Procedures
The study investigational drug was COMP360, a proprietary pharmaceutical-grade synthetic psilocybin formulation, optimized for stability and purity, developed by COMPASS Pathfinder Ltd. (five capsules of 5 mg of psilocybin)The study team reviewed the results of the screening to determine eligibility. Eligible participants who were on serotonergic medications were titrated off these medications over the screening period. During this ‘washout period’, they met with the study PI, who monitored titration and assessed response, and a clinical psychologist, who conducted a suicide assessment (C-SSRS) weekly throughout the screening period. Baseline assessments were conducted the day before the psilocybin session (day −1) (see Fig. In the 2 weeks leading up to the psilocybin session, participants met with the lead study psychologist for two preparation sessions (Extended Data Table Participants returned to the clinic the morning after the dosing visit (day 1), during which they completed post-treatment repeated assessments and met the study psychologists for a safety assessment and a 60–90-min integration session (see the ‘Inventory of Supporting Information’ document, ‘Overview of the therapeutic model’, for information on integration sessions). Participants then returned to the clinic for continued assessment at 1-week, 1-month and 3-month follow-up. Participants also received two integration sessions at day 1 and day 7. The 3-month follow-up visit was conducted via telehealth for seven participants owing to change in location.