ABSTRACT. Structural and social inequities have historically impacted the health and wellbeing of Black, Indigenous and Persons of Color (BIPOC) in the United States, resulting in health disparities that were exacerbated by the COVID-19 pandemic, which coincided with a surge of discriminatory events and hate crimes targeting minority groups. Emerging research shows that substance use, especially polysubstance use (PSU), is increasing as a means to cope with the range of stressors and psychological consequences among BIPOC adults. The extent to which PSU as a maladaptive coping process unfolds and accumulates in the current context of the pandemic and racial injustice to perpetuate and potentially expand addiction-related disparities is unknown. Furthermore, the impact of coping responses, resources and resilience factors on these processes has not been extensively studied in all BIPOC subgroups. In the current proposal, we aim to capture the nature of daily variation in acute perceived discrimination and to examine how these variations influence PSU, with emphasis on evaluating predictors of resilience to stress. This information is critical to inform the design of context-sensitive interventions tailored to momentary circumstances in addition to person-level variables to prevent maladaptive coping strategies, including PSU. Building on our current user-centered, smartphone Ecological Momentary Assessment (EMA) app, we propose to conduct an exploratory-sequential mixed methods study. In Aim 1, we will use 6-9 focus groups (FGs; N~70) to better understand discrimination experience and coping resources in the context of intersectionality of race/ethnicity and gender in relation to PSU to inform context-sensitive EMA, refined during a pilot EMA phase. Subsequently, BIPOC adults who co- use 2+ substances (N=270) will be recruited through targeted digital ads, and will complete 7-day EMA every 3 months over 4 waves. In Aim 2, a cross-over, within-subject, repeated measure, observational EMA design will be used, and multi-level logistic regression models will be developed to determine the within-person effects of perceived discrimination on PSU and identify the underlying mechanisms. In Aim 3, we will model the prospective association between changes in discrimination and PSU using the multi-wave EMA data to examine the longitudinal effects of perceived discrimination contexts on changes in PSU among BIPOC adults. IMPACT. To the best of our knowledge, this is the first multi-wave EMA study that uses a social-ecological framework and a novel, culturally appropriate, real-time assessment design to determine the impact of day-to- day discrimination and PSU in BIPOC adults. We expect our study to uncover micro-temporal etiologies of PSU disparities across BIPOC adults that will inform future targeted interventions to ameliorate the effects of acute perceived discrimination on PSU and reduce addiction-related burdens disproportionately affecting BIPOC, an u...