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Acute effects of inhaled menthol on the rewarding effects of intravenous nicotine in smokers.

ABSTRACT: OBJECTIVE:This double-blind, placebo controlled study examined whether menthol inhaled from an electronic cigarette (e-cigarette) would change subjective and withdrawal alleviating effects of intravenous nicotine in young adult smokers. METHODS:A total of 32 menthol-preferring smokers and 25 non-menthol-preferring smokers participated in the study that consisted of a random sequence of three different inhaled menthol conditions (0.0%, 0.5%, and 3.2%) across three test sessions (a single menthol condition per session). In each test session (performed at least 24 hours apart), a random order of saline, and two different nicotine infusions of 0.25 mg and 0.5 mg/70 kg of bodyweight were administered, one hour apart, concurrent with menthol inhalation. RESULTS:While menthol did not alter the positive subjective effects of nicotine, menthol significantly enhanced aversive effects of nicotine in non-menthol-preferring smokers and reduced smoking urges in menthol-preferring smokers. In addition, menthol-preferring smokers reported blunted positive subjective responses to nicotine and less severe nicotine withdrawal after overnight nicotine deprivation. Finally, compared to non-menthol-preferring smokers, menthol-preferring smokers had a significantly lower baseline nicotine metabolite ratio indicating slower nicotine metabolism within our sample of menthol-preferring smokers. CONCLUSIONS:Our findings did not support an enhancement of nicotine's positive subjective effects from inhaled menthol. However, as compared to non-menthol-preferring smokers, menthol-preferring smokers had blunted positive subjective responses to nicotine and reduced overnight withdrawal severity that may be partly due to inhibition of nicotine metabolism from chronic exposure to inhaled menthol. Collectively, these results reveal a more complex and nuanced role of inhaled menthol in smokers than previously recognized.

SUBMITTER: Valentine GW

PROVIDER: S-EPMC6329876 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Acute effects of inhaled menthol on the rewarding effects of intravenous nicotine in smokers.

Valentine Gerald W GW DeVito Elise E EE Jatlow Peter I PI Gueorguieva Ralitza R Sofuoglu Mehmet M

Journal of psychopharmacology (Oxford, England) 20180523 9

<h4>Objective</h4>This double-blind, placebo controlled study examined whether menthol inhaled from an electronic cigarette (e-cigarette) would change subjective and withdrawal alleviating effects of intravenous nicotine in young adult smokers.<h4>Methods</h4>A total of 32 menthol-preferring smokers and 25 non-menthol-preferring smokers participated in the study that consisted of a random sequence of three different inhaled menthol conditions (0.0%, 0.5%, and 3.2%) across three test sessions (a ...[more]

PMID: 29788802

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Project description:IntroductionBecause 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.MethodsIn 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.ResultsAt 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.ConclusionsAlthough 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.ImplicationsResults 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.

Project description:Despite the longstanding use and popularity of menthol as a flavorant in tobacco products, its sensory interactions with inhaled nicotine have never been measured independently of the other irritants in tobacco smoke. We therefore measured the perception of menthol in an E-cigarette with the primary goal of assessing its analgesic effect on the sensory irritation produced by inhaled nicotine.Adult cigarette smokers sampled aerosolized E-liquids containing five different concentrations of nicotine with 0%, 0.5%, or 3.5% l-menthol, as well as two commercial menthol flavors with and without nicotine. For each of the E-liquids participants used a labeled magnitude scale to rate the Overall Sensation intensity, Coolness/Cold, and Irritation/Harshness they experienced, and a Labeled Hedonic Scale to indicate how much they liked/disliked the overall flavor.The main findings were that (1) perceived Irritation/Harshness was unaffected by a low (0.5%) menthol concentration, whereas a high menthol concentration (3.5%) led to higher perceived Irritation/Harshness at low nicotine concentrations but to lower Irritation/Harshness at the highest nicotine concentration (24mg/ml); (2) a commercial Menthol-Mint flavor produced similar results; (3) nicotine tended to enhance rather than suppress sensations of Coolness/Cold; and (4) menthol tended to slightly increase liking independently of nicotine concentration.In addition to adding a sensation of coolness, menthol can reduce perceived airway irritation and harshness produced by inhalation when nicotine concentration is high, and contributes to the sensory impact of E-liquids when nicotine concentration is low.The evidence presented here indicates that menthol can potentially improve the appeal of E-cigarettes not only via its coolness and minty flavor, but also by reducing the harshness from high concentrations of nicotine. As the first direct demonstration of an analgesic effect of menthol on inhaled nicotine in humans, these data also have implications for the role of menthol flavors in other inhaled tobacco products.

Project description:IntroductionTo study the association between health care utilization and menthol cigarette use and whether the association differed between African American (AA) and non-AA smokers.MethodsWe analyzed the three most recent 2005, 2010, and 2015 National Health Interview Survey Cancer Control Supplements. After incorporating propensity score weights adjusting for observed differences between menthol and non-menthol users, we estimated Zero-Inflated Poisson models on hospital nights, emergency department visits, doctor visits, and home visits as a function of menthol use status and other covariates separately for current cigarette smokers and recent quitters (former smokers quitting cigarette smoking ≤ 4 years).ResultsAlthough current menthol smokers smoked fewer cigarettes per day than current non-menthol smokers, they did not differ from current non-menthol smokers in health care utilization. Among recent quitters, those who used to smoke menthol cigarettes had higher odds of having hospital nights than those who used to smoke non-menthol cigarettes. However, we did not find any significant association between menthol use and other health care utilization-emergency department visits, doctor visits, and home visits-among recent quitters. Moreover, compared with non-AA recent quitters, AA recent quitters had higher odds of having home visits, but fewer home visits, if they used to smoke menthol cigarettes.ConclusionMenthol use was associated with greater hospitalization among recent quitters, and the association between home visits and menthol use differed between AA and non-AA recent quitters.ImplicationsThis is the first study that used econometric models to study the association between health care utilization and menthol cigarette use and examine whether the association differed between AA and non-AA smokers. Our study found health care utilization did not differ by menthol use status for current smokers, although current menthol smokers smoked fewer cigarettes per day than current non-menthol smokers. However, we found menthol use was associated with higher odds of having hospital nights for recent quitters. We also found AA recent quitters had a different association between home visits and menthol use compared with non-AA recent quitters.

Project description:BackgroundIn 4 decades, numerous nicotine replacement therapy products have been developed. Population pharmacokinetic models can support exposure-response modeling and inform nicotine replacement therapy product development, but only limited model-based cross-study population pharmacokinetic analyses for nicotine replacement therapy products have been published.ObjectivesThe aim of this retrospective analysis was to assess the population pharmacokinetics of nicotine across intravenous, oral, transdermal and oromucosal (mouth spray, chewing gum, lozenge and inhaler) routes and formulations in healthy smoking subjects.MethodsData on 930 unique subjects (46,016 observations) from 29 single- and repeated-dose studies with multiple formulations across intravenous, oral, transdermal and oromucosal routes of administration were included. Data from intravenous and extravascular routes of administration were modelled separately for run efficiency reasons. For developing extravascular models, clearance and disposition parameters and their inter-individual variabilities were fixed to the estimates for intravenously delivered nicotine. Detectable pre-dose nicotine concentrations were modelled as a hypothetical nicotine bolus into the central compartment at the start of wash-out. Modelling repeated-dose oral and buccal administrations required a time-dependent increase in clearance or decrease in bioavailability to describe the data adequately.ResultsDisposition of intravenous nicotine was best described by a three-compartment model with initial and terminal half-lives of 7 min and 4.5 h, respectively, and the absorption of single oral doses was best described with a first-order absorption rate constant of 1.55 h-1. The data of buccal formulations were modelled with parallel oromucosal absorption and gastrointestinal absorption of a part of the dose that is swallowed. For transdermal nicotine, parallel zero- and first-order release from the patch and a transit-compartment absorption model best described the data. Key pharmacokinetic parameters were reliably estimated, with typical values for clearance (67 L/h for a 70-kg subject), volume of distribution (4.3 L/kg), oral bioavailability (40%) and transdermal bioavailability (76%) within expected ranges. The estimated fraction of the dose swallowed for buccal formulations ranged from 55% (gum) to 69% (lozenge).ConclusionsRobust population pharmacokinetic models were developed for five nicotine replacement therapy product types and for intravenous and oral nicotine. These population pharmacokinetic models are used in exposure-response analyses and simulation-based nicotine replacement therapy product design.

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Acute effects of inhaled menthol on the rewarding effects of intravenous nicotine in smokers.

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Acute effects of inhaled menthol on the rewarding effects of intravenous nicotine in smokers.

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