ABSTRACT. The parent project is an exploratory-sequential mixed methods study to document the nature of daily variation in acute perceived discrimination-related stress among adults from Black, Indigenous and People of Color (BIPOC) communities that have been historically impacted by structural and social inequities. We aim to examine how these variations influence poly-substance use (PSU) among BIPOC minoritized adults, with an emphasis on evaluating momentary predictors of resilience to stress. PSU carries elevated risks of addiction and is associated with negative health outcomes and greater comorbidity than single-substance use. This is a highly timely study because the extent to which these processes of stress and PSU are at post-pandemic, and how they coincide with poignant events involving modern displays of overt racism and discrimination, then perpetuate and aggravate addiction-related disparities is unknown. The parent grant focuses on African American, Latinx American and Asian American adults who co-use combustible cigarettes, e-cigarettes, marijuana and/or alcohol (i.e., PSU), to inform context-sensitive EMA, refined during a qualitative study phase. Subsequently, an independent sample of BIPOC adults who co-use 2+ substances (N=270) will complete 7-day EMA over 4 waves to assess time-varying contexts relevant to the experience of discrimination associated with daily variation in PSU. Native Hawaiian/Pacific Islanders (NH/PI) are an understudied NIH health disparity population deeply impacted by cultural trauma and negative social and economic factors that contribute to severe substance use disparities. Recruiting and analyzing a unique sample of NH/PI adults will strengthen the aims of the parent study by capturing unique aspects of discrimination that adversely affect individuals with various aspects of minoritized identities and its relation to PSU among NH/PI. Guided by leading NIH experts in NH/PI substance use disparities, in Aim 1, we will use 2-3 focus groups (FGs; N~20) to better understand the experience of discrimination, cultural trauma, 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. In Aim 2, an independent sample of NH/PI adults who co-use 2+ substances (N=25) will be recruited through intensive community-led efforts and targeted digital ads, and will complete 7-day EMA every 3 months over 4 waves to determine the within-person effects of perceived discrimination and cultural trauma on PSU and identify the underlying mechanisms. 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 NH/PI adults. We expect our study to uncover micro-temporal etiologies of PSU disparities across NH/PI adults that will inform fu...