Methadone 101

way. By 1963, on the cusp of the social revolution of the sixties, doctors and

public health workers had concluded what objective observers and users alike had

known for decades: that there was no treatment known which could cure more than

a small fraction of long term opiate (heroin, morphine, etc) addicts. In fact,

there wasn’t even any treatment which could honestly claim to be more successful

than no treatment at all! Every imaginable option had been tried, from

lobotomies and insulin shock to psychoanalysis and the threat of lifetime

incarceration. But in every case the result was the same: between 70 and 90

percent of these chronic addicts would return to opiates within a short time. In

light of such statistics a number of prestigious panels examined the problem and

by 1963 had come to the same conclusion: it was time to re-examine nearly fifty

years of prohibition and consider allowing doctors to prescribe addicts the

metabolic disorders, and Dr.

Marie Nyswander, a psychiatrist who’d worked at the U.S. Public Health

Hospital/Prison for addicts in Lexington, Kentucky, began experiments with

several chronic heroin addicts. In attempting to determine if addicts could be

maintained on stable doses of pharmaceutical opiates, the volunteers were given

access to the spectrum of opiates available to medical practitioners. The

researchers tried everything from morphine to dilaudid, but found that it was

extremely difficult to stabilize the subjects. The addicts were either

oversedated or in mild withdrawal most of the time, and spent their days either

“on the nod”, waiting for their next shot, or comparing the relative

merits of the drugs used. Reluctantly, Drs Dole and Nyswander concluded that the

experiment had been a failure, and decided to “detox” the addicts and

release them from the hospital. To accomplish the withdrawal, they turned to a

synthetic narcotic called methadone. Methadone had first been synthesized by

German chemists before World War Two, and after the war it was used to withdraw addicts

at Lexington. It had the advantage of being cheap, significantly orally active,

and longer lasting than opiates like morphine. For the researchers at

Rockefeller, it seemed merely a convenient and humane means of ending the

experiment with maintenance. As the addict volunteers had been built up to large

doses of narcotics by street standards, they were given relatively large doses

of methadone to stabilize their “habits” before beginning the

subjects had been switched to methadone, and before the “detox” had

begun, they began to exhibit very different behavior. Whereas for weeks they had

spent their days either feeling the effects of the narcotics or complaining of

their need for more narcotics, suddenly the focus of their days turned away from

drugs. One subject asked the researchers for supplies so that he might resume

his long neglected hobby of painting. Another inquired after the possibility of

continuing his interrupted education. In short, the addicts- who when admitted

to the hospital had looked and behaved very much alike -now began to differentiate.

They began to manifest the potential that each had obscured during years of

the brain. There were several attempts to locate these sites, but the existing

technologies were unable to distinguish between the non specific binding to

tissue and the specific binding to receptors. It must be mentioned here that the

first attempt to actually measure specific opiate binding was in the laboratory

of Dr. Vincent Dole (Ingolia & Dole, 1970). Although the technology was not

available at that time he laid the foundations for the discovery of opiate

discovery of opiate binding sites seemed almost inevitable. The first to shake

the scientific community was Solomon Snyder and his student, Candice Pert of

John Hopkins University (Pert & Snyder, 1973). Using a technique developed

by Avram Goldstein of Stanford University, Snyder and Pert located the elusive

opiate receptor (Goldstein, Lowney & Pal, 1971). That same year two other

groups headed by Eric J. Simon of New York University (1973) and Lars Terenious

in Uppsala, Sweden (1973) demonstrated specific opiate binding in nervous

tissue. The treasure Hunt had begun! “For why,” Goldstein asked,

“would God have made opiate receptors unless he had also made an endogenous

isolated a pituitary hormone which he named B-Lipotropin (Li, 1964). He noted

that one portion of this hormone had analgesic properties. One year after the

discovery of the receptor sites John Hughes at the laboratory of Hans Kosterlitz

in Aberdeen, Scotland reported the existence of an endogenous morphine-like

substance which they later purified and named Enkephalin for “in the

head” (Hughes, 1975a; Hughes, 1975b; Kosterlitz, 1976) The Aberdeen group

recognized that the peptide sequence of Enkephalin was contained within Li’s B-Lipotropin.

Li would later name the other endogenous morphine-like peptides, which also come

including Dynorphin another brain opioid peptide system found by Avram Goldstein

(Goldstein, Tachibana, Lowney, Hunkapiller & Hood, 1979). Other psychoactive

peptides have been discovered and isolated using the techniques developed in

these laboratories. In 1978 Solomon Snyder, John Hughes and Hans Kosterlitz

shared the Lasker Award for their discoveries. Paralleling the discovery of

Enkephalins, Endorphins and opiate receptors have been advances in the field of

neuroscience. These advances have led to many exciting discoveries and generated

a new interest in the functioning of the brain. We have entered a new era in our

This has been made possible through involvement of general practitioners in

methadone treatment. Drug overdoses, crime and even presence of methadone on the

tenfold (From 6 kg/year in 1990 to 58 kg/year in 1994). This fact may seem

insignificant because it concerns a country with a population no higher than

that of New York City and whose precise geographic location may not be known to

everyone. However the Belgian experience might demonstrate that it is possible

to overcome certain limitations of methadone treatment as it is generally

1970’s. But physicians who began to prescribe it to addicts at the beginning of

the 1980’s, when the heroin epidemic was worsening, were often subjected to

disciplinary sanctions by the Belgian Medical Association and sentenced by

requested that the Supreme Court revoke the Medical Association’s regulations

permitting the indictment of physicians prescribing methadone and other

substitution treatments. This request was granted. Subsequently, the regional

authorities of the French speaking part of Belgium began to encourage physicians

to treat opiate addicts with methadone. The authorities became aware of drug

addiction’s impact on criminality and on the AIDS epidemic. They knew that it

would be impossible to extend rapidly the number of methadone clinics and they

also wanted to avoid stigmatizing heroin addicts. To encourage the treatment of

addicts in normal settings, they allocated funds for training sessions for

the organization of a Consensus Conference on Methadone Treatment by our

Minister of Health. The conclusions of the Consensus Conference were sent to

every doctor in the country, as new guidelines for methadone treatment. They

official guidelines for methadone treatment, they represent a significant

innovation, compared to what happens in a lot of countries. Methadone is now

dealt with as an ordinary medication. Its effectiveness is recognized without

ambiguity. No longer is it considered an experimental treatment, accessible only

to a limited number of patients and subject to rigid controls. No longer are

patients required to have attempted previous withdrawal treatments. Addiction

can be ascertained by spontaneous withdrawal attempts recounted during patients

should not be limited, but adapted to each patient by the physician. It is

acknowledged that short-term methadone treatment are appropriate only in certain

very particular cases. Daily administration of methadone is not compulsory, but

recommended at the beginning of treatment and will generally take place in a

pharmacy chosen by the patient. The physician is free to prescribe larger

quantities of methadone at less frequent intervals, depending on how the patient

now reaches 5.000, out of an estimated total number of heroin users of 20.000 to

30.000. More than 80% of these patients are being treated by general

practitioners. Hundred of general practitioners are currently involved in

methadone treatment. Most patients receive methadone provision for one or two

weeks, but the presence of methadone on the black market has decreased, since

less addicts are seeking methadone on the streets. Drug overdoses and

criminality have decreased. Thus the very flexible method of prescribing

methadone used today in Belgium seems to have resolved some problems and does

European Methadone Association

27 rue de la Vanne

1050 Brussels, Belgium

Tel + Fax : 322 640 46 28