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September 1988

About Alcoholism - Alcoholism Information, Research, and Treatment

A Sobering Development

Many of these items are contrary to AA philosophy. Their publication here does not mean that the Grapevine endorses or approves them; they are offered solely for your information.

You're at a party. A bout with alcohol beckons, but you know you'd be too punch-drunk to drive home and would feet like you'd been pummeled tomorrow. So you back off.

But suppose there were a drug you could take that would sober you up in a flash, allowing you to knock back as much booze as you could handle without fear of arrest or hangover. What would you do?

The question is hypothetical, you say? That there is no such drug, and probably never will be?

Think again. There is such a drug. And it soon may be available commercially.

A Tulane alumnus and his team of scientists at the National Institute of Mental Health (NIMH) in Bethesda, Md., have developed a compound called Ro 15-4513, which seems capable of reversing the effects of alcohol.

The compound, according to Steven M. Paul (Arts and Sciences '72, Graduate '75, Medicine '75), blocks alcohol's interaction with the brain's matching neurotransmitter receptor, stopping the stuporous effects of drinking.

But while he is enthused about the potential of Ro 15-4513 for treating alcoholism, he and others are apprehensive about its potential for abuse. Would the drug encourage excessive drinking, they wonder? And what are the potential moral, legal, and medical costs?

That science could even think of developing an anti-alcohol drug has been possible only within the last dozen years. Before then, the brain was understood as a dense network of billions of nerve cells which communicate by electrical impulses carried across the gaps between them by chemical transmitters. But how those impulses regulated psychological states, or how they were altered by drugs, was a mystery.

Then, in 1973, scientists discovered patterns of molecules called opiate receptors which bind with a chemical released by the brain during traumatic situations to produce compensating feelings of euphoria. By mimicking this natural opiate, drugs such as morphine and heroin bind with the opiate receptors, inducing ecstasy.

Over the next few years, several other brain chemicals, or neurotransmitters, which cause mood-altering electrical changes were identified. Among them was gamma aminobutyric acid, or GABA, which regulates feelings of stress and anxiety.

According to Paul, GABA is released during stressful situations, binds to its receptor like a key fits a lock and opens a channel in the neuron membrane which allows chloride ions to flow inside. The neuron's electrical charge then goes down, sedating the stressful feelings. Just as heroin plugs into the opiate receptor, Valium and alcohol fit into the GABA lock, alleviating anxiety and relaxing the muscles.

In the late 1970s, the pharmaceutical company Hoffmann-La Roche began looking for a compound, or antagonist, that would neutralize the effects of Valium. In 1981, its chemists discovered one called Ro 15-1788 that completely blocked the tranquilizer's effects, and began developing variations of it. Three years later, they came up with Ro 15-4513.

Although the compound neutralized Valium, Hoffmann-La Roche saw no commercial potential in it, partly because the company already held a patent on a better anti-Valium drug and partly because the drug caused a toxic change in the liver enzyme and the white-blood-cell-count. The firm's researchers, however, noticed that Ro 15-513 blocked not only the effects of Valium, but those of alcohol as well. Nobody knew at that time that alcohol, like Valium, works on the GABA system. So to find out why the compound neutralized alcohol's effects, the company shared it with various university and governmental labs around the country, including Paul's.

Paul and his team received the compound just as they were beginning to establish a definitive connection between alcohol and the GABA receptor. In the fall of 1985, they tested it on rats, and the results--90 percent blockage of intoxication--were as thrilling as they were astonishing.

Immediately, Paul and his staff apprehended the drug's potential. If, they reasoned, it could be made longer-lasting and non-toxic--and if it blocked all of the pleasurable effects of drinking, thereby suppressing the craving for alcohol--it might become to alcoholism treatment what the heroin antagonist Naltrexone has become to drug addiction treatment. And on a lesser scale, it could be used to reverse the effects of acute alcohol poisoning.

But there is another potential use of Ro 15-4513, they realized--one that presents something of an ethical dilemma. Presumably, it could be swallowed by partygoers after all-night binges. That could encourage excessive drinking and aggravate the nation's already serious alcohol abuse problem.

For that reason, some observers are skeptical about Ro 15-4513. Boris Tabakoff of the National Institute on Alcohol Abuse and Alcoholism, told Esquire that he and his colleagues "ethically reject the idea of a sobering-up drug." Unless it reduces alcohol craving, he said, it would have no practical commercial application--nor should it.

Paul is sympathetic to Tabakoff's concern.

"I don't think a sobering-up drug could be used ethically by society," he said in a telephone interview. "It could be diverted for recreational purposes. Every time science comes up with something useful, it seems, society finds a way to abuse it.

"Beyond the ethics are the legal considerations," he added. "I think [pharmaceutical] companies would be unwilling to risk the liability of someone who is drunk taking the drug and then getting into an accident on the way home."

Nevertheless, Paul thinks Ro 15-4513 has tremendous potential for good. His research is continuing, and he's exploring the possibility of consulting with a pharmaceutical company that has the money and interest to develop the drug. "Eight percent of our adult population has a serious alcohol problem," he noted. "More than 15 percent of the country's medical costs are alcohol-related. Think of the benefits if we can treat alcoholism with a compound that is inert and can block its effects."

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