This is a basic human experimental study utilizing 4 groups of individuals with and without HIV and complex morbidities of cannabis use disorder and major depression who will participate in 2 sessions of the Yale Pain Stress Task (YPST) and follow-up phase to assess drug use and mood symptoms.

This study aims to address research gaps using a powerful and novel cross-diagnostic approach with multiple complementary approaches to examine the overarching hypothesis that PLWH+CM exhibit impaired stress-related HPA and HPA-immune function due to alterations in epigenetic mechanisms, and these stress-related HPA-immune and related epigenetic aberrations predict distress, craving and substance use symptoms underlying PLWH complex morbidities. This hypothesis will be tested using a combined human experimental stress challenge approach with prospective longitudinal assessment of daily distress, and substance use symptoms as well as assessment of chronic stress (C-stress), social determinants of health (SDoH), and resilience in experimental cohorts of PLWH with and without CM and those without HIV with and without CM.