Self-Administration of Intravenous Buprenorphine and the Buprenorphine/Naloxone Combination by Recently Detoxified Heroin Abusers

Abstract

Buprenorphine is a partial -opioid agonist and -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 ϭ 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.Both phase I and II clinical trials have demonstrated that buprenorphine is effective in treating opioid dependence (Bickel and Amass, 1995;Johnson et al., 2000). Despite its clear clinical utility, several lines of evidence suggest that buprenorphine has some abuse liability. Studies using nonhuman primates showed that buprenorphine serves as a reinforcer (Negus and Woods, 1995). For example, Winger and Woods (2001) showed that rates of responding maintained by buprenorphine were higher than placebo but lower than rates of responding for the full -agonists heroin and alfentanil (Winger and Woods, 2001). Another study demonstrated that buprenorphine was less reinforcing than heroin but equivalent to methadone (Mello et al., 1988). Thus, buprenorphine is self-administered by laboratory animals, and under some conditions, is self-administered at rates comparable with full -agonists.In humans, two studies examined the reinforcing effects of buprenorphine in heroin users maintained on sublingual buprenorphine in outpatient treatment settings (Petry and Bickel, 1999;Amass et al., 2000). Petry and Bickel (1999) examined the reinforcing effects of sublingual buprenorphine. Participants who were given the opportunity to choose between sublingual buprenorphine and money almost exclusively self-administered buprenorphine...

Controversies in translational research: drug self-administration

“…than placebo, demonstrating abuse potential by the i.v. route of administration for this group (Comer et al 2002a(Comer et al , 2005(Comer et al , 2008bComer and Collins 2002). These latter findings are generally consistent with the results obtained in self-administration studies with animals and appear to be borne out by international epidemiological evidence of i.v.…”

“…In detoxified heroin abusers, buprenorphine/naloxone combinations (2/0.5 and 8/2 mg) produced fewer opioid-related subjective effects, but were as reinforcing as buprenorphine alone (2 and 8 mg; Comer and Collins 2002). It may be that buprenorphine/naloxone combinations would have less abuse liability if opioid-dependent populations were studied.…”

Buprenorphine with, or without, Naloxone for Pregnant Women?–Review of Current Evidence and Practice in Massachusetts

“…Our understanding of current evidence leads us to believe that naloxone does not play an important role, particularly when administered concurrently with buprenorphine in patients on long-term buprenorphine maintenance [16,40]. The aversive effect with parenteral, but much less so with sublingual buprenorphine/naloxone combination for individuals dependent on full opiate receptor agonists, has been reported to decrease the desirability of the combination for parenteral use but the extent of the deterrent effect in practice remains controversial [11,41,43]. On the other hand, the significance of unsafe intravenous substance use is overwhelming, both from the perspective of the pregnant woman and her unborn foetus.…”

Opioid Substitution Therapy for Dependent Health Care Practitioners: Approach With Caution

“…Buprenorphine alone or in combination with naloxone is reinforcing. 3 It is unclear whether replacement therapy eliminates the use of other drugs of abuse in naturalistic (nonresearch) settings. Patients taking buprenorphine are known to stockpile their medications, either out of concern for running short or at times to ensure an adequate supply for detoxification after a lapse.…”