Plasma Menthol Glucuronide as a Biomarker of Acute Menthol Inhalation

Jatlow, Peter; Valentine, Gerald; Gueorguieva, Ralitza; Nadim, Haleh; Wu, Rongqian; O’Malley, Stephanie S.; Sofuoglu, Mehmet

doi:10.18001/trs.4.1.5

Cited by 8 publications

(9 citation statements)

References 24 publications

(25 reference statements)

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“…Participants took six inhalations, one every 15 s, over 90 s just prior to each of the three infusions. As reported elsewhere, this procedure resulted in highly significant, dose-dependent increases of venous plasma menthol glucuronide (a biomarker of menthol exposure) after inhalation that was proportional to the menthol solution concentrations inhaled by our study sample (Jatlow et al, 2018).…”

Section: Drugs Menthol Administration Each E-liquid (Prepared By Pacesupporting

confidence: 73%

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

et al. 2018

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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.

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Section: Drugs Menthol Administration Each E-liquid (Prepared By Pacesupporting

confidence: 73%

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

et al. 2018

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“…Plasma cotinine and 3-hydroxycotinine (3HC) and nicotine, were measured employing LC/MS/MS at session baseline and used to compute the nicotine metabolite ratio (NMR:3HC/cotinine), a marker of nicotine clearance which impacts heaviness of smoking and subjective nicotine effects. 32,33 Menthol glucuronide, a menthol metabolite, 34,35 also assayed by LC/MS/MS in plasma, was measured at baseline and after each block (Figure 1). Table 1).…”

Section: Outcome Measuresmentioning

confidence: 99%

Modulation of “Protective” Nicotine Perception and Use Profile by Flavorants: Preliminary Findings in E-cigarettes

DeVito

Jensen

O’Malley

et al. 2019

Nicotine &Amp; Tobacco Research

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Introduction Characterizing flavors are widely available in e-cigarettes and motivate initiation and continued use. Flavors may enhance appeal and facilitate development of addiction to tobacco products through modulation of tobacco products’ reinforcing or aversive actions. Palatable flavors (eg, fruit) may increase appeal through primary reinforcing properties. Menthol’s cooling and anesthetic effects may increase appeal by counteracting nicotine’s aversive effects. Genetics provide a method for modeling individual differences in sensitivity to nicotine’s effects. A common polymorphism, rs16969968, encoded in the α5 nicotinic acetylcholine receptor subunit gene (CHRNA5), is a well-recognized marker for smoking risk and reduces sensitivity to nicotine aversiveness. Methods This pilot study tested how flavors impacted e-cigarette appeal and self-administration. In a single testing day, cigarette smokers (N = 32; 94% menthol-smokers) self-administered e-cigarettes containing e-liquids differing in nicotine level (0 mg/mL, 24 mg/mL) and flavor (unflavored, menthol, fruit-flavored) within directed and ad libitum e-cigarette paradigms. Subjective drug effects, number of puffs, rs16969968 genotype, plasma nicotine, and menthol glucuronide levels were collected. Results Menthol partially ameliorated nicotine aversiveness; fruit did not. In nicotine’s absence, fruit flavor increased self-reported preference and ad libitum use relative to menthol-containing or unflavored e-liquids. Individuals with high-smoking-risk rs16969968 genotype (N = 7) reported greater craving alleviation following directed administration of nicotine-containing e-liquids, showed a trend rating nicotine-containing e-liquids as less harsh, and self-administered more nicotine during ad libitum compared to individuals with low-smoking-risk genotype (N = 23). Conclusions While menthol countered aversiveness of nicotine-containing e-liquids, fruit flavor increased appeal of nicotine-free e-liquids. These preliminary findings suggest menthol and fruit flavor increase e-cigarettes’ appeal through distinct mechanisms. Implications This study provides a detailed characterization of the effects of flavors (unflavored, menthol, fruit), nicotine (0 mg/mL, 24 mg/mL) and their interactions on the subjective drug effects and ad libitum self-administration of e-cigarettes. Genetics were used to assess these effects in higher-smoking-risk (diminished sensitivity to nicotine aversiveness) and lower-risk groups. Findings could inform impact of regulation of flavors or nicotine in e-cigarettes, and their impacts on vulnerable sub-populations.

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“…Furthermore, following menthol cigarette smoking, increases in plasma MG concentrations have also been demonstrated ( Hsu et al, 2017 ). In a prior study, we showed that the AUC values of plasma MG concentrations increase proportionally to the concentration of menthol in the e-liquid ( Jatlow et al, 2018 ). In this study, we demonstrate changes in plasma MG concentrations following inhalation of e-cigarettes with different menthol concentrations.…”

Section: Discussionmentioning

confidence: 98%

“…Similarly, increases in plasma MG concentrations have been documented following menthol cigarette smoking, also called the “menthol boost” ( Hsu et al, 2017 ). We have also reported that the area under the curve (AUC) values of plasma MG concentrations following e-cigarette use are proportional to the menthol concentrations in the e-liquid ( Jatlow et al, 2018 ). To our knowledge, previous studies have not examined whether plasma MG levels serve as a biomarker for the acute subjective and physiological effects of menthol-flavored tobacco products.…”

Section: Introductionmentioning

confidence: 99%

Plasma Menthol Glucuronide as a Biomarker for the Behavioral Effects of Menthol and Nicotine in Humans

et al. 2022

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This secondary analysis sought to determine if plasma menthol glucuronide (MG) concentrations predict changes in three outcomes, subjective drug effects, urges to smoke, and heart rate, following concurrent inhaled menthol and intravenous nicotine. A total of 45 menthol and non-menthol cigarettes smokers (36 male, nine female, 20 Black, and 23 White) were included in this double-blind, placebo-controlled study. Across three test sessions, participants were assigned to a different flavor condition for each session: 0% (no menthol), 0.5%, or 3.2% menthol. In each test session, participants received in a random order one intravenous delivery of saline and two intravenous deliveries of nicotine (0.25 mg/70 kg and 0.5 mg/70 kg), each 1 h apart, concurrent with menthol delivery by e-cigarettes. The main outcomes were subjective drug effects, urges to smoke, and heart rate. The results showed that following e-cigarette inhalation, changes in plasma MG concentrations or “menthol boost” increased proportionally to the menthol concentration in the e-liquids. While changes in plasma MG concentrations were not predictive of increases in heart rate or subjective drug effects that are reflective of acute effects from nicotine (i.e., feel good effects, stimulated, aversive effects), they were predictive of cooling effect, a typical effect of menthol, but only in menthol smokers in the absence of concurrent active nicotine infusion. These findings demonstrate the utility of plasma MG as a biomarker both for acute menthol exposure by e-cigarette inhalation and for the examination of the concentration-dependent behavioral and physiological effects of menthol in humans.

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Plasma Menthol Glucuronide as a Biomarker of Acute Menthol Inhalation

Cited by 8 publications

References 24 publications

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

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

Modulation of “Protective” Nicotine Perception and Use Profile by Flavorants: Preliminary Findings in E-cigarettes

Plasma Menthol Glucuronide as a Biomarker for the Behavioral Effects of Menthol and Nicotine in Humans

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