Self-administration of intravenous buprenorphine and the buprenorphine/naloxone combination by recently detoxified heroin abusers.
Buprenorphine is a partial mu-opioid agonist and kappa-opioid antagonist currently under development as a maintenance medication for heroin dependence. Because of concerns about illicit diversion of buprenorphine, a combination tablet containing buprenorphine and naloxone has been developed. The present study evaluated the reinforcing effects of intravenously administered placebo, buprenorphine alone (BUP; 2 and 8 mg), and the buprenorphine/naloxone combination (BUP/NX; 2 mg of buprenorphine plus 0.5 mg of naloxone, and 8 mg of buprenorphine plus 2 mg of naloxone) in recently detoxified heroin abusers during a 6-week inpatient study. Participants (n = 6) were detoxified from heroin over approximately 1 week immediately after admission. During the next 5 weeks, the reinforcing effects of placebo, BUP, and BUP/NX were evaluated. Participants first received a dose of drug and $20 and then were given the opportunity to self-administer either the dose or $20 during choice sessions. Progressive ratio break point values were significantly higher after active drug, compared with placebo, but they did not significantly differ as a function of dose or drug. In contrast, positive subjective ratings were higher after administration of BUP compared with BUP/NX, and these ratings increased in a dose-dependent manner. BUP and the combination had few effects on performance. Relative to placebo, both BUP and BUP/NX decreased pupil diameter, but there were no significant differences in pupil diameter as a function of drug or dose. These results demonstrate that both BUP and BUP/NX served as reinforcers under these conditions and that they may have similar abuse liability in recently detoxified individuals who abuse heroin.
Comer
Sandra D
SD
Division on Substance Abuse, New York State Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, 1051 Riverside Drive, Unit 120, New York, NY 10032, USA. sdc10@columbia.edu
Collins
Eric D
ED
D000284:Administration, Oral; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002047:Buprenorphine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D006556:Heroin Dependence / Q000523:psychology*; D006801:Humans; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects; D011680:Pupil / Q000187:drug effects; D012054:Reinforcement, Psychology; D012646:Self Administration; D011795:Surveys and Questionnaires
D004338:Drug Combinations; D009292:Narcotic Antagonists; D009294:Narcotics; D009270:Naloxone; D002047:Buprenorphine