Magnitude of response in treatment and control groups within psychedelic trials for psychiatric disorders: A meta-analysis
Shakila Meshkat, Qiaowei Lin, Rachel Sousa-Ho, Ilya Demchenko, Richard J. Zeifman, Howell Fang, Amy C. Reichelt, Yanbo Zhang, Lisa Burback, Olga Winkler, Andrew J. Greenshaw, Candice M Monson, Eric Vermetten, Rakesh Jetly, Wendy Lou, Muhammad Ishrat Husain, Matthew J. Burke, Venkat Bhat
European Psychiatry 2026 DOI: 10.1192/j.eurpsy.2026.10168 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review and meta-analysis Randomized Preregistered Peer reviewed |
|---|---|
| Sample size | 643 |
| Population | Participants in randomized controlled trials of psychedelic-assisted psychotherapy |
| Keywords | Magnitude astronomy Control management Clinical trial Drug trial Clinical psychology |
| Key findings | Treatment groups showed greater symptom reductions than control groups across depressive, PTSD, and anxiety symptoms, but control groups also exhibited substantial improvements. |
Abstract
Abstract Background Psychedelic-assisted psychotherapy has shown potential for psychiatric disorders. However, the magnitude of symptom change in control groups remains poorly understood. We aim to evaluate within-group effects in control groups and compare them to treatment groups in psychedelic trials.
Methods: A systematic search was conducted up to 1 July 2025. The study protocol was preregistered in PROSPERO (CRD420251111853).
Results: Fourteen randomized controlled trials (n = 643) were included. Direct between-arm meta-analyses showed greater symptom reductions in treatment compared with control across outcomes, including depressive symptoms (number of study arms [k] = 13; SMD = −0.82; 95% CI = −1.17, −0.47; I 2 = 60.1%), posttraumatic stress disorder (PTSD) symptoms (k = 10; SMD = −0.89; 95% CI = −1.14, −0.65; I 2 = 0%), and anxiety symptoms (k = 5; SMD = −0.66; 95% CI = −0.94, −0.38; I 2 = 0%). Subgroup analyses showed limited evidence that effects differed by placebo type for depressive or PTSD symptoms. Descriptive within-group analyses indicated symptom reductions from baseline in both control and treatment groups, with larger within-group improvements observed in treatment groups across outcomes; notably, larger within-group reductions in PTSD symptoms were observed in inactive placebo groups. Sensitivity analyses showed consistent results.
Conclusions: Control groups in psychedelic trials demonstrated substantial symptom improvement, which may reflect non-specific trial factors (including expectancy and concurrent psychotherapy). These findings emphasize the importance of robust control conditions in psychedelic research and the need for nuanced interpretation of treatment effects.