Low-Dose THC Improved Gut Health and Reduced Inflammation in HIV-Positive Monkeys on Treatment | Research

The takeaway

Long-term low-dose THC in SIV-infected macaques on antiretroviral therapy increased serotonin, improved cholesterol metabolism, and reduced inflammatory markers while maintaining viral suppression.

HIV researchers, infectious disease physicians, scientists studying cannabinoid-immune interactions.

Viral suppression maintained with reduced ART levels

What the researchers found

In SIV-infected rhesus macaques on ART, long-term low-dose THC significantly increased plasma and gut serotonin and indole-3-propionate (enhancing gut-brain communication), enriched cholesterol-metabolizing bacteria (Oscillibacter), reduced plasma cholesterol and toxic secondary bile acids, increased beta-hydroxybutyrate (suggesting improved fatty acid metabolism), and restored inflammatory acylcholines to pre-infection levels. THC-treated animals maintained viral suppression despite reduced plasma ART levels.

Why it matters

Despite effective ART, people with HIV face persistent inflammation and metabolic problems that increase risk for heart disease and other conditions. This Science Advances study provides detailed mechanistic evidence that THC supplementation could address multiple pathways of chronic inflammation and metabolic dysfunction simultaneously.

The numbers in context

THC increased plasma/jejunum serotonin and indole-3-propionate. Enriched Oscillibacter (cholesterol-metabolizing). Reduced plasma cholesterol and secondary bile acids. Increased beta-hydroxybutyrate via CBR1. Restored acylcholines to pre-infection levels. Viral suppression maintained with reduced ART levels.

How the study worked

SIV-infected rhesus macaques receiving ART were supplemented with long-term low-dose THC. Researchers measured plasma and tissue serotonin, gut microbiome composition, cholesterol and bile acid profiles, beta-hydroxybutyrate levels, and acylcholine concentrations. Mechanistic pathways were identified through receptor-specific analyses (CBR1 and CBR2 mediated). Published in Science Advances.

What this study cannot tell us

Non-human primate model; results need human validation. Small sample typical of primate studies. Specific THC dosing in macaques may not translate directly to human dosing. Long-term safety of combined THC+ART not fully characterized. Cannot determine if benefits persist after THC cessation.

How to read the evidence

Preliminary: rigorous primate study published in a top journal with clear mechanisms, but not yet replicated in humans.

When this study was published

2025 study

The bigger picture

This study provides perhaps the most comprehensive mechanistic picture of how cannabinoids could benefit people with HIV. The simultaneous improvements across gut health, cholesterol metabolism, inflammation, and serotonin signaling suggest THC acts on multiple interconnected pathways, and the maintained viral suppression despite lower ART levels hints at potential drug interaction benefits.

Questions still open

Could THC supplementation allow ART dose reduction in humans while maintaining viral suppression? Would the metabolic benefits translate to reduced cardiovascular events in people with HIV? What is the optimal THC dose for therapeutic benefit without psychoactive impairment?

Common questions

Could THC help people with HIV on medication?

In monkeys, low-dose THC improved multiple markers of inflammation and metabolic health while maintaining HIV suppression. Human trials would be needed to confirm these benefits, but the mechanistic evidence is promising.

Did THC interfere with HIV treatment?

No. In fact, THC-treated monkeys maintained viral suppression even though their ART drug levels were lower, suggesting THC may complement rather than interfere with antiretroviral therapy.

Read the original research

Supplementing HIV-ART with cannabinoids increases serotonin, BHB, and Ahr signaling while reducing secondary bile acids and acylcholines.

Science advances, 11(36), eadw4021

View on PubMed ↗Publisher’s paper ↗

Citation

Premadasa, Lakmini S; Romero, Luis; Mohan, Mahesh. (2025). Supplementing HIV-ART with cannabinoids increases serotonin, BHB, and Ahr signaling while reducing secondary bile acids and acylcholines.. Science advances, 11(36), eadw4021. https://doi.org/10.1126/sciadv.adw4021