Single-dose (10 mg) psilocybin reduces symptoms in adults with obsessive-compulsive disorder: A pharmacological challenge study
- PMID: 40618640
- DOI: 10.1016/j.comppsych.2025.152619
Single-dose (10 mg) psilocybin reduces symptoms in adults with obsessive-compulsive disorder: A pharmacological challenge study
Abstract
Background: Obsessive-compulsive disorder (OCD) is a common and disabling condition. A large proportion of patients fail to respond to first-line treatment with serotonin reuptake inhibitors either selective serotonin reuptake inhibitors (SSRIs) or clomipramine. Preliminary evidence suggests psilocybin, a serotonin receptor agonist, might be efficacious. We conducted a pharmacological challenge study to investigate the efficacy and mechanisms of effect of psilocybin in OCD. This analysis reports the clinical outcomes only.
Methods: Participants with a diagnosis of OCD of at least moderate severity, received two single doses of oral psilocybin, 1 mg followed by 10 mg, administered in fixed order separated by 4 weeks. On the day of dosing, they were treated in a day-care facility in the presence of clinicians experienced in the use of psychedelics for treating mental disorders. Psychological support was provided before, during and after dosing. Participants and raters were blinded to the order of treatment. They were assessed on the day before each dose (baseline 1, 2), on the day of dosing and at intervals over a 4-week period afterward using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) (primary clinical outcome) and secondary clinical outcomes including the Montgomery-Åsberg Depression Rating Scale (MADRS). Adverse effects were also recorded.
Results: Nineteen adult participants (aged 20-60) entered the study and 18 completed all assessments. Clinical outcomes following 1 mg and 10 mg psilocybin were compared using a linear mixed-effects model and ANOVA. A significant between-dosage effect favouring 10 mg psilocybin was found one-week after dosing on the Y-BOCS (Cohen's d = 0.82, p = 0.002). In particular, the effect one-week after dosing was statistically significant on the compulsion subscale of the Y-BOCS (Cohen's d: 0.74, p = 0.003), compared to obsession (Cohen's d: 0.50, p = 0.06). The effect diminished over the subsequent 3 weeks. No effect of psilocybin was detected on the MADRS. Psilocybin was well tolerated, with few adverse events reported at both dosages and no serious adverse events.
Conclusions: In this study, which was limited by a small sample size and the absence of randomisation, a 10 mg dose of oral psilocybin was found to be well-tolerated and potentially efficacious in patients with OCD. Psilocybin produced a rapid-onset, moderate to large effect on compulsive symptoms, which lasted up to one week after dosing. Future randomised placebo-controlled clinical trials investigating a longer course of multiple weekly doses of 10 mg psilocybin are indicated in OCD and in other obsessive-compulsive and related disorders characterised by compulsions.
Keywords: Compulsions; OCD; Ossessive-compulsive disorder; Psilocybin; Psychedelics.
Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of competing interest NAF has recently held research or networking grants from the NIHR, COST Action, Orchard, UKRI, Compass Pathways; accepted travel and/or hospitality expenses from the BAP, ECNP, RCPsych, CINP, World Psychiatric Association; received payment from Elsevier for editorial duties and the Mental Health Academy and Children and Screens for lecturing. She leads an NHS treatment service for OCD. She holds Board membership for various registered charities linked to OCD. TWR consults for Cambridge Cognition and Supernus. He also currently receives a research grant from Shionogi & Co. Editorial honoraria from Elsevier and Springer-Nature. LP reports a relationship with European Cooperation in Science and Technology, the University of Hertfordshire, Orchard, ECNP-OCRN International College of Obsessive-Compulsive Spectrum Disorders (ICOCS), that includes: funding grants. DN In the past 3 years he has received lecture fees from Takeda, Lundbeck, Otsuka and Janssen plus consulting fees from Algernon, Beckley Psytech, Leith Pharma and Amitis partners. He is a director of Gaba Labs and Chief Research Officer of Awaknlifesciences. He has shares/options in Psyched Wellness and Neurotherapeutics. DN is currently Head of the Imperial College Centre for Psychedelic Research that has received support in kind from both COMPASS Pathways and USONA (psilocybin) and Beckley Psytec (5-MEO-DMT) studies. DE is acting as a paid scientific advisor for Aya Biosciences, Lophora Aps, Clerkenwell Health, Mindstate Design Lab and is paid for delivering teaching on MMA's CPAT Course. SR receives honoraria for speaking engagements and consultations related to psychedelic therapy. She was an inaugural board member of the Board of Psychedelic Medicines and Therapies (USA), designed to bring certification standards for future psychedelic-assisted therapists. She currently lectures internationally on culturally responsive practices in psychedelic therapy with Mind Medicine Australia, the Psychedelic Liberation Training, and Vital (Psychedelics Today). RCH is a scientific advisor to TRYP Therapeutics, Journey Colab, Osmind, MindState, Entheos Labs, and Otsuka. These relationships did not influence the design of the proposed study or its interventions. These and other commercial entities may stand to indirectly benefit from any positive research on psychedelic therapies but will not benefit directly, such as by receiving intellectual property or privileged access to research results.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
