Cannabinoid Administration Attenuates the Progression of Simian Immunodeficiency Virus

Abstract

Δ⁹-Tetrahydrocannabinol (Δ⁹-THC), the primary psychoactive component in marijuana, is FDA approved to ameliorate AIDS-associated wasting. Because cannabinoid receptors are expressed on cells of the immune system, chronic Δ⁹-THC use may impact HIV disease progression. We examined the impact of chronic Δ⁹-THC administration (0.32 mg/kg im, 2 × daily), starting 28 days prior to inoculation with simian immunodeficiency virus (SIV_mac251; 100 TCID₅₀/ml, iv), on immune and metabolic indicators of disease during the initial 6 month asymptomatic phase of infection in rhesus macaques. SIV_mac251 inoculation resulted in measurable viral load, decreased lymphocyte CD4⁺/CD8⁺ ratio, and increased CD8⁺ proliferation. Δ⁹-THC treatment of SIV-infected animals produced minor to no effects in these parameters. However, chronic Δ⁹-THC administration decreased early mortality from SIV infection (p = 0.039), and this was associated with attenuation of plasma and CSF viral load and retention of body mass (p = NS). In vitro, Δ⁹-THC (10 μm) decreased SIV (10 TCID₅₀) viral replication in MT4-R5 cells. These results indicate that chronic Δ⁹-THC does not increase viral load or aggravate morbidity and may actually ameliorate SIV disease progression. We speculate that reduced levels of SIV, retention of body mass, and attenuation of inflammation are likely mechanisms for Δ⁹-THC-mediated modulation of disease progression that warrant further study.