The cholecystokinin antagonist proglumide enhances the analgesic efficacy of morphine in humans with chronic benign pain

The analgesic efficacy of morphine is sometimes only partial in patients with chronic benign pain. Among the possible factors contributing to this limitation are increased levels of cholecystokinin (CCK). We performed this prospective, placebo-controlled, double-blind, cross-over study to examine the effect of proglumide, a nonspecific CCK agonist, on analgesia in patients taking morphine on a chronic basis. Forty patients with intractable pain who were taking sustained-release morphine were recruited, and we obtained results from 36 of these patients. Median visual analog scale scores before the study were 8 and 7 after the addition of placebo for 2 wk (P = 0.16), and 6 after proglumide for 2 wk (P = 0.002). Mobility was unchanged by proglumide or placebo. Of the 36 patients, 13 elected to continue receiving proglumide after the study. We conclude that proglumide enhances the analgesia produced by morphine in some, but not all, patients with chronic benign pain. The pain-killing effect of morphine is incomplete in some patients. Increasing doses may be needed to maintain the initial effect. The peptide cholecystokinin may be partially responsible for this. In this study, we demonstrated that the cholecystokinin antagonist proglumide increases the analgesic effect of morphine in some patients with chronic benign pain.