Cannabis Use Changed Inflammatory Gene Activity in Immune Cells From People Living With HIV | Research

The takeaway

In people living with HIV, cannabis use was associated with lower inflammatory gene expression in immune cells, and CBD treatment reduced a key inflammasome marker — but some downstream effects were unexpectedly complex.

HIV researchers, immunologists, and people living with HIV interested in how cannabis affects their immune system.

What the researchers found

HIV-positive individuals' macrophages showed 83% higher NLRP3 inflammasome expression than HIV-negative controls. Moderate cannabis users had 61% less IL-1β expression than non-users. CBD treatment reduced NLRP3 expression by 22% in IL-1β-stimulated cells. However, combined CBD + IL-1β treatment unexpectedly increased some downstream cytokine gene expression (3-fold for IL-1β, 2-fold for IL-18).

Why it matters

Chronic inflammation is a major driver of cognitive decline in people living with HIV despite effective antiretroviral therapy. This study provides molecular evidence that cannabis use and CBD may modulate a specific inflammatory pathway (NLRP3) in HIV, offering potential therapeutic insight.

The numbers in context

43 PWH, 22 PWoH. NLRP3 expression 83% higher in PWH. Moderate cannabis users: 61% less IL-1β vs naïve. Daily users: 64% increase in IL-18 vs moderate. CBD + IL-1β: 22% decrease in NLRP3, but 3-fold increase in IL-1β mRNA and 2-fold increase in IL-18 mRNA.

How the study worked

Cross-sectional study of monocyte-derived macrophages from 43 people with HIV and 22 without HIV. Participants categorized by cannabis use (naïve, moderate, daily). Cells treated with CBD (30 μM), IL-1β (20 ng/mL), or both. NLRP3-related gene expression measured. Clinical correlations assessed.

What this study cannot tell us

Cross-sectional — cannot determine causation. In vitro CBD treatment may not reflect in vivo effects. Cannabis use was self-reported and products varied. Small sample. Unexpected downstream effects complicate interpretation.

How to read the evidence

Cross-sectional study with in vitro mechanistic component, providing molecular insight but limited by small sample and observational design.

When this study was published

Published 2025.

The bigger picture

The NLRP3 inflammasome is implicated in numerous inflammatory diseases beyond HIV. Understanding how cannabinoids modulate this pathway could have broad therapeutic implications, though the unexpected increase in downstream cytokines highlights the complexity of cannabinoid-immune interactions.

Questions still open

Why does CBD reduce NLRP3 but increase downstream cytokine gene expression? Does the moderate cannabis use 'sweet spot' for inflammation reflect dose-dependent effects? Could targeting the NLRP3 inflammasome with cannabinoids improve cognitive outcomes in HIV?

Common questions

Does cannabis help with HIV-related inflammation?

This study found moderate cannabis users had lower inflammatory gene expression in their immune cells, and CBD reduced a key inflammasome marker. However, some effects were unexpectedly complex, so more research is needed before clinical recommendations.

Is moderate use better than daily use for inflammation?

In this study, moderate cannabis users showed the greatest reduction in inflammatory markers, while daily users showed some increases in IL-18. This could reflect dose-dependent effects, but the study design cannot confirm this.

Read the original research

Cannabis use is associated with alterations in NLRP3 inflammasome related gene expression in monocyte-derived macrophages from people living with HIV.

Frontiers in immunology, 16, 1634203

View on PubMed ↗Publisher’s paper ↗

Citation

Walter, Kyle C; Avalos, Bryant; Ford, Mary K; Laird, Anna E; Boustani, Ali; Spencer, Matthew; Shu, Leeann; Chaillon, Antoine; Crescini, Melanie; Cookson, Debralee; Ellis, Ronald J; Letendre, Scott L; Iudicello, Jennifer; Fields, Jerel Adam. (2025). Cannabis use is associated with alterations in NLRP3 inflammasome related gene expression in monocyte-derived macrophages from people living with HIV.. Frontiers in immunology, 16, 1634203. https://doi.org/10.3389/fimmu.2025.1634203