Study of the effect of Cannabis sativa on liver and brain damage caused by thioacetamide

Cannabis sativa preparations are the most widely used illicit drugs worldwide. The present study aimed to examine the effect of C. sativa extract on liver injury caused by thioacetamide in the rat. Thioacetamide was administered at 50 mg/kg twice weekly via subcutaneous route (s.c.) for 2 weeks. Starting from the first dose of thioacetamide, rats were treated with either C. sativa at doses of 10 or 20 mg/kg (expressed as Δ⁹-tetrahydrocannabinol), silymarin (25 mg/kg) or saline, once daily s.c., for 2 weeks. Reduced glutathione (GSH), lipid peroxidation (malondialdehyde; MDA) and nitric oxide concentrations were measured in the liver and brain. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), paraoxonase 1 activities (PON1) and total proteins were determined in serum. Hepatic injury was also determined via histological examination of liver sections. The administration of only cannabis to saline-treated rats had no significant effect on serum liver enzymes or on the hepatic levels of GSH, MDA or nitric oxide. Serum PON1 decreased by 21.9 % by 20 mg/kg cannabis. The level of MDA and nitric oxide in brain decreased by only cannabis administration. In thioacetamide-treated rats, the administration of cannabis extract (10 or 20 mg/kg) did not alter the level of MDA, GSH or nitric oxide in hepatic tissue. Serum ALT or AST were not significantly altered, but ALP increased significantly by 38.9 % after treatment with 20 mg/kg cannabis. Serum PON1 activity which showed marked decrease in thioacetamide-treated rats, increased by 18.9 and 151 % after C. sativa treatment. Serum proteins increased after the administration of cannabis (by 20.4 and 21.3 %, respectively). In brain tissue, both MDA and nitric oxide were significantly decreased by cannabis. Meanwhile, treatment with silymarin resulted in significant decrease in MDA and increased GSH in the liver tissue. Serum AST, ALT and ALP were significantly decreased, while PON1 activity was increased after silymarin. In brain, MDA decreased by 27.9 % after silymarin. Cannabis alone caused histological liver damage and fibrosis and neuronal degeneration. The liver tissue damage and brain degeneration caused by thioacetamide were enhanced by cannabis but almost prevented by silymarin treatment. It is concluded that the administration of C. sativa exacerbates the thioacetamide-induced liver and brain injury.