Rationale for maintenance pharmacotherapy of opiate dependence.
At this time, 27 years after the initial studies on development of methadone for the maintenance treatment of opiate addiction were begun, it has been shown that [table; see text] methadone meets most criteria for a pharmacologic agent for chronic treatment of an addiction. It is effective after oral dosing: it has a long biological half-life in humans, it causes minimal side effects when used in chronic treatment, and it has no true toxic effects or serious side effects. Also methadone has been shown to be very effective when appropriately used in programs which combine pharmacotherapy with the best elements of "drug free" treatment, that is, counseling and psychological support. In addition to pharmacological treatment, there should be access to, if not on-site, medical and behavioral care as needed, as well as linkage to resources for various aspects of rehabilitation. At this time many of the actions, as well as the specific sites of action, and mechanisms of actions of methadone as used in chronic treatment of opiate addiction have been defined by scientific experimentation, both at the preclinical and clinical levels. It is known that methadone prevents abstinence symptoms, prevents drug hunger or craving, blocks euphorogenic effects of other opiates, and prevents relapse to illicit use of opiates. It is known that the site of action of methadone is at specific opioid receptors. Research to date suggests that there is no demonstrable down-regulation or up-regulation of opioid receptors during chronic opioid agonist perfusion, although chronic administration of the opioid antagonist naltrexone does appear to up-regulate opioid receptors. Clinical studies show that chronic use of methadone allows normalization of release and peripheral levels of one of the classes of endogenous opioids, beta-endorphin, and the related peptides derived from POMC released and processed from the anterior pituitary in humans. Also levels of beta-endorphin in cerebrospinal fluid become normal during chronic maintenance treatment, reflecting apparently normal processing and release of beta-endorphin at brain or hypothalamic sites of POMC production. Available data from studies of beta-endorphin indicate that there is a [table; see text] normalization, rather than disruption, of the endogenous opioid system in general during steady state administration of methadone, as contrasted with intermittent dosing and then abrupt withdrawal of short-acting opiates such as heroin. Although there is still much to be learned about the neurobiology of opiate addiction, at this time we do know a great deal about the effects of opiates and opioids.(ABSTRACT TRUNCATED AT 400 WORDS)
Kreek
M J
MJ
Rockefeller University, New York, New York 10021.
D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D003131:Combined Modality Therapy; D006556:Heroin Dependence / Q000503:physiopathology / Q000523:psychology / Q000534:rehabilitation; D006801:Humans; D008691:Methadone / Q000627:therapeutic use*; D018377:Neurotransmitter Agents / Q000502:physiology; D009293:Opioid-Related Disorders / Q000503:physiopathology / Q000523:psychology / Q000534:rehabilitation*; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology; D015819:Substance Abuse, Intravenous / Q000503:physiopathology / Q000523:psychology / Q000534:rehabilitation*
D018377:Neurotransmitter Agents; D017981:Receptors, Neurotransmitter; D008691:Methadone