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 via OpenAlex
Summary
AI-generated from the abstractA single dose of psilocybin (0.25 mg/kg) produced rapid and sustained reductions in obsessive-compulsive disorder (OCD) symptoms among adults with treatment-resistant OCD. In a randomized, double-blind trial, 28 adults received either psilocybin or niacin (250 mg). At 48 hours, OCD severity scores dropped by about 10 points more in the psilocybin group than in the niacin group, a large effect. At one week, 69% of psilocybin participants achieved a clinically meaningful response, compared with none in the niacin group. Benefits lasted through 12 weeks. One serious adverse event occurred. Open-label psilocybin given later also reduced symptoms. The findings suggest psilocybin may offer a new treatment approach for treatment-resistant OCD, but larger confirmatory trials are needed.
Study at a glance
| 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 |
| Registration | NCT03356483 |
| Key finding | 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.