Buprenorphine alone and in combination with naloxone in non-dependent humans

Weinhold, Linda L.; Preston, Kenzie L.; Farré, Magı́; Liebson, Ira A.; Bigelow, George E.

doi:10.1016/0376-8716(92)90061-g

Cited by 50 publications

(35 citation statements)

References 20 publications

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Section: Discussionmentioning

confidence: 99%

“…Only two other studies have evaluated the effects of the buprenorphine/naloxone combination in nonopioid-dependent individuals who abuse heroin (Weinhold et al, 1992;Strain et al, 2000). Weinhold et al (1992) demonstrated that intramuscular administration of the buprenorphine/naloxone combination reduced subjective and physiological (miosis and respiratory depression) effects, relative to buprenorphine alone, suggesting that the combination would have lower abuse liability. A more recent study comparing the effects of sublingual buprenorphine with sublingual buprenorphine/naloxone combinations in nondependent heroin abusers showed that although peak effects for some subjective measures were lower for the combination relative to buprenorphine alone, these differences were not statistically significant .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Comer¹,

Collins²

2002

J Pharmacol Exp Ther

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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...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Comer¹,

Collins²

2002

J Pharmacol Exp Ther

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“…Rather, the primary emphasis has been on designing drug combinations to decrease the risk for illicit diversion of the treatment medications. For example, several investigators have examined the feasibility of combining naloxone with either buprenorphine or methadone to prevent intravenous abuse of these opioid agonist medications (Fudala et al 1998;Loimer et al 1991;Mendelson et al , 1997Mendelson et al , 1999Preston et al 1989;Weinhold et al 1992). Naloxone has poor bioavailability by oral and sublingual routes of administration and much higher bioavailability by intravenous route.…”

Section: The Simultaneous IV Administration Of Heroin and Cocaine mentioning

confidence: 99%

Effects of Flupenthixol and Quadazocine on Self-Administration of Speedball Combinations of Cocaine and Heroin by Rhesus Monkeys

Mello

Negus

1999

Neuropsychopharmacology

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The simultaneous i.v. administration of heroin and cocaine, called "speedball," is often reported clinically, and identification of effective pharmacotherapies for polydrug abuse is a continuing challenge. This study compared the effects of treatment using combinations of dopamine and opioid antagonists with each antagonist alone onIt is increasingly recognized that drug abusers tend to use multiple drugs rather than a single drug (NIDA, 1998). Polydrug abuse often involves the concurrent abuse of cocaine and heroin, and both cocaine and continued opiate abuse have been reported in methadonemaintained patients (Condelli et al. 1991;Kosten et al. 1989b;Schottenfeld et al. 1993Schottenfeld et al. , 1997. One common form of polydrug abuse is called the speedball, which usually refers to the simultaneous intravenous administration of cocaine and heroin (NIDA, 1998;Schütz et al. 1994). Currently approved pharmacotherapies for opiate abuse have been only moderately effective in reducing polydrug abuse, and there is no consistently effective pharmacotherapy for either abuse of cocaine alone or combinations of cocaine and heroin "speedball" .Preclinical evaluation of medications for reducing Received December 10, 1998; revised March 8, 1999; accepted April 19, 1999. 576 N.K. Mello and S.S. Negus N EUROPSYCHOPHARMACOLOGY 1999 -VOL . 21 , NO . 4 polydrug abuse has been greatly facilitated by the development of animal models of speedball self-administration (Hemby et al. 1996(Hemby et al. , 1999Mello and Negus 1998;Rowlett and Woolverton 1997) and speedball discrimination (Negus et al. 1998a). Combinations of cocaine and heroin produce robust reinforcing and discriminative stimulus effects in these animal models, and cocaine and heroin may enhance each other's reinforcing and discriminative stimulus effects under some conditions (Negus et al. 1998a;Rowlett and Woolverton 1997).Similarly, neurochemical evidence suggests that selfadministration of cocaine and heroin in combination has synergistic effects on extracellular dopamine release at the nucleus accumbens in rats (Hemby et al. 1999). Dopamine levels measured by microdialysis remained at baseline levels during heroin self-administration, increased by 400% during cocaine self-administration, and increased by 1000% during speedball selfadministration, even though cocaine levels measured in dialysate samples were equivalent during cocaine and speedball self-administration (Hemby et al. 1999). Interestingly, however, the synergistic increases in dopamine levels during speedball self-administration were not accompanied by differences in operant responding maintained by cocaine and heroin alone and in combination (Hemby et al. 1999). Moreover, several other studies found that co-administration of cocaine and opioids produced discrimination stimulus and reinforcing effects that were additive or less than additive and resembled the effects of cocaine or heroin alone Negus et al. 1998b;Lamas et al. 1998;Rowlett and Spealman 1998).Taken together, these findings are cons...

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“…The increased rat ings of positive mood, liking for the drug, and seda tion are consistent with previous reports (Jaskinski et a1. 1989;Preston and Jasinski 1991;Weinhold et al 1992). The onset of the subjective effects of buprenor phine, as measured by the beep-prompted responses, occurred within 7 minutes of the intramuscular injec tion.…”

Section: Buprenorphine and Cerebral Glucose Metabolism 167mentioning

confidence: 99%

Buprenorphine Reduces Cerebral Glucose Metabolism in Polydrug Abusers

Walsh

Gilson

Jasinski

et al. 1994

Neuropsychopharmacol

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Buprenorphine is a mixed opioid agonist-antagonist, which acts as a partial mu agonist and a kappa antagonist. The present study evaluated the acute effects of buprenorphine on cerebral glucose metabolism (CMRglc) in six human substance abusers using a double-blind, placebo-controlled, counterbalanced, crossover design. Each subject participated in two positron emission tomographic (PET) studies, 1 week apart, following the injection of buprenorphine (1 mg, intramuscularly) and placebo. Buprenorphine significantly reduced CMRglc and the regional cerebral KEY WORDS: Opioid; Buprenorphine; Glucose metabolism; Drug abuse; Human brain imaging Buprenorphine, a semi-synthetic opioid drug derived from thebaine, is currently marketed in the United States as an analgesic, and is approximately 25 to 50 times as potent as morphine (Cowan et al. 1977). In hu man subjects, it produces effects that are typical of opi oid agonists (Heel et al. 1979). These include analge-

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Buprenorphine alone and in combination with naloxone in non-dependent humans

Cited by 50 publications

References 20 publications

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

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

Effects of Flupenthixol and Quadazocine on Self-Administration of Speedball Combinations of Cocaine and Heroin by Rhesus Monkeys

Buprenorphine Reduces Cerebral Glucose Metabolism in Polydrug Abusers

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