Safety, tolerability, and clinical and neural effects of single-dose psilocybin in obsessive-compulsive disorder: protocol for a randomized, double-blind, placebo-controlled, non-crossover trial.

Background

Psilocybin may help treat obsessive-compulsive disorder (OCD). To date, only one open-label study of psilocybin for OCD exists, necessitating further investigation with a randomized controlled design. The neural correlates of psilocybin's effects on OCD have also not been studied.

Objectives

This first-of-its-kind trial aims to evaluate the feasibility, safety, and tolerability of psilocybin in the treatment of OCD, provide preliminary evidence on the effects of psilocybin on OCD symptoms, and elucidate neural mechanisms that may mediate psilocybin's effects on OCD.

Design

We use a randomized (1:1), double-blind, placebo-controlled, non-crossover design to examine the clinical and neural effects of either a single dose of oral psilocybin (0.25 mg/kg) or active placebo-control agent (250 mg of niacin) on OCD symptoms.

Methods and analysis

We are enrolling 30 adult participants at a single site in Connecticut, USA who have failed at least one trial of standard care treatment (medication/psychotherapy) for OCD. All participants will also receive unstructured, non-directive psychological support during visits. Aside from safety, primary outcomes include OCD symptoms over the past 24 h, assessed by the Acute Yale-Brown Obsessive-Compulsive Scale and Visual Analog Scale ratings. These are collected by blinded, independent raters at baseline and the primary endpoint of 48 h post-dosing. Total follow-up is 12 weeks post-dosing. Resting state neuroimaging data will be collected at baseline and primary endpoint. Participants randomized to placebo will be offered the chance to return for an open-label dose of 0.25 mg/kg.

Ethics statement

All participants will be required to provide written informed consent. The trial (protocol v. 5.2) was approved by the institutional review board (HIC #2000020355) and registered with ClinicalTrials.gov (NCT03356483).

Discussion

This study may represent an advance in our ability to treat refractory OCD, and pave the way for future studies of neurobiological mechanisms of OCD that may respond to psilocybin.

Informations de copyright

Copyright © 2023 Ching, Grazioplene, Bohner, Kichuk, DePalmer, D’Amico, Eilbott, Jankovsky, Burke, Hokanson, Martins, Witherow, Patel, Amoroso, Schaer, Pittenger and Kelmendi.

Déclaration de conflit d'intérêts

The authors declare the following conflict of 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.