Effects of Buprenorphine Maintenance Dose on μ-Opioid Receptor Availability, Plasma Concentrations, and Antagonist Blockade in Heroin-Dependent Volunteers

@article{Greenwald2003EffectsOB,
  title={Effects of Buprenorphine Maintenance Dose on $\mu$-Opioid Receptor Availability, Plasma Concentrations, and Antagonist Blockade in Heroin-Dependent Volunteers},
  author={Mark K. Greenwald and Chris Ellyn Johanson and David E. Moody and James H. Woods and Michael R. Kilbourn and Robert A. Koeppe and Charles Roberts Schuster and Jon-Kar Zubieta},
  journal={Neuropsychopharmacology},
  year={2003},
  volume={28},
  pages={2000-2009}
}
The clinical effectiveness of opioid maintenance for heroin dependence is believed to result from a medication's ability to decrease μ-opioid receptor (μOR) availability thereby replacing agonist effects, alleviating withdrawal symptoms and attenuating heroin effects. We empirically tested this hypothesis in five heroin-dependent volunteers who were successively maintained on 32, 16, 2, and 0 mg daily buprenorphine (BUP) tablet doses. We predicted and confirmed that higher BUP doses would… 
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237 Citations

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TLDR
This strategy could be further combined with pharmacodynamic exploration or pharmacological MRI to investigate the neuropharmacokinetics and neuroreceptor correlate, at least at µ-OR, of the acute effects of buprenorphine in humans.
Cross-tolerance and μ agonist efficacy in pigeons treated with LAAM or buprenorphine
The effects of chronic buprenorphine on intake of heroin and cocaine in rats and its effects on nucleus accumbens dopamine levels during self-administration
TLDR
It is interesting to note that buprenorphine increased the latency to respond to drug-associated cues at the start of self-administration sessions, and possibly reduces drug seeking by reducing the salience of the drug- associated cues.
Time-Course of Buprenorphine Dose Increase in a Maintenance Program for Heroin Addicts: Retention in Treatment and Clinical Meaning
TLDR
It is not sharply clear whether the gap of effectiveness is mainly related to a higher level of agonism or the opioid blockade, but some patients do respond to 2-4-6 mg regimens by a significant rate.
Buprenorphine Antinociception is Abolished, but Naloxone-Sensitive Reward is Retained, in μ-Opioid Receptor Knockout Mice
TLDR
The results of the investigation on the roles of μ-, δ-, and κ-opioid receptors in antinociceptive responses and place preferences induced by buprenorphine support the ideas that μ-opIOid receptors mediate most of analgesic properties of bupenorphine, but thatμ- and δ- and/or λ-opiosid receptors are each involved in the rewarding effects of this drug.
Yohimbine increases opioid-seeking behavior in heroin-dependent, buprenorphine-maintained individuals
TLDR
These findings concur with preclinical data by demonstrating that yohimbine increases drug seeking; in this study, these effects occurred without clinically significant subjective distress or elevated craving, and partly depended on opioid unit dose.
Rats Maintained Chronically on Buprenorphine Show Reduced Heroin and Cocaine Seeking in Tests of Extinction and Drug-Induced Reinstatement
TLDR
Results indicate that the suppression of responding following priming injections of drugs did not result from reduced motor activity, but possibly from a reduction in the salience of drug-associated cues induced by chronic buprenorphine treatment.
Using [11C]Diprenorphine to Image Opioid Receptor Occupancy by Methadone in Opioid Addiction: Clinical and Preclinical Studies
TLDR
It is suggested that the lack of a dose-dependent relationship between methadone dose, either given chronically in human or acutely in rat, and occupancy of opioid receptor measured with [11C]diprenorphine PET is related to efficacy of this opioid agonist at very low levels of opioids receptor occupancy.
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References

SHOWING 1-10 OF 51 REFERENCES
Buprenorphine-Induced Changes in Mu-Opioid Receptor Availability in Male Heroin-Dependent Volunteers: A Preliminary Study
Opioid reinforcement in heroin-dependent volunteers during outpatient buprenorphine maintenance.
Buprenorphine: dose-related blockade of opioid challenge effects in opioid dependent humans.
TLDR
The results of this study confirm previous reports of buprenorphine blockade of opioid agonist effects in humans and extent those findings by demonstrating both a bup Renorphine dose-effect function and a dissociation between the potency of bu prenorphin's opioid blockade for self-report vs. physiological measures.
Effects of buprenorphine sublingual tablet maintenance on opioid drug-seeking behavior by humans
TLDR
High-dose buprenorphine attenuated opioid drug-seeking behavior, heroin craving self-reports and increased sensitivity to alternative reinforcement as well as influencing choice of, and operant responding for, hydromorphone versus money.
Acute administration of buprenorphine in humans: partial agonist and blockade effects.
TLDR
There is a ceiling on the effects of buprenorphine in humans that may reduce its abuse liability and increase its safety, and indicate that opioid blockade occurs after acute administration of bu p.o.m. or methadone.
Buprenorphine sublingual tablets: effects on IV heroin self-administration by humans
TLDR
It is demonstrated that the reinforcing effects of heroin were not fully antagonized by these doses of the tablet formulation of buprenorphine, and that 16 mg bupenorphine reduced heroin self-administration relative to 8 mg.
Buprenorphine treatment of opioid dependence: A review.
TLDR
The research suggests that inducting patients onto buprenorphine should lead to limited discomfort if appropriate procedures are followed, and that discontinuing bupRenorphine treatment appears to result in a mild-to-moderate opioid withdrawal syndrome that is less severe than that observed with full-efficacy agonists.
Buprenorphine: Dose-related effects on cocaine and opioid use in cocaine-abusing opioid-dependent humans
Use of buprenorphine in the treatment of opioid addiction. II. Physiologic and behavioral effects of daily and alternate‐day administration and abrupt withdrawal
TLDR
Daily administration of buprenorphine provided greater control of subtle opioid withdrawal symptoms, but subjects could tolerate a between‐dose interval of 48 hours.
Relationship of plasma buprenorphine and norbuprenorphine to withdrawal symptoms during dose induction, maintenance and withdrawal from sublingual buprenorphine.
TLDR
The long elimination half-life of buprenorphine suggested that increasing the bup Renorphine dose with alternate-day administration may provide an effective, flexible therapy regimen for the treatment of opioid dependence.
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