Psilocybin-assisted therapy for major depressive disorder: Perspective from meta-analysis.
Taro Kishi, Kenji Sakuma, Masakazu Hatano, Hiroyuki Uchida, Nakao Iwata
Journal of affective disorders August 1, 2026 Peer reviewed DOI: 10.1016/j.jad.2026.121675 via PubMed
Summary
Standard-dose psilocybin treatment significantly reduces depressive symptoms in individuals with major depressive disorder (MDD) compared to control groups, with a standardized mean difference of -1.05. It also shows higher response rates (risk ratio: 2.34) and remission rates (risk ratio: 3.38) at 2-3 weeks post-treatment. While associated with increased headaches and nausea shortly after treatment, these side effects resolve quickly. Low-dose psilocybin did not show superior efficacy compared to controls.
Study at a glance
| Design | systematic review and meta-analysis |
|---|---|
| Population | individuals with major depressive disorder |
| Key finding | Standard-dose psilocybin was superior to control in reducing depressive symptoms and increasing response and remission rates. |
Abstract
This systematic review and meta-analysis of six randomized controlled trials aimed to investigate the temporal changes in the efficacy and safety of psilocybin treatment for major depressive disorder (MDD). Separate meta-analyses were conducted for standard-dose psilocybin (25 mg/session, or 20-30 mg/70 kg/session) and low-dose psilocybin (10 mg/session or 15.05 mg/70 kg/session) subgroups. Control conditions included placebo, waiting-list control, niacin, or psilocybin 1 mg. Standard-dose psilocybin was superior to control in reducing depressive symptoms (standardized mean difference [SMD]: -1.05; 95% confidence intervals [CIs]: -1.60 to -0.50, p = 0.0002, I2 = 75%, K = 4). Sensitivity analysis excluding studies with waiting-list controls supported the superiority of standard-dose psilocybin compared with control without considerable heterogeneity (SMD: -0.70; 95% CI: -1.03 to -0.36, p < 0.0001, I2 = 43%, K = 2). This sensitivity analysis included two double-blind trials that incorporated manualized psilocybin-assisted psychotherapy. Compared with controls, standard-dose psilocybin was associated with higher response (risk ratio [RR]: 2.34; 95% CI: 1.52-3.60, p = 0.0001, I2 = 0%) and remission rates at 2-3 weeks post-treatment (RR: 3.38; 95% CI: 1.88-6.08, p < 0.0001, I2 = 0%), with response rate at 6-12 weeks post-treatment (RR: 2.61; 95% CI: 1.45-4.71, p = 0.001, I2 = 0%). Moreover, standard-dose psilocybin was related to lower all-cause discontinuation compared with control (RR: 0.39; 95% CI: 0.18-0.87, p = 0.02, I2 = 0%). Standard-dose psilocybin was associated with a higher incidence of headache (RR: 2.06; 95% CI: 1.11-3.81, p = 0.02, I2 = 57%) and nausea within 1-9 days post-treatment (RR: 10.20; 95% CI: 3.80-27.39, p < 0.0001, I2 = 0%) compared with the control; however, these symptoms resolved after this period. Low-dose psilocybin demonstrated no superior efficacy compared with the control group. This meta-analysis indicates that standard-dose psilocybin may represent a promising therapeutic option for MDD treatment. Nonetheless, future research should address the considerable methodological heterogeneity across current trials.