Comparison of smoked marijuana and oral Δ9-tetrahydrocannabinol in humans

Rationale: Although smoked marijuana contains at least 60 cannabinoids, Delta(9)-tetrahydrocannabinol (Delta(9)-THC) is presumed to be the cannabinoid primarily responsible for many marijuana-related effects, including increased food intake and subjective effects. Yet, there has been no systematic comparison of repeated doses of oral Delta(9)-THC with repeated doses of smoked marijuana in the same individuals. Objective: To compare the effects of oral Delta(9)-THC and smoked marijuana in humans under controlled laboratory conditions. Methods: Eleven healthy research volunteers, who reported smoking an average of six marijuana cigarettes per day, completed an 18-day residential study. Marijuana cigarettes (3.1% Delta(9)-THC, q.i.d.) were smoked or Delta(9)-THC (20 mg, q.i.d.) was taken orally using a staggered, double-blind, double-dummy procedure for three consecutive days. Four days of placebo administration separated each active drug condition. Psychomotor task performance, subjective effects, and food intake were measured throughout the day. Results: Relative to placebo baseline, oral Delta(9)-THC and smoked marijuana produced similar subjective-effect ratings (e.g., high and mellow), although some effects of smoked marijuana were more pronounced and less prone to the development of tolerance. Additionally, participants reported negative subjective effects (e.g., irritable and miserable) during the days after smoking marijuana but not after oral Delta(9)-THC. Both drugs increased food intake for 3 days of drug administration, but had little effect on psychomotor performance. Conclusion: These results indicate that the behavioral profile of effects of smoked marijuana (3.1% Delta(9)-THC is similar to the effects of oral Delta(9)-THC (20 mg), with some subtle differences.