Effects of Acute and Subchronic Δ9-tetrahydrocannabinol Administration on the Plasma Catecholamine, β-Endorphin, and Corticosterone Levels and Splenic Natural Killer Cell Activity in Rats

Abstract The effect of acute (1 day) or subchronic (25 days) treatment with Δ9-tetrahydrocannabinol (THC), the major psychoactive constituent of marihuana, on plasma norepinephrine (NE), epinephrine (E), corticosterone, β-endorphin (β-end), and splenic natural killer (NK) cell activity of the rat was studied. Groups of animals received subcutaneously, either THC in corn oil + saline (3 mg THC/kg); oil + saline: or THC + naloxone (2 mg naloxone/kg and 3 mg THC/kg). Acute injection of THC with or without naloxone did not significantly change plasma levels of NE, E corticosterone, β-end, or the NK cell activity. However, subchronic treatment with THC significantly reduced plasma levels of NE, E, corticosterone, and NK cell activity, compared to controls. The plasma β-end levels were significantly elevated in the THC-treated animals. In the THC + naloxone group of animals, the plasma hormone levels (corticosterone and β-end) were similar to control levels and the NK cell activity was significantly higher than in THC-treated animals. These results indicate that subchronic exposure to THC results in suppression of splenic NK cell activity. The interaction of THC with the endogenous opiate system appears to be a contributing factor leading to the NK cell suppression in rats. A direct suppressive action of THC or its metabolites on the NK cell is not ruled out by this study.