Cannabinoid administration attenuates the progression of simian immunodeficiency virus.
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.
Molina
Patricia E
PE
Department of Physiology, Alcohol Research Center, LSUHSC, New Orleans, Louisiana, USA. pmolin@lsuhsc.edu
Winsauer
Peter
P
Zhang
Ping
P
Walker
Edith
E
Birke
Leslie
L
Amedee
Angela
A
Stouwe
Curtis Vande
CV
Troxclair
Dana
D
McGoey
Robin
R
Varner
Kurt
K
Byerley
Lauri
L
LaMotte
Lynn
L
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
D000998:Antiviral Agents; D013759:Dronabinol