Twenty-nine states, the territories of Guam and Puerto Rico, and the District of Columbia have legalized medical and/or recreational cannabis use. Concurrently, the potency of delta-9 tetrahydrocannabinol (THC) has increased while perceptions regarding harms associated with regular use have become more permissive, underscoring the importance of focused effort to evaluate the impact of cannabis use on health and behavior. In particular, there is growing concern about potential adverse consequences of escalations in prenatal cannabis use (PCU). Nearly 4% of pregnant U.S. women report past month cannabis use, representing a 1.6- fold increase in the past decade. The potential impact of PCU on neonatal outcomes, including the neonatal brain, and early childhood developmental milestones has proven difficult to study in part because PCU co- occurs with other drug use, most notably tobacco, making it difficult to delineate the specific effects of PCU. Further, PCU is comorbid with other maternal psychiatric illness (delinquency, externalizing behavior) as well as familial vulnerability to problem substance use that can confound the interpretation of causal effects of PCU on offspring brain and behavior. This proposal addresses current challenges in the literature by recruiting pregnant women from an urban hospital outpatient clinic, where medical records show that ~80% of women who use cannabis do not use other drugs, with the other ~20% of women who use cannabis reporting using tobacco but very little to no alcohol or other drugs. Pregnant women with a recent history of cannabis use will be selected; women reporting prenatal cannabis use only (PCU, n=200) will be compared with women reporting no prenatal substance use (NPCU, n=200), to evaluate the role of PCU in (Aim 1) birth characteristics (e.g., birthweight) and neonatal neurobehavior (e.g., excitability); (Aim 2) neonatal subcortical morphology and structural and functional connectivity in 150 PCU and 100 sociodemographically matched NPCU infants; (Aim 3) infant social-emotional behavior and temperament at 6, 12 and 18 months of age, as well as mother-infant interactions; and (Aim 4) the extent to which brain structure and connectivity is related to infant behavior during early life. Analyses will control for an index of other obstetric characteristics as well as composite indices of maternal psychosocial health, family history and home environment. Prospective in design, women recruited within the 1st trimester will be followed, with their offspring until 18 months postpartum, affording detailed characterization of risk and protective influences that accompany PCU. PCU, tobacco and other drug use will be biochemically validated. Women reporting PCU are more likely to be socio- economically disadvantaged and thus, the economic burden of early childhood social-emotional difficulties may be particularly pronounced in this group. Results from this study will directly impact the well-being of this understudied population and their infants; it will also inform the development of a rational public health policy on cannabis use in the United States.