Opioid Antagonism of Cannabinoid Effects: Differences between Marijuana Smokers and Nonmarijuana Smokers

opioid-cannabinoid system interaction

http://www.nature.com/npp/journal/v32/n6/full/1301243a.html

Neuropsychopharmacology (2007) 32, 1391-1403

Opioid Antagonism of Cannabinoid Effects: Differences between Marijuana Smokers and Nonmarijuana Smokers

Margaret Haney


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.