Abstract
Over the past two decades, combustible cigarette smoking has slowly declined by nearly 11% in America; however, the use of electronic cigarettes has increased tremendously, including among adolescents. While nicotine is the main addictive component of tobacco products and a primary concern in electronic cigarettes, this is not the only constituent of concern. There is a growing market of flavored products and a growing use of zero-nicotine e-liquids among electronic cigarette users. Accordingly, there are few studies that examine the impact of flavors on health and behavior. Menthol has been studied most extensively due to its lone exception in combustible cigarettes. Thus, there is a broad understanding of the neurobiological effects that menthol plus nicotine has on the brain including enhancing nicotine reward, altering nicotinic acetylcholine receptor number and function, and altering midbrain neuron excitability. Although flavors other than menthol were banned from combustible cigarettes, over 15,000 flavorants are available for use in electronic cigarettes. This review seeks to summarize the current knowledge on nicotine addiction and the various brain regions and nicotinic acetylcholine receptor subtypes involved, as well as describe the most recent findings regarding menthol and green apple flavorants, and their roles in nicotine addiction and vaping-related behaviors.
Highlights
Cigarette smoking remains the leading cause of preventable disease and death worldwide, with nearly half a million deaths per year in the United States alone [1]
In 2009, the Family Smoking Prevention and Tobacco Control Act was put in place to combat adolescent tobacco use and limit cigarette sales by banning all flavor additives other than menthol from being added to combustible cigarettes, yet this refrained from addressing other tobacco products including cigars, chewing tobacco, hookah, and more
This review summarizes the current knowledge base of nicotine addiction and the major neurobiological and neurophysiological adaptations that contribute to dependence
Summary
Cigarette smoking remains the leading cause of preventable disease and death worldwide, with nearly half a million deaths per year in the United States alone [1]. Based on a recent study reporting green apple and other fruity flavors to be the most popular of ENDS flavorants [9,25], additional reports have identified popular green apple flavorants, farnesol and farnesene, to enhance nicotine reward in a mouse model, and display rewarding properties in the absence of nicotine [19,26,27] These behavioral effects were found to be caused by changes in nAChR upregulation or stoichiometry, and ventral tegmental area dopamine neuron firing. Based on these findings, it is critical we further understand how ENDS flavoring chemicals may alter the addictive properties of nicotine in an attempt to combat the growing ENDS-use epidemic. This includes their effects on nicotine’s actions in the brain and the major neurocircuitry involved in the induction of addiction
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