Nicotine Metabolism in Young Adult Daily Menthol and Nonmenthol Smokers

Fagan, Pebbles; Pokhrel, Pallav; Herzog, Thaddeus A.; Pagano, Ian; Franke, Adrian A.; Clanton, Mark S.; Alexander, Linda; Trinidad, Dennis R.; Sakuma, Kazuhiko; Johnson, C. Anderson; Moolchan, Eric T.

doi:10.1093/ntr/ntv109

Cited by 32 publications

(32 citation statements)

References 47 publications

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“…37 Salivary cotinine levels are a composite measure of nicotine and could be affected by the way the smoker absorbs or processes nicotine. Some research 38-40 suggests the theory that menthol could inhibit nicotine/cotinine metabolism, which could explain participants having higher salivary cotinine levels when smoking the nonmenthol test cigarette. African American smokers reportedly smoke fewer cigarettes per day than white smokers but have a higher incidence of lung cancer.…”

Section: Discussionmentioning

confidence: 99%

Smoking Behavior and Exposure: Results of a Menthol Cigarette Cross-over Study

et al. 2017

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Objective Our objective was to better understand differences in use behavior and exposure when smoking menthol and nonmenthol cigarettes using a 2-part cross-over design. Methods Adult daily smokers were randomly assigned to alternate between 2 weeks of exclusively smoking a menthol test cigarette or a nonmenthol test cigarette. Urine and saliva were collected for biomarker measurements, carbon monoxide (CO) was measured, and participants smoked test cigarettes through a CreSS® smoking topography device during 3 clinic visits. Participants turned in their cigarette butts from the test periods for determination of mouth level nicotine and completed subjective questionnaires related to the test cigarettes. Results Regardless of cigarette preference, participants had higher salivary cotinine when smoking the nonmenthol test cigarette, but there were no significant differences detected in urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol between the 2 test cigarettes. Mouth level nicotine, puff volume and puff duration were significantly higher when smoking the menthol brand. Both menthol and nonmenthol smokers reported significantly lower enjoyment and satisfaction scores for test cigarettes compared with their brand of choice. Conclusions Our results suggest that mentholation has an effect on measures of smoking behavior and that mouth level nicotine is a useful indicator of between-brand smoke exposure.

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Section: Discussionmentioning

confidence: 99%

Smoking Behavior and Exposure: Results of a Menthol Cigarette Cross-over Study

et al. 2017

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“…Benowitz and colleagues (2004) demonstrated that smoking menthol cigarettes reduced nicotine clearance by ~11%. In a multiethnic sample of young adult daily smokers, the NMR was found to be significantly lower among menthol compared with nonmenthol smokers after adjusting for race/ethnicity, gender, BMI, and cigarettes smoked per day (0.19 vs. 0.24, p=.03; (Fagan et al 2015). Alcohol use is positively associated with NMR (Chenoweth et al 2014) but the mechanism underlying this association is yet to be determined.…”

Section: The Nicotine Metabolite Ratio As a Biomarker Of Nicotinementioning

confidence: 96%

Precision Medicine for Tobacco Dependence: Development and Validation of the Nicotine Metabolite Ratio

Allenby

Boylan

Lerman

et al. 2016

J Neuroimmune Pharmacol

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Quitting smoking significantly reduces the risk of tobacco-related morbidity and mortality, yet there is a high rate of relapse amongst smokers who try to quit. Phenotypic biomarkers have the potential to improve smoking cessation outcomes by identifying the best available treatment for an individual smoker. In this review, we introduce the nicotine metabolite ratio (NMR) as a reliable and stable phenotypic measure of nicotine metabolism that can guide smoking cessation treatment among smokers who wish to quit. We address how the NMR accounts for sources of variation in nicotine metabolism including genotype and other biological and environmental factors such as estrogen levels, alcohol use, body mass index, or menthol exposure. Then, we highlight clinical trials that validate the NMR as a biomarker to predict therapeutic response to different pharmacotherapies for smoking cessation. Current evidence supports the use of nicotine replacement therapy for slow metabolizers, and non-nicotine treatments such as varenicline for normal metabolizers. Finally, we discuss future research directions to elucidate mechanisms underlying NMR associations with treatment response, and facilitate the implementation of the NMR as biomarker in clinical practice to guide smoking cessation.

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“…Up-regulation of nAChRs has been observed in mice following chronic exposure to menthol concentrations comparable to those in cigarette smoke (Henderson et al, 2016) and in human menthol cigarette smokers (Brody et al, 2013). Menthol may also slow nicotine metabolism (Alsharari et al, 2015; Benowitz et al, 2004; Fagan et al, 2016). …”

Section: Introductionmentioning

confidence: 99%

Studying the interactive effects of menthol and nicotine among youth: An examination using e-cigarettes

Krishnan‐Sarin

Green

Kong

et al. 2017

Drug and Alcohol Dependence

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Background Tobacco products containing menthol are widely used by youth. We used ecigarettes to conduct an experimental evaluation of the independent and interactive effects of menthol and nicotine among youth. Procedures Pilot chemosensory experiments with fourteen e-cigarette users identified low (barely perceptible, 0.5%) and high (similar to commercial e-liquid, 3.5%) menthol concentrations. Sixty e-cigarette users were randomized to a nicotine concentration (0 mg/ml, 6 mg/ml, 12 mg/ml) and participated in 3 laboratory sessions. During each session, they received their assigned nicotine concentration, along with one of three menthol concentrations in random counterbalanced order across sessions (0, 0.5%, 3.5%), and participated in three fixed-dose, and an ad-lib, puffing period. Urinary menthol glucuronide and salivary nicotine levels validated menthol and nicotine exposure. We examined changes in e-cigarette liking/wanting and taste, coolness, stimulant effects, nicotine withdrawal and ad-lib use. Results Overall, the high concentration of menthol (3.5%) significantly increased e-cigarette liking/wanting relative to no menthol (p<0.001); there was marginal evidence of nicotine* menthol interactions (p=0.06), with an increase in liking/wanting when 3.5% menthol was combined with 12 mg/ml nicotine, but not 6 mg/ml nicotine. Importantly, both 0.5% and 3.5% menthol concentrations significantly improved taste and increased coolness. We did not observe nicotine or menthol-related changes in stimulant effects, nicotine withdrawal symptoms or ad-lib use. Conclusions Menthol, even at very low doses, alters the appeal of e-cigarettes among youth. Further, menthol enhances positive rewarding effects of high nicotine-containing e-cigarettes among youth.

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Nicotine Metabolism in Young Adult Daily Menthol and Nonmenthol Smokers

Cited by 32 publications

References 47 publications

Smoking Behavior and Exposure: Results of a Menthol Cigarette Cross-over Study

Smoking Behavior and Exposure: Results of a Menthol Cigarette Cross-over Study

Precision Medicine for Tobacco Dependence: Development and Validation of the Nicotine Metabolite Ratio

Studying the interactive effects of menthol and nicotine among youth: An examination using e-cigarettes

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