A randomized clinical trial of repeated doses of psilocybin for the treatment of obsessive–compulsive disorder

Psilocybin, a psychedelic compound, was generally well-tolerated and reduced obsessive-compulsive disorder (OCD) symptoms in a small clinical trial. No serious adverse events, psychotic symptoms, or changes in suicide severity occurred. Psilocybin, but not placebo, significantly lowered scores on the Yale-Brown Obsessive Compulsive Scale. After eight weeks of treatment including at least four high doses, 73.3% of participants responded (at least 35% reduction in symptoms), and 40% achieved remission. Benefits diminished but remained substantial at six months. Higher cumulative doses were linked to greater symptom reduction. Larger trials are needed to confirm efficacy and refine protocols.

Study at a glance

Abstract

BACKGROUND: Current treatments for obsessive-compulsive disorder (OCD), including serotonin reuptake inhibitors and cognitive-behavioral therapy, are often insufficient. Psilocybin, a 5HT2a agonist psychedelic, has shown promise for treating OCD, but rigorous evidence is still needed. AIMS: This randomized clinical trial evaluated safety, tolerability, and benefit of multiple psilocybin doses in OCD patients. METHODS: = 5 per condition), followed by four additional high-dose sessions (single-blind Phase 2). OCD severity was assessed with the Yale-Brown Obsessive Compulsive Scale (YBOCS) following each session, and prospectively for 6 months. Safety was evaluated via adverse event systematic assessment, suicide severity rating, and psychosis screening. RESULTS: Psilocybin was generally well-tolerated, with no serious adverse events, or psychotic symptoms, and no significant changes in suicide severity scores. Psilocybin but not placebo significantly reduced YBOCS scores. At the end of 8-week treatment, after participants had received at least four high doses of psilocybin, 73.3% were responders (⩾35% reduction in YBOCS scores), with 40% in remission. These effects diminished but remained substantial at 6 months. Post hoc analysis of cumulative dosing correlated with YBOCS score reductions at the end of treatment. CONCLUSIONS: Administration of up to eight doses of psilocybin in a clinical research setting appears to be safe and potentially effective for patients with OCD. Larger trials are needed to further support efficacy and refine treatment protocols. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID NCT03300947.