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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:IntroductionBans of menthol characterizing flavor in cigarettes have been implemented in some localities and have been proposed more broadly. One proposed benefit of such a ban is to increase cessation rates among current menthol smokers. There is currently relatively limited data regarding how smoking behavior changes if menthol smokers switch to non-menthol cigarettes.Aims and methodsAfrican American menthol smokers interested in quitting smoking were randomized to either continue smoking menthol (n = 60) or switch to non-menthol cigarettes (n = 62) for 1 month prior to a cessation attempt. Cessation results were reported previously; this analysis reports the results from the pre-cessation visits at which amount smoked, exhaled carbon monoxide (CO) concentration, urinary cotinine concentrations, and subjective measures were assessed.ResultsOver the 4-week study period, those switching to non-menthol (vs. continuing to smoke menthol) cigarettes smoked fewer cigarettes per day (mean ratio: 0.86; 95% confidence interval [CI]: 0.76, 0.98; p = .02), reported lower withdrawal symptom severity (mean difference -1.29; 95% CI: -2.6 to -0.01; p = .05) and higher perceived effectiveness of their skills for quitting smoking (mean difference 0.56; 95% CI: 0.02-1.10; p = .05). No significant differences were found between groups in exhaled CO, urinary cotinine concentrations, or most other subjective effects including support for a ban on menthol characterizing flavor in cigarettes.ConclusionsThese results suggest that were menthol cigarettes no longer available, those that switch to non-menthol cigarettes would not change their smoking behavior in a way that is likely to be more hazardous, with some indicators suggesting that there may be some benefit.Clinicaltrials.gov # NCT02342327.ImplicationsA ban on menthol characterizing flavor in cigarettes has been proposed as a potential means by which to increase smoking cessation rates among current menthol cigarette smokers. This study evaluated how African American menthol cigarette smokers adjusted their smoking behavior after switching to non-menthol cigarettes. Although the overall differences between groups were modest, they were in a direction consistent with decreased smoking suggesting that current smokers would not adjust their behavior in a way that is likely to be more hazardous, with some indicators suggesting that there may be some benefits.

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:IntroductionMenthol has been shown to target similar brain regions and neural receptors as nicotine, yet the association between menthol cigarette use and cognitive performance remains unknown.Aims and methodsThis study examined differences in cognitive task performance between menthol (MS) and nonmenthol (NMS) cigarette smokers after acute cigarette consumption. Sixty white and black and/or African American, nonabstinent, MS (n = 30) and NMS (n = 30) were assessed presmoking and postsmoking their preferred cigarette on four computerized tasks: Continuous Performance Task (CPT; alerting attention), N-Back Task (working memory), Finger Tapping Task (motor control), and Apple Picker Task (reinforcement enhancement). Self-reported nicotine dependence and objective smoking topography measures were also compared between groups.ResultsInitial unadjusted analyses showed a significant effect of cigarette type × time on CPT speed (p = .042), where MS improved while NMS group worsened in CPT speed after smoking. After controlling for baseline cigarette craving and cigarette nicotine levels, the effect of cigarette type × time for all cognitive outcomes was statistically nonsignificant (ps > .05). However, there remained a significant effect of cigarette type, where MS versus NMS had poorer CPT (p = .046) and N-Back Task accuracy (p = .006) but faster N-Back speed (p = .039). There were no statistically significant differences between groups on reinforcement enhancement, nicotine dependence, or smoking behavior outcomes (ps > .05).ConclusionsContrary to our hypotheses, results did not find a significant effect of cigarette type on the change in cognitive performance after acute smoking in nonabstinent smokers. Further studies are needed to clarify the specific pharmacological effects of nicotine and menthol on cognitive functioning.ImplicationsThe current study is the first to compare the potential enhancement of cognitive task performance after acute cigarette smoking between satiated menthol and nonmenthol cigarette smokers. Study results suggest that acute menthol cigarette use may not enhance cognitive function above and beyond nonmenthol cigarettes to increase dependence among menthol smokers. However, the contribution of other psychological factors (eg, craving, mood) and cigarette characteristics (eg, nicotine content) may be involved in cognitive function enhancement to perpetuate dependence and smoking persistence for menthol smokers.

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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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