Methadone in the Treatment of Narcotic Addiction. Chapter 1

Interview With Vincent P. Dole

On my pilgrimage to The Rockefeller University, I asked the old professor, "Whatever made you give methadone to heroin addicts?" He replied, with a grandfatherly smoothness, that he and his wife, Marie Nyswander, had observed the sad results of alcoholism and drug addiction near the 125th Street station in New York. "We just decided that we would keep working on the problem, rather than leaving it to somebody else."

As a psychiatrist, Marie Nyswander had worked with drug addicts during the 1950s, observing the limited results of abstinence orientated treatments. Vincent Dole was a researcher in biochemistry. Both had noted the limited results of available treatment and they believed that there was a medical basis for the compulsive, anti-social behaviour of heroin users.

Dole and Nyswander also believed passionately in the science as well as the art of medicine. In their crusade they sacrificed simpler and more comfortable pursuits.

They obtained permission to treat a group of heroin addicts with certain narcotics in a formal trial setting. After trying numerous short acting drugs, daily administration of methadone was found to enable patients to curtail heroin use and return to a normal life in a majority cases (4). The collaboration changed not only their lives, but also the lives of countless others around the globe.

Medical Model

While the trial results reported in 1965 were favourable, law enforcement authorities were not supportive. The prompt and detailed documentation of the research findings in the Journal of the American Medical Association made a good case for this becoming 'normal medical treatment', and thus outside the province of the police. Subsequent laws banning the use of methadone, even in 'normal medical practice' showed that the latter-day prohibitionist sentiments came from the law makers as well as the law enforcement agencies.

Like other successful medical interventions, the 'miracle' of methadone has to be witnessed to be fully appreciated. The transformation of the addict is often dramatic. There are improvements in appearance, attitude and general health. Thanks to the foresight and courage of these pioneers, this option is now available in many developed countries where heroin injecting has become prevalent. It is also being used in some developing countries, with benefits for the addicted citizens as well as for society generally.

Extending the availability of methadone treatment has been a slow process, but the HIV epidemic of the 1980s made public health authorities reassess this modality. There has only been limited success with other manoeuvres such as behavioural therapies, self-help groups and residential rehabilitation. Other failed measures include laws aimed at the drug itself such as stronger penalties for drug possession and trafficking; increasing customs controls; spraying of crops in the third world and the use of diplomatic pressure on poor, impotent or corrupt regimes in producer countries.

Prohibition of heroin has not stopped it being widely available in most western countries. Telephone orders and home deliveries of heroin are commonplace. In places where import restrictions are relatively effective, such as New Zealand and Western Australia, consumers have made their own heroin substitute from codeine. Called 'homebake', this mixture contains monoacetyl morphine which is just as addictive as heroin.

The repeated failure of the prohibition of narcotics, however, does not justify the uncontrolled supply of opioids which some authorities have advocated. However, such drugs, including methadone, should be available to all those who need them, under a coherent plan of medical management, based upon established principles, or as a part of on-going research. Even in places with limited access to trained medical and nursing staff such as Hong Kong, it is possible for good quality methadone treatment to be made available on a broad scale.

Dole's original work was twenty years after the La Guardia Congressional Commission on drugs, and another twenty years before the appearance of HIV. The reduction in the use of needles and syringes was noted after the commencement of methadone treatment. Some of Dole's original ideas went out of favour, but most have since been shown to be correct, and reintroduced into clinical practice. These include the use of high dose methadone (>100mg daily) where necessary, the selective use of supervised urine tests, the use of intensive psychosocial assistance as well as lengthy or even indefinite periods in treatment. The drug was initially administered in the traditional setting of a hospital ward and subsequently from outpatients. Many controlled trials have since supported these foundations of methadone treatment.

While now retired from clinical practice, Dole leaves us with some important principles, based on sound Hippocratic practice. Quality research should dictate the direction of ethical practice and professional solidarity should ensure its continued availability, even when our patients may not always be held in society's highest regard.

This field has little of the glamour seen in other medical specialties. Along with indigenous people's health and geriatrics, this field relies upon a combined approach between the affected families, professionals in the field and the goodwill of funding agencies and government. Few patients are prepared to go public with grievances or consumer action, preferring to maintain their privacy. Those who do go public are not always representative of the group as a whole.

Comparable Treatments Before and Since

Just how radical was the plan to give methadone to addicts? Heroin was invented by the Bayer Company in 1898 and marketed as a non-addictive analgesic which was suitable for children and also a 'cure for morphinism'. It was not realised for ten years that it was just as addictive as morphine.

Like chariots, rockets and penicillin, methadone came about due to the pressure of war-time. German chemists were working on synthetic opioids because the allied war effort threatened the traditional middle-eastern sources of opium. The new drug was recognised as having strong analgesic properties, and a long duration of action. It has been marketed since under several names, including Dolophine, Amidone, Phenadone and Physeptone. The name methadone is a contraction of the complex chemical name, 6-dimethylamino-4,4-diphenyl-heptan-3-one hydrochloride (C21H27NO,HCl).

Narcotics are among the most efficacious drugs in the traditional pharmacopoeia. Opium was called thebacium in Latin, after the fabled city of Thebes. Galen was aware of its addictive properties when he prescribed it to Roman Emperor Marcus Aurelius who suffered from joint pains, possibly gout. Laudanum (tincture of opium) was popular with both doctors and patients in Victorian times.

It was not altogether new for physicians to prescribe narcotics for opioid addiction. Morphine has been prescribed for many years to addicts, many of whom have functioned well in society. A number were physicians themselves, such as William Halsted, the originator of the cancer curing operation. Many pharmaceutical opioids apart from heroin were also introduced as having non-addictive properties, only to prove habit-forming in subsequent clinical practice.

Other narcotic drugs have been used in the treatment of heroin addiction, both formally and de facto. Buprenorphine has been trialed as sublingual tablets (5). Levomethadyl acetate (levo-alpha-acetylmethadol, LAAM, also called 'long acting methadone')(6), dihydrocodeine (7), codeine, propoxyphene, dextromoromide and intravenous heroin itself (8) have also been used. Transdermal patches are being trialed in palliative care and may also prove useful for drug addiction treatment. No other intervention has thus far proven to be superior to methadone hydrochloride.

Naltrexone, an orally absorbed, long-acting narcotic antagonist, has been reported to be effective both for rapid detoxification under anaesthetic as well as for preventing relapse once maintenance treatment has ceased. It also has been used in the treatment of alcoholism and other forms of drug abuse, but formal evidence is awaited (9).