ABSTRACT – PROJECT 1: Vaping Behavior, the Emergence of Dependence, and Well-being Since 2014, vaping has been the most popular form of tobacco use among high school students, with over 1.7 million reporting current use in 2021. Recent evidence also indicates an increase in the proportion of adolescents who vape 20 or more days a month, highlighting a surge in the levels of use often associated with dependence. Understanding vaping behavior, including frequency and intensity of use, during the critical years of high school, and the relationship with dependence is central to vaping prevention. Prevention also relies on knowledge of the health effects of vaping that are relevant to adolescents. One such effect is dependence, a recognized psychiatric disease with an associated pathophysiology that can impact adolescent life. However, the potential health impact of vaping extends beyond dependence. Modern definitions conceptualize health as “a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity” (World Health Organization). Adolescent well-being involves a number of characteristics (e.g., perseverance, connectedness) that depend on fundamental skills (cognitive, emotional, social) acquired during this critical period of development. A large literature demonstrates how functioning within these domains is vulnerable to the impact of nicotine, suggesting that vaping, particularly when associated with dependence, is likely to impact adolescent well-being. The overall goal of Project 1 is to characterize how vaping leads to dependence and impacts the well-being of adolescents. The Specific Aims are: 1) Prospectively assess vaping behavior and the emergence of symptoms of vaping dependence during adolescence; 2) Describe how vaping is related to well- being; and 3) Leverage a mixed methods approach to improve survey measures and deepen understanding of how changes in vaping, dependence, health and well-being impact adolescent daily life. To address these aims, Project 1 will screen over 13,500 high school students (all grades) to recruit a sample of vaping and non- vaping students to participate in an online survey. The initial survey will be conducted in over 4300 students from all grades (cross-sectional). Freshmen, Sophomores and Juniors who are recruited into the online survey will form a longitudinal cohort of over 3100 students with additional waves of surveys conducted every six months. A subset (N=360; 240 vapers) of the longitudinal cohort will complete lab-based assessments at two time points, 18 months apart (i.e., corresponding to Waves 1-3 and 4-6). Finally, up to 40 participants will complete in-depth interviews after Wave 1 and up to 40 participants will complete interviews after Wave 4-6. Project 1 will provide a rich characterization of the natural history of vaping and the impact it has on adolescent development and well-being. This information is central to the overarching goal of P...