Real-Time and Long-Term Effects of Medical Marijuana on Older Adults: Protocol for a Prospective Cohort Study.

Background: Older adults represent the fastest-growing group of medical marijuana (MM) users in the United States, with chronic pain being the most common reason for use. Despite this trend, scientific evidence remains limited regarding the short- and long-term effects of MM on critical health outcomes, including cognitive function, physical and mental health, and overall quality of life, in this population. To better inform clinical practice and public policy, there is a clear need for more rigorous longitudinal studies that examine the impact of real-world MM products over time. Objective: The Study on Medical Marijuana and Its Long-Term Effects on Older Adults (SMILE) is a prospective cohort study that aims to (1) determine MM's short- and long-term effects on pain, physical, emotional, and cognitive functioning, as well as quality of life, in older adults and (2) identify MM product characteristics and patient subgroups associated with improved outcomes and side effects. Methods: This study will recruit and follow 440 older adults (aged ≥50 years; ~50% aged >65 years, ~50% male) with chronic pain for 12 months, as some initiate MM use (MM group, n=330) and others do not (comparison group, n=110). Data collection includes quarterly survey questionnaires (longitudinal changes in cannabis use, pain, physical and emotional functioning, side effects, and quality of life); baseline and 12-month cognitive assessments, pain sensory tests, and blood and urine samples for cannabis use; and periodic smartphone- and Fitbit sensor-based measurements to capture MM use patterns, real-time pain, mental health, and objective data on physical activity and sleep. Data will be analyzed using descriptive analyses, generalized linear mixed-effects models, and generalized estimating equation models to assess differences in short- and long-term effects between the MM and comparison groups, as well as subgroups among those initiating MM treatment. Results: Recruitment for the SMILE study began in July 2022, and all data collection is expected to be completed by 2026. As of October 2025, we have enrolled 399 participants, with 277 in the MM group and 122 in the comparison group. Results are expected to be published starting in 2027. Conclusions: With multisource data collected in real time and over 12 months, our study will provide much-needed scientific evidence addressing (1) whether MM can reduce pain and improve physical and emotional functioning in the short term among older adults; (2) whether the effects of MM last for 12 months and demonstrate changes in quality of life or cognition; and (3) whether health benefits and consequences differ by MM product type and whether individual differences (eg, sex, baseline pain phenotyping) moderate the relationship. Our findings will offer valuable insights for physicians and patients when considering MM as a treatment option and will help guide more informed, individualized care decisions.