title: Can the chronic administration of the combination of buprenorphine and naloxone block dopaminergic activity causing anti-reward and relapse potential?
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.
authors.affiliation: Department of Psychiatry and McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL 32610, USA. drd2gene@aol.com
authors.forename: Kenneth
authors.initials: K
authors.lastname: Blum
authors.forename: Thomas J H
authors.initials: TJ
authors.lastname: Chen
authors.forename: John
authors.initials: J
authors.lastname: Bailey
authors.forename: Abdalla
authors.initials: A
authors.lastname: Bowirrat
authors.forename: John
authors.initials: J
authors.lastname: Femino
authors.forename: Amanda L C
authors.initials: AL
authors.lastname: Chen
authors.forename: Thomas
authors.initials: T
authors.lastname: Simpatico
authors.forename: Siobhan
authors.initials: S
authors.lastname: Morse
authors.forename: John
authors.initials: J
authors.lastname: Giordano
authors.forename: Uma
authors.initials: U
authors.lastname: Damle
authors.forename: Mallory
authors.initials: M
authors.lastname: Kerner
authors.forename: Eric R
authors.initials: ER
authors.lastname: Braverman
authors.forename: Frank
authors.initials: F
authors.lastname: Fornari
authors.forename: B William
authors.initials: BW
authors.lastname: Downs
authors.forename: Cynthia
authors.initials: C
authors.lastname: Rector
authors.forename: Debmayla
authors.initials: D
authors.lastname: Barh
authors.forename: Marlene
authors.initials: M
authors.lastname: Oscar-Berman
mesh_terms: D000339:Affect; D000818:Animals; D016739:Behavior, Addictive; D001921:Brain / Q000378:metabolism; D002047:Buprenorphine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000166:cytology / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007031:Hypothalamus / Q000033:anatomy & histology / Q000502:physiology; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000502:physiology; D009293:Opioid-Related Disorders / Q000188:drug therapy / Q000517:prevention & control; D012008:Recurrence; D012201:Reward; D013378:Substantia Nigra / Q000033:anatomy & histology / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D009292:Narcotic Antagonists; D009270:Naloxone; D002047:Buprenorphine; D005947:Glucose; D004298:Dopamine