Efficacy of Psilocybin-Assisted Therapy in Major Depressive Disorder: A Systematic Review and Meta-Analysis
Angel Labra-Lorenzana, Dania Nimbe Lima Sanchez, Christian Alejandro Delaflor-Wagner, Diana Martínez-hernández, Christian Ramos-Jiménez, Christian Gabriel Toledo-Lozano
Psychiatry International June 15, 2026 DOI: 10.3390/psychiatryint7030137 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review and meta-analysis Randomized Peer reviewed |
|---|---|
| Sample size | 10 |
| Population | Adults with major depressive disorder |
| Intervention | Psilocybin-assisted psychotherapy |
| Topics | Depression Psilocybin |
| Keywords | Adverse effect Dosing Meta-analysis Clinical trial Randomized controlled trial Medline Systematic review Depressive symptoms Depression economics Certainty Research design Risk assessment Intensive care medicine Relative risk |
| Key findings | Psilocybin-assisted psychotherapy is associated with large short-term reductions in depressive symptom severity, though long-term efficacy is understudied and evidence certainty is low to moderate. |
Abstract
Background: This systematic review and meta-analysis evaluates the efficacy and safety of psilocybin-assisted psychotherapy (PAP) for adults with major depressive disorder (MDD).
Methods: A PROSPERO-registered search (CRD42024561979) of CENTRAL, Scopus, PsycINFO, and MEDLINE (2010–2024) identified clinical trials assessing PAP. Risk of bias was assessed using RoB 2 for randomized controlled trials (RCTs), while non-randomized studies were appraised separately. Evidence certainty was evaluated using GRADE.
Results: Ten trials were included; eight provided quantitative data. PAP was associated with large short-term reductions in depressive symptom severity. The overall pooled effect was large (d = 1.15, 95% CI 0.83–1.48), though within-subject designs yielded larger estimates (d = 1.63) than between-subject controlled comparisons (d = 0.96). Adverse events were transient and manageable, with no increased risk of serious adverse events on dosing days. Primary risk-of-bias concerns included functional unblinding.
Conclusions: PAP may produce clinically meaningful, large short-term reductions in depressive symptoms. However, long-term efficacy remains understudied, and the overall certainty of evidence is low to moderate. Larger, rigorously blinded trials are required.
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 |