Thirty years of substitution therapy: an assessment
Dr Jean-Jacques Déglon
Fondation Phénix, Geneva jjdeglon@

While substitution treatments have long proved to be effective, they have also shown their limitations.
This is the story of methadone, a synthetic substance with undeniably useful properties for treating drug users.

As long as drug abusers were harming and destroying only themselves people took no great interest in them.

Substitution treatment for heroin addicts with methadone was widely adopted in the USA some forty years ago after psychotherapy and short-term severance cures had proved to be ineffective. In 1962, Professor Vincent Dole, a specialist in metabolic disease at the Rockefeller University, New York, successfully tested methadone, a substance first synthesised by the Germans during the Second World War as a substitute for morphine, which was in short supply at that time.

The first clinical trials were remarkably successful and methadone cures spread throughout the United States. By the end of the 1980s, 180,000 people were on a methadone treatment programme. However, it was noted with some disappointment that the psychological stability and quality of life of many patients deteriorated seriously when they stopped taking methadone. Many relapses occurred, where patients reverted to their former patterns of abuse. Without yet knowing much about the neurobiological basis of addiction, Dole and his collaborators believed that they were probably dealing with brain dysfunction due to prior opiate abuse and that the answer was to prescribe long-term corrective medication, namely methadone.

In Europe, substitution treatments were long frowned upon because they were thought to involve the prescription of yet another drug, and it was feared that treatments of this kind might be used tools to control people's minds or constitute a kind of "chemical lobotomy". The media-peddled image of methadone as synthetic heroin gave the public the false idea that taking methadone is pleasurable, and this triggered all sorts of contradictory feelings about its acceptability as a therapeutic tool. Doctors were long viewed as partners to crime and were therefore accused of being whitecoated dealers, and some were even imprisoned, especially in Belgium.

A number of factors have led during the last few years to a radical change in thinking and to an increasingly medical approach being adopted to the treatment of dependency.
As long as drug addicts were harming and destroying only themselves, people really took very little interest in them. By contrast, when it was discovered that many of them were infected with the HIV virus and that they were transmitting AIDS to the population at large, much greater interest was shown in developing more efficient strategies for helping these populations.

Once their drugs have been withdrawn, drug abusers become hypersensitive and depressed and try to calm their psychological symptoms by taking to drugs again.

The fact that short to medium term drug withdrawal cures often failed, despite psycho-social support and the often desperate efforts of the patients to succeed, also favoured the development of medically based strategies for dealing with drug addiction. It should be noted that the results of numerous studies on exheroin addicts have shown that the majority of them relapse into addiction or their quality of life degenerates, sometimes to a debilitating degree, which makes them turn to alcohol, tranquillisers or cocaine.

Short methadone treatments lasting only a few weeks or a few months have also proved to be ineffective, leading to the use of other drug substitutes.

One explanation for the habitual relapses which occurred after severance cures from opiates or opiate substitutes is that a long-term dysfunction of the body's stress management system has occurred. All opioids are powerful anti-stress medicines, and Mary Jeanne Kreek has established that giving up opiates generates an abnormally high sensitivity to stress. The link between stress and de-pression is well known. The withdrawing addict becomes hypersensitive and depressed, and will attempt to calm his psychological sufferings by turning back to drugs. However, a single dose of heroin or cocaine can immediately rekindle an obsessive craving and trigger a relapse into addiction.

In appropriate doses, methadone does not induce either euphoria or sedation in heroin addicts because of their acquired tolerance to opiates, and because the product is slowly absorbed when taken orally. A group of patients on methadone were once subjected to psychomotor tests designed for airline pilots, and they performed better than the control group because they were less nervous. If the dosage is sufficiently high, a single daily dose suffices for the methadone to bind stably to the endorphin receptors in the brain.

In addition to its stabilising effects on the opioid systems, methadone acts on neurotransmitters such as serotonin, and especially dopamine. Sufficiently high levels of these neuro-hormones are necessary to maintain a stable mood and a feeling of well being. Most drugs of abuse (cocaine, heroin, alcohol, hashish, nicotine, etc) increase the dopamine levels in specific regions of the brain, although they do so in different ways.
In short, apart from reducing the craving for heroin, methadone also has remarkably stabilising effects in psychiatric terms and few side effects. These truly therapeutic medical effects therefore play a more important overall role than the strictly substitutive aspects.

Methadone, even when taken in high doses for decades, does not cause any medical complications, unlike many other more "ordinary" medicines.

The main factor on which the outcome of the treatment depends is the severity of the drug abusers' psychological symptoms.

Pharmacotherapy facilitates effective psychotherapy. Methadone and other medicines such as buprenorphine (Subutex®)* assist the pursuit of effective psychotherapy by restoring a state of normality, facilitating long-term abstinence and promoting a better psychosocial equilibrium. This also makes the task of social workers easier and helps to restore of good affective relationships with relatives and friends.

Methadone programmes (in which prescription of the substitute drug is combined with psychological and social counselling) are particularly remarkable in that they reduce delinquency and practically abolish heroin use if the dose of methadone is adapted to individual needs. The severity of the drug abusers' psychological symptoms is the main factor on which the outcome depends.

One can, of course, hardly expect a medicinal product to resolve social and professional problems or cure affective disorders: these require the attention of social workers and psychologists. In the absence of any such attention, when the anxiety symptoms re-appear and when tolerance has developed to the substitute drug, thus blocking any effect heroin might possibly have, these patients are in danger of resorting to alcohol, benzodiazepines or cocaine in order to calm these symptoms, which they often find intolerable

In terms of public health, the large-scale prescription of methadone to heroin addicts spectacularly reduces the incidence of overdose, delinquency, medical complications, the risk of AIDS and the financial costs involved in providing social care. When the availability of treatment reaches a sufficiently high level, the heroin trade collapses and, as a consequence, the number of new addicts decreases. This process has been observed in Geneva.

The public authorities have considerable financial advantages to gain from supporting and developing substitution programmes, as they can dramatically reduce the exorbitant medical, and social costs associated with drugs, as well as the legal and judicial costs.

Although costly psycho-social support mechanisms can be extremely useful, and even essential, those countries which are less well off can still make rapid progress in combating heroin addiction by organising the prescription of a single but rigorously monitored daily dose of methadone for those addicts who need it, for as long as may be necessary for the treatment to be effective. Part of the savings resulting from a policy of this kind can later be used to further fund the therapeutic programmes and enable them to expand their psychological and social counselling facilities.

Some subjects are thought to have a genetic deficit as the result of which a specific endorphine fails to function properly.

All the data available unfortunately confirm that only a minority of all drug addicts are able to successfully give up taking their substitute medication in the long term. It must be understood that for many young people, taking heroin has been a form of self-medication, a means of relieving underlying psychological suffering. To put it differently, why is it that some people are more receptive to drugs and become drug addicts more easily, while others can take drugs occasionally and never become dependent? Most of the American soldiers who became hooked on opiates in Vietnam were able, without too much difficulty, to give them up without relapsing once they had gone back to their country and their families, although others remained prisoners of heroin or were psychologically handicapped as the result of taking it. Some new hypotheses have been put forward in the field of genetics. Some people at birth have a genetic deficit, as the result of which a particular endorphin or one of the other chemical neurotransmitters manufactured in the brain does not function properly. This deficit might result in a form of depression which remains hidden during infancy, problems in relating to others, introversion, intellectual impairment, difficulty in concentrating or behavioural problems. Adolescents who experience psychiatricproblems, borderline depression, psychosis or obsessive/compulsive disorders, for example, feel much better mentally, at least to begin with, when they take heroin and they are tempted thereafter to try and prolong the sense of calm it brings them.

For thirty years now, substitution treatments have proved to be effective. They have allowed a considerable number of drug addicts to avoid physical and moral deterioration and early death by restoring their long-term stability and a decent, good and sometimes excellent quality of life. On the other hand, the cessation of the treatment even after a considerable period of time has frequently impaired the quality of life and led to psychological problems and a lapse into alcohol or drug addiction, particularly among those patients who suffer from an underlying psychiatric disorder in addition to drug addiction. In the case of many of these patients, drug consumption must be understood as an attempt to selfmedicate in the hope of dealing with a psychological problem. And it seems to be increasingly likely that problems of this kind are due to functional genetic and neurobiological deficits. The drug substitute thus corrects this biological defect, which is equivalent to a chronic illness. With these patients, substitution treatment is a medical treatment which compensates for the natural imbalance. It has to be maintained indefinitely, just as insulin is prescribed for diabetics and anti-epileptic drugs for those prone to seizures.

It is vital therefore to make a full diagnosis in order to identify the medical, psychological, affective, social, familial and professional problems involved, whether they are pre-existent or secondary factors with respect to drug addiction, and to propose accurately targeted therapeutic responses to these problems. A diagnosis of this kind will also indicate whether a complete end to chemical dependency can be envisaged. In conclusion, the most important message is that all drug addicts should be able to have immediate access to a form of therapy (or forms of therapy, if necessary) which are appropriate to their needs. This will enable them to rapidly recover their medical, psychological and social equilibrium and maintain a satisfactory quality of life for a long time to come, with or without substitute medication.