PROJECT SUMMARY/ ABSTRACT Polysubstance use, defined as the use of multiple substances within a specified period, increases the risk for adverse events, including fatal overdose. This is reflected in the ongoing ‘fourth wave’ of the opioid overdose epidemic, marked by an increase in stimulant-involved overdoses. Drivers of polysubstance use within social networks remain poorly understood, yet understanding them is needed to prevent potential downstream adverse effects of substance use (e.g., substance use disorder, overdose). Sexually minoritized men have an elevated prevalence of substance use, including polysubstance use, and substance use disorders, and are also overburdened by new HIV infections. Further, sexually minoritized men are at greater risk of experiencing loneliness. I hypothesize that loneliness is a potential driver of substance use outcomes and HIV transmission. A distinct construct from depression and social isolation, loneliness is defined as a subjective discrepancy between actual and desired social connections. Loneliness is a well-described risk factor for poor health, including mortality; qualitative research suggests an association between loneliness and non-fatal overdose, but this has not yet been robustly studied. The overarching goals of this R36 proposal, Dissecting the role of loneliness on substance use- and HIV-related outcomes among sexual minority men in the United States and Canada, are to delineate the impact of loneliness on substance use (i.e., drug, alcohol, and polysubstance use) and non-fatal overdose; and to assess the relationship between loneliness and HIV-related outcomes (i.e., HIV prevention, HIV risk). Aim 1 of this proposal will examine the relationship between loneliness, substance use (drug, alcohol, and polysubstance use), and HIV prevention (antiretroviral adherence among people with HIV and PrEP use among people without HIV) within a cohort of sexually minoritized men and gender-expansive groups in Chicago, Illinois. I will conduct exploratory social network analyses to examine further substance use within social networks and how loneliness moderates this relationship. Leveraging a unique data linkage between survey and administrative health data, Aim 2 of this proposal will examine the relationship between loneliness, non-fatal overdose, and HIV risk in Vancouver, Canada. This project will advance NIDA’s research priority to support dissertation research examining social factors that influence drug use outcomes and the intersection of HIV and drug use. This proposal additionally addresses NIDA’s noted interest in loneliness as a potential leverage point for substance use prevention. Findings from this R36 study will help identify individuals at risk for substance use, inform policies seeking to prevent HIV transmission and inform a future F32 and K01 award application. The proposed project and mentorship team will allow the Principal Investigator to develop expertise at the intersection of HI...