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Psilocybin

The primary psychoactive compound in psilocybin mushrooms, studied most heavily as an assisted therapy for depression, anxiety, and addiction.

State of the evidence

Synthesized

Synthesized from 25 studies in the library · AI-generated, grounded in the abstracts below

Found by searching the library for Psilocybin, magic mushrooms, psilocin, psychedelic mushrooms, then ranked by relevance.

Psilocybin, particularly at higher doses (20-30 mg) and combined with psychological support, shows rapid and sustained reductions in depression and anxiety in patients with life-threatening cancer and treatment-resistant depression, with effects lasting up to 6-12 months in open-label and controlled trials. A meta-analysis of six RCTs confirms standard-dose psilocybin is superior to control conditions for major depressive disorder, though a head-to-head trial found no significant difference versus escitalopram at 6 weeks. The evidence is promising but limited by small sample sizes, open-label designs, and lack of long-term durability data beyond 12 months.

Evidence by study

Direction is which way each study's own result points, not our rating of the study.

What the directions mean
Supports:
the study found the intervention worked, or its hypothesis held.
Opposes:
it found the opposite, no benefit or a harm.
No effect:
no significant difference either way.
Mixed:
effects in both directions within the same study.
Unclear:
the abstract does not report a direction.
Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial 2016
Supports

High-dose psilocybin produced large decreases in depression and anxiety, sustained at 6 months with ~80% showing clinically significant improvement.

RCT Sample size: 51

Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial 2016
Supports

Single-dose psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression, with 60-80% maintaining reductions at 6.5 months.

RCT Sample size: 29

Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. 2016
Supports

Psilocybin produced rapid and sustained antidepressant effects in treatment-resistant depression, with no control group.

open-label feasibility study Sample size: 12

Trial of Psilocybin versus Escitalopram for Depression 2021
No effect

No significant difference in antidepressant effects between psilocybin and escitalopram at week 6 on the primary outcome, though secondary outcomes favored psilocybin.

RCT

Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder 2020
Supports

Two psilocybin sessions produced large antidepressant effects in MDD compared to a waiting-list control.

RCT Sample size: 27

Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer 2010
Supports

Psilocybin significantly reduced anxiety at 1 and 3 months and improved depression at 6 months, with no serious adverse events.

RCT Sample size: 12

Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin 2012
Unclear

Psilocybin decreased cerebral blood flow and BOLD signal in hub regions like the thalamus and cingulate cortex, with decreased mPFC-PCC coupling predicting subjective effects.

observational (fMRI) Sample size: 30

Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study 2015
Supports

Psilocybin significantly increased abstinence from alcohol after administration, with gains largely maintained up to 36 weeks.

proof-of-concept study Sample size: 10

REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics 2019
Unclear

Proposes the REBUS model: psychedelics relax the precision of high-level priors, enabling revision of maladaptive beliefs underlying mental illness.

theoretical

Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. 2022
Supports

25 mg psilocybin significantly reduced depression at week 3 vs. 1 mg control, but sustained response at 12 weeks was not significant.

RCT Sample size: 233

Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action 1998
Opposes

Psilocybin induces a psychosis-like syndrome in humans, blocked by a serotonin-2A antagonist, suggesting a role for 5-HT2A overactivity in schizophrenia.

observational

Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. 2017
Supports

Psilocybin produced large reductions in depressive symptoms at 5 weeks (Cohen's d=2.3) that remained significant at 6 months (d=1.4).

open-label trial Sample size: 20

Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. 2011
Supports

Psilocybin at 20-30 mg/70 kg occasioned mystical-type experiences in 72% of volunteers, with sustained positive changes in attitudes, mood, and behavior at 14 months.

RCT Sample size: 18

Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction 2014
Supports

80% of participants showed seven-day point prevalence abstinence at 6-month follow-up after psilocybin-assisted smoking cessation treatment.

open-label pilot study Sample size: 15

Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness 2011
Supports

Psilocybin increased the personality trait of Openness, sustained over 1 year in those who had mystical experiences.

RCT

Changes in anxiety, quality of life, and functioning following psilocybin-assisted therapy in veterans with treatment-resistant depression. 2026
Supports

Psilocybin produced sustained improvements in anxiety (59% reduction at week 3) and quality of life through 12 months, though effects were not significant after accounting for depression improvement.

open-label trial Sample size: 15

Contribution of the Serotonin 5-HT2A Receptor to the Therapeutic Effect of Psilocin on Social Behavior Deficits in Mice Repeatedly Exposed to Social Defeat Stress. 2026
Unclear

Study investigates the role of the serotonin 5-HT2A receptor in psilocin's effect on social behavior deficits in mice.

preclinical (animal)

The role of therapeutic alliance in psilocybin treatment for treatment-resistant depression: A post hoc path analysis. 2026
Mixed

Therapeutic alliance had weaker direct effects on depression outcomes than the psychedelic experience itself, but alliance influenced the psychedelic experience.

post hoc analysis of RCT Sample size: 79

Current status and future prospects of research on psilocybin's regulation of neurotransmitters and their receptors related to the pathogenesis of tinnitus. 2026
Unclear

Reviews psilocybin's potential for tinnitus via 5-HT2A receptor activation, glutamate release, and BDNF upregulation, restoring neural plasticity.

review

Psilocybin-assisted therapy for major depressive disorder: Perspective from meta-analysis. 2026
Supports

Standard-dose psilocybin was superior to control in reducing depressive symptoms (SMD: -1.05) and associated with higher response and remission rates at 2-3 weeks.

meta-analysis

Reporting practices in psilocybin-assisted therapy trials for depression: A descriptive review and temporal overview 2026
Unclear

Identified reporting gaps in psilocybin trials: overrepresentation of prior psychedelic users, inconsistent reporting of therapy sessions, and lack of blinding success assessment.

descriptive review

Acceptability and safety of two sequential doses of psilocybin in bipolar II depression: protocol for an open-label single-arm feasibility study. 2026
Unclear

Protocol for a study exploring psilocybin's acceptability and safety in bipolar II depression, a population typically excluded from trials.

protocol (open-label feasibility study)

Sex Differences in Acute Responses to Psychedelics: Evidence for Greater Subjective Intensity and Impairment in Female Participants 2026
Unclear

Female participants reported more intense acute subjective effects and impairment under psilocybin than males, independent of drug concentration.

pooled analysis of two RCTs Sample size: 72

Psilocybin-induced behavioral and cellular effects. 2026
Unclear

Psilocybin induced c-Fos expression in the nucleus accumbens, with 5-HT2A and 5-HT2B receptors mediating effects in neurons and non-neuronal cells.

preclinical (animal)

Sex-specific outcomes of developmental stress and psilocybin intervention on the brain and behavior 2026
Unclear

Study aims to characterize sex-specific effects of psilocybin on brain and behavior after developmental stress in a mouse model.

preclinical (animal)

Points of agreement

  • Psilocybin, especially at higher doses (20-30 mg), produces rapid and substantial reductions in depression and anxiety in cancer patients and those with treatment-resistant depression.
  • The therapeutic effects are often sustained for months (6-12 months) after a single or two doses.
  • The quality of the acute psychedelic experience (e.g., mystical-type experience) is consistently associated with better clinical outcomes.
  • Psilocybin is generally well-tolerated in controlled settings, with no serious adverse events reported in most trials.

Conflicts

  • One large RCT found no significant difference between psilocybin and escitalopram for depression at 6 weeks, while other trials show large effects versus placebo or waiting-list controls.
  • Sustained response at 12 weeks was not significant in one phase 2 trial, whereas other studies report maintained benefits up to 12 months.
  • Psilocybin can induce acute anxiety and psychosis-like symptoms in some individuals, contrasting with its therapeutic effects.

Gaps

  • Long-term durability beyond 12 months is unknown.
  • Most trials exclude patients with bipolar disorder, suicidality, or psychosis, limiting generalizability.
  • Blinding success, therapist fidelity, and expectancy effects are rarely reported, making it hard to isolate drug effects from psychological support.
  • Sex differences in response are understudied, with preliminary evidence suggesting females may experience more intense acute effects.
  • Optimal dosing, number of sessions, and the role of psychotherapy components remain unclear.
Browse these studies in the library
How we analyze this

This synthesis reads the 15 most-cited and 10 most recent studies whose primary subject is Psilocybin, up to 25 in all. The most-cited set anchors the established evidence, and the recent set surfaces work that is too new to have gathered citations yet.

A study qualifies only when Psilocybin or a known alias appears in its title or keywords, so broad reviews that mention it only in passing are left out. Each study is read from its abstract, strongest evidence first, and the summary reports the direction of the results along with any conflicts and gaps.

Ask your own question in the Research Synthesis Tool

Latest monthly recap: June 2026 →

4,371 articles · 1,686 from the last two years · 14,554,128 participants across 1,322 studies reporting sample size

Common study designs

review 890 systematic review 217 experimental study 247 randomized controlled trial 156 theoretical or philosophical paper 261

Research

Synthesize the evidence → Search all →

Changes in anxiety, quality of life, and functioning following psilocybin-assisted therapy in veterans with treatment-resistant depression.

Journal of Affective Disorders November 1, 2026 Carlton M Kelly, Mathieu Fradet, Catherine Bostian et al.

A single 25-mg dose of psilocybin with psychological support was associated with sustained improvements in anxiety, quality of life, functioning, and PTSD symptoms in 15 veterans with treatment-resistant depression. Anxiety scores dropped 59% from baseline at three weeks and remained lower through 12 months. Quality of life increased 24% and functional impairment decreased 46% at three weeks, though these effects were no longer statistically significant after accounting for concurrent improvements in depression. PTSD symptom reductions were observed at all timepoints. Acute subjective experiences did not correlate with treatment response. The study is limited by its small sample and open-label design.

DOI: 10.1016/j.jad.2026.122063 (opens in new tab) Full text (opens in new tab) Anxiety Psilocybin Treatment-resistant depression Posttraumatic stress disorder +1

Contribution of the Serotonin 5-HT2A Receptor to the Therapeutic Effect of Psilocin on Social Behavior Deficits in Mice Repeatedly Exposed to Social Defeat Stress.

Neuropsychopharmacol Rep September 1, 2026 Daisuke Ibi, Rika Takaba, Keisuke Yoshida et al.

In a mouse model of social defeat stress, the serotonin 5-HT2A receptor mediates the ability of psilocin to restore deficits in social behavior. Mice repeatedly subjected to social defeat stress showed reduced social interaction, and treatment with psilocin reversed this impairment. The therapeutic effect of psilocin was blocked by a 5-HT2A receptor antagonist and absent in mice lacking the 5-HT2A receptor, indicating that this receptor is necessary for the prosocial action of psilocin. These findings suggest that the 5-HT2A receptor is a key target for psilocin's effects on social behavior deficits caused by chronic stress.

DOI: 10.1002/npr2.70152 (opens in new tab)

Psilocybin-assisted therapy for major depressive disorder: Perspective from meta-analysis.

Journal of Affective Disorders August 1, 2026 Taro Kishi, Kenji Sakuma, Masakazu Hatano et al.

A systematic review and meta-analysis of six randomized controlled trials examined how psilocybin's effects on major depressive disorder change over time. Standard-dose psilocybin (25 mg/session or 20-30 mg/70 kg/session) was superior to control conditions (placebo, waiting-list, niacin, or 1 mg psilocybin) in reducing depressive symptoms. Sensitivity analyses excluding waiting-list controls confirmed this benefit with reduced heterogeneity. Standard-dose psilocybin also produced higher response and remission rates at 2-3 weeks and sustained response at 6-12 weeks, and lower all-cause discontinuation. However, it was associated with more headaches and nausea within 1-9 days, which resolved. Low-dose psilocybin showed no superior efficacy. The authors suggest standard-dose psilocybin is a promising treatment but note considerable methodological heterogeneity across trials.

DOI: 10.1016/j.jad.2026.121675 (opens in new tab) Full text (opens in new tab) Depression Psilocybin Meta-analysis Randomized controlled trial +1

The role of therapeutic alliance in psilocybin treatment for treatment-resistant depression: A post hoc path analysis.

Journal of Affective Disorders August 1, 2026 Guy M. Goodwin, Scott T Aaronson, Oscar Alvarez et al. 2 citations

In people with treatment-resistant depression receiving 25 mg psilocybin with monitoring and support, the therapeutic alliance before dosing had only weak correlations with improvement in depression scores at three weeks. Stronger correlations were seen with the intensity of the psychedelic experience itself, particularly emotional breakthrough and visual restructuring. Path analysis suggested that therapeutic alliance helped facilitate the psychedelic experience, but it was the psychedelic experience—not the alliance—that had stronger direct effects on clinical outcomes. The alliance's direct effect on antidepressant response was limited or absent.

DOI: 10.1016/j.jad.2026.121662 (opens in new tab) Full text (opens in new tab) Psilocybin Treatment-resistant depression Psychedelic experience Psychological support +1

Current status and future prospects of research on psilocybin's regulation of neurotransmitters and their receptors related to the pathogenesis of tinnitus.

Hearing research August 1, 2026 Shuhan Lu, Zhixin Zhang, Xinmiao Xue et al.

Tinnitus, the perception of sound without an external source, lacks effective treatments. Psilocybin, a psychedelic, shows promise by activating 5-HT2A receptors, boosting glutamate release, and upregulating BDNF, which increases dendritic spine density and synaptic proteins in the hippocampus and prefrontal cortex, restoring neural plasticity. This review connects these neuroplasticity mechanisms to tinnitus-related neural changes, highlighting psilocybin's regulatory effects on excitatory (glutamate, dopamine) and inhibitory (GABA) neurotransmitters and their receptors, suggesting a novel therapeutic pathway.

DOI: 10.1016/j.heares.2026.109701 (opens in new tab) Full text (opens in new tab) 5-ht2a receptor Psilocybin Dopamine Gaba +2

Learnings from a hybrid communities of practice group therapy model to support psilocybin-assisted therapy for patients with a terminal diagnosis

Frontiers in Public Health July 20, 2026 Vivian Wl Tsang, Pamela Kryskow, Crosbie Watler et al.

A hybrid group model combining virtual resilience-based community of practice sessions with one in-person psilocybin-assisted therapy session was feasible and safe for 25 palliative cancer patients. Over one year, 31 therapy sessions were delivered across four cohorts, with 84% completing the program. Participants reported enhanced trust in self, improved outlook on life, and strengthened connection to community. Peer support, relational safety, and regulation practices were central to outcomes. The model offers a scalable, cost-effective approach for end-of-life care, though attention to individual preference, room logistics, and sensory control during group dosing is needed.

DOI: 10.3389/fpubh.2026.1767215 (opens in new tab)

A randomized, double-blind, placebo-controlled single-ascending-dose study to identify a non-hallucinogenic dose of psilocybin in healthy adults.

medRxiv July 19, 2026 Naama Levy‐Cooperman, Edward M. Sellers, Paul Glue et al.

Low doses of psilocybin (0.5 to 4.0 mg) produce perceptible pharmacological effects without causing hallucinations, cognitive impairment, or increased anxiety. In a Phase 1 randomized, double-blind, placebo-controlled trial, 56 healthy adults received a single oral dose of psilocybin or placebo. No serious adverse events occurred; side effects were comparable to placebo, mainly somnolence. Psilocin appeared rapidly in the blood with dose-proportional exposure and a short half-life. Subjective drug effects were dose-related and distinguishable from placebo at or below 2.5 mg, but hallucination and altered-states scores remained low and not different from placebo.

DOI: 10.64898/2026.07.16.26358273 (opens in new tab) Psilocybin Anxiety Mescaline Lysergic acid diethylamide +12

Quantifying psilocybin exposure in a natural product–based retreat setting: An observational field method for dose measurement

Psychedelics July 18, 2026 Sergio Pérez Rosal, Sonya C. Faber

A rapid colorimetric assay (PSILO QTest) was deployed during a 7-day psilocybin retreat in Jamaica to measure batch-level psilocybin concentration in Psilocybe cubensis mushrooms. Psilocybin content differed approximately 2.6-fold between two session batches: one batch averaged 6.095 mg/g, the other 15.75 mg/g. Estimated psilocybin-equivalent doses ranged from 15.2 to 21.3 mg in Session 1 and 47.1 to 70.7 mg in Session 2, showing that gram-based dosing poorly reflects actual psychoactive substance exposure. No serious adverse events were observed among 11 participants. The assay can be used by non-chemist facilitators to improve dose documentation in naturalistic psilocybin research.

DOI: 10.1016/j.psyche.2026.100029 (opens in new tab) Psilocybin Observational study Natural archaeology Field mathematics +3

Psilocybin produces amplified acute responses and sex-specific long-term increases in sensorimotor gating in the mGlu5 knockout mouse model of schizophrenia

Neuropsychopharmacology July 18, 2026 James J Gattuso, Ahmed Kamal, Jennyfer M. Payet et al.

In a mouse model of schizophrenia lacking the metabotropic glutamate receptor 5 (mGlu5), psilocybin (1 mg/kg) caused hyperlocomotion, while normal mice showed no such effect. Male knockout mice also had a stronger head-twitch response, indicating enhanced serotonin 2A receptor signaling. Psilocybin increased neural activity in the claustrum of normal but not knockout mice, showing that intact mGlu5 signaling is needed for this effect. Psilocybin did not change anxiety-like behavior but increased immobility in a stress test. Notably, it produced a sustained normalization of sensorimotor gating in female knockout mice nine days after treatment, suggesting sex-dependent long-term effects.

DOI: 10.1038/s41386-026-02501-3 (opens in new tab) Full text (opens in new tab) Psilocybin Serotonergic Prepulse inhibition Hallucinogen +10

Silence is golden: Documenting the speech production of participants and support providers in psilocybin administration sessions for the treatment of post-traumatic stress disorder

Journal of Psychopharmacology July 16, 2026 Robert F. Dougherty, Nadav Liam Modlin, Niall M. Mcgowan et al.

In a 12-week clinical trial of 25 mg COMP360 psilocybin for 22 participants with post-traumatic stress disorder, audio recordings showed that during drug-administration sessions speech by either party was rare: silence filled 78% of the time on average, compared to 25% to 30% in non-administration sessions. Thematic analysis of post-dosing interviews revealed that support was minimally enacted but experientially salient, autonomy was promoted through the introspective state and non-directive support, and primary modes of support during altered states included reassurance and validation. The minimal verbal interaction distinguishes this monitoring and support from conventional psychotherapies and MDMA-assisted therapy.

DOI: 10.1177/02698811261464988 (opens in new tab) Psilocybin Context archaeology Thematic analysis Focus group +6

Clinical trials

All Psilocybin trials →