Methadone-related opioid agonist pharmacotherapy for heroin addiction. History, recent molecular and neurochemical research and future in mainstream medicine

Ann N Y Acad Sci. 2000;909:186-216. doi: 10.1111/j.1749-6632.2000.tb06683.x.

Abstract

In 1963, Professor Vincent P. Dole at the Rockefeller University formed a small team to develop a pharmacotherapy for the management of heroin addiction. They hypothesized that heroin addiction is a disease of the brain with behavioral manifestations, and not merely a personality disorder or criminal behavior and began to address the specific question of whether a long-acting opioid agonist could be used in the long-term maintenance treatment of heroin addiction. Over the next 35 years, many studies documented the safety, efficacy and effectiveness of methadone pharmacotherapy for heroin addiction, but Federal regulations and stigmatization of heroin addiction prevented implementation of treatment. Finally, in 1999, NIH published a report unequivocally supporting methadone maintenance pharmacotherapy for heroin addiction. Two other effective opioid agonist treatments have been developed: the even longer acting opioid agonist l-alpha-acetylmethadol (LAAM) has been approved for pharmacotherapy for heroin addiction, and still under study is the opioid partial agonist-antagonist buprenorphine-naloxone combination. A variety of studies, both laboratory based and clinical, have revealed the mechanisms of action of long-acting opioid agonists in treatment, including prevention of disruption of molecular, cellular and physiologic events and, in fact, allowing normalization of those functions disrupted by chronic heroin use. Recent molecular biological studies have revealed single nucleotide polymorphisms of the human mu opioid receptor gene; the mu opioid receptor is the site of action of heroin, the major opiate drug of abuse, analgesic agents such as morphine, and the major treatment agents for heroin addiction. These findings support the early hypotheses of our laboratory that addiction may be due to a combination of genetic, drug-induced and environmental (including behavioral) factors and also, that atypical stress responsivity may contribute to the acquisition and persistence of, as well as relapse to, use of addictive drugs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adrenocorticotropic Hormone / metabolism
  • Corticotropin-Releasing Hormone / metabolism
  • Heroin Dependence / drug therapy*
  • Heroin Dependence / metabolism
  • Humans
  • Hypothalamo-Hypophyseal System / drug effects
  • Methadone / pharmacology
  • Methadone / therapeutic use*
  • Methadyl Acetate / therapeutic use
  • Pituitary-Adrenal System / drug effects
  • Pro-Opiomelanocortin / metabolism
  • beta-Endorphin / physiology

Substances

  • beta-Endorphin
  • Pro-Opiomelanocortin
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone
  • Methadyl Acetate
  • Methadone