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.

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Published in Pharmacology Biochemistry and Behavior, v. 152, p. 44-51.

© 2016 Elsevier Inc. All rights reserved.

This manuscript version is made available under the CC‐BY‐NC‐ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/.

The document available for download is the author's post-peer-review final draft of the article.

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This research and the preparation of this manuscript were supported by grants awarded to Dr. Joshua Lile (National Institute on Drug Abuse [NIDA] grants K01 DA018772, K02 DA031766, R01 DA025605 and R01 DA036550), a NIDA T32 training grant DA035200, and a National Center for Advancing Translational Sciences grant awarded to the University of Kentucky Center for Clinical and Translational Science (UL1TR000117).