New research in animal models indicates that consistent, low doses of tetrahydrocannabinol (THC) can counteract many of the harmful side effects associated with long-term HIV treatment. The study found that the principal active compound in cannabis helped to reduce chronic inflammation, lower cholesterol, and improve gut health without interfering with the effectiveness of the primary antiretroviral therapy and without causing psychoactive effects.
While modern antiretroviral therapy, or ART, has transformed HIV into a manageable condition by suppressing the virus to undetectable levels, the lifelong medication regimen often comes with significant costs to patient health. People living with HIV frequently suffer from chronic inflammation, which can lead to a higher risk of cardiovascular and liver disease, as well as neurological issues. This preclinical study, published in the journal Science Advances, explores a novel approach to address these comorbidities, aiming to improve the quality of life for millions of people on long-term ART.
Investigating Therapeutic THC in a Preclinical Model
The research was conducted by scientists at the Texas Biomedical Research Institute, who sought to understand how a low-dose THC regimen could benefit individuals undergoing ART. To do this, they utilized an established animal model that closely represents the condition of humans living with HIV and receiving daily antiretroviral drugs. Over the course of the multi-year study, researchers administered a daily dose of THC that was small enough to avoid inducing a “high” or other overt nervous system effects. This approach mirrors the therapeutic use of FDA-approved THC medications prescribed for conditions like chemotherapy-induced nausea and AIDS-related anorexia.
Professor Mahesh Mohan, of the Texas Biomedical Research Institute, noted that his lab is focused on finding solutions to help with the substantial side effects experienced by people living longer with HIV. During the study, lead scientist Dr. Lakmini Premadasa analyzed hundreds of small molecules called metabolites to build a detailed picture of how the low-dose THC treatment affected the body when given alongside ART. This comprehensive analysis allowed the team to pinpoint specific biological changes related to inflammation, metabolism, and organ health.
Significant Reduction in Harmful Biomarkers
One of the most significant outcomes of the study was the positive change in several key health indicators. The group receiving THC showed marked reductions in overall inflammation, a primary driver of long-term health problems in people with HIV. Furthermore, the treatment led to lower levels of cholesterol and a decrease in harmful secondary bile acids, which are linked to liver damage.
Notably, the researchers observed that the concentration of ART drugs in the blood plasma was lower in the THC-treated group. While a reduction in medication levels could be a cause for concern, in this case, it occurred without any loss of viral suppression. This finding is particularly promising because it suggests that low-dose THC could potentially reduce the toxic load of antiretroviral drugs on the liver over many years of treatment, mitigating a major source of long-term damage without compromising the therapy’s primary goal of keeping the virus in check.
A Boost to Gut Health and Serotonin Production
The study also uncovered a profound and unexpected benefit related to the gut-brain axis, the complex communication network linking the digestive system and the central nervous system. The research team found that serotonin, a critical neurotransmitter responsible for regulating mood, sleep, and digestion, was significantly higher in the group that received THC compared to the control group. This discovery points to a powerful mechanism through which THC may be improving overall well-being.
The Gut-Brain Communication Pathway
The increase in serotonin was not a minor fluctuation; the effect was observed across multiple aspects of its production pathway, which primarily occurs within the gut. The researchers identified a higher number of specialized enterochromaffin cells, which are the body’s main producers of serotonin, in the gut lining of the THC-treated models. This cellular increase suggests a direct and sustainable impact on the body’s ability to generate this vital chemical. The number of active serotonin receptors was also dramatically increased, enhancing communication between the gut and the brain.
Microbiome Modifications
Further analysis of the gut microbiome revealed another layer of the mechanism. The THC treatment appeared to foster a healthier gut environment, promoting the growth of beneficial bacteria. Specifically, the team found a greater abundance of L. plantarum, a species of good gut bacteria known to facilitate the production of serotonin. This shift in the microbiome composition contributed directly to the observed increase in available serotonin, highlighting the interconnectedness of gut bacteria, neurochemical production, and systemic health.
Future Directions and Clinical Potential
The findings from this preclinical study open up several promising avenues for future research and potential clinical applications. The strong link between low-dose THC, gut health, and serotonin production suggests that this therapy could be investigated for a range of conditions far beyond the side effects of HIV treatment. Dr. Mohan stated that the results could be explored to address health issues related to low serotonin levels, including depression, memory loss, and brain fog.
He also noted that these discoveries could even have relevance for treating symptoms of long-COVID, which often involve similar neurological and mood-related disruptions. Because diminished serotonin levels are known to interfere with gut-brain signaling, a therapeutic approach that safely improves this communication network could offer a complementary treatment for a wide variety of ailments. The next logical step would be to translate these findings into human clinical trials to confirm the safety and efficacy of using low-dose cannabinoids to improve the health of people living with HIV on long-term therapy.
