# Cannabis and Pathogenic Mechanisms influencing Blood Brain Barrier Function in HIV

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $1,242,683

## Abstract

People with HIV (PWH) remain vulnerable to central nervous system complications (e.g., neurocognitive
impairment) despite antiretroviral therapy (ART) that suppresses viral replication. While many etiologies of these
complications exist, damage to the blood-brain-barrier (BBB), inflammation, and mitochondrial dysfunction are
consistently implicated, yet seldom studied simultaneously. PWH also use cannabis more frequently than the
general population and recent evidence by our group and others indicates that cannabis may protect PWH from
BBB damage by reducing inflammation and promoting mitochondrial homeostasis. The proposed
multidisciplinary, translational project will combine a clinical observational study with two preclinical models: a)
a technologically advanced brain chip model for BBB and b) personalized ex vivo/in vitro modeling of
mitochondrial toxicity in BBB cells to determine the effects of cannabis use on the BBB in PWH. Using this
multilevel approach, we will test the hypothesis that cannabis effects on the BBB vary based on patterns of use:
moderate use will be associated with beneficial effects, due to the anti-inflammatory properties of cannabis, but
chronic daily use will have detrimental effects. In a cohort of PWH and people without HIV (PWoH) across a
range of cannabis use from naïve to daily users, we will measure in plasma and cerebrospinal fluid (CSF) a
panel of biomarkers that reflect the BBB, inflammation, and mitochondrial dysfunction. These readouts will be
correlated with advanced permeability and multicompartment diffusion magnetic resonance imaging that will
identify global and regional variations in BBB leakage along with neuronal and glial microstructural properties
(Aim 1). We will model the BBB using 3D microfluidic cultures of brain endothelial and parenchymal cell subsets
to measure the effects of HIV and cannabinoids on BBB permeability, inflammatory gene expression, and
markers of mitochondrial function (Aim 2). Because responses to HIV and cannabis are often specific to
individuals or groups of individuals, we will use monocyte-derived macrophages and sera from the PWH and
PWoH in the observational study to determine the effects of cannabis (and HIV) on BBB cellular components
(astrocytes and endothelial cells), and on mitochondrial function, inflammatory gene expression, and BBB
biomarker gene expression (Aim 3). Thus, the proposed project will provide innovative clinical readouts in a
unique cohort alongside state-of-the-art modeling of the BBB and personalized investigation of pathogenic
mechanisms. This highly innovative, multidisciplinary research proposal is very likely to generate impactful
translational knowledge regarding mechanisms of pathogenesis and guide future therapeutic interventions. With
our combined clinical and pre-clinical expertise in HIV infection, substance abuse, BBB biology and imaging, and
mitochondrial homeostasis, we are uniquely suited to perform the proposed research.

## Key facts

- **NIH application ID:** 10683027
- **Project number:** 1R01DA058405-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Jerel Adam Fields
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1,242,683
- **Award type:** 1
- **Project period:** 2023-08-15 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10683027

## Citation

> US National Institutes of Health, RePORTER application 10683027, Cannabis and Pathogenic Mechanisms influencing Blood Brain Barrier Function in HIV (1R01DA058405-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10683027. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*