Psilocybin for Treatment-Resistant OCD: A Randomized Controlled Trial
Benjamin Kelmendi, Thomas G. Adams, Terence H. W. Ching, Rachael Grazioplene, Stephen A. Kichuk, Geena Fram, Prerana Patel, Jeffrey Eilbott, Elizabeth D’amico, Sarah Shnayder, Brad Martins, Calvin Bohner, Lucia Amoroso, Anastasia Jankovsky, Giuliana DePalmer, Gerard Valentine, Gabrielle Agin-Liebes, Jamila Hokanson, Christopher Pittenger
January 15, 2026 preprint DOI: 10.31234/osf.io/atfum_v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Double-blind Open-label |
|---|---|
| Sample size | 28 |
| Population | Adults with treatment-resistant obsessive-compulsive disorder |
| Interventions | Psilocybin Niacin |
| Dose | 0.25 mg/kg |
| Duration | 48 hours post-treatment and 12-week follow-up |
| Topics | Depression Psilocybin |
| Keywords | Adverse effect Randomized controlled trial Niacin Population Obsessive compulsive Hallucinogen Clinical trial Depression economics Anesthesia Pharmacology |
| Registration | NCT03356483 |
| Key findings | A single dose of psilocybin produced rapid, large, and sustained reductions in OCD symptoms in treatment-resistant patients, with 69% achieving response at one week versus 0% with niacin. |
Abstract
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<0.001; Cohen's d=1.64). At one week, 69.2% (9/13) of psilocybin participants achieved response (≥35% Y-BOCS reduction) versus 0% (0/14) of niacin participants (P<0.001; number needed to treat, 1.4). Benefits persisted through 12 weeks in the psilocybin group. One serious adverse event occurred. In open-label treatment, A-YBOCS decreased by 6.14 points at 48 hours (95% CI, 2.56-9.72; P=0.003), with 35.7% achieving response at one week.Conclusions: A single dose of psilocybin with unstructured support produced rapid, clinically meaningful, and sustained reductions in OCD symptoms. This profile suggests a novel interventional paradigm for treatment-resistant OCD warranting larger confirmatory trials.Trial
Registration: ClinicalTrials.gov number, NCT03356483.