¹Department of Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons of Columbia University, New York, NY, USA

Correspondence: Dr M Haney, New York State Psychiatric Institute, College of Physicians and Surgeons of Columbia University, 1051 Riverside Dr., Unit 120, New York, NY 10032, USA. Tel: +1 212 543 6539; Fax: +1 212 543 5991; E-mail: mh235@columbia.edu

Received 25 July 2006; Revised 12 September 2006; Accepted 19 September 2006; Published online 8 November 2006.

Abstract

In non-human animals, opioid antagonists block the reinforcing and discriminative-stimulus effects of ⁹-tetrahydrocannabinol (THC), while in human marijuana smokers, naltrexone (50 mg) enhances the reinforcing and subjective effects of THC. The objective of this study was to test a lower, more opioid-selective dose of naltrexone (12 mg) in combination with THC. The influence of marijuana-use history and sex was also investigated. Naltrexone (0, 12 mg) was administered 30 min before oral THC (0–40 mg) or methadone (0–10 mg) capsules, and subjective effects, task performance, pupillary diameter, and cardiovascular parameters were assessed in marijuana smoking (Study 1; n=22) and in nonmarijuana smoking (Study 2; n=21) men and women. The results show that in marijuana smokers, low-dose naltrexone blunted the intoxicating effects of a low THC dose (20 mg), while increasing ratings of anxiety at a higher THC dose (40 mg). In nonmarijuana smokers, low-dose naltrexone shifted THC's effects in the opposite direction, enhancing the intoxicating effects of a low THC dose (2.5 mg) and decreasing anxiety ratings following a high dose of THC (10 mg). There were no sex differences in these interactions, although among nonmarijuana smokers, men were more sensitive to the effects of THC alone than women. To conclude, a low, opioid-selective dose of naltrexone blunted THC intoxication in marijuana smokers, while in nonmarijuana smokers, naltrexone enhanced THC intoxication. These data demonstrate that the interaction between opioid antagonists and cannabinoid agonists varies as a function of marijuana use history.