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

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 sm...

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Main Authors: Ralitza Gueorguieva, Elizabeth K. C. Schwartz, R. Ross MacLean, Elise E. DeVito, Tore Eid, Ran Wu, Stephanie S. O’Malley, Mehmet Sofuoglu
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-03-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.844824/full
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author Ralitza Gueorguieva
Ralitza Gueorguieva
Elizabeth K. C. Schwartz
Elizabeth K. C. Schwartz
R. Ross MacLean
R. Ross MacLean
Elise E. DeVito
Tore Eid
Ran Wu
Stephanie S. O’Malley
Mehmet Sofuoglu
Mehmet Sofuoglu
author_facet Ralitza Gueorguieva
Ralitza Gueorguieva
Elizabeth K. C. Schwartz
Elizabeth K. C. Schwartz
R. Ross MacLean
R. Ross MacLean
Elise E. DeVito
Tore Eid
Ran Wu
Stephanie S. O’Malley
Mehmet Sofuoglu
Mehmet Sofuoglu
author_sort Ralitza Gueorguieva
collection DOAJ
description 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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spelling doaj.art-fe487cb6b4f14bff9c8a0e25920708da2022-12-21T21:10:11ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-03-011310.3389/fphar.2022.844824844824Plasma Menthol Glucuronide as a Biomarker for the Behavioral Effects of Menthol and Nicotine in HumansRalitza Gueorguieva0Ralitza Gueorguieva1Elizabeth K. C. Schwartz2Elizabeth K. C. Schwartz3R. Ross MacLean4R. Ross MacLean5Elise E. DeVito6Tore Eid7Ran Wu8Stephanie S. O’Malley9Mehmet Sofuoglu10Mehmet Sofuoglu11Yale School of Public Health, Department of Biostatistics, New Haven, CT, United StatesYale University, School of Medicine, Department of Psychiatry, New Haven, CT, United StatesYale University, School of Medicine, Department of Psychiatry, New Haven, CT, United StatesVA Connecticut Healthcare System, West Haven, CT, United StatesYale University, School of Medicine, Department of Psychiatry, New Haven, CT, United StatesVA Connecticut Healthcare System, West Haven, CT, United StatesYale University, School of Medicine, Department of Psychiatry, New Haven, CT, United StatesYale University, School of Medicine, Department of Laboratory Medicine, New Haven, CT, United StatesYale University, School of Medicine, Department of Psychiatry, New Haven, CT, United StatesYale University, School of Medicine, Department of Psychiatry, New Haven, CT, United StatesYale University, School of Medicine, Department of Psychiatry, New Haven, CT, United StatesVA Connecticut Healthcare System, West Haven, CT, United StatesThis 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.https://www.frontiersin.org/articles/10.3389/fphar.2022.844824/fullnicotineaddictionmentholmenthol glucuronideplasma menthol
spellingShingle Ralitza Gueorguieva
Ralitza Gueorguieva
Elizabeth K. C. Schwartz
Elizabeth K. C. Schwartz
R. Ross MacLean
R. Ross MacLean
Elise E. DeVito
Tore Eid
Ran Wu
Stephanie S. O’Malley
Mehmet Sofuoglu
Mehmet Sofuoglu
Plasma Menthol Glucuronide as a Biomarker for the Behavioral Effects of Menthol and Nicotine in Humans
Frontiers in Pharmacology
nicotine
addiction
menthol
menthol glucuronide
plasma menthol
title Plasma Menthol Glucuronide as a Biomarker for the Behavioral Effects of Menthol and Nicotine in Humans
title_full Plasma Menthol Glucuronide as a Biomarker for the Behavioral Effects of Menthol and Nicotine in Humans
title_fullStr Plasma Menthol Glucuronide as a Biomarker for the Behavioral Effects of Menthol and Nicotine in Humans
title_full_unstemmed Plasma Menthol Glucuronide as a Biomarker for the Behavioral Effects of Menthol and Nicotine in Humans
title_short Plasma Menthol Glucuronide as a Biomarker for the Behavioral Effects of Menthol and Nicotine in Humans
title_sort plasma menthol glucuronide as a biomarker for the behavioral effects of menthol and nicotine in humans
topic nicotine
addiction
menthol
menthol glucuronide
plasma menthol
url https://www.frontiersin.org/articles/10.3389/fphar.2022.844824/full
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