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

Abstract

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.

Comparison of the discriminative stimulus and response rate effects of Δ9-tetrahydrocannabinol and synthetic cannabinoids in female and male rats

“…THC also is more potent in inducing acute antinociception and reducing inflammatory pain in female than in male rats (Craft et al, 2013a; Tseng and Craft, 2001). Preclinical results are consistent with findings from the human laboratory showing that women report greater sensitivity to the subjective effects of smoked cannabis (Cooper and Haney, 2014) and to lower doses of orally administered THC (Fogel et al, 2016); however, they are less sensitive than men to the subjective effects of higher doses of THC, an effect that the authors suggest may be related to greater tolerance at these doses (Fogel et al, 2016). Hence, although fewer women than men use cannabis for recreational purposes (SAMHSA, 2014), women may be more susceptible to developing addiction once use is initiated, a phenomenon that has been referred to as “telescoping” (Becker and Hu, 2008).…”

Sex and Gender Interactions on the Use and Impact of Recreational Cannabis

“…Similarly, a second study found that while prevalence of CUD was greater among males, females reported a shorter duration from onset of cannabis use to onset of CUD compared to men (mean of 5.8 vs. 4.7 years) [26]. Clinical research also indicates greater abuse liability among females, such that females reported greater subjective effects at lower doses of oral THC (5 mg), while males reported greater subjective effects at higher doses (15 mg) [27]. The authors suggest these sex differences in subjective effects may contribute to the more rapid progression to dependence (telescoping) observed in females [27].…”

“…Clinical research also indicates greater abuse liability among females, such that females reported greater subjective effects at lower doses of oral THC (5 mg), while males reported greater subjective effects at higher doses (15 mg) [27]. The authors suggest these sex differences in subjective effects may contribute to the more rapid progression to dependence (telescoping) observed in females [27]. Clearly, more robust research on cannabis telescoping is needed to inform tailored prevention and harm reduction approaches for women and girls, in particular.…”

Cannabis Withdrawal: a Review of Neurobiological Mechanisms and Sex Differences

“…Akin to other drugs of abuse, findings from multiple studies demonstrate that the reinforcing effects of cannabis and the subjective effects of THC may differ between males and females [14, 62, 63] and considerable pre-clinical data seemingly indicate that the ECS is sexually dimorphic [64–67]. In the U.S., past-year prevalence of cannabis use and cannabis use disorder has increased in both males and females [1, 2].…”