Characterization of the Effects of Chronic Marijuana Use and its Routes of Administration on the Brain, Inflammation, Immune Function and Pain in People with HIV Infection

Varan Govind
University of Miami

Co-Authors: Teddy Salan¹, Suresh Pallikkuth¹, Denise Vidot¹, Eva Widerstrom-Noga¹, Robert Cook^2
1University of Miami ²University of Florida

Despite the success of antiretroviral therapy (ART) in suppressing HIV and achieving virological control, chronic-inflammation and immune-activation persist in people living with HIV (PLWH). This plays a major role in causing HIV disease progression and developing non-AIDS comorbidities such as neuropathic pain, anxiety, depression, and cognitive dysfunction. Varying proportions of PLWH use medicinal or recreational marijuana (MJ) to alleviate these symptoms. The effects of MJ and its different routes of administration on the immune system, and brain structure and metabolism have not been investigated fully in PLWH. This cross-sectional study aims to characterize the effects of marijuana (MJ) and its routes of administration on the 1) metabolism, morphology, and neural circuits of the whole-brain, 2) systemic inflammation, and immune-cell phenotypes associated with activation, exhaustion and homing, and 3) pain and behavioral measures in HIV+/HIV- chronic MJ users (MJ+), compared to MJ-non-users (MJ-). A total of 128 subjects will be enrolled into four groups: MJ+HIV+ (n=48), MJ+HIV- (n=48), MJ-HIV+ (n=16) and MJ-HIV- (n=16). MJ users will be equally divided into those who smoke blunts, joints, or vape pens. A comprehensive MRI protocol will acquire diffusion kurtosis imaging (DKI) for evaluating brain white-matter neuronal integrity and gray-matter microstructural changes, whole-brain MR spectroscopic imaging (MRSI) for mapping metabolite concentrations as a measure of neuroinflammation and neuronal viability, and neuromelanin MRI, a proxy for dopamine, to investigate the effects of chronic MJ use on dopamine levels in the brain. Blood-based measures will evaluate multiple plasma markers of immune activation, gut barrier disruption, and systemic inflammation. Taken together, these measures will allow us to establish relationships between peripheral immune activation and inflammation, CNS inflammation, and pain. Preliminary findings from our prior studies on HIV showed higher systemic inflammation and immune activation and brain metabolic and structural alterations in PLWH. For the present study, we hypothesize that MJ use will modulate the extent of these alterations, and that THC and CBD metabolites in blood will associate with brain-imaging and blood-based markers, and pain and behavioral measures in HIV+/HIV- MJ+ groups.