Peter Jatlow1, Gerald Valentine2, Ralitza Gueorguieva3, Haleh Nadim4, Ran Wu5, Stephanie S O'Malley6, Mehmet Sofuoglu7. 1. Professor Emeritus in Laboratory Medicine and in Psychiatry, Yale School of Medicine, New Haven, CT. 2. Clinician in Psychiatry, Department of Psychiatry, Yale School of Medicine, New Haven, CT. 3. Senior Research Scientist in Biostatistics, Director of Biostatistics in Psychiatry, Yale School of Public Health, New Haven, CT. 4. Research Associate, Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT. 5. Statistician, Department of Psychiatry, Yale School of Medicine, New Haven, CT. 6. Professor, Department of Psychiatry, Yale School of Medicine, New Haven, CT. 7. Professor, Department of Psychiatry, VA CT Healthcare System and Yale School of Medicine, New Haven, CT.
Abstract
OBJECTIVES: Menthol is often added to cigarettes and e-cigarette solutions for its cooling and anti-irritant effects, and may contribute to development of nicotine dependence, particularly in vulnerable populations such as adolescents, and among African Americans. Menthol is rapidly metabolized to menthol glucuronide (MG) with little or no unconjugated menthol measurable in venous blood. Human challenge studies of the effects of inhaled menthol, and of its interactions with nicotine, would benefit from a quantitative measure of acute menthol exposure. Our objective was to determine whether plasma MG concentrations might be a suitable quantitative biomarker of acute menthol exposure following its inhalation. METHODS: We performed a secondary analysis of plasma MG concentrations obtained during a study of the effects of inhaled menthol on behavioral responses to intravenous nicotine. MG concentrations were followed over time in venous plasma from 48 participants following inhalation of aerosols from e-cigarettes employing solutions containing either of 2 menthol concentrations or placebo. RESULTS: Whereas plasma MG concentrations were variable, they showed a dose-dependent increase following menthol inhalation. CONCLUSIONS: Measurement of plasma MG may be useful to assess inter-individual differences in acute menthol exposure in human challenge studies involving menthol inhalation.
OBJECTIVES: Menthol is often added to cigarettes and e-cigarette solutions for its cooling and anti-irritant effects, and may contribute to development of nicotine dependence, particularly in vulnerable populations such as adolescents, and among African Americans. Menthol is rapidly metabolized to menthol glucuronide (MG) with little or no unconjugated menthol measurable in venous blood. Human challenge studies of the effects of inhaled menthol, and of its interactions with nicotine, would benefit from a quantitative measure of acute menthol exposure. Our objective was to determine whether plasma MG concentrations might be a suitable quantitative biomarker of acute menthol exposure following its inhalation. METHODS: We performed a secondary analysis of plasma MG concentrations obtained during a study of the effects of inhaled menthol on behavioral responses to intravenous nicotine. MG concentrations were followed over time in venous plasma from 48 participants following inhalation of aerosols from e-cigarettes employing solutions containing either of 2 menthol concentrations or placebo. RESULTS: Whereas plasma MG concentrations were variable, they showed a dose-dependent increase following menthol inhalation. CONCLUSIONS: Measurement of plasma MG may be useful to assess inter-individual differences in acute menthol exposure in human challenge studies involving menthol inhalation.
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