During his regular trips to China, David Lee, an organic chemist at Research Triangle Institute, noticed that many households he visited kept an herbal tea on hand-a mixture of seven different Chinese herbs, including the kudzu plant. Loosely translated, the Chinese name for this tea means “drunkenness dispeller.” It’s a common practice in Northern China to drink it to sober up after drinking alcohol and to relieve hangovers.

In 1991, Lee and scientists at Shin-Yang University in China began testing an herbal compound derived from this tea using rats that had been injected with alcohol. They found that it improved the rats’ motor coordination, or made them less “drunk.”

Meanwhile, Amir Rezvani and David Overstreet, both research associate professors of psychiatry at UNC-CH’s Skipper Bowles Center for Alcohol Studies, had been working with rats that voluntarily drink a significant amount of alcohol. In 1989 Rezvani had discovered this alcohol-preferring quality in Fawn-Hooded rats, named for the orangish-tan patches on their heads and shoulders. Later they began working with Finnish and P-rats, strains of rats that have been selectively bred to prefer alcohol over water.

The rats have free access to food and water at all times, with a 10 percent alcohol solution available on a varying schedule. The rats seem to drink because they crave the effect they get from alcohol, not because they like its taste. Rezvani has discovered that if the rats are injected with alcohol before it’s made available for drinking, “they drink less in direct proportion to how much alcohol you gave them,” Overstreet says.

In 1992, Hugh Criswell, a research associate professor at the Biological Sciences Research Center at UNC-CH, introduced Lee to Overstreet and Rezvani. Lee suggested that they test his Chinese compound to see if it would reduce their rats’ alcohol craving. The pair had mixed reactions.

I was open-minded about it,” Overstreet says, “but I was sort of feeling that probably it wouldn’t work. It’s unusual for a compound to both reduce drunkenness by alcohol and also inhibit alcohol drinking.”

My reaction was a little bit different from yours, David,” Rezvani says. “I was excited about it; I wasn’t as surprised because a lot of modern medicines come from plants. So I thought, it’s possible.”

Why not?” Overstreet says.

Rezvani and Overstreet tested the herbal compound first in the Fawn-Hooded rats. The compound significantly reduced the rats’ alcohol intake, so they tested it in the P-rats and got similar results.

The researchers wanted to find out exactly what plants in the compound were active in reducing alcohol intake. They have focused on two of the seven plants in the mixture, kudzu and sweet orange. Lee and other chemists in his lab have derived from the kudzu plant a pure chemical called “puerarin.” So far the chemical they have extracted from the sweet orange plant is only 80 percent pure, which is a problem. When the rats’ alcohol intake is reduced, is it because of the 80 percent pure chemical or because of a potent substance in the impurity?

You can’t really determine that until you get a pure compound,” Overstreet says. “Did you ever see the movie “Medicine Man?” Sean Connery was in the Brazilian forest, and he had found a chemical which cured cancer, but then he couldn’t find it again. He thought it was in some plants, so he kept moving to where these plants were. Towards the end of the movie, they rediscovered the chemical, but it wasn’t coming from the plants, it was coming from the ants who were parasites on the plants. The point is that sometimes you don’t know what the real active compound is when you’re dealing with mixtures.”

They have conducted various tests using the seven-herb compound and the chemicals derived from it. “One paradigm that we used, we put the rat on scheduled access, which means that the bar is open only one hour, from ten to eleven in the morning,” Rezvani says. “They learn to drink as much as they can during that one hour because they know-that’s it.” The first time alcohol was offered, some of the rats began immediately to drink it, “like crazy,” as Rezvani describes it. After the rats had been on this schedule for about one week, they were given a derivative of the compound 15 minutes before alcohol was made available, and they drank significantly less.

The researchers selected another group of rats and gave them free access to alcohol around the clock, then took the alcohol away for 24 hours. The next day the rats drank 20 to 30 percent more alcohol. Rezvani explains, “It seems that they are trying to compensate for the day that they didn’t get it; they drink a lot. But if we inject them with the herbal compound, you can block or reduce that rebound, and they drink either less than normal, or they drink normally.”

Other experiments are encouraging as well. It seems that the rats do not develop tolerance to the compound; there is no change in its reduction of alcohol drinking after repeated doses. Also important is the finding that the compound does not affect how the rats metabolize alcohol.

If you have a drug which slows down alcohol metabolism,” Rezvani says, “then you will have alcohol in the blood for a longer period of time. You will drink less because you have the alcohol that you need. You want a drug that really has an effect on your reward system in the brain, a drug that reduces craving and prevents relapse.”

This reward system is complex. Brain cells, called neurons, “talk” to each other by releasing chemicals known as neurotransmitters. When a neuron is stimulated, it releases a neurotransmitter, which then binds to receptors on a second neuron, which in turn sends a chemical message to the next neuron, and so on. In the reward pathway of the brain, this process causes feelings of euphoria and pleasure. There is evidence that drinking alcohol causes neurons to release dopamine and serotonin, two neurotransmitters involved in the reward system. Other studies show that when alcohol-preferring rats are given a drug which increases the amount of serotonin available in their brain, they drink less alcohol.

Overstreet and Rezvani are working with the three different strains of rat to learn more about how serotonin levels and other factors influence alcohol intake. The Fawn-Hooded rats and the P-rats have genetic serotonin deficiencies, while the Finnish rats have normal serotonin levels. But the Finnish rats still drink alcohol-much more, in fact, than the Fawn-Hooded rats. The researchers hope that by learning more about the rats’ drinking behavior, they will uncover clues as to why people crave alcohol. They look forward to a day when we may be able to subtype alcoholics, prescribing different courses of treatment according to their biochemical makeup.

But the researchers stress that alcoholism is an elusive, complex disease that is influenced by biological, psychosocial, and environmental factors. Overstreet explains that a drug now available to help reduce alcohol craving, Naltrexone, is effective only in conjunction with intensive counseling. He thinks that the same would be true of any drug eventually derived from the herbal compound. Possibly such a drug would be helpful in combination with Naltrexone. Or maybe because of how the herbal compound acts chemically, it may work in a sub-group of alcoholics in which Naltrexone does not. But we may never have, Rezvani says, a “magic bullet for alcoholism.”

The Potency of Plants

In 1992, the university issued a press release stating that two professors of psychiatry had reduced the alcohol intake of alcohol-preferring rats by giving them a compound derived from a mixture of seven Chinese herbs, including kudzu. In the next six months, David Overstreet and Amir Rezvani fielded more than 60 telephone calls, mostly from people who wanted to get some of the mixture for a friend or relative. The callers thought that their loved ones could “take this herbal medicine and maintain the myth that they’re not alcoholic,” Overstreet says, “because they’re taking something that’s natural and good for you.”

The idea of using an herbal remedy to help fight alcoholism might sound strange. But many modern medicines, including aspirin and morphine, were derived from plants or herbal preparations, Rezvani says. In 1992 the National Institutes of Health established the Office of Alternative Medicine, which awards small grants for the study of treatments such as herbal medicine, hypnosis, and acupuncture.

The basic idea was to get the Easterners and the Westerners together,” Overstreet says, “to get the Eastern-approach people to become more scientific in their studies.”