Sex differences in the acute effects of smoked cannabis: evidence from a human laboratory study of young adults

Rationale Animal studies have found robust sex differences in the pharmacokinetics and pharmacodynamics of Delta(9)-tetrahydrocannabinol (THC). However, the human evidence remains equivocal, despite findings that women may experience more severe consequences of cannabis use than men. Objectives The objective of this secondary analysis was to examine sex differences in THC pharmacokinetics and in acute subjective, physiological, and cognitive effects of smoked cannabis in a sample of regular cannabis users (use 1-4 days per week) aged 19-25 years. Methods Ninety-one healthy young adults were randomized to receive active (12.5% THC; 17 females, 43 males) or placebo (< 0.1% THC; 9 females, 21 males) cannabis using a 2:1 allocation ratio. Blood samples to quantify concentrations of THC, 11-OH-THC, and 11-Nor-carboxy-THC (THC-COOH), as well as measures of subjective drug effects, vital signs, and cognition were collected over a period of 6 h following ad libitum smoking of a 750-mg cannabis cigarette. Results Females smoked less of the cannabis cigarette than males (p = 0.008) and had a lower peak concentration of THC and THC-COOH than males (p <= 0.01). Blood THC concentrations remained lower in females even when adjusting for differences in estimated dose of THC inhaled. There was very little evidence of sex differences in visual analog scale (VAS) ratings of subjective drug effects, mood, heart rate, blood pressure, or cognitive effects of cannabis. Conclusions Females experienced the same acute effects of smoked cannabis as males at a lower observed dose, highlighting the need for more research on sex differences in the pharmacology of THC, especially when administered by routes in which titrating to the desired effect is more difficult (e.g., cannabis edibles).