The National Institutes of Health (NIH) awarded Professor Mahesh Mohan, D.V.M., Ph.D., and collaborators more than $3.5 million over five years to investigate the effects of cannabinoids on Human Immunodeficiency Virus (HIV) associated neurocognitive disorder (HAND). This research project aims to evaluate whether delta-9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) alone or in combination can potentially alter DNA methylation, which is a biological process that can create a change in the expression of certain genes.
Using Indian rhesus macaques with Simian immunodeficiency virus (SIV), the monkey equivalent of HIV, researchers will be able to study if changes in gene DNA methylation levels impact inflammation in the brain, which is the underlying cause of HAND. Understanding these basic biological processes will allow scientists to create better therapeutic options. Researchers will also study whether JWH133, a synthetic cannabinoid (CB), affects DNA methylation and could serve as an alternate therapeutic intervention.
We're focusing on neuro-inflammation that affects the brain even in patients on anti-retroviral therapy (ART). There are a few mechanisms that drive this inflammation, but we want to look at immune cells in the blood and cerebrospinal fluid at different stages of SIV infection. Cannabinoids have previously shown great promise for the treatment of neurological disorders; therefore, we want to see if it can exert therapeutic effects in HIV patients suffering from HAND."
Dr. Mahesh Mohan, principal investigator for the study
Three decades ago, AIDS was a devastating disease with no cure. As a result, the manifestations were more acute. Due to the scientific advances made over time, including many that utilize nonhuman primate models of AIDS, we now have the ability to treat many AIDS patients, and increase their life-span. However, this is laying bare the more chronic effects of HIV infection, especially those of the neurocognitive variety.
In particular, HAND is a major comorbidity that affects 50% of HIV infected patients who are on ART. The disorder affects brain function causing difficulties in attention, concentration, decision-making and memory. Dr. Mohan says evidence shows that neuro-inflammation persists in HIV patients on ART and is an important driver of HAND; however, little is known about the molecular mechanisms behind the inflammation. Separating the cells in blood, cerebrospinal fluid and brain gives researchers a closer look at the cellular changes leading to neuroinflammation. In addition, these studies will utilize metabolomics, microbiome profiling, PET/CT imaging and newly developed techniques at Texas Biomed to evaluate the impact of cannabinoids on cognitive function and neuroinflammation.
"We believe we will have some very interesting findings. Our study will add more mechanistic understanding for researchers regarding the factors behind HAND, and potentially lead to the development of more cannabinoid-based therapies," Dr. Mohan said. "Finding the best therapeutic approach whether it is a single drug, a combination cannabinoid regimen or a synthetic cannabinoid drug is important."