Animal studies have found robust sex differences in the pharmacokinetics and pharmacodynamics of Δ9-tetrahydrocannabinol (THC). However, the human evidence remains equivocal, despite findings that women may experience more severe consequences of cannabis use than men.
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.
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.
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.
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).
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The authors acknowledge Dr. Christine Wickens for her involvement with the design and development of the study for which this data was originally collected.
This study was supported by a Canadian Institutes of Health Research operating grant (FRN114939). Additional support for the work was provided by the Canada Foundation for Innovation and the National Institute on Drug Abuse Drug Supply Program (placebo cigarettes). Dr. Le Foll is supported by a clinician-scientist award from the Department of Family and Community Medicine, Faculty of Medicine, University of Toronto. The funders had no role in the design of the trial, collection or analysis of data, or preparation of manuscripts.
Conflict of interest
Dr. Le Foll reports non-financial support from Prairie Plant Systems (supply of the active cannabis free of charge) during the conduct of the study and non-financial support from GW Pharmaceuticals (supply of Sativex free of charge) outside the submitted work. Dr. Le Foll also received funding from Canopy Health Innovation after the completion of the study. No other authors have anything to disclose.
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Matheson, J., Sproule, B., Di Ciano, P. et al. Sex differences in the acute effects of smoked cannabis: evidence from a human laboratory study of young adults. Psychopharmacology 237, 305–316 (2020). https://doi.org/10.1007/s00213-019-05369-y
- Sex differences
- Young adults