Psilocybin-assisted psychotherapy for treatment-resistant obsessive–compulsive disorder: protocol for an open-label pilot study
Nicole Ledwos, Jenna Baer, Muhammad Ishrat Husain, Daniel M. Blumberger, Rachel Patterson, Elizabeth Hollingdrake, Ezmond S.l. Cheung, Colin Hawco, Christoph Zrenner, Brigitte Zrenner, Jamie D. Feusner, Susan L. Rossell, David Castle, Gwyneth Zai
BJPsych Open December 15, 2025 DOI: 10.1192/bjo.2025.10895 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label pilot trial Randomized Pilot study Peer reviewed |
|---|---|
| Sample size | 10 |
| Population | Adults with treatment-resistant obsessive–compulsive disorder |
| Intervention | Psilocybin-assisted psychotherapy |
| Dose | 25 mg |
| Duration | 12-week trial, with measures up to 1-week post-dose |
| Topics | Psilocybin Psychedelic-assisted therapy |
| Keywords | Protocol science Pilot trial Field mathematics Research design Intervention counseling Psychotherapist |
| Citations | 2 |
| Key findings | The study will provide preliminary data on the feasibility, tolerability, safety, and clinical effects of psilocybin-assisted psychotherapy for treatment-resistant OCD. |
Abstract
Background: Obsessive–compulsive disorder (OCD) is a debilitating mental disorder commonly treated with selective serotonin reuptake inhibitors, atypical antipsychotic augmentation and cognitive–behavioural therapy. However, up to 60% of people with OCD do not respond to these treatments. Therefore, a novel intervention, psilocybin-assisted psychotherapy (PAP), is an option of interest. Moreover, there is a need to better understand the mechanisms underpinning PAP’s effect on OCD symptoms.
Aims: We aimed to (a) establish the feasibility, tolerability and safety of administering PAP to adults with treatment-resistant OCD; (b) provide preliminary data on the clinical effects of PAP for treatment-resistant OCD, to inform the design of larger clinical trials; and (c) compare neuroimaging and neurophysiological markers pre- and post-PAP in treatment-resistant OCD.
Method: In this 12-week open-label trial, ten adults with treatment-resistant OCD will receive one 25 mg dose of psilocybin combined with psychological support. Feasibility, tolerability and safety will be assessed throughout. Clinical outcomes will be measured with the Yale–Brown Obsessive–Compulsive Scale. Exploratory measures will include brain imaging examining changes in dynamic connectivity from pre to post treatment, electroencephalogram to investigate changes in brain dynamics associated with psilocybin under acute conditions, and transcranial magnetic stimulation-electroencephalogram measures between baseline, provocation of OCD symptoms and up to 1-week post-dose.
Results: The study will provide important preliminary data on the feasibility and efficacy of PAP in adults with treatment-resistant OCD, as well as inform our understanding of neurobiological mechanisms.
Conclusions: The findings of the study will inform the design of larger randomised controlled trials and advance the field of psychedelic-assisted therapies.