Project Summary Female cigarette smokers have been shown to be more sensitive than males to non-nicotine sensory cues, which may explain lower rates of smoking cessation and lowered response to nicotine replacement therapies among females. Additionally, evidence suggests females have higher use of non-tobacco e-cigarette flavors and value flavor availability. This funded K01 is designed to elucidate how sex may influence the sensory perception of the popular e-cigarette flavor components, sweetness and cooling, and how this impacts appeal and reinforcing efficacy. Sensory perception, appeal, reinforcing efficacy of three e-cigarette flavors (sweet flavor, cooling flavor, and unflavored) are studied when presented in an e-cigarette with moderate nicotine concentration alone (Aim 1) and concurrently (Aim 2). We hypothesize that compared to an unflavored e-cigarette liquid, sweet and cooling flavor components will be generally rated as more appealing and reinforcing among both males and females, but females will have more pronounced differences in appeal and reinforcing efficacy of sweet and cooling flavors compared to the unflavored e-liquid (Aim 1). Additionally, we hypothesize that females compared to males will work harder and demonstrate greater abuse liability for flavored e-liquids in nicotine containing e-cigarettes when concurrently available with unflavored e-liquids in nicotine containing e-cigarettes (Aim 2). The outcomes of this project will provide new information about how the difference in response by sex to the non-nicotine sensory cues of flavor inform e-cigarette use and behavior. Regulatory efforts to restrict popular flavor components, like sweet and/or cooling flavors in e- cigarettes may have potentially a greater impact on female cigarette smokers than males on use of e- cigarettes as a potential harm reduction tool. Through expert mentoring, directed readings, formal coursework and seminars, direct experimental training, attendance at scientific meetings, manuscript and grant preparation, expertise to conduct the proposed research will be gained in the following areas: (1) chemosensory psychophysics as it relates to tobacco regulatory science, (2) sex-related research as it relates to tobacco regulatory science, and (3) advanced statistical training aimed at developing data analysis techniques to investigate sex differences & flavored tobacco product use. Taken together, this research project and training plan in the currently funded K01 will provide an important framework for career development in tobacco regulatory science. This supplement is proposed to provide additional funding support for the PI given they will be experiencing a critical life event during Year 2 of the parent grant. The PI will be having a child in July 2023 and will be on maternity leave through October. Given recruitment and data collection will be paused during this time, the supplement will be used to increase research support (with a research a...