Understanding Cannabis Use Disorder in Midlife and Older Adults: The Role of Age and Sex

Background: The primary psychoactive ingredient in cannabis interacts with the endocannabinoid system (eCB), which declines with age, potentially reducing its ability to regulate homeostasis and altering responses to cannabis. Indeed, animal studies suggest age-related differences in response to cannabis that result in mixed effects in older individuals. Importantly, biological sex modifies the eCB system, which complicates interpreting these effects. Objective: The goal of this study was to understand how individual variation in human endocannabinoid system function due to age and sex influences cannabis’s effects in middle-aged and older adults. Methods: Self-reported measures of cannabis use behaviors, memory, mental and physical health, cannabis use disorder (CUD) symptom severity, and sleep quality were collected from 107 adults (age range= 35-78, 54 females) who use cannabis. Partial correlations examined associations between age and outcomes controlling for years of use. Biological sex was assessed as a moderator. Results: Regression analyses revealed a significant age × sex interaction for CUD symptoms and mental health scores. Specifically, CUD symptom severity decreased, and mental health scores improved with age in females but not in males. Sensitivity analysis suggested that participants who reported medical-only use exhibited a steeper decline in CUD symptom severity with age than recreational-only or hybrid-use participants. Conclusions: This study contributes to the growing body of literature on cannabis use in aging populations and underscores the need to consider age, sex, and reason for use when evaluating cannabis-related outcomes such as CUD risk in the emerging demographic of middle-aged and older adults who use cannabis.