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 via OpenAlex
Summary
AI-generated from the abstractPsilocybin-assisted psychotherapy (PAP) is associated with large short-term reductions in depressive symptom severity among adults with major depressive disorder. A meta-analysis of ten clinical trials found an overall large effect (d = 1.15), with within-subject designs showing 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. However, long-term efficacy remains understudied, and the overall certainty of evidence is low to moderate. Larger, rigorously blinded trials are needed.
Study at a glance
| Characteristics | Systematic review and meta-analysis Randomized Peer reviewed |
|---|---|
| Sample size | 10 |
| Population | Adults with major depressive disorder |
| Intervention | Psilocybin-assisted psychotherapy |
| Topics | Depression |
| Keywords | Adverse effect Dosing Meta-analysis Clinical trial |
| Key finding | 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.