A preliminary investigation of tobacco co-use on endocannabinoid activity in people with cannabis use

Tobacco is commonly co-used with cannabis. This is unfortunate because tobacco co-use exacerbates select clinical consequences associated with cannabis use. Evidence demonstrates that low levels of anandamide, a prominent endocannabinoid, correlate with worse clinical outcomes. Fatty acid amide hydrolase (FAAH) degrades anandamide, and greater FAAH levels may underlie poorer clinical outcomes in people who co-use relative to those who use only cannabis. Therefore, we tested whether tobacco co-use increases FAAH levels beyond those associated with cannabis use alone. Cannabis-using participants (N = 13) were parsed into individuals with daily tobacco use (CT, n = 5) and no current tobacco use (CAN, n = 8). We evaluated group differences in FAAH, quantified using positron emission tomography and [¹¹C]CURB, while controlling for sex and FAAH genotype in the prefrontal cortex, hippocampus, thalamus, sensorimotor striatum, substantia nigra, and cerebellum. A significant group x ROI interaction for [¹¹C]CURB λk₃ [F(5, 45)= 3.15, p = 0.016] emerged. Bonferroni-corrected post-hoc tests indicated greater FAAH levels in CT compared to CAN in the substantia nigra (p = 0.023, d=1.54) and cerebellum (p = 0.003, d=1.76), while a trend emerged in the sensorimotor striatum (p = 0.054, d=1.33). Preliminary findings suggest that tobacco co-use is associated with elevated FAAH activity relative to cannabis-only use, which may underlie poorer clinical outcomes associated with co-use.