An Open-Label Multidose Psilocybin Intervention for Obsessive-Compulsive Disorder

Importance

Obsessive-Compulsive Disorder (OCD) has a 2% global prevalence, but only about 50% of patients respond to conventional treatment, underscoring the need for additional effective interventions.

Objective

To assess the feasibility, safety, and preliminary evidence for efficacy of repeated psilocybin administration in OCD patients who had previously attempted psychotherapy or pharmacotherapy.

Design

Waitlist-controlled open label randomized clinical trial.

Setting

Data were collected at the Johns Hopkins University School of Medicine.

Participants

Data were analyzed from 30 participants (total randomized N=37, by age, sex and OCD severity) with a failed previous attempt at either pharmacotherapy or evidence-based psychotherapies such as exposure response prevention (ERP).

Intervention

Participants received two psilocybin doses over two weeks (20 mg followed by 30 mg, if well-tolerated) under supportive conditions. The immediate-treatment arm received the drug within a month following enrollment, and the waitlist-control arm received identical support and dosing after an 8-week waiting period.

Main Outcome

Clinician-administered Y-BOCS scores was collected one week post each drug administration and one month post session 2. Self-assessed reports were collected for acute subjective effects (Mystical Experience Questionnaire (MEQ), Challenging Experience Questionnaire (CEQ), and 11-Dimensional Altered States of Consciousness (11D-ASC)), State-Trait Anxiety Inventory (STAI), Beck Depression Inventory-II (BDI-II), and Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q).

Results

A total of 37 participants were enrolled in the study (age: 38.4±11.6 years; 21 [56.75%] female), with 30 [81.08%] completing the 1-month follow-up. We show that two successive doses of psilocybin over two weeks were well-tolerated, leading to reduction in OCD symptoms. Compared with the waitlist group (N=14), the immediate-treatment group (N=16) showed a reduction in the Y-BOCS scores (F(2,56)=16.17, p<0.001, η ² □=0.37) post session. This improvement persisted one month after the second psilocybin dose for both groups post treatment crossover for waitlisted group (F(3,84)=29.91, p<0.001, η ² □=0.52). Y-BOCS scores were correlated with several acute subjective effects measures, including total scores on MEQ, and individual factors on CEQ and 11D-ASC. Conclusions and Relevance: Repeated psilocybin administration is tolerable and potentially efficacious in reducing OCD symptoms. These results support further investigation of multi dose psilocybin protocols as a viable therapeutic approach.

Trial Registration

ClinicalTrials.gov Identifier NCT05546658

Key points

• Psilocybin was generally safe and tolerated across repeated dosing

• Psilocybin produced reductions in OCD symptom severity

• Quality of the psychedelic experience was correlated with therapeutic benefit