Cannabis Effects on Neurocognition and HIV-Related Outcomes: Protocol for a Longitudinal Observational Cohort Study

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Abstract
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 HIV prevention. Rigorous research into the effects of cannabis on neurocognitive functions remains limited, particularly among populations with a high burden of HIV. Objective: This study aims to (1) evaluate associations between cannabis use and neurocognition, (2) evaluate associations between cannabis use and engagement in HIV status–neutral care outcomes (eg, pre-exposure prophylaxis 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 aged 16 to 29 years 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 (functional magnetic resonance imaging, executive function tasks), and (3) biospecimen collection. Triangulation approaches combine objective and self-reported measures. Results: The Frontal Lobe Outcomes and Well-Being (FLOW) Study was funded by the National Institutes of Health in April 2023, with data collection commencing in October 2023. As of April 2026, 148 participants have been enrolled and completed baseline assessments, with 63 participants completing their first follow-up appointment and 4 participants completing their second follow-up appointment. Following a temporary administrative pause from March to August 2025 and subsequent federal review confirming regulatory compliance, the study resumed operations in July 2025. Recruitment is currently ongoing, with data collection expected to continue through June 2027. Preliminary analyses are pending completion of longitudinal data collection. 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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