Efficacy and Safety of Psilocybin in Treatment-Resistant Major Depression: The EPISODE Randomized Clinical Trial

Psilocybin is tested for efficacy and safety in treatment-resistant major depression in the EPISODE randomized clinical trial. Participants were randomized to multiple treatment arms with different dosing schemes, and the study assessed depressive symptom outcomes including the HAMD17 and other depression scales through follow-up time points. The trial also evaluated safety outcomes, including adverse events and severe adverse events, with detailed supplemental materials such as the trial protocol and statistical analysis plan. Published online March 18, 2026, the results are presented as a primary investigation in JAMA Psychiatry, targeting an evidence base for psychedelic-assisted therapy in a population with limited response to standard treatments.