Sex differences in the acute effects of cannabis on human cognition: A systematic review

Acute cannabis exposure can transiently impair cognitive performance, increasing the risk of accidental injury and potentially disrupting activities of daily living. Although sex differences in responses to cannabis have been reported, no systematic review has examined whether these extend to acute cognitive effects. Our primary aim was to examine sex differences in the acute effects of cannabis (including isolated delta-9-tetrahydrocannabinol [THC]) on cognition in humans. Our secondary aim was to determine if sex differences in the acute effects of cannabis vary by cognitive domain, route of administration, or dosing paradigm. Following PRISMA guidelines, we conducted a comprehensive literature search across Embase, MEDLINE, APA PsycInfo, Cochrane Library, and Web of Science databases. Of 1,625 unique records, 169 underwent full-text screening, and 29 studies met inclusion criteria. Six of 29 articles (20.7 %), representing eight of 216 cognitive outcomes (3.7 %), found statistical evidence of sex differences in acute cognitive effects of cannabis/THC. All six found increased effects in female participants in at least one cognitive variable; one study additionally found increased effects in male participants, and one study found divergent cognitive effects in male and female participants. There were no clear patterns by cannabis dosing paradigm, route of administration, or cognitive domain. Overall, we found limited evidence that sex significantly influences the acute cognitive effects of cannabis, though methodological heterogeneity precludes any firm conclusions. Future studies should prioritize the measurement of sex-related factors, such as hormonal modulation of cannabinoid pharmacokinetics and pharmacodynamics.