title: Cannabinoid administration attenuates the progression of simian immunodeficiency virus.
abstract: Δ(9)-Tetrahydrocannabinol (Δ(9)-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 Δ(9)-THC use may impact HIV disease progression. We examined the impact of chronic Δ(9)-THC administration (0.32 mg/kg im, 2 × daily), starting 28 days prior to inoculation with simian immunodeficiency virus (SIV(mac251); 100 TCID(50)/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. Δ(9)-THC treatment of SIV-infected animals produced minor to no effects in these parameters. However, chronic Δ(9)-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, Δ(9)-THC (10 μm) decreased SIV (10 TCID(50)) viral replication in MT4-R5 cells. These results indicate that chronic Δ(9)-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 Δ(9)-THC-mediated modulation of disease progression that warrant further study.
authors.affiliation: Department of Physiology, Alcohol Research Center, LSUHSC, New Orleans, Louisiana, USA. pmolin@lsuhsc.edu
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Molina
authors.forename: Peter
authors.initials: P
authors.lastname: Winsauer
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Edith
authors.initials: E
authors.lastname: Walker
authors.forename: Leslie
authors.initials: L
authors.lastname: Birke
authors.forename: Angela
authors.initials: A
authors.lastname: Amedee
authors.forename: Curtis Vande
authors.initials: CV
authors.lastname: Stouwe
authors.forename: Dana
authors.initials: D
authors.lastname: Troxclair
authors.forename: Robin
authors.initials: R
authors.lastname: McGoey
authors.forename: Kurt
authors.initials: K
authors.lastname: Varner
authors.forename: Lauri
authors.initials: L
authors.lastname: Byerley
authors.forename: Lynn
authors.initials: L
authors.lastname: LaMotte
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D001835:Body Weight; D016516:CD4-CD8 Ratio; D013759:Dronabinol / Q000008:administration & dosage* / Q000494:pharmacology*; D007273:Injections, Intramuscular; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000187:drug effects*; D016019:Survival Analysis; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D013759:Dronabinol