Buprenorphine effects in methadone-maintained volunteers: effects at two hours after methadone.
Buprenorphine is an opioid partial agonist being developed for possible 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 methadone in methadone-maintained volunteers produced neither agonist-like nor antagonist-like effects. The purpose of this study was to examine the effects of buprenorphine challenges given 2 hr after a daily methadone dose in maintained volunteers. Seven male volunteers maintained on 30 mg of methadone daily underwent pharmacologic challenges two to three times per week. Medication challenges consisted of double-blind i.m. injections of buprenorphine (0.5-8.0 mg), the opioid antagonist naloxone (0.1 and 0.2 mg), the prototypic opioid mu agonist hydromorphone (5 and 10 mg) or saline. Assessments of physiologic measures, volunteers' self-reports and observer ratings of drug effects were collected in a laboratory session for 2 hr after drug administration, and then for 8 additional hr postsession. Results from the laboratory session showed that on subject and observer ratings naloxone produced typical antagonist-like effects, hydromorphone produced mild agonist-like effects and buprenorphine produced antagonist-like effects. Interestingly, buprenorphine's antagonist activity was not directly dose-related; its most prominent antagonist effects occurred at the 1- and 2-mg doses. These results are consistent with buprenorphine's action as a partial mu opioid agonist and demonstrate that antagonist-like effects can occur under some conditions suggesting buprenorphine should have a low abuse liability in methadone-maintained patients.
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224.
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Strain
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Preston
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Liebson
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Bigelow
D000328:Adult; D002047:Buprenorphine / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008691:Methadone / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D009270:Naloxone / Q000494:pharmacology; D009293:Opioid-Related Disorders / Q000188:drug therapy; D011597:Psychomotor Performance / Q000187:drug effects; D011680:Pupil / Q000187:drug effects; D013375:Substance Withdrawal Syndrome
D009270:Naloxone; D002047:Buprenorphine; D008691:Methadone