# Implications of cannabis use and cumulative adversity exposure for brain structure and function in young adults living with HIV.

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $637,391

## Abstract

Antiretroviral therapy (ART) has lessened but not eliminated the central nervous system (CNS) impact of
human immunodeficiency virus (HIV). With effects on cognition and brain integrity now subtler, yet chronic with
unknown long-term implications, the potential of comorbid conditions to moderate, obscure or ameliorate HIV
effects is increasingly important. Young adults (“youth”) have high rates of both new HIV infection and
understudied common comorbidities with significant potential to influence HIV’s CNS presentation: cannabis
use and cumulative adversity. Both may alter immune functioning and inflammation as pathways for their
influence on HIV’s CNS effects, in addition to their independent impact. Our preliminary data show that worse
cognitive and neuroimaging outcomes in youth with HIV (YWH) compared to controls (e.g., worse memory and
executive functioning, thinner prefrontal cortex, altered functional activation using magnetoencephalography
[MEG]) are attenuated or, in some cases, reversed by light to moderate, but not heavy, cannabis use. We
hypothesize that worse cognitive and neuroimaging outcomes in treated YWH, compared to controls, in the
context of no cannabis use will be ameliorated by mild to moderate cannabis use, while high cannabis use
frequency will be associated with worse outcomes in both groups. Of importance, fully understanding the
interplay of HIV and cannabis may require consideration of lifetime experiences of adversity. Strong evidence
shows that exposure to adverse circumstances, such as maltreatment, violence, and stress, can alter immune
and CNS systems, and such exposure is common among YWH and comparable seronegative risk groups. We
will assess the influence of cumulative adversity in mediating effects of cannabis and HIV. The proposed study
will determine the interactive effects of HIV, cannabis and cumulative adversity on CNS structure and function
in 75 YWH (age 18-24) and 75 comparable controls. We will use innovative neuroimaging approaches (MEG to
measure functional activity and advanced diffusion approaches), along with brain structure and metabolism
and neurocognitive assessment. We will examine mediation of HIV, cannabis and cumulative adversity
interactions by inflammation and immune activation, assessed using plasma biomarkers. Examining the
interplay of these influences on CNS function and structure will be facilitated by careful characterization of
substance use, assessment of cumulative adversity burden rather than single traumatic events, and advanced
statistical techniques. Thus, we will examine interactive HIV and cannabis effects on key brain systems; model
underlying mechanisms; and examine an important yet understudied influence, cumulative adversity. The
study has potential for high impact by improving detection of HIV’s CNS effects and our understanding of
pathogenesis. It would enable better prevention of CNS decline, institution of CNS-targeted treatments and
cure strategies, and in genera...

## Key facts

- **NIH application ID:** 10598488
- **Project number:** 5R01DA047906-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** CHRISTINE FENNEMA-NOTESTINE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $637,391
- **Award type:** 5
- **Project period:** 2019-07-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10598488

## Citation

> US National Institutes of Health, RePORTER application 10598488, Implications of cannabis use and cumulative adversity exposure for brain structure and function in young adults living with HIV. (5R01DA047906-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10598488. Licensed CC0.

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