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

Hua W.; Lazarus P.; Adebile T.; Muscat J. · Cannabis and cannabinoid research · 2026

**Background & Methods** This cross-sectional analysis examined associations between marijuana use and nicotine metabolism in 2,984 current cigarette smokers using National Health and Nutrition Examination Survey (NHANES) data from 2013-2018. Marijuana use was assessed via self-reported measures (monthly use for ≥1 year and frequency of use), and nicotine metabolite ratio (NMR)—calculated as serum trans-3'-hydroxycotinine to cotinine ratio—was analyzed using survey-weighted multinomial models adjusted for sociodemographic covariates. **Key Findings** - Monthly marijuana use for 1 or more years was associated with significantly lower NMR, with 41% reduced odds of being in the highest NMR quartile (aOR = 0.59, 95% CI = 0.41-0.85) compared to non-users, indicating slower nicotine metabolism. - Weekly marijuana users demonstrated the strongest association, with 47% reduced odds of highest NMR classification (aOR = 0.53, 95% CI = 0.31-0.91), suggesting dose-dependent effects with more frequent use. - Daily and monthly marijuana use frequency showed similar patterns of reduced odds for highest NMR quartile classification (aOR = 0.54 and 0.73, respectively), though these did not reach statistical significance, potentially due to smaller sample sizes. **Dosage & Administration** Not reported. The study assessed frequency categories (weekly, monthly, daily) but did not specify cannabis dose, potency, cannabinoid composition, or route of administration. **Safety & Adverse Effects** Not reported. The study focused on pharmacokinetic interactions without documenting adverse events or safety outcomes associated with cannabis use among cigarette smokers. **Evidence Quality** This study has several limitations affecting evidence quality. As a cross-sectional analysis, causality cannot be established, and the observational design is susceptible to confounding and reverse causation bias. Self-reported marijuana and cigarette use introduces potential recall bias. The NHANES sample may not represent all U.S. smokers. The mechanism underlying the NMR reduction remains unclear, and the authors acknowledge that pharmacokinetic studies are needed to determine whether cannabinoids directly inhibit CYP2A6 enzyme activity. Overall, this represents preliminary epidemiologic evidence (Level 3-4) suggesting a potential association warranting mechanistic investigation before clinical application for smoking cessation.

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