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, W Lou, Muhammad Ishrat Husain, Matthew J. Burke, Venkat Bhat
European Psychiatry January 1, 2026 DOI: 10.1192/j.eurpsy.2026.10168 via OpenAlex
Summary
AI-generated from the abstractControl groups in psychedelic-assisted psychotherapy trials show substantial symptom improvement, likely due to non-specific factors such as expectancy and concurrent psychotherapy. A meta-analysis of 14 randomized controlled trials (643 participants) found that treatment groups had greater symptom reductions than control groups for depressive symptoms, PTSD symptoms, and anxiety symptoms. For PTSD, inactive placebo groups showed larger within-group improvements. The findings underscore the need for robust control conditions and careful interpretation of treatment effects in psychedelic research.
Study at a glance
| 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 Psychiatry |
| Key finding | 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.