Compass Psychological Support Model for COMP360 Psilocybin Treatment of Serious Mental Health Conditions

Introduction

Patient safeguarding during high-dose psilocybin treatment is presented as a central ethical and clinical priority because the drug commonly produces intense alterations in cognition, perception, affect, and suggestibility that can be therapeutic but also distressing or destabilising. Earlier research and contemporary trials indicate that psychoeducation, preparation, and psychological support are important to promote safety and allow participants to derive therapeutic benefit. However, the field lacks standardised, manualised approaches to psychological support, which complicates comparisons across studies and raises regulatory concerns about consistent delivery and minimising bias in trials of investigational medicinal products. Kirlic and colleagues set out to describe the Compass Psychological Support Model (CPSM), a manualised framework developed to support participants receiving COMP360, Compass Pathfinder Ltd’s proprietary synthetic psilocybin formulation, within Compass-sponsored clinical trials. The paper explains the CPSM’s principles and three-stage structure (preparation, administration, integration), and outlines the therapist selection, training, mentoring, and fidelity-assessment procedures devised to ensure consistent, high-quality delivery in the Phase 3 multicentre, randomised, controlled, double-blind programme for treatment-resistant depression across Europe and North America.