S2114 Association Between Marijuana Use and Sepsis in Patients With Chronic Gastrointestinal Diseases: A Cross-Sectional Analysis From All of Us

Introduction: Preclinical studies suggest cannabinoids suppress cell-mediated and humoral immunity, potentially increasing susceptibility to infection. Conversely, they also exert anti-inflammatory effects that may reduce sepsis severity in animal models. Patients with inflammatory bowel disease (IBD), cirrhosis, and chronic pancreatitis are at elevated risk of sepsis and may use marijuana for symptom relief. However, the association between marijuana use and sepsis development in this population remains poorly understood. This study aimed to evaluate the relationship between marijuana use and sepsis among individuals with chronic gastrointestinal (GI) diseases using data from the NIH All of Us Research Program. Methods: We conducted a cross-sectional analysis of adults with IBD, cirrhosis, or chronic pancreatitis, identified via self-report or electronic health records (EHR). Marijuana use was classified as “ever” or “never” based on survey data and further categorized by use within the past 3 months. EHR data were used to identify chronic GI conditions and comorbidities. The primary outcome was sepsis, defined using validated diagnostic codes. Multivariable logistic regression estimated adjusted odds ratios (aORs) for sepsis, adjusting for age, sex, race/ethnicity, smoking, alcohol use, diabetes, and steroid use. Results: Among 17,308 participants, 53.9% reported marijuana use and 11.2% had sepsis. Marijuana use was associated with lower odds of sepsis (aOR: 0.84; 95% confidence interval [CI]: 0.77-0.91; P< 0.001). Participants who used marijuana more than 3 months ago had significantly lower odds of sepsis (aOR: 0.82; 95% CI: 0.75-0.90), while recent users showed a trend toward protection, though not significant (aOR: 0.91; 95% CI: 0.77-1.06). Non-Hispanic Blacks, Hispanics, male sex, smoking, diabetes, and steroid use were independently associated with increased risk of sepsis. Conclusion: In this large observational study, marijuana use was associated with lower odds of sepsis development among individuals with chronic GI diseases. These findings highlight the need for larger, prospective studies in humans to confirm these associations and explore the immunologic mechanisms by which cannabinoids may influence infection risk while ensuring any potential therapeutic use does not promote unsafe consumption.