Low-Dose Cannabinoids Show Potential to Restore Serotonin Levels and Reduce Inflammation in HIV, Study Finds

Emerging research suggests that low-dose cannabinoids may help reduce chronic inflammation and restore gut-derived serotonin levels in individuals living with human immunodeficiency virus (HIV), offering a possible new therapeutic pathway to address long-standing comorbidities associated with the condition.

Chronic immune activation is considered a hallmark of HIV, even in patients achieving viral suppression through antiretroviral therapy (ART), with persistent inflammation contributing to a wide array of complications, including cardiovascular, hepatic, and neurologic disorders.^1,2

In a novel study, scientists at the Texas Biomedical Research Institute discovered that very low concentrations of delta 9-tetrahydrocannabinol (THC) could raise serotonin levels that were altered due to HIV and additionally help reestablish the signaling processes that are vital for gut–brain communication.¹ These findings, published in Science Advances, reveal additional details regarding the biological interactions of cannabinoids with the digestive system and the immune system regulation.²

“People living with HIV experience chronic inflammation, which leads to many comorbidities such as cardiovascular disease, liver disease, and some neurological diseases,” said Professor Mahesh Mohan, DVM, PhD. “Our lab is interested in finding solutions to help address this.” He added, “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. 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.”¹

Linking Gut Serotonin, HIV Pathology, and Cannabinoid Activity

Most of the time, the gastrointestinal tract is the main place where serotonin is produced. The release of serotonin is the main factor that changes the whole intestinal function, immune activity, and also communication along the gut–brain axis. HIV-related inflammatory processes and the virus's effects on the cells of the gut lining can interfere with the production of serotonin, which can eventually lead to neurological and metabolic complications and a worsening overall quality of life for patients.

Researchers in the Texas Biomed study used simian immunodeficiency virus (SIV) models to evaluate whether THC could normalize serotonin signaling disrupted by infection. In particular, the THC amounts utilized were significantly less than those that would have caused a psychoactive effect, pointing to a possible therapeutic window that would lessen the impairment and still bring about measurable biological effects.^1,2

The team observed that THC stimulated the release of serotonin from enterochromaffin cells in the gut, helping counteract infection-related deficits.^1,2 This restoration of signaling may also influence immune parameters, as serotonin plays a key role in modulating inflammation, leukocyte activity, and cytokine responses.³

Implications for Cognitive and Mood Disorders in HIV

After suppression of the viral load, depression, neurocognitive impairment, and chronic fatigue are still common in the population of individuals living with HIV. Disrupted serotonin signaling and ongoing inflammation contribute significantly to these conditions.^2,3 Because cannabinoids also interact with receptors involved in pain modulation, mood regulation, and neuroprotection, researchers believe this strategy could eventually support adjunctive treatment approaches for multiple HIV-related comorbidities.

Low-dose cannabinoid therapy may also have implications for long-COVID research, as reported by Mohan, given similar serotonin deficits and inflammatory patterns observed in individuals with prolonged post-viral symptoms.¹

Next Steps for Research

Although the preclinical results are promising, investigators emphasize the need for comprehensive human studies to evaluate optimal dosing, long-term safety, and interactions with ART. Understanding whether low-dose cannabinoid therapy can improve biomarkers of inflammation, neurocognitive symptoms, or gastrointestinal function in people living with HIV will be critical before clinical adoption.

Researchers also note the importance of assessing patient-specific factors—including drug-drug interactions, comorbid mental health conditions, and potential hepatic implications—given the complexity of HIV care.

Conclusion

Even with effective ART, chronic inflammation is still a major cause of significant morbidity in people living with HIV. One of the first studies showing serotonin restoration via low-dose cannabinoid therapy is quite convincing to the next therapeutic research. With the progress in science, pharmacists have a good position to help patients with their questions about cannabinoid treatment, keep an eye on the possible ART interactions, and be available for the patient’s care continuation regarding inflammation, mental health, and quality of life.

REFERENCES

1. Low-dose THC reduces side effects of HIV treatment. EurekAlert! Published November 6, 2025. Accessed December 4, 2025. https://www.eurekalert.org/news-releases/1104892

2. Premadasa LS, Romero L, Mohan M. Supplementing HIV-ART with cannabinoids increases serotonin, BHB, and Ahr signaling while reducing secondary bile acids and acylcholines. Science Advances. 2025;11(36). doi:10.1126/sciadv.adw4021

3. Mack A, Joy J. MARIJUANA AND AIDS. Nih.gov. Published 2015. Accessed December 4, 2025. https://www.ncbi.nlm.nih.gov/books/NBK224400/