670. CAN WE RE-MEDICALISE THE PSYCHEDELIC EXPERIENCE?

Abstract Background Despite the widespread availability of multiple antidepressant treatments, depression remains a common and sometimes debilitating disorder. A significant proportion of patients with major depressive disorder fail two or more antidepressant treatments and are considered to have treatment-resistant depression (TRD). Recent attention has turned to psilocybin and other psychedelic compounds as potential rapidly acting and durable episodic treatments for psychiatric disorders including depression. Aims & Objectives To explore the efficacy and safety of crystalline psilocybin in the treatment of TRD Method COMP 001 was the first large, multinational, randomized controlled trial to evaluate the investigational drug COMP360, a proprietary pharmaceutical-grade synthetic psilocybin formulation, optimized for stability and purity, developed by the sponsor COMPASS Pathfinder Ltd in patients with TRD. Results This was a dose-ranging study that randomized 233 participants equally to 25mg or 10mg, or the 1mg control treatment. Participants down-tapered and washed out any previous antidepressant medications, and received a single administration of COMP360 as monotherapy, after which they were followed for 12 weeks. On the primary efficacy measure, large dose-dependent reductions from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) scores were evident starting from Day 2. Clinically meaningful differences in MADRS score improvements between the 25mg and 1mg doses were statistically significant through week 6 and remained numerically evident at week 12. Results of secondary and additional efficacy measures were consistent with MADRS results. The intensity of the psychedelic experience entailing boundlessness was associated with clinical outcome. Discussion & Conclusions COMP360 was generally well-tolerated; in both studies over 90% of adverse events were either mild or moderate in severity. Suicidality remains a concern in TRD studies. These results suggested that COMP360 has potential to become an important contribution to the treatment for TRD. Further clinical development of COMP360 in rigorous, large, randomized controlled studies is underway.