Isabella Matthews

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.

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.

Background: Black cisgender gay, bisexual, and other sexual minority men (SMM) and transgender women (TW) continue to be heavily affected by HIV. Further research is needed to better understand HIV prevention and care outcomes in this population. In particular, there is a need for research examining the impact of substance use and sleep health on HIV prevention and treatment outcomes among Black SMM and TW. Objective: This paper outlines the study methods being used in the recently launched follow-up study to the Neighborhoods and Networks (N2) study, which we refer to as N2 Part 2 (N2P2). N2P2 aims to address this gap in the literature, build off the findings of the original N2 study, and identify socioenvironmental determinants of health, including whether neighborhood and network factors mediate and moderate these relationships. Methods: Building on the N2 cohort study in Chicago from 2018 to 2022, N2P2 used a prospective longitudinal cohort design and an observational-implementation hybrid approach. With sustained high levels of community engagement, we aim to recruit a new sample of 600 Black SMM and TW participants residing in the Chicago metropolitan statistical area. Participants are asked to participate in 3 study visits across an 18-month study period (1 visit every 9 months). Four different forms of data are collected per wave: (1) an in-person survey, (2) biological specimen collection, (3) a daily remote ecological momentary assessment for 14 days after each study visit, and (4) data from electronic health records. These forms of data collection continue to assess neighborhood and network factors and specifically explore substance use, sleep, immune function, obesity, and the implementation of potential interventions that address relevant constructs (eg, alcohol use and pre-exposure prophylaxis adherence). Results: The N2P2 study was funded in August 2021 by the National Institute of Drug Abuse (R01DA054553 and R21DA053156) and National Heart, Lung, and Blood Institute (R01HL160325). This study was launched in November 2022. Recruitment and enrollment for the first wave of data collection are currently ongoing. Conclusions: The N2P2 study is applying innovative methods to comprehensively explore the impacts of substance use and sleep health on HIV-related outcomes among an HIV status–neutral cohort of Black SMM and TW in Chicago. This study is applying an observational-implementation hybrid design to help us achieve findings that support rapid translation, a critical priority among populations such as Black SMM and TW that experience long-standing inequities with regard to HIV and other health-related outcomes. N2P2 will directly build off the findings that have resulted from the original N2 study among Black SMM and TW in Chicago. These findings provide a better understanding of multilevel (eg, individual, network, and neighborhood) factors that contribute to HIV-related outcomes and viral suppression among Black SMM and TW. International Registered Report Identifier (IRRID): DERR1-10.2196/48548