1. ¹Schizophrenia Biological Research Center, VA Connecticut Healthcare System, West Haven, CT, USA
2. ²Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT, USA
3. ³Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
4. ⁴Division of Biostatistics, Department of Epidemiology and Public Health, Yale University, New Haven, CT, USA
5. ⁵Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA
6. ⁶Nathan Kline Institute, Orangeburg, NY, USA

Correspondence: Dr DC D'Souza, Psychiatry Service, 116A, VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT 06516, USA. Tel: +1 203 932 5711ext. 2594, 2571; Fax: +1 203 937 4860; E-mail: deepak.dsouza@yale.edu

Received 2 February 2004; Revised 9 April 2004; Accepted 13 April 2004; Published online 2 June 2004.

Abstract

Recent advances in the understanding of brain cannabinoid receptor function have renewed interest in the association between cannabinoid compounds and psychosis. In a 3-day, double-blind, randomized, and counterbalanced study, the behavioral, cognitive, and endocrine effects of 0, 2.5, and 5 mg intravenous delta-9-tetrahydrocannabinol (-9-THC) were characterized in 22 healthy individuals, who had been exposed to cannabis but had never been diagnosed with a cannabis abuse disorder. Prospective safety data at 1, 3, and 6 months poststudy was also collected. -9-THC (1) produced schizophrenia-like positive and negative symptoms; (2) altered perception; (3) increased anxiety; (4) produced euphoria; (5) disrupted immediate and delayed word recall, sparing recognition recall; (6) impaired performance on tests of distractibility, verbal fluency, and working memory (7) did not impair orientation; (8) increased plasma cortisol. These data indicate that -9-THC produces a broad range of transient symptoms, behaviors, and cognitive deficits in healthy individuals that resemble some aspects of endogenous psychoses. These data warrant further study of whether brain cannabinoid receptor function contributes to the pathophysiology of psychotic disorders.