Psilocybin for Treatment-Resistant OCD: A Randomized Controlled Trial

Background: Obsessive-compulsive disorder (OCD) affects 2-3% of the population worldwide. 40-60% of patients do not respond to first-line interventions. We evaluated the efficacy and safety of a single dose of psilocybin in patients with treatment-resistant OCD. Methods: In this phase 2, randomized, double-blind trial, we randomly assigned 28 adults with treatment-resistant OCD to receive a single dose of psilocybin (0.25 mg/kg; n=14) or niacin (250 mg; n=14), in a supportive controlled setting. Primary outcomes were Acute Yale-Brown Obsessive-Compulsive Scale (A-YBOCS) from baseline to 48 hours post-treatment and weekly Y-BOCS assessments through 12 weeks. Secondary outcomes included depression symptoms (MADRS) and functional disability (SDS). All participants initially assigned to niacin crossed over to open-label psilocybin after 1 week. Results: At 48 hours, A-YBOCS scores decreased from 24.07±6.02 to 14.31±8.83 in the psilocybin group versus no change (24.29±4.81 to 24.36±3.95) in the niacin group (between-group difference, 9.83 points; 95% CI, 5.19-14.91; P