Opioid antagonism of cannabinoid effects: differences between marijuana smokers and nonmarijuana smokers.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology June 2007 DOI: 10.1038/sj.npp.1301243 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study (within-subject, placebo-controlled) Peer reviewed |
|---|---|
| Sample size | 43 |
| Population | Marijuana smokers (n=22) and nonmarijuana smokers (n=21), men and women |
| Interventions | Naltrexone THC Methadone |
| Dose | Naltrexone 12 mg; THC 0-40 mg; Methadone 0-10 mg |
| Topics | Cannabis |
| Key findings | In marijuana smokers, 12 mg naltrexone blunted intoxication from 20 mg THC and increased anxiety at 40 mg THC; in nonmarijuana smokers, it enhanced intoxication from 2.5 mg THC and decreased anxiety at 10 mg THC. No sex differences were observed, though nonmarijuana-smoking men were more sensitive to THC alone than women. |
Abstract
In non-human animals, opioid antagonists block the reinforcing and discriminative-stimulus effects of Delta(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.