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

Abstract

<h4>Background</h4>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.<h4>Aims</h4>This randomized clinical trial evaluated safety, tolerability, and benefit of multiple psilocybin doses in OCD patients.<h4>Methods</h4>Fifteen participants were randomized to receive 4 weekly sessions of high-dose (300 µg/kg), low-dose (100 µg/kg) psilocybin, or active placebo (lorazepam) in a double-blind Phase 1 (<i>n</i> = 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.<h4>Results</h4>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.<h4>Conclusions</h4>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.<h4>Clinical trial registration</h4>ClinicalTrials.gov ID NCT03300947.

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