Psilocybin-assisted psychotherapy for treatment-resistant obsessive–compulsive disorder: protocol for an open-label pilot study
BJPsych Open – December 15, 2025
Source: OpenAlex
Summary
Up to 60% of individuals with Obsessive-Compulsive Disorder (OCD) don't improve with standard therapies. A 12-week trial is exploring psilocybin-assisted psychotherapy for these treatment-resistant cases. Ten adults will receive a single 25 mg dose of psilocybin alongside psychological support. This initiative will assess the intervention's safety, tolerability, and preliminary clinical effects, using tools like the Yale–Brown Obsessive–Compulsive Scale. Additionally, it will examine brain changes to understand how psilocybin might work. These preliminary findings will guide larger studies into this promising approach for severe 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.