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 Peer reviewed DOI: 10.1192/j.eurpsy.2026.10168 via OpenAlex
Summary
Psychedelic-assisted psychotherapy trials show that treatment groups experience greater symptom reductions compared to control groups. In 14 randomized controlled trials with 643 participants, treatment groups had significantly lower depressive symptoms (SMD = -0.82), PTSD symptoms (SMD = -0.89), and anxiety symptoms (SMD = -0.66). Control groups also showed substantial symptom improvement, indicating the influence of non-specific factors like expectancy and concurrent psychotherapy. This highlights the need for strong control conditions in psychedelic research.
Study at a glance
| Design | systematic review |
|---|---|
| Sample size | 643 |
| Population | participants in randomized controlled trials of psychedelic-assisted psychotherapy |
| Key finding | Treatment groups showed greater symptom reductions compared to control groups across various psychiatric outcomes. |
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.