Project Summary Exposure to racial discrimination has long been identified as a key social determinant of substance use that stratifies by race/ethnicity. Starting in 2020, displays of racism and their impacts have intensified, and the recent volatile climate during the COVID-19 pandemic provides a unique opportunity to assess mechanisms that link discrimination and other social determinants of health with racial/ethnic disparities in drug use, but there has not been the requisite science on this topic as it deserves. Existing research on the discrimination-substance use association is plagued by both external validity (i.e., non-representative sampling with low generalizability to overall U.S.) and internal validity (i.e., low temporal precision from annual inter-survey intervals to detect prospective, potentially causal association). Additionally, there is little evidence to guide clinicians and policymakers on interventions that can disrupt discrimination’s impact on substance use in the modern social, economic, and public health context. This secondary analysis of the nationally-representative Understanding America Study (UAS, n~9,000 U.S. adults) aims to elucidate the nature and mechanisms of the association of discrimination with race/ethnicity inequalities in substance use. To chart the broad effects of the pandemic, this study will harmonize longitudinally bi-weekly (March 2020-July 2021) and monthly (August/September 2021- June 2022) survey waves with a total of 38 timepoints. Time-varying measures include 1) frequency of discrimination experience, racism, and COVID-19 related discrimination, and 2) substance use (past-week use of alcohol, cigarettes, e-cigarettes, cannabis, and other drugs, poly-substance use, and binge drinking) along with key public health (e.g., COVID-19 illness and vaccination), economic (e.g., economic insecurity, housing insecurity, and employment instability), and behavioral factors (e.g., resilience and coping strategies). We will combine person-level data (38 survey waves) with state-level geocoded data on hate crime incidence, statutory provisions, and other public health or economic context. Intensive longitudinal multi-level modeling will be conducted to partition between- and within-subject variance and address between-person confounds, thus overcoming the biases inherent in other annual-interval national substance use surveillance with low temporal precision and recall errors. Through three inter-related aims and theory-driven hypothesis testing, we will 1) examine whether within-person changes in discrimination are associated with substance use and if associations are moderated by race and ethnicity (Aim 1), 2) determine person- and environment-level factors that exacerbate or buffer against the association of discrimination with substance use (Aim 2), and 3) assess mechanisms that explain race/ethnicity differences in the association of discrimination with substance use (Aim 3). Findings from this study ...