Project Summary/Abstract Cannabis use is prevalent among adolescents and young adults. Despite knowledge about adverse effects, there are few efficacious prevention and treatment efforts aimed at cannabis use in this population. Exercise is one promising avenue for both which has received limited attention in this context. Exercise interventions have been linked to increased abstinence rates in the treatment of substance use disorders. Studies also suggest that the association between exercise and substance use may depend on factors such as substance and exercise type. Specifically, sports participation has been consistently linked to increased alcohol and decreased tobacco use, but its association with cannabis use is less understood and may be moderated by factors such as age, sex, and specific sport. The role of exercise-related cognitive improvements in influencing outcomes has not yet been examined. Considering loosening cannabis laws, lower perceived risk of cannabis use among adolescents, and the extent of neural changes taking place during adolescence, understanding the complex associations between exercise, cognition, and cannabis use is crucial in informing future prevention and treatment efforts aimed at this population. The proposed NRSA training grant will leverage data from two ongoing longitudinal studies (R01 DA033156, U01 DA041156) to examine associations between exercise, cognition, and cannabis use. Specifically, this proposal will examine decision making as a mediator of the association between exercise and cannabis use among adolescents over a 1-year period (Aim 1). It will also examine the moderating influence of exercise on the association between cannabis use and memory performance among adolescents over a 1-year period (Aim 2). Finally, this project will examine the neural underpinnings of the associations between exercise and cognition in a sample of preadolescent children by analyzing BOLD activation during fMRI monetary incentive delay and N-back tasks (Aim 3). Through a carefully crafted training plan, the PI will gain advanced understanding of the effects of addiction and exercise on brain and cognitive function (Training Goals 1 and 2), as well as the skills necessary to conduct advanced longitudinal and fMRI data analyses (Training Goals 3 and 4). This application will foster the development of PI Pacheco-Colón as an independent researcher focused on disentangling risk and protective factors from consequences of adolescent substance use, and longitudinally examining the impact of early substance use on adolescent brain and cognitive development.