Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder
J Clin Psychiatry 2006;67(11):1735-1740
© Copyright 2017 Physicians Postgraduate Press, Inc.
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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
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.