Breaking the chains of depression: A systematic review and meta-analysis of psilocybin therapy
Faheem Ahmed Khan, Nuruliarizki Shinta Pandupuspitasari, Tewin Tencomnao, Siriporn Chuchawankul
Journal of Affective Disorders December 17, 2025 DOI: 10.1016/j.jad.2025.120882 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review and meta-analysis Peer reviewed |
|---|---|
| Intervention | Psilocybin |
| Topics | Depression Psilocybin |
| Keywords | Hallucinogen Cognition Mood disorders Systematic review Psychotherapist Clinical psychology Substance use Depression economics Medline |
| Citations | 2 |
| Key findings | Psilocybin significantly reduces symptoms of anxiety and major depressive disorder (SMD = -1.438) and mood disorders (SMD = -1.476). |
Abstract
Psilocybin, a naturally occurring hallucinogenic substance present in certain mushrooms, has drawn growing attention as a therapeutic breakthrough for several mental and psychiatric conditions. Psilocybin originated in spiritual and cultural traditions and has become the focus of extensive scientific research. This meta-analysis and systematic review aggregate results from the literature to evaluate the therapeutic function of psilocybin following PRISMA 2020. Although it is now used to treat addiction, end-of-life anxiety, and treatment-resistant depression, new research indicates that it could additionally be used to treat obsessive-compulsive disorder, eating disorders, and neurodegenerative diseases. Psilocybin's regulation of serotonin 5-HT2A receptors, which improves neuroplasticity, disrupts maladaptive cognitive processes and encourages emotional integration, is the backend of its therapeutic benefits. The meta-analysis results indicate that psilocybin has an outstanding capacity to reduce the symptoms of anxiety/MDD (SMD = -1.438, 95 % CI: -1.729 to -1.146, p < 0.001) and mood disorders (SMD = -1.476, 95 % CI: -1.773 to -1.178, p < 0.001). Sustained improvements are frequently observed after a single therapy session. The results of this meta-analysis and systematic review highlight psilocybin's potential as a potent and immediate treatment for mental health issues that are difficult to treat. Although the results are resistant to publication bias (fail-safe N > 5500), they highlight the significance of addressing unsolved hurdles to clinical adoption and customizing therapies for particular groups. Psilocybin has the potential to transform psychiatry and give millions of people suffering from crippling mood disorders fresh hope as research progresses and regulations change.
Comparable studies
Other systematic reviews and meta-analyses on psilocybin for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern‐era clinical studies Patients with cancer- or illness-related anxiety and depression, major depressive... | 2020 | Systematic review | n = 188 |
| The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis People with elevated symptoms of anxiety and depression | 2020 | Meta-analysis | n = 117 |
| Psychedelics in the treatment of unipolar mood disorders: a systematic review Patients with broadly defined unipolar mood disorders | 2016 | Systematic review | n = 423 |
| Psychedelic therapy for depressive symptoms: A systematic review and meta-analysis. Participants in studies of psychedelic therapy for depressive symptoms (Major... | 2023 | Systematic review with meta-analysis | n = 14 |
| Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review. Patients with life-threatening diseases and symptoms of anxiety or depression | 2018 | Systematic review | n = 445 |
Citations in the library
Cited by 4
- A conceptual framework based on current and emerging treatments for treatment-resistant depression: mechanistic evolution, clinical evidence, and future directions. Expert Review of Neurotherapeutics July 1, 2026
- Psilocybin and Mental Health Outcomes: Scoping Review with ☸SAIMSARA SAIMSARA Journal June 15, 2026
- Level of Preparedness to Use Psilocybin Among Individuals Seeking Psychedelic Risk Reduction: A retrospective study of a pilot psychiatric consultation service medRxiv August 19, 2026
- The subtle science: a systematic review of psilocybin magic mushroom and truffle microdosing Frontiers in Psychiatry August 19, 2026
Cites 81
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
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- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
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and 76 more in the library