Antiviral and Anti-inflammatory Effects of Cannabidiol in HIV/SIV Infection

"Persistent reservoirs and chronic immune activation are hallmarks of HIV, despite the effectiveness of antiretroviral therapy (ART) in suppressing viral replication. Here, we use rhesus macaques and primary and induced pluripotent stem cell (iPSC)-derived human immune cells to evaluate cannabidiol’s antiviral and anti-inflammatory capacity during HIV/SIV infection. We show that cannabidiol, in the absence of ART, suppresses viral replication and establishment of the viral reservoir to levels comparable to first-line therapies during acute SIV infection of rhesus macaques. This antiviral effect of cannabidiol extended to in vitro HIV infection of human macrophages, T cells, and microglia. Immunologically, we observe cannabidiol slowed CD4+ T cell decline and polarization, decreased CD14+CD16+ monocyte expansion, and interferon-inducible cytokine release in rhesus macaques. We identify comparable effects on cytokine production with in vitro cannabidiol treatment of human macrophages, T cells, and microglia. Importantly, we find cannabidiol inhibits cytokines only when an immune response is elicited by HIV, suggesting it is not broadly immunosuppressive. Finally, we determine cannabidiol regulates endocannabinoid receptors, modulators, and transporters and inhibits NF-kb and STAT1 activation when mediating its antiviral and anti-inflammatory effects. These findings identify potential beneficial effects of cannabidiol during untreated HIV arguing for clinical trials to evaluate safety and appropriateness for adjunctive use with ART."

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CC BY 4.0