India's National Magazine
From the publishers of THE HINDU

Vol. 15 :: No. 12 :: June 06 - 19, 1998

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MEDICINE

On drug abuse and brain damage

Interview with Dr. J.C.M. Brust.

Substance abuse is as old as history. No society has been free from this malady. There is evidence that it can damage the brain and the mind, increase the risk of strokes, seizures, dementia, liver diseases, cancer and hypertension, and cause foetal damage. For instance, in the United States, the occurrence of convulsions in those who consume 15-100 gm of alcohol a day (two cocktails or three cups of wine is equivalent to 50 gm of alcohol) is three times more than that in teetotaller; it is 20 times more in those who consume over 200 gm of alcohol a day.

While illegal drugs cause 2.5 per cent of all deaths in the U.S., legal addictive substances such as tobacco and alcohol cause 20 per cent and 5 per cent respectively. To be harmful, substance abuse need not be regular. In the U.S., over 50 per cent of men and 40 per cent of women indulge in 'binge drinking' (imbibing large quantities of alcohol occasionally), which is more harmful than regular drinking.

Research shows that substance abuse can stem from genetic traits. Family and adoption studies show that there is 25 per cent chance that the child of a substance abuser will abuse substances.

S. THANTHONI

The most interesting line of research in the area of substance abuse pertains to the understanding of the basis of neural anatomy (the reward circuit in the brain that stimulates pleasure from drugs), neural disorders (the neurological complications caused by substance abuse), and pharmacology (treatment of neurological complications).

In the last four decades there has been considerable increase in awareness about the anatomical and neurochemical basis of the reward circuit. However, it has not found application in pharmacology and treatment. This is because the treatment for drug abuse is not simple; even if the effect of a drug on the neural system is understood, it is complicated by lifestyles and habits such as smoking and 'binge drinking'.

According to Dr.J.C.M. Brust, Professor of Neurology at the Columbia University's College of Physicians and Surgeons and an authority on the neurological complications related to alcohol and drug abuse, the solution to the problem of substance abuse lies in the development of neuro-pharmacology and molecular genetics. When the relationship between the neurosystem and substance abuse is better understood, neuro-pharmacology and the treatment for substance abuse will improve, says Dr. Brust, who has been Director of Neurology of all the affiliated colleges of the University, including the Harlen Hospital Centre, since 1975.

Dr. Brust is a multifaceted personality: his name appears in the book The Best Doctors in America; he is a jazz enthusiast and plays the saxophone; he is keen on discovering the link between music and the brain.

A recipient of several honours, including the Lewis P. Rowland Award for Excellence in Residency Teaching at Columbia University and the Charles Bomfalk Award for Excellence in Student Teaching at Columbia University, Dr. Brust is on the editorial boards of and is a referee for the top 20 medical journals. An examiner of the American Board of Psychiatry and Neurology since 1977, he has to his credit over 100 peer-reviewed articles and five books. He has also written on drug dependence, neurological complications of substance abuse, stroke, epilepsy, alcohol and substance abuse and alcohol and speech therapy in several books.

The Public Health Centre, Chennai, through its Department of Neurology, and the VHS Medical Centre, through its Departments of Neurology and Psychiatry and de-addiction centre (headed by Dr. Krishnamoorthy Srinivas and Dr. Lakshmi Vijayakumar), has done a great deal of work in the field of substance abuse prevention.

The prestigious Dr. N.N. Gupta oration award was presented by the King George Medical College, Lucknow in 1991, to Dr. Krishnamoorthy Srinivas. The oration outlined the details of the magnitude of the problem of alcohol abuse in Tamil Nadu.

Dr. Brust, who is a visiting professor to the T.S. Srinivasan Department of Clinical Neurology and Research, was in Chennai recently to deliver a guest lecture at the K. Gopalakrishna Department of Neurology. He spoke to Asha Krishnakumar on a variety of issues, including the most common drugs that are abused; their effect on the brain and the foetus; the genetic factor underlying substance abuse; the temporal pattern of substance abuse in the U.S.; frontier research in the field; and the neuro-pharmacological developments in the treatment of substance abuse.

Excerpts from the interview:

What is substance abuse?

It is the use of substances in a way that society disapproves. It is so called because either the substances are illegal or, even if legal, they are used excessively, as is common with tobacco and alcohol.

This should not be confused with substance dependence, which is a psychic need to take the drug continuously. That is, a craving for the drug. In contrast, physical dependence is a state when drugs are taken continuously and not stopped as it can be either unpleasant or life-threatening. When we speak of addiction, we mean psychic dependence.

What are the substances that are most commonly abused?

The two legal drugs that are abused are tobacco and alcohol. Then there are opiate drugs such as marijuana, morphine and heroin; psycho-stimulants, including, theromine, cocaine and so on; sedatives such as valium; plants such as mescaline (a cactus); hallucination-causing drugs such as LSD; and enhancers such as magic markers; a group of drugs called phencyclidine; and, lastly, anti-cholinergic drugs, which are also found in plants.

What are the common neurological complications of substance abuse?

Usually an overdose - and certainly its withdrawal - leads to specific neurological complications such as strokes, seizures, suicidal tendencies and various infections.

The concept of overdose varies from person to person. And each class of drugs produces a particular neurochemical reaction. Heroin and opiates, for example, lead to coma, respiratory depression. The pupils become small. Cocaine and thalamine cause delirium, excitement, abnormal movements, seizures, high fever and hypertension. Sedatives and alcohol affect behaviour patterns. This, again, varies from person to person.

An overdose of these drugs hit with varying degrees of severity. I do not know the direct symptom of an overdose of LSD. But one can go crazy if one does not have the daily dose. An overdose of heroin and opiates produces similar syndromes with headaches, nausea, vomitting and diahorrea. Sedatives and alcohol can produce a withdrawal-type syndrome, delirium tremens (D.T.), which is not caused by opiates. Cocaine withdrawal causes depression and can lead to suicidal tendencies but not seizures, delirium and so on.

As for the neurological complications of substance abuse, some drugs cause seizures either as a direct toxic effect, as in the case of cocaine, or as a withdrawal phenomenon, as in the case of alcohol. Anybody who injects drugs runs the risk of infection. You can divide the infections into AIDS (Acquired Immune Deficiency Syndrome) and non-AIDS. Before AIDS, infections such as meningitis were common.

Drugs often make the user susceptible to strokes: in the case of alcohol, for example, an allergic stroke; in the case of cocaine, a withdrawal stroke, probably related to high blood pressure. Some drugs seem to cause a reaction in the blood vessels, causing thrombosis, which leads to blood clots.

Do drugs cause lasting intellectual trauma?

In the case of some drugs it certainly does happen. For instance, in alcohol there is loss of memory. This may most often be due to nutritional deficiency, which alcoholics suffer from. Cocaine causes intellectual impairment, but the issue is still controversial. Opiates probably don't. I say this because the treatment for heroin abuse is methadone, an opiate-based drug. The treatment can go on for decades and the patient does not seem to have any side-effects or dysfunction. If you take methadone, you may not function too well; it would make you drowsy. But it will not harm your brain.

Besides, it is difficult to study the direct effect of drugs on the brain very clearly because there are many things that affect the functioning of the brain - your lifestyle and so on.

What are the effects of substance abuse on a foetus?

It is pretty certain that alcohol damages the foetus. Women should not drink particularly if they are pregnant. This may be the case with other drugs as well. Our institution in New York is studying the effect of cocaine on the foetus. Lifestyle-problems are difficult to isolate from the specific effects of cocaine.

The effects of alcohol have been best studied. Children born to mothers who drink have small brain sizes and characteristically abnormal faces, and are small sized.

Is substance abuse preventable?

Certainly. Certain societies are more prone to drug abuse than others. Where you have social disruption you are more likely to have drug abuse. In the U.S. it is prevalent more in the inner cities. If drugs are available, people would take them. To my knowledge there have never been a society that did not use some of these substances. And society decides which drug is acceptable and which isn't. In the U.S., for example, in the 1920s, marijuana was legal and alcohol illegal. But today it is the other way around.

Why was prohibition reversed in the U.S.?

Prohibition was reversed because the social cost of prohibition exceeded the damage done by alcohol itself. The crime, the chaos and the lack of respect for law were considered too high a price to pay for prohibition. This was also the era of civil liberties.

So I don't think that you are ever going to have an effective preventive policy. This has to be tackled one at a time.

Alcohol and tobacco are extremely harmful. Tobacco kills 20 per cent of the U.S. population every year. But if it is banned, it would lead to a lot of problems. So educating the people is very important.

What is the most commonly abused drug in the U.S.?

Among the legal drugs it is tobacco, followed by alcohol. And among the illegal drugs it is marijuana.

If you are talking about a drug that can cause psychic dependence, we should include caffeine. It is perceived to be harmless. Nobody has as yet implicated it for causing toxic symptoms.

Is substance abuse genetic?

It is positively genetic, but this is complicated. In this regard alcohol is the best studied. There are probably many, many genes that cause this. Adoption studies have proved this. It is common for children of alcoholics to be adopted away. Studies show that the adopted child is generally likely to be an alcoholic, like his biological parents. This is corroborated by studies of twins. If one of the twins is an alcoholic, the other is very likely to be one too.

What issues are on the frontiers of research in the field of substance abuse and neurological complications?

The most exciting research is in understanding the basis of neural anatomy, neural disorders and pharmacology. There is a pathway in the brain, called the reward circuit. Studies on animals show that drugs stimulate the reward circuit, which gives the animals pleasure. When the circuit is cut, the animals are no longer interested in taking the drugs. This circuit is a very complicated system with a lot of different mini transmitters. The study of this circuit will give a lot of insights into the way drugs affect the neurosystem.

There has also been research on prevention and treatment. We have quite an effective treatment for heroin abuse, called methadone (based on opiates). It is not our idea to give somebody an opiate and they stay addicted to it. But if you take methadone, you can function as a normal human being - go to school, work, read and so on. There is no equivalent to methadone. There are a large number of treatments for cocaine-abuse, alcoholism, and so on. Every condition has a dozen different treatments. Obviously none is the best, as otherwise there wouldn't be so many different treatments.

If methadone is prescribed in large doses for a prolonged period, will not the person then get addicted to the drug?

Yes, most patients are given methadone for life and they get dependent on it. But it is better than taking heroin because with methadone you can function normally.

How expensive is the treatment for substance abuse?

Using methadone, for instance, is an alternative to committing crimes to procure drugs. There is a tremendous social cost in this. Methadone has proved to be cost-effective. In the U.S., methadone is not particularly expensive, but it cannot be given by any doctor. Methadone for maintenance is dispensable only at federally registered centres. It is a controlled drug which has been around for a long time and in a number of countries.

There is an opiate, naltrexone, that has been tried for alcoholism. Whatever the treatment cost, it would still be cost-effective; whatever money you put into treatment, you will be saving many times that.

Have treatments kept pace with advances in basic sciences?

We now know a lot more about how these drugs work in the brain than we did 25 years ago. But I am not sure if treatments have kept pace. As we understand precisely what each drug does in the brain, we can design the treatments with specific impact.

But we are not there as yet. We have made enormous progress in understanding the reward circuit I spoke about earlier. But it has not yet been translated into effective pharmaco-therapy. The most effective treatment for any substance abuse is still methadone. And we have had it for 30 years. Research is on in this area, but there is as yet no major breakthrough.

What is the role of drug companies in introducing addictive drugs?

Dr. J.C.M. Brust with Dr. Krishnamoorthy Srinivas at the K. Gopalakrishna Department of Neurology in Chennai.

In the mid-19th century, morphine was widely used in the U.S. as heroin is now. Heroin was originally introduced by Bayer as a treatment for morphine addiction. It is one of those drugs sold across the counter, like a cough syrup. It was said to be a non-addictive drug, introduced with good intentions.

There are small companies today that sell these drugs across the counter. There is an amphetamine-like drug called PPA, which is used in diet remedies. They are sold across the counter and are potentially dangerous. They cause strokes, seizures and high blood pressure. Yet they are sold through mail order catalogues.

The major drug companies, however, are not irresponsible. Demarol is the most commonly used opiate for pain. When introduced, it was termed a non-addictive drug. But it turned out to be highly addictive. People who got addicted to it first were doctors and nurses.

It is said that moderate drinking is good for health and that it reduces the chances of heart attacks by 50 per cent. What is the clinical explanation for this?

It is said that low-level alcohol intakes reduce chances of heart attacks. It is probably true of occlusive strokes as well. That is said to be true for the American Caucasian population. I am not sure whether it applies to others as well.

Alcohol affects a lot of blood components. It affects the lipids. Even a small intake of alcohol seems to raise the level of HDLs (high density lipo proteins), which is good for the blood vessels, and lowers the level of LDLs (low density lipo proteins), which is bad for the blood vessels. But somebody who does not drink should not start drinking because of this.