Article

Molecular Neurobiology

, Volume 44, Issue 3, pp 250-268

Can the Chronic Administration of the Combination of Buprenorphine and Naloxone Block Dopaminergic Activity Causing Anti-reward and Relapse Potential?

  • Kenneth BlumAffiliated withDepartment of Psychiatry and McKnight Brain Institute, University of Florida College of MedicineThe National Institute for Holistic Addiction Studies (NIFHAS)G & G Holistic Addiction Treatment CenterDepartment of Clinical Neurology, Path FoundationDominion Diagnostic LaboratoryDepartment of Nutrigenomics, LifeGen, Inc.Centre for Genomics and Applied Gene Therapy, Institute of Integrative Omics and Applied Biotechnology (IIOAB) Email author 
  • , Thomas J. H. ChenAffiliated withDepartment of Occupational Safety and Health, Chang Jung Christian University
  • , John BaileyAffiliated withDepartment of Psychiatry and McKnight Brain Institute, University of Florida College of Medicine
  • , Abdalla BowirratAffiliated withDepartment of Neuroscience and Population Genetics, EMMS Nazareth–The Nazareth Hospital
  • , John FeminoAffiliated withMeadows Edge Recovery Center
  • , Amanda L. C. ChenAffiliated withDepartment of Engineering and Management of Advanced Technology, Chang Jung Christian University
  • , Thomas SimpaticoAffiliated withDepartment of Psychiatry, University of Vermont College of MedicineCommunity Mental Health Institute, Center for Clinical & Translational Science, University of Vermont
  • , Siobhan MorseAffiliated withThe National Institute for Holistic Addiction Studies (NIFHAS)G & G Holistic Addiction Treatment Center
  • , John GiordanoAffiliated withThe National Institute for Holistic Addiction Studies (NIFHAS)G & G Holistic Addiction Treatment Center
    • , Uma DamleAffiliated withDepartment of Psychiatry and McKnight Brain Institute, University of Florida College of MedicineDepartment of Clinical Neurology, Path Foundation
    • , Mallory KernerAffiliated withDepartment of Psychiatry and McKnight Brain Institute, University of Florida College of MedicineDepartment of Clinical Neurology, Path Foundation
    • , Eric R. BravermanAffiliated withDepartment of Psychiatry and McKnight Brain Institute, University of Florida College of MedicineDepartment of Clinical Neurology, Path FoundationDepartment of Neurological Surgery, Weill Cornell College of Medicine
    • , Frank FornariAffiliated withDepartment of Psychiatry and McKnight Brain Institute, University of Florida College of MedicineDominion Diagnostic Laboratory
    • , B. William DownsAffiliated withDepartment of Psychiatry and McKnight Brain Institute, University of Florida College of MedicineDepartment of Nutrigenomics, LifeGen, Inc.
    • , Cynthia RectorAffiliated withDepartment of Psychiatry and McKnight Brain Institute, University of Florida College of MedicineDepartment of Child and Adult Psychiatry, American Behavioral Consultants
    • , Debmayla BarhAffiliated withDepartment of Psychiatry and McKnight Brain Institute, University of Florida College of MedicineCentre for Genomics and Applied Gene Therapy, Institute of Integrative Omics and Applied Biotechnology (IIOAB)
    • , Marlene Oscar-BermanAffiliated withDepartment of Psychiatry and McKnight Brain Institute, University of Florida College of MedicineDepartments of Psychiatry and Anatomy & Neurobiology, Boston University School of Medicine, and Boston VA Healthcare System

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Abstract

Opiate addiction is associated with many adverse health and social harms, fatal overdose, infectious disease transmission, elevated health care costs, public disorder, and crime. Although community-based addiction treatment programs continue to reduce the harms of opiate addiction with narcotic substitution therapy such as methadone maintenance, there remains a need to find a substance that not only blocks opiate-type receptors (mu, delta, etc.) but also provides agonistic activity; hence, the impetus arose for the development of a combination of narcotic antagonism and mu receptor agonist therapy. After three decades of extensive research, the federal Drug Abuse Treatment Act 2000 (DATA) opened a window of opportunity for patients with addiction disorders by providing increased access to options for treatment. DATA allows physicians who complete a brief specialty-training course to become certified to prescribe buprenorphine and buprenorphine/naloxone (Subutex, Suboxone) for treatment of patients with opioid dependence. Clinical studies indicate that buprenorphine maintenance is as effective as methadone maintenance in retaining patients in substance abuse treatment and in reducing illicit opioid use. With that stated, we must consider the long-term benefits or potential toxicity attributed to Subutex or Suboxone. We describe a mechanism whereby chronic blockade of opiate receptors, in spite of only partial opiate agonist action, may ultimately block dopaminergic activity causing anti-reward and relapse potential. While the direct comparison is not as yet available, toxicity to buprenorphine can be found in the scientific literature. In considering our cautionary note in this commentary, we are cognizant that, to date, this is what we have available, and until such a time when the real magic bullet is discovered, we will have to endure. However, more than anything else this commentary should at least encourage the development of thoughtful new strategies to target the specific brain regions responsible for relapse prevention.

Keywords

Buprenorphine Dopamine Naloxone Opioid dependence Relapse Suboxone Subutex