Efficacy and Safety of Psilocybin-Assisted Therapy for Depression: A Meta-Analysis of Randomised Controlled Trials
Siti Nashria Rusdhy, Andrian Fajar Kusumadewi, Carla Raymondalexas Marchira, Mustika Suci Mahardikaningrum, Teresa Lalita Wiryarini, Devira Ayu Wulandari
Open Access Indonesian Journal of Medical Reviews April 21, 2026 DOI: 10.37275/oaijmr.v6i2.883 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review and meta-analysis Randomized Peer reviewed |
|---|---|
| Sample size | 514 |
| Population | Adults with major or treatment-resistant depression |
| Intervention | Psilocybin-assisted therapy |
| Topics | Depression Psilocybin |
| Key findings | Psilocybin-assisted therapy yields a large pooled effect on depressive symptom reduction, but the evidence is rated low certainty due to methodological limitations. |
Abstract
Psilocybin-assisted therapy shows promise for depression, though current evidence relies on Phase 2 trials with notable methodological limitations. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating psilocybin-assisted therapy for major or treatment-resistant depression up to February 2024. We evaluated depressive symptom severity using random-effects meta-analysis, moderator analyses, Cochrane Risk of Bias 2, and GRADE methodology. Nine RCTs (N=514) were included. Psilocybin therapy demonstrated a large pooled effect size for symptom reduction (SMD = 1.270, 95% CI: 0.865–1.676, p<0.001). However, substantial heterogeneity was observed (I² = 79.1%). Comparator type significantly moderated outcomes, with waitlist controls showing substantially larger effects than active/placebo controls. Overall GRADE certainty of evidence was rated LOW due to risk of bias, heterogeneity, short-term outcomes, and publication bias concerns. In conclusion, while psilocybin-assisted therapy yields a large pooled effect estimate for depression, current findings are preliminary. Results are heavily qualified by methodological constraints, including waitlist-inflated efficacy, compromised blinding from subjective psychedelic effects, and the confounding influence of integrated psychological support. Confirmation through robust Phase 3 trials is required before supporting routine clinical implementation.
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 |