Justin Matheson1,2, Beth Sproule3,4,5, Patricia Di Ciano6,7,8,9, Andrew Fares6,7, Bernard Le Foll6,5,8,10, Robert E Mann7,11, Bruna Brands6,7,12. 1. Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, 27 King's College Circle, Toronto, Ontario, M5S 3H7, Canada. justin.matheson@camh.ca. 2. Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, Ontario, M5S 2S1, Canada. justin.matheson@camh.ca. 3. Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, Ontario, M5S 3M2, Canada. 4. Pharmacy Department, Centre for Addiction and Mental Health, 1001 Queen Street, Toronto, Ontario, M6J 1H4, Canada. 5. Department of Psychiatry, Faculty of Medicine, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8, Canada. 6. Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, 27 King's College Circle, Toronto, Ontario, M5S 3H7, Canada. 7. Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, Ontario, M5S 2S1, Canada. 8. Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, Ontario, M5S 2S1, Canada. 9. Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8, Canada. 10. Department of Family and Community Medicine, Faculty of Medicine, University of Toronto, 500 University Avenue, 5th Floor, Toronto, Ontario, M5G 1V7, Canada. 11. Dalla Lana School of Public Health, University of Toronto, 155 College Street, Toronto, Ontario, M5T 3M7, Canada. 12. Controlled Substances Directorate, Health Canada, Ottawa, Ontario, Canada.
Abstract
RATIONALE: 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. 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).
RCT Entities:
RATIONALE: 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. 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).
Entities:
Keywords:
Cannabis; Sex differences; THC; Young adults
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