ACUTE ADMINISTRATION OF BUPRENORPHINE IN HUMANS - PARTIAL AGONIST ANDBLOCKADE EFFECTS

Buprenorphine, a mixed opioid agonist-antagonist, is being investigate d as a treatment for opioid dependence. This study compared the acute subjective and physiological effects of sublingual buprenorphine to th ose of p.o. methadone over a wide range of doses and compared the abil ity of both drugs to alter the effects of an opioid challenge. Male in patient volunteers (n = 9) with histories of opioid abuse participated in this double-blind, double-dummy study. Sublingual buprenorphine (0 , 0.5, 2, 8, 16 and 32 mg) and p.o, methadone (3.75, 15 and 60 mg) wer e administered once weekly according to a Latin-square design, and sub jects were monitored on a variety of physiological and subjective meas ures. Twenty-four hours later, subjects were tested with ascending dos es of i.m. hydromorphone (0, 1 and 4 mg) given 45 min apart. Buprenorp hine and methadone produced typical opioid agonist effects of long dur ation, including pupillary constriction, respiratory depression and el evations on subject-rated and observer-rated indices of euphoria, seda tion and opioid-like symptoms. The buprenorphine dose-effect curves we re nonlinear and maximal effects for most physiological and subjective measures were observed between 4 and 8 mg, with no greater effects ob served at higher doses. The methadone dose-effect curves were linear a cross the range of doses tested. High doses of buprenorphine and metha done both attenuated the response to hydromorphone challenge 24 hr lat er. These data indicate that there is a ceiling on the effects of bupr enorphine in humans that may reduce its abuse liability and increase i ts safety, and indicate that opioid blockade occurs after acute admini stration of buprenorphine or methadone.