Neuroscience and biobehavioral reviewsJan 26, 2026

How study methods influence psilocybin therapy outcomes in depression: A review and analysis

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗

Updated Feb 1, 2026

Abstract

Seven randomized-controlled trials with 522 participants found psilocybin-assisted therapy (PAT) to have a large and significant antidepressant effect.

PAT is associated with a significant reduction in depressive symptoms based on standardized mean difference.
Larger effects were observed in studies using bodyweight-adjusted doses of psilocybin.
Longer preparation, dosing, and integration sessions with non-manualized psychotherapy may influence the effectiveness of PAT.
Subgroup analyses indicated non-significant differences in outcomes related to methodology variations.
This review provides preliminary insights for clinicians in optimizing future PAT protocols for treating depression.

Simplified

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 with 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.

Full Text

Full text is available at the source.

View Full Text ↗

How study methods influence psilocybin therapy outcomes in depression: A review and analysis

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the psychedelic science brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the psychedelic science brief