Confound, Cause, or Cure: The Effect of Cannabinoids on HIV-Associated Neurological Sequelae

• Published in: Viruses Vol. 13; no. 7; p. 1242
• Main Authors: Starr, Alexander, Jordan-Sciutto, Kelly L, Mironets, Eugene
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26.06.2021; MDPI
• Subjects: Animal cognition; Animals; Anti-HIV Agents - pharmacology; Anti-HIV Agents - therapeutic use; Anti-inflammatory agents; antiretroviral; Antiretroviral drugs; Antiretroviral therapy; Brain research; Cannabinoids; Cannabinoids - pharmacology; Cannabinoids - standards; Cannabinoids - therapeutic use; Cannabis; CB1; CB2; Central nervous system; Clinical Trials as Topic; Cognition; Cognitive ability; Cytokines; Drug abuse; Drug Evaluation, Preclinical; Encephalitis; Enzymes; Excitotoxicity; HAND; HIV; HIV Infections - complications; HIV Infections - therapy; HIV-1 - drug effects; Human immunodeficiency virus; Humans; Immune system; In Vitro Techniques; Infections; Inflammation; Laboratories; Life cycles; Marijuana; Mice; Nervous system; Neuroinflammatory Diseases - therapy; Neurological complications; Neuropathogenesis; Neurotoxicity; Pathogenesis; Pharmacology; Psychotropic Drugs - pharmacology; Psychotropic Drugs - standards; Psychotropic Drugs - therapeutic use; Review; antiretroviral; cannabinoids; CB2; CB1; HIV; HAND
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v13071242

The persistence of human immunodeficiency virus-1 (HIV)-associated neurocognitive disorders (HAND) in the era of effective antiretroviral therapy suggests that modern HIV neuropathogenesis is driven, at least in part, by mechanisms distinct from the viral life cycle. Identifying more subtle mechanisms is complicated by frequent comorbidities in HIV populations. One of the common confounds is substance abuse, with cannabis being the most frequently used psychoactive substance among people living with HIV. The psychoactive effects of cannabis use can themselves mimic, and perhaps magnify, the cognitive deficits observed in HAND; however, the neuromodulatory and anti-inflammatory properties of cannabinoids may counter HIV-induced excitotoxicity and neuroinflammation. Here, we review our understanding of the cross talk between HIV and cannabinoids in the central nervous system by exploring both clinical observations and evidence from preclinical in vivo and in vitro models. Additionally, we comment on recent advances in human, multi-cell in vitro systems that allow for more translatable, mechanistic studies of the relationship between cannabinoid pharmacology and this uniquely human virus.