Open-label multidose psilocybin intervention shows preliminary reductions in obsessive-compulsive disorder symptoms

A small randomized, waitlist-controlled open-label trial at Johns Hopkins evaluated two supportive psilocybin sessions for adults with obsessive-compulsive disorder who had previously tried pharmacotherapy or evidence-based psychotherapy. Thirty-seven participants were randomized and 30 completed the one-month follow-up. Participants received 20 mg initially, followed approximately two weeks later by 30 mg when the first dose was well tolerated, or 20 mg again after challenging effects. Compared with an eight-week waitlist, immediate treatment produced substantial reductions in clinician-rated Y-BOCS scores, affecting both obsessions and compulsions, and improvements persisted for one month after the second session. At one month, 50% met the study's responder definition and 36.7% met remission criteria. Psilocybin was generally tolerated, with anxiety and headaches among the reported adverse events and no unexpected serious events. Greater mystical, bliss, unity, and disembodiment effects were associated with greater symptom reduction, while paranoia was associated with smaller reductions. Interpretation is limited by the small sample, open-label design, lack of an active comparator, medication tapering, attrition, and short follow-up. The authors characterize the findings as preliminary and call for adequately powered randomized trials with active controls and longer-term assessment.