# Pathogenesis of Neuroinflammation and Neurocognitive Impairment In HIV-infected Young Adult Cannabis Users

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $781,208

## Abstract

Project Summary
 HIV-associated neurocognitive disorders (HAND) and neurocognitive impairment (NCI) remain long-term
complications of HIV infection despite effective antiretroviral therapy (ART). Even in early HIV infection and in
young adults who comprise 37% of new HIV infections, HAND impacts daily functioning and increases
morbidity. This impact of HAND in the young will impact the productivity of the work force worldwide. Currently,
our mechanistic insight into HAND pathogenesis in people living with HIV (PLWH) remains limited, and no
validated biomarkers exist to diagnose and manage NCI. HAND is believed to result from sustained
neuroinflammation. Unfortunately, growing evidence suggests inflammation is modulated by drugs of abuse,
including the drug of choice among young adults with HIV: marijuana. Marijuana's immunomodulatory effects
are largely anti-inflammatory, including suppression of T cell function and monocyte activation, the latter of
which is pivotal to HAND immunopathogenesis. This proposal leverages an existing multi-institutional
infrastructure focused on drugs of abuse in adult and adolescent HIV+ patients. Data from our group has found
that 1) THC treatment reduces monocyte activation; 2) compared to unimpaired, impaired patients have
increased CSF markers of neuronal injury (neurofilament (NFL), and 3) single cell RNA sequencing (scRNA-
seq) of cerebrospinal fluid (CSF) from HIV-infected subjects reveals differentiated myeloid cells expressing
damage-associated microglia (DAM) genes (APOE and TREM2) and other markers of monocyte activation.
 This proposal will investigate the role of marijuana in modulating neuroinflammation and HAND and identify
a set of candidate biomarkers with potential to perform in the immunomodulatory context of substance abuse.
An ideal candidate biomarker is one that can perform in the context of HIV driven inflammation and
immunomodulation by drugs of abuse. This proposal will be the first to perform comprehensive, multi-domain
immune and transcriptomic profiling to investigate the effects of marijuana on systemic and neuroinflammation,
and its impact on cognition in young people living with HIV (YLWH). Within four groups (NCI-/MJ-, NCI+/MJ-,
NCI-/MJ+, NCI+/MJ+) we will 1) quantify differences in CNS and peripheral inflammatory biomarkers and
markers of neuronal injury; 2) evaluate the potential anti-inflammatory and neuroprotective impact of marijuana
use; 3) determine the impact of marijuana on the cerebrospinal fluid (CSF) cellular transcriptome via single cell
RNA sequencing (scRNA-seq) to identify inflammatory pathways for future interventions; and 4) using novel
PET/MR techniques, quantify microglial activation and neuroinflammation and synaptic density via radiotracers
(peripheral benzodiazepine receptor (PBR)111 and UCB-J, respectively). Via these objectives, this proposal
will provided needed insight into HAND pathogenesis in the context of drug use. From an increased
understanding of its...

## Key facts

- **NIH application ID:** 9944479
- **Project number:** 5R01DA048627-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** DAVID MARTIN MURDOCH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $781,208
- **Award type:** 5
- **Project period:** 2019-06-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9944479

## Citation

> US National Institutes of Health, RePORTER application 9944479, Pathogenesis of Neuroinflammation and Neurocognitive Impairment In HIV-infected Young Adult Cannabis Users (5R01DA048627-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9944479. Licensed CC0.

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