Drug use among youth in the US has high relevance to public health, as it is associated with negative social, mental, and physical health outcomes. Prevention scientists have identified risk factors for drug use vulnerability among adolescent populations; however, such models have largely failed to explain risk for African Americans. Therefore, as noted by NIDA and others, culture-specific risk models are necessary to better understand vulnerability to drug use among African American youth. My long-term career goal is to establish myself as an externally funded expert in developmental risk for drug use and addiction among African Americans. The purpose of the K01 proposal is develop content and methodological expertise on cultural and physiological mechanisms that impact drug risk for African American youth. Thus, with training in these areas, the overall objective of this research project is to 1) examine inflammatory pathways through which discrimination impacts drug use vulnerability among African American youth, 2) protective variables that moderate risk, and 3) potential variations of risk based on assessment modality. The first two objective will be completed using Dr. Gene Brody’s SHAPE dataset, a longitudinal study of 500 African American youth aged 16-21 years. For the third objective, I will recruit 150 African American youth aged 16-18 years to examine inflammatory functioning and drug use vulnerability based on discrimination type and measurement modality across a 12-month period. Testing such models is significant, as it will clarify our understanding on the magnitude of the effect discrimination has on drug use risk among African American youth and specific pathways through which the risk pathway operates. Furthermore, such findings are significant as they will directly impact intervention programming by identifying specific targets within the risk process and important cultural factors to include that can buffer risk. In the final stages of this K01 award period, I will submit an R01 to NIDA to investigate the prospective effect multiple forms of chronic stress have on inflammation and negative affect among African American youth to determine critical periods to intervene within the risk process.