PROJECT SUMMARY/ABSTRACT Cannabis use among older adults is on an unprecedented rise, yet relatively little is known about its possible harms and whether findings of sex differences in cannabis use that have been identified in adolescent and young adults extend to this population. To date, preclinical and clinical studies have demonstrated that women are more likely to use cannabis for stress reduction and have increased cannabis craving after stress compared to men. Ovarian hormones have been identified as potential mechanisms of these stress-related disparities, but whether hormonal changes in mid-to-late life influence cannabis use is unknown. Furthermore, while the effects of heavy cannabis use on cognition have been extensively studied in emerging and young adults, it is unknown whether cannabis affects age-related cognitive decline and risk for Alzheimer’s disease and related dementias (ADRD) and if stress is implicated, given that stress response also confers risk for ADRD. Coupled with the possible effects of age-related loss of ovarian hormones on ADRD risk, the extant literature has led us to propose the overall hypothesis that older women may be at greater risk of the adverse effects of regular cannabis use than men. We therefore propose a cross-sectional study of 200 regular cannabis-using men and women ages 50-80 from whom we will collect behavioral and biological markers of cognitive function and ADRD risk, reproductive history, ovarian hormones, and measures of chronic and acute stress. Our goals are to examine cognitive function in cannabis-using older men and women (Aim 1), evaluate the impact of stress on cannabis use and cognitive functioning in older adults (Aim 2), and examine the impact of ovarian hormones on cognitive functioning, stress, and cannabis craving. The results from this project will be critical to devising a comprehensive theoretical model of how cannabis impacts cognitive aging that can be empirically tested in a subsequent longitudinal study. Findings may directly inform sex-specific public health messaging regarding cannabis use as well as identify potential clinical interventions for older adults.

PROJECT NARRATIVE Cannabis is the most frequently used illicit substance by older adults, and its use among persons ages 50+ is rising. Little is known about the potential harms of cannabis use in this population such as its impact on cognitive decline and risk for Alzheimer’s disease and related dementias, and whether sex differences in stress and hormones influence these risks. We therefore propose to study regular cannabis-using older men and women to answer these questions to inform public health messaging regarding cannabis use and to identify potential clinical interventions for older adults.