# Cannabis use frequency and its impact on monocyte-mediated inflammation in HIV patients

> **NIH NIH R01** · MICHIGAN STATE UNIVERSITY · 2024 · $514,512

## Abstract

PROJECT SUMMARY/ABSTRACT
An estimated 37 million people worldwide are infected with human immunodeficiency virus (HIV). Combined
antiretroviral therapy (ART) has turned HIV into a chronic infection with significantly longer life expectancy.
New health issues have surfaced as HIV patients live longer. Specifically, 50% of HIV-infected (HIV+)
individuals exhibit neurocognitive impairment, termed HIV-associated neurocognitive disorder (HAND). A key
event leading to HAND is persistent low-level chronic inflammation resulting in neuronal damage and cell
death. A major contributor to HIV-induced neuroinflammation is activated monocytes, which are significantly
elevated in patients’ with HIV-associated dementia (HAD). A hallmark of HIV infection is chronic, systemic
inflammation in part through translocation of microbial derived products from the gut which, activates
monocytes and promote migration across the blood-brain barrier (BBB). Upon entry, activated monocytes
release neurotoxic and proinflammatory factors (e.g., IL-1), which are thought to contribute to HAND.
Recently, evidence has emerged implicating the importance of inflammasome activation as a contributing
mechanism to neuroinflammation and HAND. Preliminary results presented in this application show that
inflammasome activation in monocytes, as evidenced by IL-1 secretion, promotes astroglial cell inflammation.
These findings support a critical role for inflammasome activation in monocytes as a mechanism driving
neuroinflammation. In particular, immunohistocytochemistry of brain tissue from post-mortem HIV patients with
HAD showed significant infiltration of proinflammatory CD16+ monocytes. By contrast, cannabinoid exposure
displays anti-inflammatory properties in HIV-infected patients, which we and others have reported. The anti-
inflammatory properties of cannabis are attributed largely to the canonical ligand, ∆9-tetrahydrocannabinol
(THC), which exerts psychotropic activity through cannabinoid receptor (CB) 1 and the non-psychotropic-
mediating CB2, while cannabidiol (CBD) does not act through CB1/CB2. Likewise, the CB2 selective agonist,
JWH-015, represents a potential strategy for understanding the role of CB2 in limiting HIV-associated
neuroinflammation. In fact, preliminary results demonstrate that a CB2 selective agonist impairs monocyte
secretion of IL-1, a hallmark of inflammation and inflammasome activation. Mechanistic studies are proposed
to test the hypothesis: CD16+ monocytes from non-cannabis using HIV+ subjects exhibit greater
inflammasome formation and subsequent astrocyte activation compared to cannabis using HIV+ subjects,
which is associated with the frequency of cannabis use.

## Key facts

- **NIH application ID:** 10875505
- **Project number:** 5R01DA053047-04
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Norbert E Kaminski
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $514,512
- **Award type:** 5
- **Project period:** 2021-09-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10875505

## Citation

> US National Institutes of Health, RePORTER application 10875505, Cannabis use frequency and its impact on monocyte-mediated inflammation in HIV patients (5R01DA053047-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10875505. Licensed CC0.

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