Psilocybin for Treatment-Resistant OCD: A Randomised Controlled Trial
Ben Kelemndi, Thomas G. Adams, Terence H. W. Ching, Rachael Grazioplene, Stephen A. Kichuk, Geena Fram, Prerana Patel, Jeffrey Eilbott, Elizabeth D’amico, Sarah Shnayder, Bradford Martins, Calvin Bohner, Lucia Amoroso, Anastasia Jankovsky, Giuliana DePalmer, Gerald W Valentine, Gabriella Agin-Liebes, Jamila Hokanson, Christopher Pittenger
SSRN Electronic Journal 2026 preprint DOI: 10.2139/ssrn.6218466 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Open-label |
|---|---|
| Sample size | 28 |
| Population | Adults aged 18–65 years with treatment-resistant OCD (Y-BOCS score ≥19 and ≥2 failed adequate treatment trials) |
| Interventions | Psilocybin Niacin |
| Dose | 0.25 mg/kg orally |
| Duration | 48 hours and 1 week primary endpoints; benefits persisted through 12 weeks |
| Topics | Psilocybin |
| Keywords | Adverse effect Randomized controlled trial Population Niacin Intention-to-treat analysis Clinical trial Significant difference |
| Citations | 1 |
| Registration | NCT03356483 |
| Key findings | A single dose of psilocybin produced rapid, clinically meaningful, and sustained OCD symptom reductions in treatment-resistant OCD. |
Abstract
Background: Obsessive-compulsive disorder (OCD) affects 2–3% of the population worldwide, and 40–60% of patients do not respond to first-line treatments. We evaluated the efficacy and safety of a single dose of psilocybin in adults with treatment-resistant OCD.Methods: In this phase 2, randomised, double-blind, placebo-controlled trial at the Connecticut Mental Health Center, Yale University (New Haven, CT, USA), adults aged 18–65 years with treatment-resistant OCD (Y-BOCS score ≥19 and ≥2 failed adequate treatment trials) were randomly assigned (1:1) using permuted blocks to receive a single dose of psilocybin (0·25 mg/kg orally) or niacin (250 mg orally). Independent raters were masked to treatment assignment through 1-week assessments. The primary analysis followed intention-to-treat principles. Primary outcomes were change in A-YBOCS from baseline to 48 hours and Y-BOCS from baseline to 1 week. This trial is registered at ClinicalTrials.gov, NCT03356483, and is now complete.Findings: Between Nov 1, 2018, and June 30, 2023, 194 individuals were assessed for eligibility; 28 enrolled and randomly assigned (14 to psilocybin, 14 to niacin; 14 female, 13 male, one non-binary). At 48 hours, A-YBOCS scores decreased by 9·76 points (95% CI 6·00–13·52) in the psilocybin group versus +0·07 (−2·21 to 2·35) in the niacin group (between-group difference 9·83 points (95% CI 5·04–14·62); p<0·0001). At 1 week, 69·2% (9/13) of psilocybin participants achieved response (≥35% Y-BOCS reduction) versus 0% (0/14) of niacin participants (p<0·0001; number needed to treat 1·4). Benefits persisted through 12 weeks. In open-label crossover, 35·7% (5/14) achieved response at 1 week. One serious adverse event (suicidal ideation) occurred; no treatment-related deaths occurred.Interpretation: A single dose of psilocybin produced rapid, clinically meaningful, and sustained OCD symptom reductions, suggesting a novel interventional paradigm for treatment-resistant OCD warranting larger confirmatory trials.