Impact of new tobacco product design and synthetic additives on use initiation and preference behavior

The tobacco industry has been rapidly introducing products with novel designs and constituents, in response to regulatory interventions, to maintain nicotine dependence in people who quit smoking and to attract new consumers. Oral nicotine pouches (ONPs) are a rapidly growing new smokeless tobacco product category introduced to the US market in 2019 by several tobacco companies. ONP’s contain a white powder, claimed to be tobacco-free, consisting of filler, nicotine and a wide variety of flavors. More recently, “non-menthol” cigarettes were introduced in California and Massachusetts, two states that banned menthol cigarettes, targeting former menthol smokers. Currently, only limited data are available about the chemical composition of these products, and their behavioral and addictive effects, especially in adolescents initiating product use. In this proposal, we hypothesize that: (i) product design and formulation of these novel products enables efficient and fast release of nicotine and flavors; (ii) flavors released from nicotine pouches are especially attractive to adolescents and promote nicotine intake; and (iii) additives released from “non-menthol” cigarettes facilitate smoke inhalation and increase nicotine inhalation. These hypotheses are based on our published work and preliminary data demonstrating that ONPs contain significant amounts of synthetic high- intensity sweeteners, that some ONPs contain a less irritating form of nicotine, and that “non-menthol” cigarettes contain synthetic cooling agents replacing menthol. The following Specific Aims will be pursued: Aim 1: Analyze the chemical composition of nicotine pouch products and “non-menthol” cigarettes for flavors, sweeteners and tobacco-derived or tobacco-free racemic nicotine. Aim 2: Examine the behavioral effects of sweeteners and nicotine forms on initiation of consumption of oral nicotine pouch extracts in mice. Aim 3: Quantify the effects of synthetic cooling agents in “non-menthol” cigarettes on the sensory respiratory irritation response in mice.