Molecular Neurobiology

, Volume 44, Issue 3, pp 250–268 | Cite as

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

  • Kenneth Blum
  • Thomas J. H. Chen
  • John Bailey
  • Abdalla Bowirrat
  • John Femino
  • Amanda L. C. Chen
  • Thomas Simpatico
  • Siobhan Morse
  • John Giordano
  • Uma Damle
  • Mallory Kerner
  • Eric R. Braverman
  • Frank Fornari
  • B. William Downs
  • Cynthia Rector
  • Debmayla Barh
  • Marlene Oscar-Berman
Article

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 

Notes

Acknowledgments

We thank the staff of PATH Foundation NY. The writing of this article was funded in part by LifeGen, Inc., San Diego, CA, USA. Other support came from NIAAA grants R01-AA07112 and K05-AA00219 and the Medical Research Service of the US Department of Veterans Affairs (to MO-B).

Authors’ Contributions

KB wrote the first draft of the paper. The figures were developed by Margret Madigan, an AB. The entire final article was edited by Margaret Madigan. JF, JG, JB, SS, TS, MO-B, UD, MK, SM, FF, BWD, THJC, ALCC, DB, and ERB reviewed and edited the manuscript. UD was responsible for literature search and appropriate reference style. All the authors read and approved the final manuscript.

Competing Interests

The patented KB220Z therapy has been exclusively licensed to LifeGen, Inc., whereby KB and BWD owns stock. JG, and FF are partners with LifeGen, Inc. All other authors declare that they have no competing interest.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Kenneth Blum
    • 1
    • 8
    • 9
    • 10
    • 12
    • 13
    • 15
  • Thomas J. H. Chen
    • 2
  • John Bailey
    • 1
  • Abdalla Bowirrat
    • 3
  • John Femino
    • 4
  • Amanda L. C. Chen
    • 5
  • Thomas Simpatico
    • 6
    • 7
  • Siobhan Morse
    • 8
    • 9
  • John Giordano
    • 8
    • 9
  • Uma Damle
    • 10
  • Mallory Kerner
    • 10
  • Eric R. Braverman
    • 10
    • 11
  • Frank Fornari
    • 12
  • B. William Downs
    • 13
  • Cynthia Rector
    • 14
  • Debmayla Barh
    • 15
  • Marlene Oscar-Berman
    • 16
  1. 1.Department of Psychiatry and McKnight Brain InstituteUniversity of Florida College of MedicineGainesvilleUSA
  2. 2.Department of Occupational Safety and HealthChang Jung Christian UniversityTainanRepublic of China
  3. 3.Department of Neuroscience and Population GeneticsEMMS Nazareth–The Nazareth HospitalNazarethIsrael
  4. 4.Meadows Edge Recovery CenterNorth KingstownUSA
  5. 5.Department of Engineering and Management of Advanced TechnologyChang Jung Christian UniversityTainanRepublic of China
  6. 6.Department of PsychiatryUniversity of Vermont College of MedicineBurlingtonUSA
  7. 7.Community Mental Health Institute, Center for Clinical & Translational ScienceUniversity of VermontBurlingtonUSA
  8. 8.The National Institute for Holistic Addiction Studies (NIFHAS)North Miami BeachUSA
  9. 9.G & G Holistic Addiction Treatment CenterNorth Miami BeachUSA
  10. 10.Department of Clinical NeurologyPath FoundationNew YorkUSA
  11. 11.Department of Neurological SurgeryWeill Cornell College of MedicineNew YorkUSA
  12. 12.Dominion Diagnostic LaboratoryNorth KingstownUSA
  13. 13.Department of NutrigenomicsLifeGen, Inc.San DiegoUSA
  14. 14.Department of Child and Adult PsychiatryAmerican Behavioral ConsultantsLebanonUSA
  15. 15.Centre for Genomics and Applied Gene TherapyInstitute of Integrative Omics and Applied Biotechnology (IIOAB)Purba MedinipurIndia
  16. 16.Departments of Psychiatry and Anatomy & NeurobiologyBoston University School of Medicine, and Boston VA Healthcare SystemBostonUSA

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