Project Summary/Abstract Along with alcohol and tobacco, cannabis use amongst pregnant women is increasing in the United States. Therefore, it is necessary to identify the persistent and transient effects of prenatal cannabis exposure on neurobehavioral development and substance initiation during critical periods of development. Specifically, developmental milestones and neurobehavioral disinhibition, independently serve as potential clinical markers for later childhood behaviors and substance use. However, the roles of developmental milestones and neurobehavioral disinhibition in the association between prenatal cannabis exposure and risk for neurobehavioral dysregulation and adolescent substance initiation are largely unknown. Through the proposed project we aim to (ia.) characterize gross motor developmental milestone attainment from ages 3 mths-2 yrs in those exposed to prenatal cannabis to those unexposed; (ib.) evaluate milestone attainment as a mediator linking prenatal cannabis exposure and neurobehavioral disinhibition; (iia.) evaluate the impact of prenatal cannabis exposure on neurobehavioral disinhibition at age 9; and (iib.) examine the mediating role of neurobehavioral disinhibition in the association between prenatal cannabis exposure and adolescent substance initiation (15 yrs). The proposed aims will be addressed using the nationally representative Adolescent Brain Cognitive Development study data that includes measures of prenatal cannabis exposure, developmental milestones, neurobehavioral disinhibition, and adolescent substance initiation. A propensity score will be used to control for familial characteristics associated with the likelihood of being exposed to cannabis during pregnancy while examining the direct effect of prenatal cannabis exposure on our proposed developmental outcomes. A combination of path analysis and data reduction strategies will be employed to evaluate the direct and indirect effects of prenatal cannabis exposure on early substance misuse. Overall, the proposed project will bridge the gap in our current understanding of the impacts of prenatal cannabis exposure across development and how it influences clinical markers that may aid in the early identification of children effected by prenatal cannabis exposure as well as inform guidelines and interventions for expectant mothers.