Investigating sex differences in the acute effects of smoked cannabis: a potency-ranging, controlled administration, human laboratory experiment.

Rationale: Sex differences in the effects of cannabis have been demonstrated in animals, though the human evidence is more equivocal. In particular, more work is needed to better understand interactions between sex and dose in determining acute pharmacological effects of cannabis, especially at higher potencies of Δ9-tetrahydrocannabinol (THC).

Objectives: Sex differences were examined following a range of potencies of smoked cannabis (0%/0 mg, 6.25%/47 mg, 12.5%/94 mg, 22.0%/165 mg THC).

Methods: Thirty-five adults (18 females; 17 males) who used cannabis 1-5 days/week participated in a within-subject, double-blind, placebo-controlled, randomized, and counterbalanced human laboratory experiment. Analyses compared peak change from baseline scores between females and males for smoking topography, blood and oral fluid THC and metabolites concentrations, vital signs, pharmacokinetic-pharmacodynamic relationships, subjective effects, mood, and cognition.

Results: Females and males smoked similar amounts in each condition, yet females spent significantly more time smoking across all conditions. While both sexes achieved similar blood THC concentrations, females had significantly lower oral fluid THC concentrations. Aside from differences in the onset of some peak subjective effects, minimal evidence of sex differences was found in other outcomes, as well as in pharmacokinetic-pharmacodynamic relationships.

Conclusions: Our findings indicate inconsistent sex differences in the acute effects of smoked cannabis across a range of potencies. While previous research has examined the influences of sex on the effects of THC, to our knowledge this was the first study to evaluate sex differences testing a large range of smoked cannabis potencies (up to 22%/165 mg THC) under placebo-controlled laboratory conditions.