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Cannabis, inflammation, and the brain in persons with HIV

INVESTIGATORS: Jennifer Iudicello, PhD

STUDY LOCATION: University of California, San Diego

PROJECT TITLE: Cannabis, inflammation, and the brain in persons with HIV

FUNDING SOURCE: NIH

PROJECT TYPE: Observational Study

STATUS:  Active

ABSTRACT:

Neuropsychiatric (e.g., stress, depression) and neurocognitive complications are common among persons with HIV (PWH) during antiretroviral therapy (ART) and are linked to adverse health-related outcomes. A central underlying etiology for the persistence of these complications is persistent systemic- and neuro-inflammation, driven by low levels of HIV RNA and proteins, myeloid activation, and other mechanisms. In the brain, microglia are a central component of the neuroinflammatory response. Cannabis is one of the drugs most commonly used by PWH, with prevalence rates exceeding that of the general population. There is growing evidence of beneficial effects of cannabis among PWH, which may reflect the anti-inflammatory action of cannabinoids. Cannabinoids modulate inflammatory responses via the endocannabinoid (EC) system (ECS), and have benefits in chronic inflammatory disorders, though less is known about the effects of cannabis on inflammation in PWH. Moreover, the cannabis exposure (e.g., dose, frequency) that may be effective, ineffective, or harmful is not understood. Since the ECS appears to influence the immune response and risk for neurodegenerative diseases, its modulation may have therapeutic applications. However, little research has examined the effects of cannabis on the ECS in PWH. The proposed study seeks to address key gaps in the cannabis and HIV field using a combination of in vivo and ex vivo methods to identify the biological mechanisms underlying the effects of chronic cannabis use on persistent inflammation in PWH and its corresponding impact on neuropsychiatric and neurocognitive complications. We will also examine how components of the ECS may mediate the relationship between cannabis use and inflammation by measuring soluble ECs, cannabinoid receptor expression, and intracellular cannabinoid metabolizing enzymes (CMEs). Knowledge gained from this study will provide valuable insights into strategies for treatment of persistent inflammation in PWH and its health-related consequences.