BUPRENORPHINE, MORPHINE AND NALOXONE EFFECTS DURING ASCENDING MORPHINE MAINTENANCE IN HUMANS

One purpose of this study was to characterize the acute effects of the partial mu-opioid agonist buprenorphine administered to human subject s undergoing maintenance treatment with ascending doses of morphine. A second purpose was to examine the development of tolerance, cross-tol erance and physical dependence under the same morphine maintenance con ditions. Six opioid-dependent volunteers were treated chronically with ascending morphine doses of 15, 30, 60 and 120 mg/day. Each morphine dosing level was maintained for weeks, with test drugs administered du ring the second week of maintenance on each morphine dose. Both morphi ne (30 mg i.m.) and buprenorphine (6 mg i.m.) constricted pupils and p roduced reports of opioid-like subjective effects. The magnitude of th ese effects was inversely related to the morphine main tenance dose, w ith no effects being detected at higher maintenance levels. Naloxone ( 0.3 mg) produced little effect at lower morphine maintenance doses but precipitated withdrawal at higher maintenance doses. Buprenorphine fa iled to precipitate withdrawal even when subjects were treated with 12 0 mg/day morphine. These findings indicate that dose-dependent toleran ce to morphine, cross-tolerance to buprenorphine and physical dependen ce develop during morphine maintenance. The finding that buprenorphine does not act as an antagonist under these dosing conditions further s upports the clinical observation that there are conditions under which patients dependent on short-acting opioids can be comfortably transfe rred directly to buprenorphine maintenance treatment.