Influence of Marijuana Components (THC and CBD) on Human Mononuclear Cell Cytokine Secretion In vitro

Abstract

Cytokines are a class of polypeptides produced by cells of the immune system. They coordinate the immune response to an antigenic challenge and play key roles in immunomodulation and host defense (1,2), and exert also metabolic effects (3,4). Therefore, a change in cytokine secretion caused by drugs of abuse could have an impact on immunological systems and metabolism. Delta-9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, has been shown to modulate virus and mitogen induced cytokine secretion in mice. Intraperitoneal administered THC (5-100 mg/kg) decreased the plasma concentration of alpha-/beta-interferon (IFN) significantly (5). Chronic in vivo exposure of mice to THC (50 mg/kg for 56 days) also reduced the secretion of alpha-/beta-IFN in cultured, mitogen-stimulated spleen cells (6). In vitro culture of murine spleen cells together with THC (2.5–10 M-g/ml) showed dose-dependent responses in the alpha-/beta-IFN secretion. Low concentrations had no effect on alpha-/beta-IFN secretion, while 5 to 10 yg/ml were significantly suppressive (6). However, all these immunomodulatory concentrations were high and well above the pharmacological range of 1-100 ng/ml of THC found in the plasma of human marijuana smokers (7). Friedman et al., also investigated the effect of THC on the secretion of different cytokines by cultured murine spleen cells using bioassays (8). Only concentrations above the pharmacological range were used (5–10 μg/ml). All suppressed in a dose-dependent manner the secretion of cytokines. Lipopolysaccharide (LPS)-induced secretion of IFN (alpha-/beta) in splenocytes, adherent and nonadherent cells was reduced to 85%, a reduction was also observed by chronic administration of THC to these cells.