THE EFFECTS OF BUPRENORPHINE IN BUPRENORPHINE MAINTAINED VOLUNTEERS

Buprenorphine is a mu opioid partial agonist currently used as an anal gesic, and being developed for the treatment of opioid dependence. The purpose of this study was to determine the abuse liability of parente ral buprenorphine in volunteers maintained on daily sublingual (SL) bu prenorphine (8 mg). In a residential laboratory, eight volunteers unde rwent pharmacologic challenges two times per week. Medication challeng es were 16 h after the daily dose of buprenorphine, and consisted of d ouble-blind IM injections of buprenorphine (4, 8, 16 mg), the prototyp ic mu opioid agonist hydromorphone (9 and 18 mg), or saline. Assessmen ts consisted of physiologic monitoring, subjects' self-reports, and a trained observer's ratings of drug effects, and were collected for 0.5 h before and 2.0 h following injection. Supplemental doses of IM bupr enorphine produced opioid agonist-like effects, indicating some abuse potential of parenteral buprenorphine in buprenorphine-maintained pati ents. There was incomplete cross-tolerance to the effects of hydromorp hone, suggesting that higher maintenance doses of buprenorphine may be needed to maximize clinical efficacy. However, there was a lack of gr aded dose-effects for hydromorphone, suggesting that buprenorphine's c ombination of partial agonist effects and high affinity for opioid rec eptors may limit the magnitude of effects of supplemental full agonist s. Finally, participants tolerated cumulative doses of maintenance bup renorphine plus challenge buprenorphine without adverse effects, sugge sting higher doses of buprenorphine can be safely administered to opio id dependent patients.