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Yale TCORS Project 3: Nicotine Delivery Rate and Its Abuse Potential: Impact of Menthol

Principal Investigator(s): Mehmet Sofuoglu

Funding Mechanism: National Institutes of Health – TCORS Grant

ID number: 2 U54 DA036151-06

Award Date: 8/15/18

Institution: Yale University

Rapid delivery to the brain enhances the abuse potential of drugs of abuse, including nicotine. As proposed by Shihadeh and Eissenberg, nicotine flux, or the rate at which an e-cigarette delivers nicotine, is the most critical factor for evaluating its abuse potential. In this model, when an e-cigarette delivers nicotine at rates above a certain (undetermined) threshold, it can have high abuse potential and may initiate or maintain tobacco addiction. In contrast, when the nicotine flux is optimal, the e-cigarette may have low addiction potential while providing sufficient nicotine delivery to help smokers quit smoking by alleviating urges to smoke. This proposed “optimal nicotine flux” concept has yet to be assessed in human studies. In addition, flavors and other e-cigarette ingredients may affect nicotine flux; notably, menthol may have such an effect through inhibition of nicotinic receptors and slowing of nicotine metabolism. The goal of this project is to examine the impact of nicotine delivery rate on nicotine’s abuse potential and its potentially beneficial effects of alleviating smoking urges and withdrawal. Researchers will also determine whether switching from menthol to non-menthol cigarettes changes the impact of nicotine delivery rate on the study outcomes. To achieve these goals, researchers will conduct two studies in adult (aged 18-30) smokers. Study 1 will recruit equal numbers of menthol (n=35) and non-menthol (n=35) smokers for five experimental sessions, which will be at least 24 hours apart. Each session will include one randomly-assigned infusion that will be either saline or a single dose of nicotine (1 mg per 70 kg body weight) delivered at four different infusion rates (0.24, 0.096, 0.048 or 0.024 μg per kg body weight per second). In Study 2, menthol-preferring smokers (n=38) will be randomized to a menthol or non-menthol cigarette smoking condition for two weeks and will then be crossed over to the alternative smoking condition for two weeks. For both studies, the main outcome measures will be measures of abuse potential (subjective drug effects and reinforcement) smoking urges, tobacco withdrawal, plasma nicotine concentrations, nicotine metabolite ratio, heart rate, and blood pressure. Study findings may inform standards for nicotine delivery rates that minimize the addictive risks of e-cigarettes and other electronic nicotine delivery systems.

Yale TCORS: Flavors, Nicotine and Other Constituents (YCSTP) Related Resources

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