Do flavors and nicotine concentration alter the experience from e-cigarettes among adults who smoke: A randomized double-blind experimental study

Background: Understanding flavor and nicotine impact on e-cigarette experiences is critical to supporting any potential benefit of e-cigarettes for adults who smoke. Aims: This study compared flavors (menthol, cherry, vanilla, and tobacco) and interactions with nicotine concentrations among younger and older adults who smoke cigarettes. Methods: In a double-blind study (NCT#03635333), younger (21–34 years, n = 58) and older (35–50 years, n = 63) adults who smoke cigarettes were randomized to 6 mg/ml (lower) or 18 mg/ml (higher) freebase-nicotine e-cigarettes (between-subject factor). In four separate sessions under abstinence, each participant sampled e-cigarettes in one flavor/session in their assigned nicotine condition. Primary outcomes of reward (Drug Effects Questionnaire) and appeal (labeled Hedonic scale) were assessed. Sensory effects (e.g., intensity, cooling), withdrawal, stimulation, and craving were also assessed. Mixed-effects models assessed main effects and interactions of age, nicotine concentration, and flavor. Results/Outcomes: A main effect of flavor on reward ( p = 0.02) and a trend for flavor on appeal ( p = 0.07) were observed, with menthol flavor being rated higher than all others. Higher nicotine trended toward increased reward ( p = 0.06). No effects of age on reward or appeal were observed. While nicotine × flavor interactions were not significant for these outcomes, analyses observed higher reward and appeal for menthol at the higher nicotine concentration ( p = 0.006). Menthol flavor was more intense and cooling ( p < 0.001) than other flavors. Craving declined more over time ( p = 0.003) following higher (vs lower) nicotine concentration. Conclusions/Interpretation: Among adults who smoke cigarettes, menthol flavor, particularly at higher nicotine, may play a greater role in promoting e-cigarette use compared to sweet and tobacco flavors.