# Mechanism of Cannabidiol Effects on HIV Expression, Neuroinflammation, and HIV Cognitive Disease in Chronically-infected Immunocompetent Mice

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $720,231

## Abstract

This application is submitted in response to RFA-DA-20-022 and proposes basic
research
non-psychoactive
commonly experienced by PLWH. However, its long-term HIV infection and progression of HIV
disease remain largely undetermined. Our preliminary results in mice infected by chimeric HIV, EcoHIV, show
that CBD has both anti-inflammatory and immunosuppressive functions in the brain; strikingly the canonical
innate antiviral effector, interferon (IFN)-, was reduced in brains of infected CBD treated mice. Directly
relevant to this RFA, we show that CBD increases HIV expression in mouse brain up to 10-fold. Moreover,
despite anti-inflammatory effects of CBD alone, the drug failed to mitigate HIV mediated inflammatory gene
expression. These results suggest that CBD use can increase HIV expression in PLWH and thereby
exacerbate HIV-related diseases including NCI. We hypothesize that increased HIV brain infection by CBD
results from its impairment of antiviral immunity including IFN functions. The Specific Aims are to: 1)
Optimize CBD mediated increase in EcoHIV brain infection and assay its consequences in mouse behavioral
tests including responses in the presence of antiretroviral drugs and during chronic infection, tests of CB
receptor participation using knockout mice, and pilot HIV burden/ expression studies from brains of deceased
PLWH using cannabis. 2) Determine beneficial or deleterious effects of CBD on HIV control by immunity in
brains of EcoHIV-infected mice including assay of antigen-specific responses ex vivo, innate responses in vivo
and ex vivo, and gene expression profiling of brain lymphocyte, macrophage and microglia by single cell RNA-
seq and bioinformatics. 3) Using information from Aim 2, test the hypothesis that CBD increases HIV
expression in the brain and NCI by disruption of IFN responses including assay of post-transcriptional
modification in IFN induction, epigenetic modification in promoters of IFN stimulated genes, and IFN specificity
using knockout mice. Our approaches will include combined CBD and antiretroviral treatment of EcoHIV-
infected mice, QPCR for measurement of virus burden in tissues, behavioral tests of learning, isolation and
functional evaluation of mononuclear cells from the brain, brain cell lineage specific RNA seq, mechanistic
studies of CBD effects upon IFN signaling pathways and epigenetic changes determining IFN responsive gene
expression, key receptor knockout mice for responses to EcoHIV/CBD, and curated brain tissue from NNTC of
HIV-infected persons using cannabis and no other drugs of abuse. This application meets the RFA
requirements of “research models of chronic/persistent HIV-induced inflammation under conditions of ART”; for
evaluation of “the role of cannabinoids in HIV-associated chronic inflammation”; and to “Delineate ….. beneficial
or deleterious effects of cannabinoid use on HIV-induced inflammation”.
science and preclinical
in EcoHIV-infected mice to model cannabidiol (CBD) effects in...

## Key facts

- **NIH application ID:** 10448403
- **Project number:** 5R01DA052844-03
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Alejandra Borjabad
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $720,231
- **Award type:** 5
- **Project period:** 2020-09-30 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10448403

## Citation

> US National Institutes of Health, RePORTER application 10448403, Mechanism of Cannabidiol Effects on HIV Expression, Neuroinflammation, and HIV Cognitive Disease in Chronically-infected Immunocompetent Mice (5R01DA052844-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10448403. Licensed CC0.

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