Antioxidant and blood flow profiling in individuals with HIV

About This Grant

Project Summary Marijuana (MJ) use among people living with HIV (PWH) is up to three times more prevalent than in the general population. MJ can be consumed by ingesting cannabis (e.g., edibles like pills) or smoking (i.e., inhaling MJ smoke), providing benefits to PWH, such as reduced stress, anxiety, pain, and depression. The impact of MJ edibles on the cognitive function of PWH has not been explored. However, MJ smoke contains many of the same toxins and carcinogens as tobacco (TC) smoke, which may increase oxidative stress and negatively affect the antioxidant glutathione levels (GSH – a marker of oxidative stress) in the brain of PWH. Advanced edited magnetic resonance spectroscopy (MRS) can measure GSH in PWH who smoke MJ and provide insights into how MJ smoking contributes to oxidative stress and resulting cognitive impairment. Furthermore, the toxins in MJ smoke elevate the risk of inflammation and plaque formation in blood vessels, causing vasoconstriction or vasodilation, which alters cerebral blood flow (CBF). These mechanisms leading to adverse hemodynamic perturbations may be more pronounced in PWH who smoke MJ than in those who consume MJ edibles. Alterations in CBF may result in insufficient oxygen for mitochondria needed to synthesize adenosine triphosphate (ATP)-dependent GSH for antioxidant protection against reactive oxygen species (ROS), leaving PWH smokers vulnerable to oxidative stress and neuronal damage. In this proposal, we will assess brain GSH and CBF in PWH who use MJ (smoking vs. edibles). We will also compare the effects of MJ smoke with TC smoke on GSH levels in PWH. In Aim 1, we will evaluate GSH profiles in five groups of individuals using advanced edited MRS: PWH MJ smokers, PWH who use MJ edibles, PWH TC smokers, PWH who do not smoke TC and do not smoke MJ or take MJ edibles (TC–/MJ–), and seronegative (SN) TC–/MJ–. We hypothesize that both PWH MJ smokers and PWH TC smokers will exhibit similar GSH levels, though these levels will be the lowest among all groups, indicating that smoking leads to an overproduction of ROS and increased oxidative stress. PWH who consume MJ edibles and PWH TC–/MJ– will have comparable GSH levels, suggesting that edibles do not induce oxidative stress, while PWH TC–/MJ– will display lower GSH than SN TC–/MJ–, indicating ongoing oxidative stress due to HIV. In Aim 2, we will evaluate regional CBF in PWH who smoke MJ and those who use MJ edibles. We hypothesize that PWH who smoke MJ will demonstrate impaired CBF (the lowest), indicating ROS-mediated vascular changes related to smoking, which will correlate with lower GSH levels. This proposal aligns with NIDA’s agenda to develop targeted mitochondrial function and dynamics indicators, including oxidative stress. Measurements of GSH and cerebral blood flow will offer insights into the pathophysiology linked to HIV infection and MJ use, potentially paving the way for new therapeutic strategies addressing oxidative stress and neuronal injury.