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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.

Research indicates that psilocybin, particularly at higher doses (e.g., 20–30 mg/70 kg), can produce rapid and sustained reductions in depression and anxiety in clinical populations, with effects lasting up to 6–12 months in some studies, though a head-to-head trial found no significant difference from escitalopram. Evidence is strongest for treatment-resistant depression and cancer-related distress, but many studies are small, open-label, or lack long-term durability data. The therapeutic effect appears linked to mystical-type experiences and 5-HT2A receptor activation, but the underlying mechanisms and optimal dosing remain under investigation.

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 and sustained decreases in depressed mood and anxiety, with about 80% of participants showing clinically significant improvement at 6-month follow-up.

randomized controlled trial 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 (0.3 mg/kg) plus psychotherapy produced rapid, robust, and enduring reductions in anxiety and depression, with 60–80% of participants maintaining clinically significant improvements at 6.5 months.

double-blind, placebo-controlled, crossover trial Sample size: 29

Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance 2006
Supports

Psilocybin occasioned mystical-type experiences with substantial personal meaning and spiritual significance, rated as having sustained positive effects at 2 months.

double-blind study Sample size: 36

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

Psilocybin was well tolerated and associated with marked reductions in depressive symptoms at one week and three months after treatment.

open-label feasibility trial Sample size: 12

Trial of Psilocybin versus Escitalopram for Depression 2021
No effect

Psilocybin did not show a significant difference in antidepressant effects compared to escitalopram at week 6, though secondary outcomes generally favored psilocybin.

randomized controlled trial

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

Psilocybin with therapy produced large, statistically significant reductions in depression severity compared with a waiting list control, with 71% response at week 1 and 54% remission at week 4.

randomized controlled trial Sample size: 24

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

Psilocybin was safe and associated with reduced anxiety and improved mood, with significant reductions in trait anxiety at 1 and 3 months after treatment.

double-blind, placebo-controlled study Sample size: 12

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

Psilocybin decreased cerebral blood flow and BOLD signal in hub regions like the thalamus and cingulate cortex, and reduced mPFC-PCC connectivity, with the magnitude of decrease predicting subjective effect intensity.

within-subjects, placebo-controlled, task-free fMRI study Sample size: 30

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

Abstinence from alcohol increased significantly following psilocybin administration, with gains largely maintained at follow-up to 36 weeks.

single-group proof-of-concept study Sample size: 10

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

Argues that psychedelics relax the precision weighting of high-level priors, enabling revision of pathological beliefs, which may underlie their therapeutic effects.

theoretical or philosophical paper

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

A single 25 mg dose of psilocybin significantly reduced depression scores at three weeks compared to a 1 mg control, while the 10 mg dose did not show a significant difference.

phase 2 double-blind randomized controlled trial Sample size: 233

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

Psilocybin-induced psychosis-like effects were blocked by serotonin-2A antagonists, indicating that its psychotomimetic action is mediated by 5-HT2A receptor activation.

experimental study

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

Two doses of psilocybin produced large, rapid reductions in depressive symptoms that persisted for six months, with effect sizes remaining large at 3 and 6 months.

open-label trial Sample size: 20

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

Psilocybin at 20 and 30 mg/70 kg occasioned mystical-type experiences with persisting positive effects on attitudes, mood, and behavior, rated as undiminished at 14 months.

randomized controlled trial 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

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

Psilocybin with psychological support was associated with improvements in anxiety, quality of life, functioning, and PTSD symptoms, though effects were largely correlated with concurrent improvements in depressive symptoms.

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
Supports

Psilocin reverses social behavior deficits in stressed mice through activation of the serotonin 5-HT2A receptor.

experimental study using a mouse model

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

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

observational cohort with correlation and path analysis 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
Supports

Reviews evidence that psilocybin's activation of 5-HT2A receptors and subsequent neuroplasticity mechanisms may synergistically regulate excitatory and inhibitory neurotransmitter systems relevant to tinnitus.

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 and produced higher response and remission rates at 2-3 weeks and 6-12 weeks post-treatment, with lower all-cause discontinuation.

systematic review and meta-analysis

Psychedelic drug action at dendrites is gated by behavioral state and serotonin receptors 2026
Supports

Psilocybin transiently increases dendritic calcium event rates in apical tufts in a brain state- and 5-HT2A receptor-dependent manner, and alters the predictive relationship between acute dendritic calcium signaling and subsequent spine formation.

experimental study

Learnings from a hybrid communities of practice group therapy model to support psilocybin-assisted therapy for patients with a terminal diagnosis 2026
Supports

Group-administered psilocybin-assisted therapy supported by virtual communities of practice is feasible, safe, and provides psychosocial benefits for palliative cancer patients.

qualitative study Sample size: 25

A randomized, double-blind, placebo-controlled single-ascending-dose study to identify a non-hallucinogenic dose of psilocybin in healthy adults. 2026
Supports

Low doses of psilocybin produce perceptible pharmacological effects without significant perceptual alterations, cognitive impairment, or increased anxiety.

Phase 1, randomized, double-blind, placebo-controlled, single ascending dose study Sample size: 56

Psilocybin produces amplified acute responses and sex-specific long-term increases in sensorimotor gating in the mGlu5 knockout mouse model of schizophrenia 2026
Mixed

Disrupted mGlu5 signaling amplifies acute responses to psilocybin and reveals a sex-dependent long-term effect on sensorimotor gating, with sustained normalization in female KO mice.

experimental study using knockout mouse model

Quantifying psilocybin exposure in a natural product–based retreat setting: An observational field method for dose measurement 2026
Unclear

Psilocybin concentration varied 2.6-fold between batches, making gram-based dosing inadequate for estimating psychoactive substance exposure.

observational field evaluation Sample size: 11

Points of agreement

  • Psilocybin, especially at higher doses, produces rapid and sustained reductions in depression and anxiety in clinical populations.
  • The therapeutic effects are often linked to the quality of the acute psychedelic experience, such as mystical-type experiences.
  • Psilocybin's mechanism involves activation of the serotonin 5-HT2A receptor, leading to neuroplastic changes.
  • Psilocybin is generally well tolerated with no serious adverse events in the studied populations.

Conflicts

  • One RCT found no significant difference between psilocybin and escitalopram for depression, while other studies show psilocybin superior to placebo or waiting list.
  • The role of therapeutic alliance versus the psychedelic experience itself in driving outcomes is debated, with one study suggesting the experience has stronger direct effects.
  • Dose-response relationships are inconsistent: some studies show benefit at 25 mg but not 10 mg, while others use lower doses with positive effects.

Gaps

  • Long-term durability beyond 6-12 months is not well established.
  • Most studies are small, open-label, or lack active comparators.
  • Blinding is challenging due to the subjective effects of psilocybin.
  • Diverse populations (e.g., veterans, palliative, treatment-resistant) are underrepresented.
  • Optimal dosing and the separation of therapeutic from hallucinogenic effects remain unresolved.
  • The role of psychological support and therapeutic alliance needs further clarification.
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: August 2026 →

4,249 articles · 1,700 from the last two years · 14,599,197 participants across 1,348 studies reporting sample size

Common study designs

review 909 systematic review 222 experimental study 240 randomized controlled trial 154 theoretical or philosophical paper 285

Research

Synthesize the evidence → Search all →

Psilocybin and Chronic Neuropathic and Centralized Pain: Converging Mechanisms in Central Sensitization, Neuroplasticity, and Network Organization

Anesthesia Research September 11, 2026 M. S. Neves, C. T. P. Gusmão, Raimundo Chiyo et al.

Background/Objectives: Neuropathic and chronic centralized pain disorders remain difficult to treat because they involve central sensitization, maladaptive neuroplasticity, neuroimmune activation, affective amplification, and large-scale network dysfunction. Psilocybin, a serotonergic psychedelic acting primarily through 5-HT2A receptor agonism, has emerged as a candidate modulator of chronic...

DOI: 10.3390/anesthres3030026 (opens in new tab) Full text (opens in new tab)

Multilevel Mechanisms and Clinical Efficacy of Psilocybin in Depression Treatment: A Systematic Review

International Journal of Molecular Sciences September 10, 2026 Xizhen Zhang, Xiaowen Zhang, Haiyu Zhang et al.

Depression, characterized by persistent low mood and anhedonia, represents a prevalent affective disorder imposing substantial medical and economic burdens. Current first-line antidepressants are limited by delayed onset and treatment resistance. Psilocybin (PSI) has re-emerged as a promising therapeutic agent with rapid, sustained antidepressant effects. This systematic review was conducted...

DOI: 10.3390/ijms27188052 (opens in new tab)

354. Effects of psilocybin treatment on cognitive function in Japanese patients with treatment-resistant depression: an open-label study

International Journal of Neuropsychopharmacology September 9, 2026 Sota Tomiyama, K Yonezawa, K Kusudo et al.

Abstract Background Cognitive dysfunction is associated with impaired psychosocial functioning in patients with major depressive disorder (MDD). Patients with treatment-resistant depression (TRD) exhibit more pronounced cognitive dysfunction than those with non-resistant MDD, underscoring the need for effective therapeutic strategies. Psilocybin has emerged as a promising treatment for...

DOI: 10.1093/ijnp/pyag040.263 (opens in new tab)

433. Psilocybin reveals diverse antidepressant efficacies across different preclinical models of depression

International Journal of Neuropsychopharmacology September 9, 2026 Z Wang, W Chen, C Hu et al.

Abstract Background Within the rapidly expanding field of psychedelic research, psilocybin, along with its active metabolite psilocin, has emerged as a highly promising candidate in the search for innovative treatments for neuropsychiatric disorders. In this context, preclinical research using animal disease models has produced somewhat inconsistent results when employing standard tests to...

DOI: 10.1093/ijnp/pyag040.302 (opens in new tab)

429. Association between subjective experiences and symptom improvement following psilocybin therapy in Japanese patients with treatment-resistant depression: an open-label study

International Journal of Neuropsychopharmacology September 9, 2026 Lisa Harada, K Yonezawa, K Kusudo et al.

Abstract Background Despite sequential treatments with conventional antidepressants, many patients with depression experience insufficient clinical improvement, referred to as treatment-resistant depression (TRD). Psilocybin, a serotonergic psychedelic acting as a 5-HT2A receptor agonist, has attracted increasing attention as a novel treatment, with clinical trials demonstrating rapid and...

DOI: 10.1093/ijnp/pyag040.300 (opens in new tab)

562. Repeated psilocybin administration does not induce rewarding effects and increases ventral tegmental dopaminergic activity during withdrawal

International Journal of Neuropsychopharmacology September 9, 2026 V Bruno, Martha López-canul, B Richardson et al.

Abstract Background Psilocybin has shown therapeutic potential for several neuropsychiatric disorders; however, concerns remain regarding its abuse liability and long-term neurobiological effects following repeated use. While acute psychedelic administration is generally considered to have low addictive potential, the consequences of repeated exposure on reward processing, withdrawal-related...

DOI: 10.1093/ijnp/pyag040.095 (opens in new tab)

Craving Reduction and Smoking Outcomes in Psilocybin-Assisted and Standard Cessation Care.

Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999) September 9, 2026 Lisbeth Strandberg, Thiago P Fernandes, Irina I Shoshina et al.

Smoking cessation outcomes are heterogeneous, and factors associated with these differences are not fully understood. We examined longitudinal smoking trajectories across distinct smoking profiles and evaluated whether early craving and affective symptom changes were associated with verified abstinence. Participants in this observational cohort were classified as dependence-predominant or...

DOI: 10.47626/1516-4446-2026-5060 (opens in new tab) Full text (opens in new tab) Psilocybin Tobacco use disorder Craving Smoking cessation

643. A mechanism-informed clinical trial of psilocybin-assisted therapy for opioid use disorder: rationale and neurobiological framework

International Journal of Neuropsychopharmacology September 9, 2026 O Mallon

Abstract Background Opioid Use Disorder (OUD) is associated with substantial morbidity and mortality, with relapse remaining common despite the availability of opioid agonist and antagonist pharmacotherapies. Scotland continues to experience a disproportionate burden of drug-related deaths relative to other parts of the United Kingdom and Europe, reflecting the ongoing clinical and public...

DOI: 10.1093/ijnp/pyag040.113 (opens in new tab)

701. Efficacy and safety of COMP360 psilocybin therapy in anorexia nervosa: a proof-of-concept study

International Journal of Neuropsychopharmacology September 9, 2026 G Goodwin

Abstract Background There are no approved medications for treating anorexia nervosa (AN) despite having the highest mortality rate of all psychiatric conditions. Talk therapies have limited efficacy, with relapse rates as high as 52% and poor long-term outcomes. Aims & Objectives This study evaluated the effects and safety of COMP360 psilocybin, a novel treatment, in individuals with anorexia...

DOI: 10.1093/ijnp/pyag040.475 (opens in new tab)

Clinical trials

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