Safety, Tolerability, and Efficacy of Psilocybin in Patients With Obsessive-Compulsive Disorder: A Phase I Modified Dose-Escalation Study

Phase I modified dose-escalation pilot (Department of Psychiatry, University of Arizona Health Sciences Center, Tucson; collaborator: University of Texas Health Sciences Center, San Antonio) of oral psilocybin in 9 adults (7 male, 2 female, ages 26–62, mean 40.9 ± 13.2) with DSM-IV obsessive-compulsive disorder and at least one prior adequate serotonin reuptake inhibitor (SRI) trial failure (mean 3.4 ± 1.9 treatment failures; baseline Y-BOCS 18–36, mean 24.1 ± 5.9). Up to four single-dose exposures per subject were administered at least one week apart under medical supervision in an outpatient psychopharmacology research clinic with subsequent overnight observation on an affiliated psychiatric inpatient unit. Dose levels: very low (VLD) 25 µg/kg, low (LD) 100 µg/kg, medium (MD) 200 µg/kg, and high (HD) 300 µg/kg. LD, MD, and HD were assigned in fixed ascending order (open-label); the VLD was inserted randomly and in double-blind fashion at any time after the first dose. Subjects wore eyeshades, listened to a standardised music programme, and were accompanied by trained sitters during each 8-hour session. Primary outcomes: Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and a visual analog scale (VAS) for overall OC symptom severity at 0, 4, 8, and 24 hours post-ingestion; Hallucinogen Rating Scale (HRS) at 8 hours; vital signs at 0, 1, 4, 8, and 24 hours. Twenty-nine total psilocybin doses were administered (all 9 received LD; 7 received VLD and MD; 6 received all four). Approved by the University of Arizona Human Subjects Committee and the U.S. Food and Drug Administration (FDA) under an Investigational New Drug application. Funded by the Multidisciplinary Association for Psychedelic Studies (MAPS), the Heffter Research Institute (with support from Peggy Hitchcock), and the Nathan Cummings Foundation. No public registry ID exists: the trial pre-dates the 2005 ICMJE registration mandate and the 2007 FDAAA requirement, and the paper reports no NCT/IND/protocol number.