BUPRENORPHINE EFFECTS IN METHADONE-MAINTAINED VOLUNTEERS - EFFECTS AT2 HOURS AFTER METHADONE

Buprenorphine is an opioid partial agonist being developed for possibl e use in the treatment of opioid dependence. In a previous study up to 8 mg of buprenorphine administered 20 hr after a daily dose of methad one in methadone-maintained volunteers produced neither agonist-like n or antagonist-like effects. The purpose of this study was to examine t he effects of buprenorphine challenges given 2 hr after a daily methad one dose in maintained volunteers. Seven male volunteers maintained on 30 mg of methadone daily underwent pharmacologic challenges two to th ree times per week. Medication challenges consisted of double-blind i. m. injections of buprenorphine (0.5-8.0 mg), the opioid antagonist nal oxone (0.1 and 0.2 mg), the prototypic opioid mu agonist hydromorphone (5 and 10 mg) or saline. Assessments of physiologic measures, volunte ers' self-reports and observer ratings of drug effects were collected in a laboratory session for 2 hr after drug administration, and then f or 8 additional hr postsession. Results from the laboratory session sh owed that on subject and observer ratings naloxone produced typical an tagonist-like effects, hydromorphone produced mild agonist-like effect s and buprenorphine produced antagonist-like effects. Interestingly, b uprenorphine's antagonist activity was not directly dose-related; its most prominent antagonist effects occurred at the 1- and 2-mg doses. T hese results are consistent with buprenorphine's action as a partial m u opioid agonist and demonstrate that antagonist-like effects can occu r under some conditions suggesting buprenorphine should have a low abu se liability in methadone-maintained patients.