ABSTRACT In the United States, overdose is the leading cause of adult deaths with more than 136 Americans dying from overdosing on opioids every day. Medical cannabis has been approved in many states as a treatment for pain disorders and as a potential substitute for prescription opioids, in what is considered by many to be a controversial policy. While state-level aggregate data suggests that states with medical cannabis laws have lower rates of prescription opioid and benzodiazepine use, these results may be confounded by the fact that policies aimed at curbing the opioid epidemic occurred concurrently with medical cannabis legislation in many states. The effects of medical cannabis alone can be isolated using longitudinal, patient-level data. Adults aged ≥50 represent a vulnerable group with highest rates of prescription opioid and benzodiazepine use. They are the largest consumers of prescription medications, and are three times more likely to be prescribed opioids and benzodiazepines to alleviate pain, sleep disorders/insomnia, and anxiety. This group also has multiple medical comorbidities and are hence more susceptible to the detrimental effects of medical cannabis, with prescription drug use patterns being especially problematic among women as they are prescribed these drugs more often, consume them in larger quantities, and use them for longer periods of time. Relevant to NOSI: NOT-DA-20-014, the proposed project will characterize the relationship between medical cannabis use, concomitant prescription opioid and benzodiazepine use, and subsequent health outcomes in the Yale-New Haven Healthcare System (YNHHS) in Connecticut. This system covers a population of approximately 1.5 million, with approximately 750,000 patients seen annually. This will be accomplished by innovative linkage between YNHHS's electronic healthcare records and Connecticut's Prescription Drug Monitoring Program, which, uniquely, includes medical cannabis products, and other statewide census data. Specific Aim 1: To characterize the longitudinal association between medical cannabis use and change in concomitant use of prescription opioids and benzodiazepines. By examining patient-level, longitudinal data (using propensity-score methods), we will clarify the strength of the association, the direction of the association, and the temporal relationship of the association. Specific Aim 2: To determine the association between medical cannabis prescription and healthcare utilization/medical outcomes (e.g., hospitalization, treatment services utilization, overdose) among adults aged ≥50 using patient-level data in the Yale-New Haven Health catchment area. We will investigate association between medical cannabis prescription and all-cause mortality, new-onset drug overdose, emergency department visits, and hospitalization.