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

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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.

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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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Authors and Affiliations

  1. Department of Psychiatry and McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, 32610, USA

    Kenneth Blum & John Bailey

  2. Department of Occupational Safety and Health, Chang Jung Christian University, Tainan, Taiwan, Republic of China

    Thomas J. H. Chen

  3. Department of Neuroscience and Population Genetics, EMMS Nazareth–The Nazareth Hospital, Nazareth, Israel

    Abdalla Bowirrat

  4. Meadows Edge Recovery Center, North Kingstown, RI, 02852, USA

    John Femino

  5. Department of Engineering and Management of Advanced Technology, Chang Jung Christian University, Tainan, Taiwan, Republic of China

    Amanda L. C. Chen

  6. Department of Psychiatry, University of Vermont College of Medicine, Burlington, VT, 05401, USA

    Thomas Simpatico

  7. Community Mental Health Institute, Center for Clinical & Translational Science, University of Vermont, Burlington, VT, 05401, USA

    Thomas Simpatico

  8. The National Institute for Holistic Addiction Studies (NIFHAS), North Miami Beach, FL, 33162, USA

    Kenneth Blum, Siobhan Morse & John Giordano

  9. G & G Holistic Addiction Treatment Center, North Miami Beach, CA, 33162, USA

    Kenneth Blum, Siobhan Morse & John Giordano

  10. Department of Clinical Neurology, Path Foundation, New York, NY, 10010, USA

    Kenneth Blum, Uma Damle, Mallory Kerner & Eric R. Braverman

  11. Department of Neurological Surgery, Weill Cornell College of Medicine, New York, NY, 10010, USA

    Eric R. Braverman

  12. Dominion Diagnostic Laboratory, North Kingstown, RI, 02852, USA

    Kenneth Blum & Frank Fornari

  13. Department of Nutrigenomics, LifeGen, Inc., San Diego, CA, 92101, USA

    Kenneth Blum & B. William Downs

  14. Department of Child and Adult Psychiatry, American Behavioral Consultants, Lebanon, TN, 37087, USA

    Cynthia Rector

  15. Centre for Genomics and Applied Gene Therapy, Institute of Integrative Omics and Applied Biotechnology (IIOAB), Nonakuri, Purba Medinipur, West Bengal, India

    Kenneth Blum & Debmayla Barh

  16. Departments of Psychiatry and Anatomy & Neurobiology, Boston University School of Medicine, and Boston VA Healthcare System, Boston, MA, 02118, USA

    Marlene Oscar-Berman

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  1. Kenneth Blum
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Correspondence to Kenneth Blum.

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Blum, K., Chen, T.J.H., Bailey, J. et al. Can the Chronic Administration of the Combination of Buprenorphine and Naloxone Block Dopaminergic Activity Causing Anti-reward and Relapse Potential?. Mol Neurobiol 44, 250–268 (2011). https://doi.org/10.1007/s12035-011-8206-0

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