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J Pharmacol Exp Ther. 1992 Jun;261(3):985-93.

Acute effects of buprenorphine, hydromorphone and naloxone in methadone-maintained volunteers.

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Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.


Buprenorphine is an opioid agonist-antagonist being evaluated for treatment of opioid dependence. This study characterized the effects of buprenorphine in comparison to naloxone, hydromorphone and saline, in methadone-dependent volunteers. In a residential laboratory, 6 volunteer male opioid abusers maintained on 30 mg of methadone daily underwent pharmacological challenges 2 to 3 times per week. Pharmacological challenges consisted of a double-blind i.m. injection of: buprenorphine (dose range 0.5-8.0 mg), hydromorphone (5 and 10 mg), naloxone (0.1 and 0.2 mg) or saline. Injections were given 20 hr after the last dose of methadone. Measures included physiologic indices, and self-report and observer ratings of drug effects. Naloxone and hydromorphone produced characteristic antagonist-like and agonist-like effects, respectively, on subjective, observer and physiologic indices. None of the doses of buprenorphine were consistently or systematically identified as an opioid agonist or antagonist on any of the measures. Thus buprenorphine produced minimal effects in methadone-dependent patients. The lack of agonist effects suggests buprenorphine has a low abuse potential in methadone-dependent patients. The lack of antagonist effects suggests buprenorphine can be administered safely to subjects dependent on a low dose of methadone. This lack of effect of buprenorphine distinguishes it from other mixed agonist antagonists previously tested, which produced antagonist effects in this procedure.

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