Sex differences in the subjective effects of oral Δ9-THC in cannabis users

•Retrospective analysis of drug discrimination data was conducted to examine sex differences in acute effects of Δ9-THC.•Subjects received a range of Δ9-THC doses (0, 5, 15 and a “high” dose of either 25 or 30 mg).•Drug effects were assessed using drug discrimination, subjective effects, psychomotor performance, and physiological measures.•Dose-dependent sex differences were found.•Observed sex differences might contribute to the differential development of dependence in men and women.

Previous studies suggest that there are sex differences in endocannabinoid function and the response to exogenous cannabinoids, though data from clinical studies comparing acute cannabinoid effects in men and women under controlled laboratory conditions are limited. To further explore these potential differences, data from 30 cannabis users (N = 18 M, 12 F) who completed previous Δ9-tetrahydrocannabinol (Δ9-THC) discrimination studies were combined for this retrospective analysis. In each study, subjects learned to discriminate between oral Δ9-THC and placebo and then received a range of Δ9-THC doses (0, 5, 15 and a “high” dose of either 25 or 30 mg). Responses on a drug-discrimination task, subjective effects questionnaire, psychomotor performance tasks, and physiological measures were assessed. Δ9-THC dose-dependently increased drug-appropriate responding, ratings on “positive” Visual Analog Scale (VAS) items (e.g., good effects, like drug, take again), and items related to intoxication (e.g., high, stoned). Δ9-THC also dose-dependently impaired performance on psychomotor tasks and elevated heart rate. Sex differences on VAS items emerged as a function of dose. Women exhibited significantly greater subjective responses to oral drug administration than men at the 5 mg Δ9-THC dose, whereas men were more sensitive to the subjective effects of the 15 mg dose of Δ9-THC than women. These results demonstrate dose-dependent separation in the subjective response to oral Δ9-THC administration by sex, which might contribute to the differential development of problematic cannabis use.