With the “graying of America,” approximately 29% of the United States population will be 55 or older in 2019; over the next 35 years, the 50+ population will more than double. As individuals age, the prevalence of chronic pain increases; recent reports indicate that approximately 50% of older adults experience bothersome pain, and the prevalence of pain peaks during ages 50-65. Historically, opioids have been the primary therapy for chronic pain, however, they have limited efficacy for long-term treatment. Further, over the past decade, rates of opioid use disorders and opioid-related overdoses have increased at an alarming rate, resulting in a national epidemic. The development of tolerance, altered metabolism and unpredictable sensitivity also increase the risk of using these medications, especially in older adults with conditions making them prone to adverse consequences. Although the analgesic effects of marijuana (MJ) have been known for centuries, and the National Academy of Sciences recently reported there is “conclusive or substantial evidence” that cannabinoids are efficacious for the treatment of chronic pain, its Schedule I status has precluded its use in mainstream medicine. However, as the majority of states have now passed medical marijuana (MMJ) laws, many are open to MMJ use, and the proportion of older adults using MJ continues to grow. Most research thus far has focused on the impact of recreational MJ use among adolescent/young adult users, in whom cognitive decrements have been reported; however, consequences in older adults who are increasingly using MJ for medical purposes remain unknown. Recent pilot data from older MMJ patients demonstrated significant reductions in medication use, notably the use of opioids, after 3 months of MMJ treatment, aligned with studies demonstrating that states with legalized MMJ report both fewer prescriptions written and opioid-related overdoses. Additionally, we observed significant improvements in cognitive performance, clinical state, and ‘normalized’ patterns of brain activation. We propose a novel longitudinal study to quantify the impact of ‘real world’ MMJ products on multiple domains, including medication use (e.g. opioids) and pain in older adults aged 50-75. Further, we will quantify the impact of MMJ use on cognitive function and clinical state as well as neurobiologic markers using multimodal neuroimaging, which have not previously been assessed in older adults. Patients will be evaluated at baseline, prior to initiating MMJ treatment, and after 3, 6, and 12 months of treatment; analyses will be completed to determine beneficial vs detrimental cannabinoid combinations/ratios. A matched group of older adults with chronic pain not seeking MMJ treatment will serve as a control group. It is imperative to determine under which conditions MMJ may be helpful or harmful in this vulnerable population. This project fills an important gap regarding positive and negative consequences of MMJ use...