (15 and 15) before and after they received intravenous psilocybin.
Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects
A double-blind, dose-escalation study in which 18 healthy, mostly hallucinogen-naive adults each received five sessions with placebo or psilocybin at ascending or descending doses (0, 5, 10, 20, and 30 mg/70 kg).
Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance
A 2006 Johns Hopkins double-blind study had 36 hallucinogen-naive healthy adults receive a high dose of psilocybin and a comparison drug (methylphenidate) under supportive conditions, in counterbalanced order.
Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action
A 1998 human study by Vollenweider and colleagues tested which receptor drives psilocybin's psychoactive effects.
Homological scaffolds of brain functional networks
In this 2014 study, Petri and colleagues applied topological data analysis to fMRI scans from healthy volunteers who received either placebo or intravenous psilocybin.
Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness
This 2011 Johns Hopkins study (Journal of Psychopharmacology, 25(11):1453-1461) analyzed data from healthy adults who received psilocybin and placebo-like comparison doses under supportive...
Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later
This 2008 Johns Hopkins follow-up (Journal of Psychopharmacology, 22(6):621-632) revisited healthy adult volunteers roughly 14 months after they received psilocybin under supportive conditions...
Safety & epidemiology
Acute Adverse Effects of Therapeutic Doses of Psilocybin: A Systematic Review and Meta-Analysis
A 2024 systematic review and meta-analysis of six randomized, double-blind trials (528 participants treated for depression or anxiety, including major depressive disorder, treatment-resistant...
Adverse Events in Studies of Classic Psychedelics: A Systematic Review and Meta-Analysis
A 2024 systematic review and meta-analysis pooling 114 studies (3,504 participants) examined how often adverse events were reported across classic-psychedelic research.
Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences
A 2016 anonymous online survey (n=1,993) in which respondents recalled their single most psychologically difficult or challenging experience after taking psilocybin mushrooms.
Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population
A 2015 cross-sectional study pooling five years of the US National Survey on Drug Use and Health (2008-2012), covering over 190,000 adults.
Psychedelics not linked to mental health problems or suicidal behavior: A population study
An observational analysis of a U.S. National Survey on Drug Use and Health sample of 135,095 adults, including roughly 19,300 who reported lifetime use of a classic psychedelic. The authors...
Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies
A 2011 pooled analysis combining eight double-blind, placebo-controlled experiments (110 healthy volunteers, studies run 1999-2008) to characterize psilocybin's acute, short-term and long-term subjective effects.
Human hallucinogen research: guidelines for safety
A methods and safety review by Johns Hopkins researchers that proposes widely cited guidelines for conducting human studies with hallucinogens such as psilocybin.
Reviews & meta-analyses
Efficacy and safety of psychedelics for the treatment of mental disorders: A systematic review and meta-analysis
This 2024 systematic review and meta-analysis pooled 126 included articles covering several classic and related psychedelics (psilocybin, LSD, ayahuasca, MDMA).
Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis
This systematic review and meta-analysis pooled randomized trials comparing psilocybin against control conditions for depressive symptoms.
Efficacy and acceptability of psilocybin for primary or secondary depression: A systematic review and meta-analysis of randomized controlled trials
This 2024 meta-analysis pooled 8 randomized controlled trials covering 524 adults with primary or secondary depression.
Psychedelic therapy for depressive symptoms: A systematic review and meta-analysis
This 2023 systematic review examined fourteen psychedelic-therapy studies using psilocybin, ayahuasca, or LSD, with seven randomized trials carried forward into the meta-analysis.
Classic serotonergic psychedelics for mood and depressive symptoms: a meta-analysis of mood disorder patients and healthy participants
This 2021 meta-analysis pooled 12 randomized, double-blind trials (257 participants in total: 124 healthy volunteers and 133 people with mood disorders) of classic serotonergic psychedelics,...
Efficacy of psychedelic treatments on depressive symptoms: A meta-analysis
This 2020 meta-analysis pooled eight studies of serotonergic psychedelic (5-HT2A agonist) treatments and their effect on depressive symptoms.
Psilocybin as a New Approach to Treat Depression and Anxiety in the Context of Life-Threatening Diseases-A Systematic Review and Meta-Analysis of Clinical Trials
This 2020 systematic review with meta-analysis pooled three randomized controlled trials (n=92), most involving patients with advanced cancer, to assess psilocybin's effect on depression and anxiety.
A Meta-Analysis of Placebo-Controlled Trials of Psychedelic-Assisted Therapy
This 2020 meta-analysis identified nine randomized, placebo-controlled trials of psychedelic-assisted therapy published since 1994, covering psilocybin, LSD, ayahuasca, and MDMA.
The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis
This 2020 meta-analysis pooled four studies (117 participants total), three of which were randomized and placebo-controlled, to examine psilocybin's reported effects on anxiety and depression symptoms.
Foundational & historical
Pahnke's "Good Friday Experiment": A Long-Term Follow-Up and Methodological Critique
A 1991 long-term follow-up published in the Journal of Transpersonal Psychology.
Implications of LSD and Experimental Mysticism
A 1966 theoretical paper in the Journal of Religion and Health in which Pahnke and Richards proposed a nine-category typology for describing mystical experience.
Drugs and Mysticism: An Analysis of the Relationship between Psychedelic Drugs and the Mystical Consciousness
This 1963 Harvard doctoral dissertation (a thesis, not a journal article) documents the double-blind 'Good Friday' or Marsh Chapel Experiment that Walter Pahnke conducted in 1962.
Psilocybin, ein psychotroper Wirkstoff aus dem mexikanischen Rauschpilz Psilocybe mexicana Heim
This 1958 report in Experientia is the foundational chemical-identification paper for psilocybin.
For educational purposes only. Each summary reports what the cited study found and is not medical advice or an endorsement. This site makes no medical claims about psilocybin.