Dronabinol, a synthetic agonist at cannabinoid receptors, was reported to decrease the pruritus of cholestasis, in an uncontrolled observation. We hypothesized that the reported antipruritic effect of dronabinol might have resulted from an increased threshold to experience nociception (i.e. pruritus) by the drug. To test this hypothesis, we studied the effect of WIN 55, 212-2, a cannabinoid agonist, on the threshold to experience nociception, using a tail-flick assay in rats with cholestasis secondary to bile duct resection and in sham-resected controls. The administration of WIN 55, 212-2 was associated with a significant increase in the mean tail-flick latency in both groups as compared to baseline. Pruritus is a nociceptive stimulus; accordingly, drugs that increase the threshold to nociception in human beings may be a novel approach to the treatment of this symptom in patients with liver disease.