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.

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.

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.

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.

The findings of the study will inform the design of larger randomised controlled trials and advance the field of psychedelic-assisted therapies.