The efficacy and safety of psilocybin-assisted therapy for major depressive disorder: a meta-analytic review of clinical outcomes
Mental Wellness April 21, 2026 Mohsen Khosravi, Domenico de Berardis, Massimo Tusconi
A systematic review and meta-analysis of 13 clinical trials with 606 participants found no statistically significant overall antidepressant effect of psilocybin-assisted psychotherapy for major depressive disorder and treatment-resistant depression. The pooled standardized mean difference was -0.79 with a 95% confidence interval from -3.98 to 2.40, and extreme heterogeneity across studies was observed. The type of control group accounted for most of the variation between studies, with waitlist and low-dose comparators exaggerating effect sizes. Session frequency moderated outcomes, with 2 to 5 sessions yielding larger effects and more intensive protocols reducing benefit. Psilocybin's antidepressant efficacy appears highly context-dependent rather than universally robust.