Introduction

Tobacco and alcohol are the leading and third leading causes of preventable death in the United States, respectively, representing an exceedingly large economic burden and loss of human life.1,2 Use disorders of these substances are also highly comorbid, with 80%-90% of patients with alcohol use disorder being smokers.3 While each substance has their own associated risks, combined use may have additive effects on substance dependence, as well as negative physical and mental health outcomes including increased prevalence of certain cancers and psychiatric comorbidities.4 It is therefore vital to understand the interactions between these substances such that the consequences of their use can be minimized both individually and in combination.

To understand this relationship, research must match the dynamic nature of substance use, adapting quickly to the changing landscape—particularly that of nicotine. Cigarette use has been steadily declining, while new forms of nicotine use have been growing at alarming rates, especially among vulnerable populations.5,6 Past 30-day e-cigarette use among middle and high school students has grown from 0.6% and 1.5% to 4.7% and 19.6%, respectively, between 2011 and 2020.7,8 Although adolescent alcohol use has been steadily decreasing during this period, its use remains high with adolescents reporting past 30-day use at 29.2% in 2019.9 Nicotine and alcohol are also some of the most commonly co-used substances among adolescents, with nearly one in four adolescents reporting past 30-day use of both substances.10 Despite these facts, there is very little research investigating the interactions specific to e-cigarette and alcohol co-use (for summaries of reported findings, see Supplementary Table 1), and investigations in adolescents is even more limited.

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Excellent previous reviews have extensively evaluated the genetic,11,12 pharmacological,3,4,11,13-16 metabolic,17,18 and behavioral,4,11,15,19,20 mechanisms of interactions between nicotine and alcohol in great detail. Here, we have reviewed and updated the current state of knowledge in the field based on the clinical addiction-related outcomes of these interactions, and where available, the impact of sex and gender. Finally, we add our contention that further research must be carefully designed within the specific context of vaping, and how it might differ from previous investigations on the topic. As nicotine vaping and alcohol co-use is the focus, we attempt to give special attention to studies that use nontobacco nicotine routes of administration, though much of the research interchanges tobacco, particularly cigarettes, and nicotine. Throughout, we highlight adolescent co-use, where available, as this population is especially vulnerable to the consequences of substance use and is also where the most growth in vaping has been concentrated.21-23

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Category: WHICH