Cannabinoids may worsen gastric dysmotility induced by chronic cisplatin in the rat

Although cannabinoids have traditionally been used for the treatment and/or prevention of nausea and/or emesis, anorexia and weight loss induced by clinical use of antineoplastic drugs, their efficacy and safety in long-term treatments are still controversial. Our aim was to analyze the effects of the non-selective cannabinoid agonist WIN 55 212-2 (WIN) on gastrointestinal (GI) dysmotility and other adverse effects induced by repeated cisplatin administration in the rat.

Male Wistar rats received two intraperitoneal injections once a week for 4 weeks: the first one was WIN, at non-psychoactive doses (0.5 or 1 mg kg(-1)), its vehicle or saline; the second one was cisplatin (2 mg kg(-1)) or saline. Radiographic techniques were used to determine the acute (after first dose), chronic (after last dose), and residual (1 week after treatment finalization) effects of cisplatin and/or WIN on GI motility. Bodyweight gain, food ingestion, and mechanical sensitivity were also tested.

Weekly cisplatin induced mechanical allodynia, which WIN prevented, as well as weight gain reduction and anorexia, which WIN did not. Gastric emptying was dose-dependently delayed by cisplatin and this effect was enhanced upon chronic treatment. WIN aggravated cisplatin-induced gastric dysmotility. One week after treatment finalization, only minor alterations of GI motor function were found in rats treated with cisplatin, WIN or both.

WIN weekly administered at low doses prevents neuropathy, but does not prevent anorexia or weight loss and aggravates gastric dysmotility induced by cisplatin. Cannabinoids should be handled with caution if chronically administered during chemotherapy.