Low-Dose THC May Enhance Tolerance of HIV Treatment, Animal Study Suggests

Recent preclinical research from the Texas Biomedical Research Institute has explored the impact of low-dose tetrahydrocannabinol (THC) on the effectiveness and side effects of antiretroviral therapy (ART) in the context of HIV infection. The findings, published in the journal Science Advances, provide new insights into potential strategies for improving the tolerability of HIV treatment regimens.

The study involved two groups of rhesus macaques, each comprising eight animals infected with the simian immunodeficiency virus (SIV), a close equivalent to human HIV in primates. Both groups received a standard ART protocol consisting of tenofovir, emtricitabine, and dolutegravir administered via subcutaneous injection. One group was additionally treated with low-dose THC twice daily, starting at 0.18 mg/kg and gradually increasing to 0.32 mg/kg over a period of six months following SIV infection. The other group received a placebo.

After five months of treatment, both groups achieved undetectable viral loads, indicating successful viral suppression by ART. However, notable differences emerged in several biological parameters among the THC-treated animals. The researchers observed lower serum concentrations of antiretroviral drugs in the THC group, which may indicate that THC accelerates the metabolism of these medications. This process could potentially reduce the liver toxicity associated with long-term ART use.

Additionally, the animals receiving THC exhibited elevated serotonin levels. Serotonin, a neurotransmitter involved in mood regulation, sleep, and gastrointestinal function, appeared to increase through several mechanisms. The THC group showed a higher number of enterochromaffin cells in the gut, which are responsible for producing serotonin. There was also a notable increase in the abundance of Lactiplantibacillus plantarum, a beneficial gut bacterium, and upregulation of serotonin receptors, facilitating enhanced communication along the gut-brain axis via the vagus nerve.

The gut microbiome of the THC-treated group was more balanced and contained higher levels of beneficial bacteria such as Oscillibacter, a genus associated with cholesterol regulation. Oscillibacter can convert cholesterol into coprostanol, a process thought to contribute to improved lipid profiles and cardiovascular health.

Further findings indicated that THC increased levels of beta-hydroxybutyrate (BHB), a molecule involved in fat metabolism, through activation of the cannabinoid-1 receptor (CBR1). This increase suggests enhanced oxidation of secondary bile acids, which may positively affect metabolic and cardiovascular outcomes. Moreover, THC administration appeared to normalize levels of long-chain acylcholines, which are typically elevated by ART and SIV infection and are linked to inflammation and heart toxicity.

The researchers emphasize that these results are preliminary and derived from animal models. Further studies are required to determine whether similar effects would be observed in humans, especially when both ART and THC are administered orally. The potential benefits of low-dose THC as a supportive therapy in HIV treatment could also have wider implications for conditions related to intestinal inflammation, such as irritable bowel syndrome, chronic liver diseases, and neurodegenerative disorders like Alzheimer's and Parkinson's disease.

As the scientific community continues to investigate adjunct therapies for chronic viral infections, these findings open new avenues for research into the role of cannabinoids in enhancing treatment outcomes and reducing adverse effects associated with long-term medication use.