Project Abstract We propose to conduct research that will determine the impact of relevant behaviors on HIV prevention among Young Black Sexual Minority Men (YBSMM), such as heavy cannabis use. Data from our group and others demonstrate heavy cannabis use as prevalent and increasing in YBSMM, is associated with HIV acquisition, use as a sex-drug, greater likelihood of membership in an HIV transmission cluster, and decreased HIV testing. We propose to explore mechanisms, specifically neurocognitive impacts of heavy cannabis use, linking heavy cannabis use to HIV prevention outcomes, and whether motivations for cannabis use, amidst a changing cannabis regulatory, social acceptance and legal landscape, modify its effects on HIV prevention. In the proposed study, we will rigorously examine links between heavy cannabis use, neurocognition, sex behavior and PrEP care engagement. First, we will elucidate the effects of cannabis use on neurocognition – specifically, brain systems supporting risk/reward (RR) processing, as well as higher order organizational functions collectively referred to as executive function (EF) in YBSMM. Second, we will explore how cannabis use, directly and via neurocognitive impacts, is associated with HIV prevention, and particularly PrEP care engagement (primary outcome). The proposed study will integrate and expand these lines of research within the context of traditional health department and CDC supported HIV prevention programs that engage YBSMM in the South Side of Chicago and adjacent suburbs, home to the largest contiguous majority Black population in the US. We will use rigorous objective measures to assess cannabis use (e.g., quantification of cannabis metabolites in plasma), neurocognition (e.g., neuroimaging) and PrEP outcomes (e.g., EMR measured persistence), and triangulate that data using validated survey measures. We will also rigorously account for other substance use, as a proportion of YBSMM who use cannabis also use other substances (e.g., alcohol), and there is increasing recognition of the need to study substance use as it occurs in real-world settings, including polysubstance use. We will assess these factors longitudinally over 1.5 years (3 times 9 months apart) in a cohort of 280 YBSMM, to permit examination of within-individual biological changes and the dynamic nature of cannabis use and its association with prevention care outcomes. We aim to: 1) Determine cross-sectional and longitudinal associations between cannabis use and neurocognition (i.e., neural response to risk/reward processing and executive function) in a cohort of YBSMM; 2) Evaluate overall, direct and indirect (via neurocognition) associations between cannabis use and PrEP care (e.g., persistence [primary]) and HIV transmission behaviors (e.g., group sex [secondary]); and 3) Determine whether motivations for cannabis use modify associations between cannabis use and HIV prevention outcomes. Identifying neurocognitive mechanisms through w...