Methodological moderators of psilocybin-assisted therapy in depression: A systematic review and meta-analysis
Omer A. Syed, Benjamin Tsang, Sean M. Nestor, Nir Lipsman, Muhammad Ishrat Husain, Fahad Alam, Peter Giacobbe
Neuroscience & Biobehavioral Reviews January 24, 2026 DOI: 10.1016/j.neubiorev.2026.106573 via OpenAlex
Summary
AI-generated from the abstractPsilocybin-assisted therapy (PAT) shows a large and significant antidepressant effect in treating major depressive disorder, based on a meta-analysis of seven randomized controlled trials involving 522 participants. Larger effects were associated with bodyweight-adjusted dosing, longer preparation, dosing, and integration sessions, and non-manualized psychotherapy, though subgroup differences were not statistically significant. The review provides preliminary guidance for clinicians designing PAT protocols.
Study at a glance
| Characteristics | Systematic review and meta-analysis Randomized Peer reviewed |
|---|---|
| Sample size | 522 |
| Population | Adults with major depressive disorder in randomized controlled trials |
| Topics | Depression Psilocybin |
| Keywords | Antidepressant Meta-analysis Depressive symptoms Clinical trial |
| Key finding | Psilocybin-assisted therapy has a large and significant antidepressant effect, with larger effects linked to bodyweight-adjusted doses and extended therapy sessions. |
Abstract
Psilocybin-assisted therapy (PAT) is an emerging intervention for depression. Though several clinical trials report promising results for PAT in treating depression, there remains a need for consensus on optimal methodologies and standardization of PAT protocols. The objective of this review was to assess the efficacy of PAT in treating depressive symptoms and to systematically examine the influence of methodological moderators underlying antidepressant responses. We searched the electronic databases of PubMed, MEDLINE, PsychInfo and Embase for randomized-controlled trials (RCTs) using PAT as a treatment intervention for major depressive disorder. The primary outcomes were standardized mean difference (SMD) of change in depressive symptoms pre- versus post-treatment sessions, and the difference in antidepressant treatment effects among various PAT methodologies in a subgroup analysis. Seven RCTs involving 522 participants were analyzed. The overall random effects model found PAT to have a large and significant antidepressant effect. The subgroup analyses found larger effects, albeit non-significant differences in subgroup heterogeneity, associated with studies that administered psilocybin in bodyweight-adjusted doses and provided longer preparation, dosing, and integration sessions and provided non-manualized psychotherapy. This study presents the first systematic examination of PAT methodologies influencing antidepressant effects and provides preliminary insights for clinicians in designing future PAT protocols for depression.