ABSTRACT Opioid-related overdose rates among African Americans have increased exponentially. Given African American opioid users have the lowest treatment completion rates when compared to other races/ethnicities there is increased risk for mortality and morbidity. As a result, there is a dire need to better understand this fatal epidemic among this historically underserved group. Using the theory of Subcultural Evolution and Drug Use which suggests cultural and generational influences are linked to drug use patterns and risks among African Americans, the Research Examining Factors Associated with the Opioid Crisis among Underserved African Americans (REFOCUS) project will employ a within-racial group, mixed-methods design among African American adults in the community. The overall objective is to better understand the complex structural, social, and cultural factors that differentially influence NMPOU, other nonmedical prescription drug use and treatment service use among African Americans. Ultimately, our goal is to gather data that will inform culturally-tailored interventions to reduce NMPOU and better facilitate initiation and completion of treatment. The REFOCUS project has three aims: 1) To understand cultural and generational characteristics associated with NMPOU, other NMPDU, illicit drug use and treatment service use. We will conduct in-depth interviews with approximately 40 African American nonmedical prescription opioid users stratified by gender and age to understand NMPOU across the lifespan within the context of lived experience. Using thematic analysis, data will be gathered to culturally-tailor the survey. 2) To assess structural, social and cultural patterns of NMPOU, other NMPDU, illicit drug use and treatment service use among 800 (400 = male and 400 = female) African American NMPO users. We will conduct cross-sectional face-to-face culturally-informed surveys (modified by information obtained in Aim 1) and drug testing using targeted recruitment and stratified sampling by age and gender. 3) To pretest messaging generated from initial findings that will inform targeted interventions specific to African American nonmedical prescription opioid users. We will conduct in-depth, semi-structured interviews and using health communication techniques, we will develop a library of cultural, gender, and generational specific messages related to decreasing NMPOU and increasing treatment engagement and retention. We will test these messages that will be constructed from Aim 1 and Aim 2 data with approximately 40 African American nonmedical prescription opioid users stratified by gender and age. This pretesting task will prepare us to conduct a fully powered RCT as the next step in our research. This underrepresented new investigator led project directly aligns with the PAR and NIDA’s priority focus area of “addressing real-world complexities”. As this high-impact project focuses on a marginalized group underrepresented in opioid use resear...