Tiny doses of THC show big benefits for HIV treatment

THC, short for tetrahydrocannabinol, is the primary active compound found in cannabis. In this preclinical research, scientists used extremely low doses that did not cause noticeable nervous system effects such as euphoria or a "high."

Researchers observed several potential benefits, including higher levels of serotonin and reductions in inflammation, cholesterol, and toxic secondary bile acids. One of the most striking findings was that levels of ART medications in the bloodstream were lower, even though viral suppression remained intact. Because ART drugs can strain the liver over time, this reduction may be especially meaningful. The study was conducted in animal models that closely reflect people living with HIV who are receiving ART, and the results were recently published in Science Advances.

Why Managing HIV Treatment Side Effects Matters

Modern ART is highly effective at suppressing HIV to undetectable levels. What was once a fatal diagnosis has become a manageable long-term condition. However, people living longer with HIV often face ongoing health challenges caused by both the virus and prolonged medication use.

"People living with HIV experience chronic inflammation, which leads to many co-morbidities such as cardiovascular disease, liver disease and some neurological diseases," said Professor Mahesh Mohan, DVM, Ph.D. "Our lab is interested in finding solutions to help address this."

This research builds on earlier work from Dr. Mohan's lab exploring the medical potential of low-dose THC, similar to FDA-approved THC medications used to treat seizures, chemotherapy-induced nausea and vomiting, and AIDS-related anorexia and weight loss.

Extensive Analysis Reveals No Negative Effects

Over a three-year period, Lakmini Premadasa, Ph.D., a Staff Scientist in Dr. Mohan's lab, examined hundreds of metabolites, which are small molecules essential for normal biological processes. Her goal was to determine whether daily low-dose THC, taken alongside ART, affected other systems throughout the body.

"There were no downsides," Dr. Premadasa said. "I kept looking because I couldn't believe it could all be good, but I really could not find any negative impacts."

Reduced Drug Toxicity Without Losing Viral Control

To conduct the study, researchers worked with two groups of rhesus macaques infected with simian immunodeficiency virus (SIV), the animal equivalent of HIV. Both groups received ART for five months, but only one group was also given low-dose THC. The other group received a placebo.

By the end of the study period, SIV levels were suppressed to undetectable levels in both groups. However, the similarities ended there. Animals that received THC had significantly lower concentrations of ART drugs circulating in their blood compared to those given ART alone.

"This was unexpected," Dr. Premadasa said. "This suggests that THC is helping to metabolize the antiretroviral drugs faster, which is actually much better to protect the liver from toxicity associated with some currently prescribed ART drugs."

Low-Dose THC and Gut-Brain Health

Another major discovery involved serotonin, a neurotransmitter that plays a key role in mood, sleep, and digestion. Levels of serotonin were substantially higher in the THC-treated group than in the control group.

The changes occurred across several stages of serotonin production, which largely takes place in the gut. Dr. Premadasa identified higher numbers of serotonin-producing enterochromaffin cells and increased levels of beneficial gut bacteria (L. plantarum) that support serotonin synthesis. She also found increased expression of serotonin receptors, which help transmit signals from the gut to the brain through the vagus nerve, strengthening communication along the gut-brain axis.

"This is an exciting finding that could be investigated further to address a range of conditions related to low serotonin levels, including depression, memory loss, brain fog and perhaps long-COVID symptoms," Dr. Mohan said. "Reduced serotonin levels are known to disrupt signaling between the gut and brain, so improving those serotonin levels and communication with low-dose cannabinoids could offer a new or complementary treatment approach."

Additional Benefits for Heart and Liver Health

The group receiving THC also showed a healthier and more balanced gut microbiome, with increased levels of beneficial bacteria known to help lower cholesterol. Researchers also observed reduced levels of secondary bile acids, which can be harmful at high concentrations and contribute to blockage of liver bile ducts (cholestasis), inflammation and scarring (cirrhosis) and end-stage liver disease.

Levels of metabolites involved in breaking down fatty acids were higher as well. These changes are linked to reduced buildup of artery-clogging plaque and improved cardiovascular health. In the THC-treated group, levels of plaque-forming fatty acids known as long-chain acetylcholines returned to levels seen before infection. In contrast, animals that received only ART continued to show elevated levels of these harmful fatty acids.

What Comes Next for This Research

Because the study was conducted in nonhuman primates, further research will be needed to determine whether the same effects occur in people. The findings may also be relevant for other conditions associated with gut inflammation, including irritable bowel syndrome, chronic liver disease, and neurodegenerative disorders such as Alzheimer's and Parkinson's diseases.

The research team is now examining cannabidiol, or CBD, a nonpsychoactive compound, when combined with THC and delivered orally or by injection alongside ART. Future studies will also explore additional cannabinoids and plant-based aromatic compounds known as terpenes. Researchers emphasize that commercially available cannabinoid products may not produce the same effects due to differences in dosage, formulation, and metabolism. Individuals should consult a healthcare provider before using any cannabinoid-based treatments.

Funding: National Institutes of Health award numbers R01DA042524 (M.M.) and R01DA052845 (M.M.), P30AI161943, P51OD011104 and P51OD111033.