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Modern humans must learn how to relate to psychoactives
responsibly, treating them with respect and awareness,
working to minimize harms and maximize benefits, and
integrating use into a healthy, enjoyable, and productive life.
Better Than Well
Apr 6, 1996
The Economist
Society's moral confusion over drugs is neatly illustrated by its differing reactions to Prozac and ecstasy.

Every week, according to the most conservative estimates, half a million Britons take a pill to make them happy. This pill was originally developed as an appetite suppressor. Now it is an adjunct to partying. In America, some 5m people regularly take a different sort of pill. This one was developed as an anti-depressant. Now it is widely used as a chemical accessory by those who think it is unfair that they should ever feel low.

The British users are breaking their country's law. The Americans are not. Which raises an important question. If it is not acceptable to take a drug with the awkward name of 3,4-methylenedioxymethamphetamine (better known as MDMA, and even better known as ecstasy) to make you feel happy when you just want to have fun, why is it acceptable to take the anti-depressant fluoxetine (better known as Prozac) to make you feel happy if you are not actually clinically depressed?

When Prozac -- made by Eli Lilly, an American pharmaceutical firm -- came on the market in 1987, it was halied as a "wonder-drug." Unlike previous anti-depressants, it appears to have no serious (and few trivial) side effects. Its sales have soared. They are expected to hit $4 billion a year by 2000, according to analysts at Lehman Brothers, an American investment bank.

Ecstasy is older. It was developed in 1914 and became popular in the 1970s as an adjunct to psychotherapy because of its ability to reduce anxiety and facilitate communication. German marriage-guidance counsellors regularly recommended it. It, too, is good business. A tablet can cost as little as 3.50 pounds ($5) to make and sells on the streets for around 15 pounds. This suggests that the British market alone is worth well over 300m pounds a year.

Both drugs affect the level of serotonin, a neurotransmitter in the brain that is thought to influence sleep, appetite, aggression and mood. Neurotransmitters are chemicals that carry messages between nerve cells. They are secreted by one cell and picked up by receptor proteins on the surface of a neighbor. Once the message has been delivered, a neurotransmitter is either destroyed or sucked back into the cell the made it -- a process known as re-uptake.

Both Prozac and ecstasy work by inhibiting the re-uptake of serotonin. This means that the messenger molecules hang around in the gap between the cells and the message gets amplified. Ecstasy, in addition to blocking re-uptake, causes a surge of serotonin to be released into the gap -- so that not only is it not removed, but there is more of it there in the first place. Since clinical depression seems to be associated with a lack of serotonin at certain receptor sites (extremely low levels of serotonin have been found, for instance, in some suicides), the idea of using serotonin re-uptake inhibitors as anti-depressants has been popular for some time.

So there are some parallels. But there is also an important difference between the drugs -- one which might be thought to justify banning one but not the other. Though it has been accused of causing violence in rare cases (the "Prozac defense" was once fashionable among lawyers, but 65 consecutive convictions have dampened their enthusiasm) Prozac does not seem to harm its users. Very occasionally, ecstasy (or, more particularly, dehydration associated with its use) kills.

This does not, however, seem to have been the reason why MDMA was actually proscribed. In 1971, when the drug was banned in Britain, this problem was almost unknown. Things had not changed much by 1985, when the drug was first scheduled in America. This is hardly surprising. Death is rare -- it occurs in only one per 3 1/2m uses. Fatal dehydration generally happens in a hot environment. And it is preventable by drinking a judicious, though not excessive, amount of water (too much can kill you, too).

The formal reason for the drug's proscription was fear of neurotoxicity -- that it might cause a persistent drop in serotonin levels in the brain. But America's Drug Enforcement Agency (DEA), instead of placing it in schedule three, which would have allowed continued medical use, put it in schedule one -- denying it even to doctors.

Better living through chemistry

The neurotoxic effects of MDMA are real. Regular users may suffer a drop of a third in the level of serotonin-derived chemicals in the fluid of their spinal cords, according to research by George Ricaurte, a neurologist at Johns Hopkins University in Baltimore. But such effects do not appear to be very troubling -- at least not in the doses that people actually use. Slightly reduced sleep, less impulsive behaviour and less hostility are the main symptoms. And other drugs which are neurotoxic in laboratory experiments do not seem to cause difficulties in the outside world. Fenfluramine, another appetite surppressor, has been in use for 25 years and been taken by around 50m people without any sign of a problem.

The decision to put MDMA into schedule one, therefore, seems odd. It came despite the opinion of Francis Young, a federal judge who was asked to review the evidence, that it should have gone in schedule three. The explanation seems tobe that the mid-1980s also saw MDMA's recreational use change from small groups of people taking it in private, to large groups of people taking it in public. Ecstasy was being born and the DEA wished to strangle it.

The history of Prozac casts the propriety of the ban in sharp relief. Strictly, America's Food and Drug Administration recognises Prozac as suitable for the treatment only of depression and obsessive-compulsive disorder. In practice it is being prescribed (quite legally, if warnings are given) for panic disorders, premenstrual tension, premature ejaculation and chronic back-pain. But, increasingly, people are being prescribed it simply because they want it. And those who are unable to find a friendly doctor to fill in a prescription are turning to the black market.

Peter Kramer, a psychiatrist at Brown University, in Provdence, Rhode Island, says Prozac users feel "better than well" -- a sentiment no doubt echoed by many a user of ecstasy. As Dr. Kramer puts it in his book "Listening to Prozac," "until the advent of Prozac most ethical questions involving psychotherapeutic drugs turned on clinical trade-offs." But because Prozac has proved so safe, it is much more widely prescribed than previous anti-depressants. The question is whether a line can be drawn between therapeutic and non-therapeutic use of the drug. And if it can be, should it be?

There are two ways of dealing with this question. One is to duck it. Some doctors argue (with a certain circular logic) that if something is treatable with an anti-depressant then it must, by definition, be depression. The drug is then restoring a state which would "naturally" exist if the person were well. So, the argument goes, unlike ecstasy (where the act of taking the drug provides immediate pleasure) Prozac does not actually create pleasure. In the words of a spokesman for Eli Lilly, the drug does not make people into super-people.

The other way of answering the question is to admit that Prozac, like ecstasy, is often used recreationally, to enhance pleasure, rather than to treat depression -- and, if this is not approved of, to ban its use in these cases. But why ban the recreational use of drugs?

The motive often seems to be what Dr. Kramer refers to as "pharmacological Calvinism." The use of drugs for fun rather than therapy is widely disapproved of. There is, too, a feeling that doctors -- who, it is to be hoped, know what they are doing -- should be in charge of the process of giving drugs out. But, in that case, why not let doctors give out MDMA as well? There is also a belief that, at least with mental problems, behavioural therapy is morally superior to chemotherapy. But the two are intimately linked. Eric Hollander, of the Mount Sinai School of Medicine, in New York, for example, recently showed that treating obsessive-compulsive disorder with drugs produced the same changes in the activity of patients' brains -- uncoupling the action of four groups of nerves that are unhealthily locked together -- as threating them with psychotherapy. It hardly seems that one method is morally inferior just because it is easier.

Nor does it seem reasonable to stop people taking drugs to achieve easily an effect which might be won in other ways with difficulty. Good information about the risks and benefits, and proper supervision of manufacture, are always important (and are a good argument for legalising what people clearly want). But given these, it is not clear that pills should always be popped under a doctor's supervision. So, when Calvinists ask if people taking Prozac to eliminate elements of their personalities, such as shyness, is so very far removed from the recreational use of ecstasy, the answer appears to be "no." But what is wrong with that?