Druggable targets of the endocannabinoid system: Implications for the treatment of HIV-associated neurocognitive disorder

• Published in: Brain research 2019-12, Vol.1724, p.146467-146467, Article 146467
• Main Authors: Wu, Mariah M., Zhang, Xinwen, Asher, Melissa J., Thayer, Stanley A.
• Format: Article
• Language: English
• Subjects: 2-Arachidonoylglycerol; Anandamide; Cannabinoid receptor; Fatty acid amide hydrolase; HIV-1; Monoacylglycerol lipase
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2019.146467

•Nearly half of all HIV-infected individuals experience cognitive and motor deficits.•HIV-induced neuronal injury results from excitotoxic and inflammatory mechanisms.•The endocannabinoid (eCB) system provides on-demand protection against excitotoxicity and neuroinflammation.•We discuss the potential of drugs that modulate eCB signaling to treat HIV-associated neurocognitive disorder. HIV-associated neurocognitive disorder (HAND) affects nearly half of all HIV-infected individuals. Synaptodendritic damage correlates with neurocognitive decline in HAND, and many studies have demonstrated that HIV-induced neuronal injury results from excitotoxic and inflammatory mechanisms. The endocannabinoid (eCB) system provides on-demand protection against excitotoxicity and neuroinflammation. Here, we discuss evidence of the neuroprotective and anti-inflammatory properties of the eCB system from in vitro and in vivo studies. We examine the pharmacology of the eCB system and evaluate the therapeutic potential of drugs that modulate eCB signaling to treat HAND. Finally, we provide perspective on the need for additional studies to clarify the role of the eCB system in HIV neurotoxicity and speculate that strategies that enhance eCB signaling might slow cognitive decline in HAND.