Effect of Cannabis sativa on the indomethacin-induced gastric mucosal damage

Abstract

The effect of Cannabis sativa on the development of gastric mucosal lesions induced in rats by indomethacin administration was studied. The extract of Cannabis sativa was prepared from the dried flowering tops and leaves of the plant by extraction with chloroform. Rats were treated with indomethacin at a dose of 20 mg/kg s.c. for two consecutive days alone or in combination with the cannabis extract (at doses equivalent to 10 or 20 mg/kg Δ9-tetrahydrocannabinol, i.p.). Rats were euthanized 24 hr after the last treatment when gastric secretory responses and number and severity of gastric mucosal lesions were determined. Lipid peroxidation (malondialdehyde), nitric oxide, and reduced glutathione in gastric homogenates were measured and gastric mucosal histopathology was done. Results indicated that treatment with Cannabis sativa significantly inhibited the development of indomethacin-induced gastric mucosal lesions in a dose-dependent manner. Cannabis decreased gastric acid secretion in rats treated with indomethacin. The increase in gastric lipid peroxidation, nitric oxide and the decrease in reduced glutathione were ameliorated by cannabis extract. Indomethacin resulted in multiple mucosal erosions, necrosis, leukocytic infiltration and vascular congestion. These changes were prevented by Cannabis treatment. In conclusion, the systemic administration of Cannabis exerted protective effect against the indomethacin-induced gastric damage which involved inhibition of gastric acid and oxidative stress. This suggests the involvement of cannabinoid receptors in gastric mucosal protection.