Federal Regulation of Methadone Treatment (1995) / Chapter Skim
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Pharmacology and Medical Aspects of Methadone Treatment
Pharmacology and Medical Aspects of Methadone Treatment
Pages 37-60
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From page 37... ...
This chapter provides an overview of the development of pharmacotherapeutic approaches to the treatment of opiate addiction and summarizes the key basic scientific investigations of the physiological underpinnings of opiate effects, including the discovery of the endogenous opioid system. In addition, the chapter describes the pharmacological and medical characteristics of methadone as a medication for the treatment of opiate addiction.
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From page 38... ...
However, both acute and chronic tolerance may also be influenced by environmental variables, such as setting, conditioning, and learning. The pharmacological approach to long-term treatment of heroin addiction, first undertaken in early 1964, was rooted in what was then a hypothesis that opiate addiction is a metabolic disease, caused by either intrinsic or druginduced alterations in physiology.
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From page 39... ...
In view of the anticipated limitations of morphine as a maintenance agent, a search was made for a medication that would block withdrawal symptoms of heroin addicts and that would be orally effective, long-acting, nonsedating, and devoid of adverse side effects. Methadone, a synthetic opiate compound originally synthesized in Germany for use as an analgesic in World War II, was selected for study in 1964.
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From page 40... ...
Soon thereafter, attention focused on three separate classes of endogenous opioid ligands that bind to the specific opioid receptors. In animals, many of the well-known opiate effects have been reproduced by administering large amounts of these endogenous opioids.
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From page 41... ...
A "metabolic disease" concept has been suggested, in addition, which holds that some individuals may be predisposed to heroin addiction because variations in their genes result in abnormal levels of endogenous opioid peptides, levels that can be "corrected" by taking heroin (Goldstein, 1994~. The effect of heroin addiction on the genetic regulation of the endogenous opioid system is currently an active area of research that is beginning to reveal intriguing clues about the biological underpinnings of addiction.
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From page 42... ...
Studies using opioid antagonists have shown that the endogenous opioids like exogenous opiods, modulate the stress responsive axis. However, whether the effects of the antagonists are mediated wholly through central actions of the brain opiods, or whether peripheral ~Endorphin plays a role remains to be determined.
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From page 43... ...
When methadone was given to heroin addicts, it seemed to prevent signs and symptoms of withdrawal for 24 hours. During oral administration of methadone to opiate addicts on doses selected to be less than those to which tolerance had been developed, the "high" or euphoria, and all other perceived opiate effects, are minimal or even absent.
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From page 44... ...
Effects, Side Effects, and Special Pharmacological Issues In the original maintenance research in 1964, divided methadone doses were used very briefly, but, as already mentioned, soon it was found that a single daily dose of methadone could suppress withdrawal symptoms for 24 hours. Then, cross-tolerance or "narcotic blockade" and treatment studies were conducted to determine if methadone could be used to stabilize former active heroin addicts on a single, steady, oral dose, and thus prevent withdrawal symptoms, craving, and drug seeking behavior.
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From page 45... ...
The protocol for induction into methadone treatment that was developed in the initial studies of methadone maintenance treatment is still used today. During the first few weeks of maintenance treatment, the daily dose gradually is increased at a rate slow enough to prevent any appearance of narcotic-like effects.
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From page 46... ...
Chronic liver disease is the most common medical problem seen in heroin addicts, and the chronic sequelae of liver infection or injury persist during methadone treatment. The majority of heroin addicts entering methadone maintenance treatment have biochemical evidence of chronic liver disease, and, until very recently, 80 to 90 percent have serological evidence of exposure to hepatitis B and/or hepatitis C
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From page 47... ...
Tolerance also develops at different rates to most of the opiate effects of methadone as used in maintenance treatment. Most of the initial opiate effects, predominantly somnolence, can be avoided by starting treatment at relatively low doses and increasing the dose gradually to appropriate treatment levels.
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From page 48... ...
INTERACTIONS OF METHADONE WITH OTHER DRUGS A fundamental public health issue related to methadone maintenance was whether or not a methadone-maintained patient would be in jeopardy of overdose if he or she self-administered heroin during methadone treatment. As noted above, the 1964 cross-tolerance studies documented that the risk of morbidity or death in methadone patients receiving a full treatment dose (60 to 120 mg per day)
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From page 49... ...
It is estimated that at least one in four or five heroin addicts, and former addicts maintained on methadone, abuse alcohol. Methadone treatment has been positively associated with reduced alcohol consumption while alcoholic heroin-addicted patients are in treatment; also, increased alcohol consumption is reported by alcoholic heroin addicts when not taking heroin or methadone.
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From page 50... ...
In multiple studies, over 80 percent of the injecting heroin addicts entering methadone treatment had markers of prior infection and 5 to 15 percent had hepatitis B antigenemia.2 However, studies have also shown that after 10 years or more in maintenance treatment, the percentage of patients with hepatitis B antigenemia drops to less than 5 percent. By the late 1970s a second and lethal form of hepatitis, caused by a viroid-like circular RNA agent (delta agent)
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From page 51... ...
it was fn~,n`1 thnt HIV-1 infection had reached the drug-~nJect~ng population in New York City in 1978 and infection had progressed rapidly until 1983-1984, when the prevalence of HIV-1 infection reached a level of over 50 percent of intravenous users in the inner city area. Of public health importance, investigators further found that heroin addicts in New York City who had entered effective methadone maintenance treatment programs before the 1978 advent of the AIDS epidemic and who remained in treatment displayed a much lower incidence of HIV-1 infection in 1984 than did untreated heroin addicts: less than 10 percent of such methadone patients were infected in 1984, compared to over 50 percent of untreated heroin addicts.
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From page 52... ...
In: Problems of Drug Dependence, 1979; Proceedings of the 41st Annual Scientific Meeting of the Committee on Problems of Drug Dependence, L.S. Harris, ea., NIDA Research Monograph 27 Series., Rockville, Md., Pp.
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From page 53... ...
In: National Association for the Prevention of Addiction to Narcotics, Proceedings of the Fourth National Conference on Methadone Treatment.
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From page 54... ...
1986b. A preliminary study of beta-endorphin during chronic naltrexone maintenance treatment in ex-opiate addicts.
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In: Problems of Drug Dependence, 1988; Proceedings of the 50th Annual Scientific Meeting of the Committee on Problems of Drug Dependence.
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From page 56... ...
1986. Long term follow-up studies of the medical status of adolescent former heroin addicts in chronic methadone maintenance treatment: Liver disease and immune status.
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From page 57... ...
In: Problems of Drug Dependence, 1992: Proceedings of the 54th Annual Scientific Meeting of the Committee on Problems of Drug Dependence, NIDA Research Monograph Series, Rockville, Md.
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From page 58... ...
Hepatitis C virus serology in parenteral drug users with chronic liver disease. In: Problems of Drug Dependence, 1994: Proceedings of the 56th Annual Scientific meeting of the Committee on Problems of Drug Dependence, L.S.
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From page 59... ...
In: Problems of Drug Dependence, 1992; Proceedings of the 54th Annual Scientific Meeting of the Committee on Problems of Drug Dependence.
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From page 60... ...
1994. Mu opioid receptor mRNA levels following chronic naltrexone administration.
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