Abstract
BACKGROUND: Cannabis use has been linked to lower systemic inflammation, but the pathways connecting cannabis use and systemic inflammation are unclear. Here we investigate whether body mass index (BMI) accounts for the association between cannabis use and systemic inflammation in a cohort of sexual and gender minority youth assigned male at birth (n = 712). METHODS: Substance use was assessed across six biannual visits. Cannabis use was measured using the Cannabis Use Disorders Identification Test-Revised (CUDIT-R) and urine screening for tetrahydrocannabinol (THC). At the final visit, BMI was measured, and a plasma sample was collected to measure biomarkers of systemic inflammation: C-reactive protein (CRP), interleukin-6, interleukin-1β, and tumor necrosis factor-α. Inflammatory markers were log(2)-transformed. Age, gender, race/ethnicity, education, HIV status, cigarette use, alcohol use, and polydrug use were included as covariates. RESULTS: In models including all covariates except BMI, greater cumulative CUDIT-R score was associated with lower CRP (β = -0.14; 95% CI: -0.22,-0.05) and lower interleukin-6 (β = -0.12; 95% CI: -0.21,-0.04). These associations were attenuated when BMI was added to the model. Mediation analyses revealed an indirect effect of cumulative CUDIT-R score on CRP (β = -0.08; 95% CI: -0.12,-0.05) and interleukin-6 (β = -0.08; 95% CI: -0.12,-0.05), mediated by BMI. Models using urine THC or self-reported frequency to operationalize cannabis use produced similar results. We found no clear evidence that HIV status moderates these associations. CONCLUSIONS: These results suggest that BMI may partially account for the apparent anti-inflammatory effects of cannabis use. Research on the mechanisms linking cannabis use, adiposity, and inflammation may uncover promising intervention targets.