EFFECTS OF BUPRENORPHINE AND METHADONE IN METHADONE-MAINTAINED SUBJECTS

Buprenorphine, a partial mu opioid agonist, is an experimental medicat ion under development for the treatment of opioid dependence as an alt ernative to methadone maintenance. The present study examined the rela tionship between level of opioid physical dependence and response to b uprenorphine administration as part of a program to develop procedures for transferring patients from methadone to buprenorphine treatment. This laboratory study characterized the agonist and antagonist effects of acute doses of buprenorphine and methadone in subjects maintained on either 30 (n = 7) or 60 (n = 6) mg/day oral methadone. Test doses o f placebo [sl. and PO), methadone (15, 30, and 60 mg PO) and buprenorp hine (2, 4, and 8 mg sl.) were administered to volunteers residing on a closed residential unit. Subjective, physiological, observer-rated, and cognitive/psychomotor measures were collected for 6.5 h after test doses. Test doses of methadone, but not buprenorphine, constricted pu pils and produced dose-related increases on subjective report measures reflecting opioid agonist drug effects. Agonist effects of methadone were more prominent in the 30 mg than in the 60 mg methadone maintenan ce condition. Buprenorphine, but not methadone, precipitated opioid wi thdrawal signs and symptoms that were more prominent in the 60 mg than in the 30 mg methadone maintenance condition. These findings suggest that abrupt transition from methadone to buprenorphine may produce pat ient discomfort that is positively related to both methadone maintenan ce dose and buprenorphine transition dose.