Antinociceptive, subjective and behavioral effects of smoked marijuana in humans

The purpose of this study was to determine whether marijuana produced dose- dependent antinociception in humans and, if so, whether endogenous opiates modulate this effect. A total of five male regular marijuana users particip ated in three test sessions during which they smoked cigarettes containing 0% (placebo) and 3.55% Delta(9)-tetrahydrocannabinol (Delta(9)-THC) (active ). Each of four controlled smoking bouts per session, spaced at 40-min inte rvals, consisted of nine puffs from active and placebo cigarettes (three ci garettes, three puffs per cigarette, one puff per min). During successive b outs, participants smoked 0, 3. 6 and 9 (0, 3, 9 and 18 cumulative) puffs f rom active marijuana cigarettes, with the remainder of puffs from placebo c igarettes. Test sessions were identical, except for naltrexone 0, 50 or 200 mg p.o. (randomized, double-blind) administration 1 h before the first smo king bout on the different days. Before smoking, between smoking bouts and postsmoking, participants completed an assessment battery that included ant inociceptive (finger withdrawal from radiant heat stimulation), biological, subjective, observer-rated signs and performance measures. Marijuana produ ced significant dose-dependent antinociception (increased finger withdrawal latency) and biobehavioral effects. Naltrexone did not significantly influ ence marijuana dose-effect curves, suggesting no role of endogenous opiates in marijuana-induced antinociception under these conditions. (C) 2000 Else vier Science Ireland Ltd. All rights reserved.