Safety, feasibility, tolerability, and clinical effects of repeated psilocybin dosing combined with non-directive support in the treatment of obsessive-compulsive disorder: protocol for a randomized, waitlist-controlled trial with blinded ratings.

Background: To date, few randomized controlled trials of psilocybin with non-directive support exist for obsessive-compulsive disorder (OCD). Results and participant feedback from an interim analysis of an ongoing single-dose trial (NCT03356483) converged on the possibility of administering a higher fixed dose and/or more doses of psilocybin in future trials for presumably greater benefits.
Objectives: This trial aims to evaluate the safety, feasibility, tolerability, and clinical effects of two doses of psilocybin paired with non-directive support in the treatment of OCD. This trial also seeks to examine whether two doses of psilocybin lead to greater OCD symptom reduction than a single dose, and to elucidate psychological mechanisms underlying the effects of psilocybin on OCD.
Design: A randomized (1:1), waitlist-controlled design with blinded ratings will be used to examine the effects of two doses of oral psilocybin paired with non-directive support vs. waitlist control on OCD symptoms. An adaptive dose selection strategy will be implemented (i.e., first dose: 25 mg; second dose: 25 or 30 mg).
Methods and Analysis: This single-site trial will enroll 30 adult participants with treatment-refractory OCD. Aside from safety, feasibility, and tolerability metrics, primary outcomes include OCD symptoms assessed on the Yale-Brown Obsessive-Compulsive Scale - Second Edition (Y-BOCS-II). A blinded independent rater will assess primary outcomes at baseline and the primary endpoint at the end of the second dosing week. Participants will be followed up to 12 months post-second dosing. Participants randomized to waitlist will be rescreened after 7 weeks post-randomization, and begin their delayed treatment phase thereafter if still eligible.
Ethics: Written informed consent will be obtained from participants. The institutional review board has approved this trial (protocol v. 1.7; HIC #2000032623).
Discussion: This study seeks to advance our ability to treat refractory OCD, and catalyze future research seeking to optimize the process of psilocybin treatment for OCD through understanding relevant psychological mechanisms. Clinical trial registration : ClinicalTrials.gov, identifier NCT05370911.
Competing Interests: TC serves as a continuing faculty member in the Psychedelic-Assisted Therapy Training Program offered by Integrative Psychiatry Institute (IPI), and consults for Transcend Therapeutics. CP serves/has served as a consultant for Biohaven, Teva, Lundbeck, Brainsway, Ceruvia Lifesciences, Transcend Therapeutics, Nobilis Therapeutics, and Freedom Biotech, receives royalties and/or honoraria from Oxford University Press and Elsevier, and has filed a patent on the use of neurofeedback in the treatment of anxiety, which is not relevant to the current work. BK is co-founder and Chief Scientific Advisor for Transcend Therapeutics and has consulted for Ceruvia Lifesciences and Lobe Sciences. CP and BK have filed a patent on the use of psilocybin in the treatment of obsessive-compulsive disorder (#US17/466,111). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 Ching, Amoroso, Bohner, D’Amico, Eilbott, Entezar, Fitzpatrick, Fram, Grazioplene, Hokanson, Kichuk, Martins, Patel, Schaer, Shnayder, Witherow, Pittenger and Kelmendi.)