Evaluation of the Electronic Cigarette Withdrawal Syndrome: Mechanistic Targets for Intervention

PROJECT SUMMARY ABSTRACT Electronic cigarettes (e-cigarettes) are among the most important issues in public health today. Although e- cigarettes have shown promise as a cessation aid for traditional cigarettes, the public health benefits of these products may be undermined by the soaring rates of initiation among previously nicotine-naïve youth and the propensity for these products to foster nicotine dependence. There are a growing number of people who report wanting to quit using e-cigarettes and not being able to do so successfully, underscoring the need for research to determine factors that impede e-cigarette cessation. When smokers abstain abruptly from combustible cigarette use, a withdrawal syndrome emerges that includes core symptoms of negative affect and craving, impaired cognitive functioning, and disturbed sleep, all of which ultimately hinder cessation attempts. However, there is very limited controlled research on e-cigarette withdrawal, and it is unknown the extent to which nicotine contributes to any emergent e-cigarette withdrawal syndrome. This project will use a rigorous residential laboratory design to evaluate e-cigarette withdrawal expression and experimentally determine the role of nicotine in this syndrome. Healthy adults who exclusively use e-cigarettes (N=120) will undergo monitored e-cigarette abstinence over seven days (1 week) in a residential unit. We will evaluate the contribution of nicotine to withdrawal expression by assigning participants to one of three conditions: active nicotine patch, placebo patch control, or no patch to control for expectancies. Standardized behavioral and biological measures associated with withdrawal including patient report, cognitive task performance, and biometrics will be collected throughout to establish a rigorous timecourse of withdrawal and evaluate the contribution of nicotine to these symptoms. Three Specific Aims are designed to test core features of nicotine withdrawal mirroring three core areas of nicotine/tobacco withdrawal described in the DSM-5. Specific Aims will evaluate the timecourse and contribution of nicotine to withdrawal-induced changes in subjective mood (Specific Aim 1), cognitive performance (Specific Aim 2), and sleep disturbance (Specific Aim 3). An Exploratory Aim will evaluate the impact of withdrawal on motivation and return to use. We hypothesize negative affect and craving will increase, cognitive performance will decrease, and sleep will be impaired during the residential abstinence period. We also hypothesize that withdrawal symptoms will be attenuated with nicotine patch relative to both control conditions. This research will use a rigorously-controlled residential study to provide vital information about the clinical significance of behavioral and biological e-cigarette withdrawal symptoms and demonstrate the role of nicotine in the expression of withdrawal to inform the viability of translating established and readily accessible nicotine replacement interventions to e-cigarette cessation.