Cannabinoids in hair and their prospective association with mental and physical health outcomes in adolescents

Background: Cannabis is one of the most widely used drugs in early adolescence, a crucial time for development. Cannabinoids within the cannabis plant (e.g., delta-9-tetrahydrocannabinol [THC], and cannabidiol [CBD]) are suggested to have a range of health implications. These may differ by sex, given sex differences in the endocannabinoid system (ECS). Yet, how aspects of mental and physical health are related to cannabis use as measured by hair concentrations, both within early adolescence and across sexes, is so far inconclusive. Methods: We analyzed hair toxicology data from three cannabinoid analytes (THC, CBD, and 11-nor-9-carboxyTHC [THCCOOH]) and multiple mental and physical health measures in 9-15 year-old youth (49 % female) from the Adolescent Brain Cognitive Development (ABCD) Study (N = 2262). Two-part linear regression models were fit to assess the effects of cannabis constituent presence, concentrations, and THC concentrations + CBD presence on externalizing and internalizing symptoms, physical and strengthening exercise, asthma presence, and sleep duration. Secondary analyses fit the same models but stratified by sex. Finally, to further characterize these relationships, we conducted two exploratory analyses: we assessed health variables prospectively and concurrently predicting cannabinoid concentrations. False discovery rate corrections were employed for all analyses. Results: In the full sample, greater THC concentrations predicted more frequent strength exercise one year later; greater CBD concentrations predicted fewer strength exercise days; and greater THCCOOH concentrations predicted shorter sleep duration. Among males, cannabinoids differentially predicted exercise days; greater THC and THCCOOH concentrations predicted shorter sleep duration. Among females, greater THC and THCCOOH concentrations predicted strength exercise frequency, and THC concentrations predicted shorter sleep duration. In exploratory models, asthma presence predicted THCCOOH concentration one year later. Concurrently, THC concentration alone and in the presence of CBD predicted both sleep duration and lower exercise days, while THCCOOH concentration predicted lower exercise days, less asthma presence, as well as greater internalizing and externalizing symptoms. Conclusion: In a nationwide study of youth ages 9-15 years old, we found cannabinoid hair concentrations predicted differences in health outcomes a year later, suggesting potential differential mechanisms for THC and CBD effects on health. Furthermore, sex-specific observations in these prospective associations emphasize the importance of considering sex assigned at birth when investigating correlates of cannabis use. Analysis of cannabinoid hair concentrations can reveal key links to mental health, physical activity, and sleep, aiding understanding of complex cannabis effects.