Delta-9-Tetrahydrocannabinol alleviates doxorubicin-induced weight loss but does not affect dextran sodium sulphate-induced colitis

Gastrointestinal mucositis is a common adverse effect of chemotherapy. Inflammatory bowel diseases (IBD) are a spectrum of chronic inflammatory disorders of the digestive tract. Mucositis and IBD/colitis are characterized by weight loss and intestinal inflammation. Previous animal studies suggest that the cannabinoid, ∆9-tetrahydrocannabinol (THC), attenuates intestinal inflammation. We aimed to investigate the effect of THC oil on doxorubicin-induced gastrointestinal mucositis and dextran sodium sulphate (DSS) induced colitis in mice. Wild-type C57BL6 mice were used for the experiments. The mice received a daily dose of THC oil at either 10 mg/kg or 20 mg/kg or vehicle by oral gavage. Mucositis was induced by intraperitoneal injection of doxorubicin, while colitis was induced by supplementing the drinking water with 2% DSS. Gastrointestinal toxicity was evaluated by weight, intestinal lengths, histopathological evaluation, and expression of genes related to chemotherapy-induced mucositis and intestinal inflammation. Treatment with THC significantly reduced weight loss and increased the length of the small intestine in the doxorubicin-treated mice. No effects on gene expression of pro-inflammatory cytokines were observed. No effect of THC was observed in DSS-induced colitis. THC reduced doxorubicin-induced weight loss, possibly due to increased appetite, but did not affect doxorubicin-induced intestinal inflammation or DSS-induced colitis in mice.