E-cigarette use and nicotine dependence among hospitalized youth: influence of nicotine metabolism and CYP2A6 variability.

BACKGROUND: Youth e-cigarette use is a public health concern, yet cessation approaches remain suboptimal. In adults, faster nicotine metabolism is linked with better cessation outcomes with varenicline compared to nicotine replacement therapy (NRT). This remains unexplored in youth, for whom NRT is first-line treatment. This study examined whether nicotine metabolism is associated with nicotine dependence among hospitalized youth aged 14-21 who currently use e-cigarettes. METHODS: This cross-sectional study assessed e-cigarette use, nicotine dependence, saliva nicotine metabolism ratio (NMR) (slow [1st quartile], normal [2nd-4th quartile]), and CYP2A6 genetic variation. Activity score (AS) was used for CYP2A6 genotype-predicted phenotype (slow metabolizers, AS ≤ 1.5, normal metabolizers, AS > 1.5). Analyses included Fisher's exact, Wilcoxon rank-sum, and logistic regression. RESULTS: Among 106 hospitalized youth (mean age 16 ± 1.3), 38% reported near-daily e-cigarette use and 50% had medium-to-high nicotine dependence. Dependence varied by e-cigarette use (p < 0.001) and nicotine metabolism (p = 0.027), with 87% of dependent youth classified as fast metabolizers. CYP2A6 phenotype was associated with NMR (p < 0.001) but not with dependence or use. CONCLUSION: Nicotine dependence in youth using e-cigarettes was linked to nicotine metabolism. The predominance of fast metabolizers among dependent youth suggests varenicline may be more appropriate than NRT as first-line treatment. Future work should evaluate metabolism-informed cessation treatment for youth.