ABSTRACT The prevalence of vaping nicotine has skyrocketed among adolescents in recent years, yet no NIH-funded trials have developed or evaluated vaping cessation interventions. An ideal treatment must directly target established vaping risk factors. Depressive symptoms, which are common among adolescent vapers (36%), have recently been identified as a predominant vaping-related risk factor. The relationship between depressive symptoms and vaping is bidirectional such that depressive symptoms prospectively predict vaping initiation and sustained e- cigarette use exacerbates depression. Among smokers with depressive symptoms, tailored interventions that target both depression and tobacco use are necessary for cessation. Thus, an ideal treatment for adolescent vapers with depressive symptoms likely must also directly target depressed mood. Brief Behavioral Activation (BA) is a well-established, evidence-based treatment for depression and smoking cessation. An adapted version of Brief BA for adolescent vaping cessation could offer a promising approach to simultaneously target depressive symptoms in the service of promoting vaping cessation. To have maximum population-level impact, this intervention must be delivered via real-world clinical outlets and disseminable platforms. Primary care providers are on the front lines of adolescent vaping treatment but have limited treatment resources. Tailoring Brief BA for adolescent vaping cessation and delivery via a mobile app could offer an ideal strategy to disseminate evidence- based, depression-specific vaping cessation treatment via primary care. The goal of this high risk-high reward study is to develop, refine, and evaluate a depression-specific Brief BA for adolescent vaping cessation mobile app (“Goal2QuitVaping”). Via an established partnership between MountainPass Technology LLC and the Medical University of South Carolina, we will develop Goal2QuitVaping consistent with feedback gathered during focus groups with end-users. Software development will build upon our prior and ongoing research developing app adaptations of Brief BA for primary care depression and smoking cessation treatment. Goal2QuitVaping will subsequently be improved via iterative usability testing. We will then conduct a two-group feasibility randomized controlled trial of 1) Goal2QuitVaping vs. 2) treatment as usual for vaping cessation within primary care. Go/no go decision benchmarks for Phase II include: 1) development of Goal2QuitVaping, 2) demonstrated Goal2QuitVaping treatment feasibility and acceptability, defined as ³70% app retention across follow-up and end-user self-reported benefit of Goal2QuitVaping use, and 3) efficacy data suggesting that Goal2QuitVaping use is associated with decreases in depressive symptoms and nicotine vaping. Research activities are coupled with strong commercialization opportunities which together will propel our company toward Phase II and beyond to address the public health need for evidenc...