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Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder

Francisco A. Moreno, M.D.; Christopher B. Wiegand, M.D.; E. Keolani Taitano, Ph.D.; and Pedro L. Delgado, M.D.

Background: Anecdotal reports suggest that psychedelic agents may relieve symptoms of obsessive-compulsive disorder (OCD). This modified double-blind study investigated the safety, tolerability, and clinical effects of psilocybin, a potent 5-HT1A and 5-HT2A/2C agonist, in patients with OCD.

Method: Nine subjects with DSM-IV-defined OCD and no other current major psychiatric disorder participated in up to 4 single-dose exposures to psilocybin in doses ranging from sub-hallucinogenic to frankly hallucinogenic. Low (100 mg/kg), medium (200 mg/kg), and high (300 mg/kg) doses were assigned in that order, and a very low dose (25 mg/kg) was inserted randomly and in double-blind fashion at any time after the first dose. Testing days were separated by at least 1 week. Each session was conducted over an 8-hour period in a controlled environment in an outpatient clinic; subjects were then transferred to a psychiatric inpatient unit for overnight observation. The Yale-Brown Obsessive Compulsive Scale (YBOCS) and a visual analog scale measuring overall obsessive-compulsive symptom severity were administered at 0, 4, 8, and 24 hours postingestion. The Hallucinogen Rating Scale was administered at 8 hours, and vital signs were recorded at 0, 1, 4, 8, and 24 hours after ingestion. The study was conducted from November 2001 to November 2004.

Results: Nine subjects were administered a total of 29 psilocybin doses. One subject experienced transient hypertension without relation to anxiety or somatic symptoms, but no other significant adverse effects were observed. Marked decreases in OCD symptoms of variable degrees were observed in all subjects during 1 or more of the testing sessions (23%-100% decrease in YBOCS score). Repeated-measures analysis of variance for all YBOCS values revealed a significant main effect of time on Wilks lambda (F = 9.86, df = 3,3; p = .046), but no significant effect of dose (F = 2.25, df = 3,3; p = .261) or interaction of time and dose (F = 0.923, df = 9,45; p = .515). Improvement generally lasted past the 24-hour timepoint.

Conclusions: In a controlled clinical environment, psilocybin was safely used in subjects with OCD and was associated with acute reductions in core OCD symptoms in several subjects.

(J Clin Psychiatry 2006;67:1735-1740)

Received Dec. 19, 2005; accepted April 10, 2006. From the Department of Psychiatry, University of Arizona, Tucson (Drs. Moreno, Wiegand, and Taitano); and the Department of Psychiatry, University of Texas Health Sciences Center, San Antonio (Dr. Delgado).

This study was supported by grants from the Multidisciplinary Association for Psychedelic Studies; the Heffter Research Institute, which included funding support from Peggy Hitchcock; and the Nathan Cummings Foundation, with the support and encouragement of Richard A. and Roberta Friedman Cummings.

Presented at the 58th annual meeting of the Society of Biological Psychiatry, May 15-17, 2003, San Francisco, Calif.; the 42nd annual meeting of the American College of Neuropsychopharmacology, Dec. 7-11, 2003, San Juan, Puerto Rico; and the 44th annual meeting of the New Clinical Drug Evaluation Unit, June 1-4, 2004, Phoenix, Ariz.

Dr. Moreno is a consultant for Cyberonics and Forest and has received grants from Cyberonics. Dr. Delgado has been a consultant for and been on the speakers/advisory boards of Eli Lilly and Wyeth; has received grant/research support from AstraZeneca; has received honoraria from Eli Lilly, Wyeth, and Pierre Fabre; and is a stock shareholder in Pfizer. Drs. Wiegand and Taitano report no additional financial or other relationship relevant to the subject of this article.

Acknowledgments are listed at the end of the article.

Corresponding author and reprints: Francisco A. Moreno, M.D., Department of Psychiatry, College of Medicine, University of Arizona Health Sciences Center, 1501 N. Campbell Ave. 7-OPC, Tucson, AZ 85724 (e-mail: