<b>Data for E-Liquid Flavor Alters Nicotine Exposure, Puff Topography, and Subjective Effects Under Ad Libitum Use Conditions</b>

<p dir="ltr"><i>Introduction:</i> Electronic nicotine delivery systems (ENDS) are most often used with e-liquids having fruit, and menthol or mint flavor, with tobacco flavor being least prevalent. This study evaluated the effect of a tobacco, fruit, and menthol e-liquid flavor on ENDS abuse liability.</p><p dir="ltr"><i>Methods: </i>Fifty-two regular ENDS users participated in a double-blinded, randomized, crossover-design study. Study conditions were ENDS (KangerTech CUPTI) with tobacco, menthol, or fruit flavor e-liquids with 1.2% (all flavors) or 0% (fruit only) freebase nicotine concentration. On separate days participants used the study products for 10 prescribed puffs and 1 h of <i>ad libitum</i> use. Plasma nicotine concentration, puff topography, and subjective effects were measured.</p><p dir="ltr"><i>Results:</i> Following <i>ad libitum</i> use, tobacco flavor ENDS were associated with significantly lower plasma nicotine levels than other nicotine-containing ENDS. Significantly fewer puffs were taken from the tobacco flavor ENDS than other products, and the 0% nicotine fruit flavor ENDS was associated with greater puff duration and puff volumes than other products. Tobacco flavor was rated significantly lower than other flavors on product liking (e.g., “tastes good” or “pleasant”), while only the 0% nicotine fruit flavor ENDS was associated with significantly greater withdrawal symptoms (e.g., ENDS craving, or urge to use an ENDS) compared to the other flavors.</p><p dir="ltr"><i>Conclusions:</i> Tobacco flavor ENDS were rated lower on liking, and associated with less nicotine exposure and fewer puffs taken, but comparably attenuated withdrawal symptoms to other flavor ENDS, while the non-nicotine fruit flavor did not affect withdrawal symptoms.</p>