7. PROJECT SUMMARY/ABSTRACT This R01 proposal is responsive to priority research areas #2 (Addiction) and #4 (Behavior) within RFA-OD-17- 013 and seeks to address several limitations in the research on menthol smoking. Although the FDA banned characterizing flavors in cigarettes, menthol cigarettes are still available to consumers. Experimentation with menthol cigarettes has been linked to progression to regular smoking and nicotine dependence in youth and young adults (YAs, defined here as ages 18-24)1-5, a vulnerable group of tobacco users. A key unanswered question is whether menthol increases the appealing and reinforcing properties of cigarette smoking6-8, which may facilitate progression to regular smoking and addiction among newer users. The subjective appeal and reinforcing effects of smoking are important indicators of the neurobiological systems that underlie smoking addiction and abuse liability,9 and have been shown to motivate subsequent smoking. Only a handful of controlled investigations have examined the differential appealing and reinforcing effects of smoking menthol and non-menthol cigarettes,10-12 but most have methodological limitations13,14, including small sample sizes and omission of YA smokers.12-18 These studies also do not measure, with a sufficient level of accuracy, degree of sequencing, and timing that is needed to address the context-dependent fluctuations in menthol- related appeal and reinforcement in real time.19 We will recruit menthol (n = 150) and non-menthol (n = 150) YA smokers who initiated smoking in the past 6-months, and measure appeal/reinforcement for menthol and non-menthol cigarettes and the impact of appeal/reinforcement on changes in smoking (progression, nicotine dependence, and cigarette harm perceptions) at a 6-month follow-up. Appeal/reinforcement will be assessed via two complementary measurement paradigms: one in the laboratory using a well-validated behavioral economic choice task20-22 and the other in the natural environment using ecological momentary assessment (EMA). Laboratory studies provide a great deal of efficiency and internal control, allowing for causal inference of acute subjective response to menthol smoking that cannot be captured through subjective self-report; while EMA allows for similar causal sequencing of behavior, but in an ecologically valid format in the smoker’s natural environment. It is hypothesized that, compared to non-menthol smokers, menthol smokers will show greater appeal/reinforcement, both in the laboratory and via EMA, and will be more likely to show progression to regular smoking, increases in nicotine dependence, and lower cigarette harm perceptions by a 6-month follow-up. The association between menthol preference and smoking outcomes will be reduced or non-significant after including measures of appeal/reinforcement in the model; suggesting that menthol’s appeal/reinforcement accounts for smoking progression. This research will isolate the unique effect...