1. ¹Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Department of Health and Human Services, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA
2. ²Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA
3. ³Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
4. ⁴Department of Medicine, Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
5. ⁵Psychobiology Section, Medications Discovery Research Branch, Department of Health and Human Services, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA

Correspondence: Dr SR Goldberg, Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Department of Health and Human Services, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. Tel: +1 410 550 1522; Fax: +1 410 550 1648; E-mail: sgoldber@intra.nida.nih.gov

Received 19 December 2007; Revised 18 January 2008; Accepted 25 January 2008; Published online 27 February 2008.

Abstract

Accumulating evidence suggests the endocannabinoid system modulates environmental cues' ability to induce seeking of drugs, including nicotine and alcohol. However, little attention has been directed toward extending these advances to the growing problem of cannabis use disorders. Therefore, we studied intravenous self-administration of ⁹-tetrahydrocannabinol (THC), the main psychoactive constituent of marijuana, using a second-order schedule of drug seeking. Squirrel monkeys' lever responses produced only a brief cue light until the end of the session, when the final response delivered THC along with the cue. When a reinstatement procedure was used to model relapse following a period of abstinence, THC-seeking behavior was robustly reinstated by the cue or by pre-session administration of THC, other cannabinoid agonists, or morphine, but not cocaine. The cannabinoid antagonist rimonabant blocked cue-induced drug seeking, THC-induced drug seeking, and the direct reinforcing effects of THC. Thus, rimonabant and related medications might be effective as treatments for cannabinoid dependence.