Real-Time and Long-Term Effects of Medical Marijuana on Older Adults: A Prospective Cohort Study - ABSTRACT Older adults represent a fast-growing segment of medical marijuana (MM) users in this country, with chronic pain as the most cited reason for use. There is a critical need to systematically examine MM’s short- and long- term effects on the core outcomes including pain intensity, physical, emotional, and cognitive functioning, and overall quality of life, and to track its side effects in older adults (NOT-DA-20-014). While the ubiquity of mobile technology provides a unique opportunity to measure MM use and its outcomes in vivo, it has not been applied in MM and pain research. In addition, our research shows that telomere length, a measure of cellular aging, is negatively associated with chronic pain stage, but no study has used telomere length as a biomarker to examine MM’s long-term effects on biological aging in older adults. Further, while contributing to the differentiated response to MM, individual differences (e.g., sex, baseline pain phenotyping, expectancy) have not been adequately explored in prior research. To address these gaps, we propose the first prospective cohort study that innovatively combines technology-based ecological momentary assessments (EMA) and in- person visits over 12 months to obtain both subjective and objective data on MM’s effects. The main goals of this project are to 1) determine MM’s short- and long-term effects on pain, physical, emotional, and cognitive functioning, and quality of life in older adults, and 2) identify MM product characteristics and patient subgroups associated with improved outcomes or side effects. To accomplish these goals, we will recruit and follow 440 older adults (³ 50 years, 50% male) with chronic pain as some initiate MM (n=330) and other do not (n=110). Subjective and objective data will be collected at in-person visits (baseline & 12 months) and via smartphone- and sensor-based measurement bursts at 1, 3, 6, and 9 months. The specific aims are: 1) Determine whether MM use leads to short-term changes in pain intensity level, physical and emotional functioning measured in real-time; 2) Determine whether MM use leads to longer-term changes over 12 months, including pain intensity, emotional, physical, and cognitive functioning, health-related quality of life, and telomere length; and 3) Among those initiating MM, examine which MM product characteristics (i.e., THC:CBD ratio, administration route, dose) predict more improvements in outcomes defined in Aims 1&2 or more side effects, and whether individual differences (e.g., sex, baseline pain phenotyping, expectancy) moderate the relationship. With multisource data collected in real-time and over 12 months, our results will contribute to the greatly needed scientific evidence on: 1) whether MM can reduce pain and improve physical/emotional functioning in short term among older adults; 2) whether effects of MM last for 12 months and demonstrate quality of life improvements or cognitive changes; 3) whether health benefits and consequences differ by MM product type; and 4) which subgroups of patients may benefit more from MM use.