Self-administration of intravenous buprenorphine and the buprenorphine/naloxone combination by recently detoxified heroin abusers

Abstract

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.

Figure 1

Progressive ratio break point values for drug (top panel) and money (bottom panel) as a function of dose and choice session. Break point values could range between 0 and 2800. Data points represent the mean across 6 participants and 4 choice sessions (solid bars), and the mean across 6 participants during each of the 4 choice sessions. Error bars represent ± 1 standard error of the mean (S.E.M.). * indicates significant differences from placebo; brackets indicate significant differences between those two data points (P<0.01).

Figure 2

Selected Drug Effects Questionnaire ratings as a function of dose. Data points represent mean ratings for the 6 participants across the sample and no drug sessions. Error bars represent ± 1 standard error of the mean (S.E.M.). * indicates significant differences from placebo (P<0.01).

Figure 3

Drug Effects Questionnaire ratings of “Good Effects” during the sample session and subsequent no drug sessions as a function of dose and time. Data points represent mean ratings for the 6 participants. Error bars represent ± 1 standard error of the mean (S.E.M.). * indicates significant differences from placebo at that time point (P<0.01).

Figure 4

Visual analog scale ratings of “Good Effects” during the sample and no drug sessions as a function of dose and time. Data points represent mean ratings for the 6 participants. Error bars represent ± 1 standard error of the mean (S.E.M.). * indicates significant differences from placebo at that time point (P<0.01). BL, baseline.

Figure 5

Pupil diameter during the sample and no drug sessions as a function of buprenorphine dose and time. See Figure 4 legend for additional details. Asterisks were aligned vertically for some data points to improve clarity.