Introduction

The rapid growth of the cannabis industry, changes in public perceptions about the risks of cannabis,¹ and increasing rates of cannabis use² make it imperative that research is conducted to better understand the effects of cannabis in humans. This information will enable the expanding population of cannabis consumers, as well as healthcare professionals and policymakers, to make informed decisions about the risks and benefits of cannabis use. To fully understand the effects of cannabis, potential sex differences must be considered. Animal research on the endocannabinoid system has revealed a sexually dimorphic system that interacts with gonadal hormones.^3–5 Correspondingly, the small literature on sex differences in humans hints at intriguing differences in men’s and women’s experiences with cannabis.

Cannabis use, dependence, and treatment

The most well documented sex difference in human cannabis users is that men are more likely to use and become dependent on cannabis.^6–16 Men are also more likely to use cannabis for medicinal purposes¹⁷ and initiate use at a younger age.^18–20 While there is some evidence that the “gender gap” in cannabis use is decreasing^17,21,22 existing sex differences in cannabis use may reflect women’s increased perceptions of risks associated with regular use.^1,23,24 Further, while men are more likely to become dependent on cannabis, women demonstrate a more rapid progression from first use to cannabis use disorder.^25–30 Consistent with these results, young males are more likely to enter treatment for cannabis abuse³¹ but women tend to enter treatment for cannabis abuse after fewer years of use and less cumulative use than men.²⁶

Withdrawal

Research findings on sex differences in self-reported symptoms of cannabis withdrawal are equivocal: some studies suggest that women report experiencing more withdrawal symptoms than men,^32,33 and others fail to find sex differences in withdrawal symptoms.^10,25,34,35 Some of the studies that failed to detect significant sex differences in withdrawal symptoms reported that the men in their samples reported greater use and dependence on cannabis.^10,25 Therefore, it may be that women’s decreased cannabis use and dependence helps to explain the lack of significant sex differences in withdrawal symptoms in those studies.

Agrawal et al. also failed to find sex differences in the overall prevalence of withdrawal symptoms; however, they did find that women were more likely to report nausea, and men were more likely to report goose bumps and pupil dilation, as withdrawal symptoms.³⁵ Herrmann et al. also found that women reported more nausea, as well as stomach pain, irritability, restlessness, anger, and outbursts during their last quit attempt than did men.³² Finally, Copersino and colleagues found that women were more likely to report upset stomach whereas men were more likely to report cannabis cravings and increased sex drive during cannabis withdrawal.³⁶ Therefore, while it is unclear whether women experience worse withdrawal than men, evidence indicates that women are prone to experience different withdrawal symptoms, particularly nausea and upset stomach.

Acute effects

Research involving the administration of cannabis or delta-9-tetrahydrocannabinol (THC) suggests that women report significantly more dizziness than men.³⁷ Findings on the subjective effects of cannabis or THC intoxication are equivocal: one study found that women give higher ratings than men for the subjective effects of smoked cannabis,³⁸ one found that men report greater subjective effects of oral THC (2.5, 5, 10 mg) than women do,³⁹ and one indicated that sex differences in subjective effects of oral THC vary as a function of dose, with women reporting greater subjective effects than men at low doses (5 mg) and men reporting greater subjective effects than women at high doses (15 mg).⁴⁰ Finally, Penetar et al. found shorter latencies to detect the effects of smoked cannabis and longer duration of the effects of smoked cannabis in men compared to women.⁴¹ These inconsistent results may reflect differences in in the populations tested (regular cannabis users^37,38,40,41 vs. non-users³⁹), the route of administration used (smoked cannabis^37,38,41 vs. orally administered THC^37,39,40), and sex differences in frequency and quantity of cannabis used (only one study matched men and women on frequency and quantity of use³⁸). Clearly additional research is needed before strong conclusions regarding sex differences in the subjective effects of cannabis can be reached.

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