The Frontal Lobe Outcomes and Well-being (FLOW) Study: Cannabis Effects on Neurocognition and HIV-related outcomes (Preprint)

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BACKGROUND Heavy cannabis use may impact neurocognitive functions, particularly prefrontal and limbic systems responsible for risk/reward processing and executive function, which are essential for certain health behaviors, such as human immunodeficiency virus (HIV) prevention. Rigorous research into the effect of cannabis on neurocognitive functions remains limited, particularly among populations with a heavy burden of HIV. OBJECTIVE Evaluate associations between cannabis use and neurocognition; (2) Evaluate associations between cannabis use and engagement in HIV status-neutral care outcomes (e.g., PrEP persistence, viral suppression); and (3) Assess whether cannabis use motivations modify associations between cannabis use and engagement in HIV status-neutral care outcomes. METHODS This longitudinal cohort study is enrolling a community-based sample of individuals ages 16-29 residing in Chicago using multiple recruitment strategies. Participants complete 3 in-person assessments annually over 2 years that include: (1) computer-assisted questionnaires, (2) neurocognitive assessments (fMRI, executive function tasks), and (3) biospecimen collection. Triangulation approaches combine objective and self-reported measures. RESULTS Building on pilot findings, we expect to identify distinctive neural and behavioral signatures among individuals who use cannabis heavily. Behaviorally, we anticipate heavy users will demonstrate initial risk-taking tendencies but retain capacity for adaptive learning. Neuroimaging analyses are expected to reveal enhanced ventral striatum activation during reward feedback, consistent with heightened reward sensitivity, and decreased hippocampal activation during safe decision-making, suggesting altered memory processing during risk assessment. These patterns may explain difficulties in treatment-seeking behaviors and engagement with HIV prevention while also indicating preserved learning capacity relevant for intervention design. CONCLUSIONS This study addresses critical knowledge gaps by examining potential associations between cannabis use, neurocognition, and HIV. While geographic specificity, structural barriers, measurement challenges, and sample size constraints present some limitations, our methodological approaches — including longitudinal design, triangulation of both objective and self-reported measures, and rigorous neurocognitive assessments — strengthen the investigation. Findings will advance understanding of how cannabis use impacts neurocognition and HIV-related health behaviors, potentially informing targeted interventions that address both substance use and HIV transmission.

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