Effects of non-tobacco flavors and nicotine on e-cigarette product appeal among young adult never, former, and current smokers

•The effect of e-cigarette flavor and nicotine on appeal in young adults was tested.•Sweet, menthol was more appealing than tobacco flavors in non-smokers, smokers.•Nicotine had acute unappealing qualities in both non-smokers and smokers.•Never smokers had largest preferences for non-tobacco flavors, away from nicotine.•Sweet, menthol flavors suppressed nicotine’s unappealing qualities in non-smokers. E-cigarette regulations targeting products that disproportionately appeal to never-smokers may optimize population health. This laboratory study of young adults tested whether differences in appeal between e-cigarettes with non-tobacco-flavored (vs. tobacco-flavored) and nicotine-containing (vs. nicotine-free) solutions varied by smoking history. Current (N = 53), former (N = 25), and never (N = 22) cigarette smokers who vape (Mean[SD] age = 25.4[4.4] years) administered standardized e-cigarette doses varied by a Flavor (fruit, menthol, tobacco) × Nicotine (nicotine-containing [6 mg/mL], nicotine-free) within-subject double-blind design. Participants rated each dose’s appeal (0–100 scale). Covariate-adjusted interactions tested whether smoking history moderated flavor and nicotine effects. Appeal was higher for fruit and menthol than tobacco flavors in each group. The fruit vs. tobacco appeal difference was greater in never smokers (fruit–tobacco estimate = 19.6) than current smokers (estimate = 12.1) but not former smokers (estimate = 12.6). The menthol vs. tobacco difference was greater in never smokers (menthol–tobacco estimate = 17.3) than former (estimate = 6.0) and current (estimate = 7.2) smokers. Appeal was lower for nicotine-containing than nicotine-free solutions in each group; this difference was greater in never smokers (nicotine–nicotine-free estimate = −17.3) than former (estimate = −7.0) and current (estimate = −10.6) smokers. Compared to tobacco flavors, nicotine’s appeal-reducing effects were suppressed by fruit and menthol flavors in never smokers. Higher appeal of non-tobacco-flavored (vs. tobacco-flavored) and lower appeal of nicotine-containing (vs. nicotine-free) e-cigarettes may be widespread in young adults but disproportionately amplified in never smokers. Non-tobacco flavors may suppress nicotine’s appeal-lowering qualities in never smokers. The impact of regulating non-tobacco flavors in e-cigarettes may vary by smoking history.