Safety and side-effects of buprenorphine in the clinical management of heroin addiction

Lange, W; Fudala, Paul J.; Dax, Elizabeth M.; Johnson, Rolley E.

doi:10.1016/0376-8716(90)90078-s

Cited by 92 publications

(60 citation statements)

References 30 publications

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“…This could account for the fact that there was not an increase in MOR 3 NTX responding even at the highest dose of naltrexone. Our inability to precipitate withdrawal from buprenorphine is consistent with the clinical literature (Heel et al, 1979;Lewis, 1985;Lange et al, 1990;Bickel and Amass, 1995;Ling et al, 1998). However, the opioid antagonist naloxone administered almost 2 h after buprenorphine completely reversed the effect of buprenorphine on squirrel monkeys responding in a shock-titration procedure (Dykstra, 1985).…”

Section: Discussionsupporting

confidence: 88%

Discriminative Stimulus Effects of Acute Morphine Followed by Naltrexone in the Squirrel Monkey: A Further Characterization

White

Holtzman²

2005

J Pharmacol Exp Ther

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The discriminative stimulus effects of acute morphine followed by naltrexone have been described previously in nonhuman primates. The purposes of this study were to 1) extend the pharmacological characterization of the discrimination by testing -opioid agonists other than morphine and opioid-like compounds other than naltrexone and 2) to examine further the relationship between agonist pretreatment time and manifestation of the cue produced by morphine followed by naltrexone. Subjects were trained to discriminate 1.7 mg/kg morphine 3 0.1 mg/kg naltrexone (MOR 3 NTX) versus saline followed by 0.1 mg/kg naltrexone. When combined with 0.1 mg/kg naltrexone, all agonists tested, save buprenorphine, meperidine, and nalbuphine, produced dose-dependent increases in MOR 3 NTX-appropriate responding, culminating in criterion levels of responding. Comparing agonist ED 50 values revealed a rank order of potency of etorphine Ͼ Ͼ fentanyl Ͼ Ͼ levorphanol Ͼ heroin Ն methadone Ն nalbuphine Ն morphine. ED 50 values for buprenorphine and meperidine could not be calculated. MOR 3 NTX-appropriate responding after doses of agonist that produced criterion or near criterion levels of responding was also a function of naltrexone dose. After morphine pretreatment, diprenorphine and nalorphine, but not buprenorphine, dose-dependently substituted for naltrexone. The MOR 3 NTX discrimination also depended upon the interval between morphine and NTX administration. Finally, 1-h pretreatment with morphine and etorphine, but not buprenorphine, followed by naltrexone generalized to 4 h MOR 3 NTX. These results suggest a minimum efficacy requirement of acutely administered agonists together with the naltrexone training dose for stimulus control of behavior. However, in some cases this requirement can be overcome with higher doses of naltrexone.The administration of an opioid antagonist after a single injection of a morphine-like drug elicits characteristic physiological and behavioral changes, in addition to subjective symptoms (e.g., negative mood states) (for review, see Harris and Gewirtz, 2005), much like the withdrawal syndrome after chronic morphine administration (Martin, 1983). These findings not only serve as evidence of acute opioid dependence but also suggest a common, underlying mechanism with chronic opioid dependence. The phenomenon of acute dependence is predominantly mediated via -opioid receptors and is stereoselective (Ramabadran, 1983;Adams and Holtzman, 1990; Holtzman, 1997, 1999;White and Holtzman, 2003). The severity of withdrawal from acute opioid dependence is critically dependent upon the doses of agonist and antagonist used as well as the interval between agonist and antagonist administration (Harris and Gewirtz, 2005).Drug discrimination affords a useful animal model for studying interoceptive drug effects, including those associated with morphine withdrawal (Holtzman, 1990). Previously, we trained squirrel monkeys to discriminate 1.7 mg/kg morphine (4-h pretreatment) followed by 0.1 mg/kg naltrexone (15-min pr...

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Section: Discussionsupporting

confidence: 88%

Discriminative Stimulus Effects of Acute Morphine Followed by Naltrexone in the Squirrel Monkey: A Further Characterization

White

Holtzman²

2005

J Pharmacol Exp Ther

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“…This unique combination of NO . 3 Buprenorphine and Mu Receptor 327 pharmacological properties confers potential advantages, including enhanced safety over existing medications for treating opioid abuse (Lange et al 1990).Buprenorphine sublingual (SL) liquid has been shown to decrease heroin self-administration in singledose human laboratory studies (Mello and Mendelson 1980;Mello et al 1981Mello et al , 1982; the dose-dependency of its effects on reinforcement has been less well characterized. In a clinical study, Johnson et al (1995) compared the short-term efficacy of placebo, 2 and 8 mg/day buprenorphine in a parallel group, randomized design during a two-week initial maintenance period.…”

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confidence: 99%

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confidence: 99%

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Buprenorphine-Induced Changes in Mu-Opioid Receptor Availability in Male Heroin-Dependent Volunteers A Preliminary Study

Zubieta

Greenwald

Lombardi

et al. 2000

Neuropsychopharmacology

118

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Medications for the treatment of substance abuse may be developed for a variety of purposes (e.g., ameliorate toxicity, treat overdoses) but a primary goal is to attenuate the subjective, behavioral, or physiological effects of the drug of abuse. Buprenorphine is a high affinity, mu opioid partial agonist, with kappa antagonist action (Cowan et al. 1977;Heel et al. 1979;Lewis et al. 1983). This compound is being evaluated as an alternative to methadone maintenance and detoxification in the treatment of opioid dependence (Bickel and Amass 1995). Buprenorphine's mu receptor ( OR) agonist actions could reduce opiate craving and prevent withdrawal, thus improving compliance with treatment compared to conventional opiate receptor antagonists (e.g., naltrexone). At the same time, its partial efficacy and high affinity at OR's provide long lasting functional antagonism, making it an effective means of blocking the effects of abused opiates. This unique combination of NO . 3 Buprenorphine and Mu Receptor 327 pharmacological properties confers potential advantages, including enhanced safety over existing medications for treating opioid abuse (Lange et al. 1990).Buprenorphine sublingual (SL) liquid has been shown to decrease heroin self-administration in singledose human laboratory studies (Mello and Mendelson 1980;Mello et al. 1981Mello et al. , 1982; the dose-dependency of its effects on reinforcement has been less well characterized. In a clinical study, Johnson et al. (1995) compared the short-term efficacy of placebo, 2 and 8 mg/day buprenorphine in a parallel group, randomized design during a two-week initial maintenance period. In this study, active doses were more effective than placebo in decreasing heroin use, however, there were no differences in therapeutic efficacy between 2 and 8 mg. Schottenfeld et al. (1993) used a within-subject study design in which heroin-dependent outpatients received ascending/descending maintenance doses of buprenorphine ranging from 2 to 16 mg/day. Sixteen milligrams produced significant decreases in opioid-positive urine samples, relative to lower doses. Thus, available data suggest that, relative to placebo, buprenorphine doses ranging from 2 to 8 mg are equally capable of decreasing opioid use, whereas doses of 16 mg have greater efficacy. This may suggest that the effect of buprenorphine in decreasing opiate self-administration may not be dose-dependent, at least in lower dose ranges. In fact, in a recently completed laboratory study in heroindependent volunteers, maintenance doses of 2, 4, and 8 mg buprenorphine showed equal efficacy in decreasing the reinforcing effects of hydromorphone (Greenwald et al. 1999).On the other hand, laboratory studies have demonstrated that SL buprenorphine blocks many of the subjective effects of hydromorphone, a full mu opioid agonist, in a dose-dependent manner. For instance, Bickel et al. (1988) showed that maintenance on buprenorphine (2, 4, 8, 16 mg) produced dose-related decreases in subjective effects to cumulative hydromorphone (0, 6,...

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“…Buprenorphine maintenance has also been studied extensively for the treatment of heroin dependence and has been shown to have outcomes comparable to those of methadone maintenance. 3 Buprenorphine maintenance treatment of prescription opioid dependence is increasing in frequency and appears to be effective. 4 However, no data exist for buprenorphine maintenance treatment of addiction to fentanyl or sufentanil, the most common drugs of abuse among anesthesia personnel.…”

Section: W E Congratulate Mayo Clinic Proceedings and The Authors Hammentioning

confidence: 99%

Opioid-Abusing Health Care Professionals: Options for Treatment and Returning to Work After Treatment

Seppala

Oreskovich

2012

Mayo Clinic Proceedings

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Safety and side-effects of buprenorphine in the clinical management of heroin addiction

Cited by 92 publications

References 30 publications

Discriminative Stimulus Effects of Acute Morphine Followed by Naltrexone in the Squirrel Monkey: A Further Characterization

Discriminative Stimulus Effects of Acute Morphine Followed by Naltrexone in the Squirrel Monkey: A Further Characterization

Buprenorphine-Induced Changes in Mu-Opioid Receptor Availability in Male Heroin-Dependent Volunteers A Preliminary Study

Opioid-Abusing Health Care Professionals: Options for Treatment and Returning to Work After Treatment

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