Comparison of Intravenous Buprenorphine and Methadone Self-Administration by Recently Detoxified Heroin-Dependent Individuals

Abstract

Although buprenorphine is used worldwide as a safe and effective maintenance medication for opioid dependence, some countries have reported a growing incidence of abuse of this medication. Buprenorphine is considered to have lower abuse potential because of its partial agonist profile, but no studies have directly compared the reinforcing effects of buprenorphine with those of full opioid agonists in humans. The present double-blind, placebo-controlled inpatient study compared the reinforcing and subjective effects of intravenously administered buprenorphine (0.5, 2, and 8 mg) and methadone (5, 10, and 20 mg). Participants (n ϭ 6) were detoxified from heroin during the first 1 to 2 weeks after admission. During subsequent weeks, participants received a sample drug dose and $20 on Monday, and they could self-administer either the sampled dose or $20 during one choice session per day on Thursday and Friday. Participants responded under a modified progressive ratio schedule during each choice session. All active doses maintained higher progressive ratio break points (largest completed ratio) than placebo. There were no significant differences in break point values between buprenorphine and methadone or among the different doses of drug. However, several subjective ratings, including "good drug effect", "high", and "liking" dose-dependently increased after administration of buprenorphine and methadone. The peak ratings for these effects did not significantly differ for the two drugs. These results demonstrate that under these experimental conditions, buprenorphine and methadone were equally effective in producing reinforcing and subjective effects.Buprenorphine, a partial opioid agonist and opioid antagonist, is used clinically to treat pain, and more recently, it has been used as a safe and effective maintenance therapy for opioid dependence. The partial agonist profile of buprenorphine was defined by several studies conducted in both laboratory animals and humans showing that its effects are less robust than those of full agonists, particularly when the intensity of the stimulus (e.g., pain intensity) is high. For example, in a warm water tail withdrawal procedure, buprenorphine produces maximal analgesic effects when the water temperature is low but not when it is high (Walker et al., 1995;Morgan et al., 1999;Barrett et al., 2001). Similarly, in a drug discrimination paradigm, buprenorphine consistently substitutes fully for other agonists when the training dose is low (Preston and Bigelow, 2000) but not when it is high (Picker et al., 1993). The partial agonist profile of buprenorphine is also revealed under conditions of opioid tolerance: the effects of buprenorphine are reduced more than those of other agonists in opioid-tolerant animals. For example, in rats chronically treated with buprenorphine, the analgesic effects of buprenorphine itself were reduced to a greater extent than the analgesic effects of other agonists, such as etorphine or morphine (Paronis and Holtzman, 1992;Walker and Young, 2001)....

Abuse Liability of Prescription Opioids Compared to Heroin in Morphine-Maintained Heroin Abusers

“…Although reports of buprenorphine abuse have been relatively rare in the United States, several other countries around the world have reported a growing problem with it. Consistent with the epidemiological data, our previous studies showed that buprenorphine was self-administered above placebo levels in non-opioiddependent, recently detoxified individuals Comer et al, , 2005. The purpose of the present study was to compare the reinforcing, subjective, physiological, and performance effects of fentanyl, oxycodone, buprenorphine, morphine, and heroin in morphine-maintained heroin abusers.…”

“…Interestingly, buprenorphine was the only drug that did not produce any impairments in performance of the divided attention task. In two of our previous studies in non-opioid-dependent individuals, buprenorphine did produce impairments in performance of the DAT (Comer et al, , 2005, but it did not significantly impair performance of the DAT in a third study . A final interesting finding in the present study was the improvement in performance of the DAT after fentanyl administration.…”

“…In several previous studies conducted in our laboratory, buprenorphine did serve as a robust reinforcer (Comer et al, , 2005. The primary difference among the studies is that participants were maintained on morphine in the present experiment.…”

“…The oxycodone doses were chosen based on previous studies demonstrating a roughly equipotent relationship between intravenously delivered oxycodone and morphine for treating pain (Foley, 1985). The highest buprenorphine doses were chosen based on several previous studies conducted in our laboratory demonstrating that they were well tolerated and behaviorally active Comer et al, , 2005.…”

“…Like those of the full mu agonist fentanyl, the reinforcing effects of the partial mu opioid agonist buprenorphine have been studied fairly extensively in laboratory animals (eg Mello et al, 1988;Winger and Woods, 2001). However, only a few studies have examined the reinforcing effects of buprenorphine in human research volunteers (Amass et al, 2000;Comer et al, , 2005. Although reports of buprenorphine abuse have been relatively rare in the United States, several other countries around the world have reported a growing problem with it.…”