Impact of Cannabis (Marijuana) on Nicotine Metabolism in U.S. Adults Who Smoke Cigarettes: Findings from NHANES 2013–2018

BACKGROUND: A pharmacologic approach for smoking cessation is enzyme inhibition. Cytochrome P450 2A6 (CYP2A6)-mediated nicotine metabolism is a key target, yet no safe or effective inhibitors are currently available. We examined associations between marijuana use and the nicotine metabolite ratio (NMR) in adults who smoke. METHODS: -3'-hydroxycotinine (3-HCOT) to cotinine and categorized into quartiles based on weighted population cutoffs. Survey-weighted multinomial models adjusted for sociodemographic covariates were used. RESULTS: Among 2984 adults who currently smoke, marijuana use every month for 1 or more years was associated with lower NMR. Compared with those who didn't use marijuana, participants who used marijuana every month for 1 or more years had reduced odds of being in NMR quartile 4 (adjusted odds ratio [aOR] = 0.59, 95% confidence interval [CI] = 0.41-0.85); no significant association was observed for quartile 2 or 3. When the frequency of marijuana use (DUQ230) was modeled categorically, weekly users had reduced odds of quartile 4 classification relative to never users (aOR = 0.53, 95% CI = 0.31-0.91). Monthly and daily use frequency showed a similar direction of association with reduced odds of quartile 4 classification (aOR = 0.73, 95% CI = 0.37-1.44; and aOR = 0.54, 95% CI = 0.28-1.04, respectively), though these did not reach statistical significance. CONCLUSIONS: People who smoke cigarettes and co-use marijuana had a lower NMR. Pharmacokinetic studies are needed to further determine whether cannabinoids affect nicotine metabolism. IMPACT: The nonpsychoactive forms of cannabinoids may be useful for the treatment of tobacco use disorder.