Effects of Very Low Nicotine Content Cigarettes on Smoking Behavior and Biomarkers of Exposure in Menthol and Non-menthol Smokers

Abstract

Introduction Because 30% of cigarettes sold in the United States are characterized as menthol cigarettes, it is important to understand how menthol preference may affect the impact of a nicotine reduction policy. Methods In a recent trial, non-treatment-seeking smokers were randomly assigned to receive very low nicotine cigarettes (VLNC; 0.4 mg nicotine/g tobacco) or normal nicotine cigarettes (NNC; 15.5 mg/g) for 20 weeks. On the basis of preference, participants received menthol or non-menthol cigarettes. We conducted multivariable regression analyses to examine whether menthol preference moderated the effects of nicotine content on cigarettes per day (CPD), breath carbon monoxide (CO), urinary total nicotine equivalents (TNE), urinary 2-cyanoethylmercapturic acid (CEMA), and abstinence. Results At baseline, menthol smokers (n = 346) reported smoking fewer CPD (14.9 vs. 19.2) and had lower TNE (52.8 vs. 71.6 nmol/mg) and CO (17.7 vs. 20.5 ppm) levels than non-menthol smokers (n = 406; ps < .05). At week 20, significant interactions indicated that menthol smokers had smaller treatment effects than non-menthol smokers for CPD (–6.4 vs. –9.3), TNE (ratio of geometric means, 0.22 vs. 0.10) and CEMA (ratio, 0.56 vs. 0.37; ps < .05), and trended toward a smaller treatment effect for CO (–4.5 vs. –7.3 ppm; p = .06). Odds ratios for abstinence at week 20 were 1.88 (95% confidence interval [CI] = 0.8 to 4.4) for menthol and 9.11 (95% CI = 3.3 to 25.2) for non-menthol VLNC smokers (p = .02) relative to the NNC condition. Conclusions Although menthol smokers experienced reductions in smoking, toxicant exposure, and increases in quitting when using VLNC cigarettes, the magnitude of change was smaller than that observed for non-menthol smokers. Implications Results of this analysis suggest that smokers of menthol cigarettes may respond to a nicotine reduction policy with smaller reductions in smoking rates and toxicant exposure than would smokers of non-menthol cigarettes.

Risk Perceptions of Low Nicotine Cigarettes and Alternative Nicotine Products across Priority Smoking Populations

“…If these individuals instead continue to smoke cigarettes (i.e., LNC cigarettes), then the full benefits of a nicotine reduction policy for these minoritized groups may be attenuated and, as a result, widen existing smoking disparities. However, another interpretation is that more people from minoritized groups would quit tobacco altogether—as the robust VLNC literature indicates that use of VLNC cigarettes increases the likelihood of making a quit attempt or achieving abstinence [ 12 , 13 , 18 , 68 , 69 , 70 , 71 , 72 ]—versus switching to ANDS products. These findings merit further exploration.…”

Reducing the relative value of cigarettes: Considerations for nicotine and non-nicotine factors

“…A recent review commenting on the effects low nicotine cigarette-use in smokers with mental health conditions and socioeconomic disadvantages concluded that these priority populations would likely reduce cigarette smoking without worsening psychiatric symptoms or sustained compensatory smoking in response to a reduced-nicotine product standard for cigarettes (Tidey et al, 2019). Several studies measuring puff topography characteristics, such as total puff volume, similarly demonstrate reductions in toxicant exposure as a function of CPD reduction and smoking less intensely on the cigarette (Donny et al, 2015;Tidey et al, 2016;Higgins et al, 2017a, Denlinger-Apte et al 2019b). In sum, much of the available evidence suggests reducing nicotine content to very low levels would decrease smoking and toxicant exposure as intended.…”

Using Product Standards to Render the Most Harmful Tobacco Products Minimally Addictive: Maximum Nicotine Level, Non-Nicotine Constituents, and Scope

“…28 Preclinical studies further suggest that menthol in particular may interact with nicotine to directly affect the central nervous system, by altering cholinergic neuron structure and function and/or nicotine pharmacokinetics. 28–30 These findings suggest that the effects of nicotine reduction could differ between menthol and non-menthol products; however, analyses of clinical trials to date suggest that both menthol and non-menthol smokers would likely benefit from nicotine reduction even when their reduced-nicotine cigarettes reflect their menthol preference (see Denlinger-Apte et al 31 ).…”

“…Partially inhibiting MAO, to the extent seen in smokers, can also sufficiently increase self-administration of low doses of nicotine. 32 The potential for MAO-inhibiting effects of tobacco smoke to reduce the addictive threshold of nicotine supports developing a product standard that caps nicotine levels as low as possible. Furthermore, to ensure that increasing MAO-inhibition caused by cigarettes cannot be used to offset a lowered nicotine content, tobacco constituents that inhibit MAO could be identified, tracked, and potentially regulated.…”