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New Treatments for Alcoholism on Horizon

By Rich McManus

On the Front Page...

Though there is still much to be done in matching dose and medication to the person suffering the brain disease, alcoholism is the subject of new medical breakthroughs, according to a trio of speakers at Clinical Center Grand Rounds on Mar. 27. As an example, in one instance described during an hour-long session devoted to "Alcoholism: New Potions and Remedies," a hardened alcoholic of many years standing, who used to drink a case of beer every other day, was transformed within 3 weeks into a teetotaler.

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The patient, a 42-year-old rancher who had begun drinking at age 10 and had accumulated some 11 driving-while-intoxicated offenses, plus 25 arrests for public drunkenness, in addition to failing treatment for alcohol dependence 6 times, was put on an experimental medication by physicians at the University of Texas Health Sciences Center in San Antonio, said Dr. Nassima Ait-Daoud, an assistant professor there who presented the case. Within 7 weeks of initiating therapy, the man no longer craved alcohol. He has been off medication for 3 years, remains abstinent, has regained social stability and now counsels other alcoholics, added Ait-Daoud.

The physician-researchers, all of whom are funded by the National Institute on Alcohol Abuse and Alcoholism, are optimistic that advances in pharmacogenetics will yield great benefits in the treatment of alcohol dependence. "The new medications are really becoming practical additions to psychotherapy" in treating alcoholism — believed to be both a brain and behavioral illness — said Dr. Bankole Johnson, Wurzbach distinguished professor of psychiatry at UT, San Antonio. "Matching the right type of medicine for the right type of person (there is evidence of biological differences between early- and late-onset alcoholics) can be highly beneficial. In the future, pharmacogenetic studies can tailor treatment even more effectively."

More than 14 million Americans are believed to suffer from alcohol abuse and dependence; the cost to society is estimated at $184 billion annually, "or about the same range as cancer and heart disease," reported Dr. Fulton Crews, director of the Bowles Center for Alcohol Studies and professor of pharmacology and psychiatry at the University of North Carolina, Chapel Hill. "A lot of that cost is in lost productivity."

Some 10 percent of employed males are alcohol-dependent, and 5 percent of all deaths are alcohol-related, he continued. The peak age of dependence is 25-45, though drinking usually starts 10-15 years earlier. While the amount one drinks is not a criteria for alcoholism, some 20 percent of the nation's drinkers are consuming 80 percent of the booze, Crews noted. "You have a small percentage of drinkers consuming a large percentage of all the alcohol consumed."

There are six criteria for defining a patient as alcoholic, half of which are loss-of-control issues, and the rest involving one's preoccupation with obtaining and consuming alcohol.

"Alcoholism is progressive and chronic," Crews said. Its earliest symptoms are behavioral (fighting, arrests, accidents), and the disease is marked by both psychological and physical dependence.

While there is a "very strong genetic component" to alcoholism, the disease is not totally governed by inheritance; Crews estimates the cause as 60 percent hereditary and 40 percent environmental. Most susceptible to the disease are so-called "low responders," as measured both subjectively and hormonally — it takes more alcohol to affect these individuals, which translates into a tendency to consume heavily.

A 1994 study of drug use and addiction in the U.S. showed that more than 90 percent of Americans have experimented with alcohol, and about 70 percent drink at least occasionally. About 15 percent of those who experiment become alcohol-dependent at some point in life. This compares to a dependency rate of 25 percent in those who experiment with smoking tobacco, and around 4 percent in marijuana smokers.

Summarizing the pharmacology of alcohol's effect on the brain, Crews noted that chronic alcohol alters a variety of signaling pathways, blunting "pro-survival" pathways and increasing neurotoxic ones.

Crews' lab is currently exploring the hypothesis that binge drinking leads to chronic abuse. He showed evidence that brain volume, chiefly cortical gray matter, reduces over time in heavy drinkers, with the frontal regions of the brain most severely affected. "The degeneration we have seen is somewhat selective, corresponding to losses in such abilities as executive function and problem-solving." He has also demonstrated that alcohol abuse impairs creation of neuroprogenitor cells, or cells destined to become mature brain cells.

Using an animal model of 4-day bingeing, Crews reported "a significant increase in neuron death. Binge drinking does cause damage." But it is not yet clear that it leads to alcoholism.

Adolescent age turns out to be a major risk factor for alcoholism — "you have a much lower risk of becoming an alcoholic if you start drinking after age 21," he said.

Fortunately, the brain regenerates during abstinence, said Crews, adding that an alcoholic must remain dry for long enough for the brain's executive-function capacity to return. Metabolic recovery from alcoholism can take place after about 2 weeks, he said. "Recovery is greater in abstainers than relapsers," he observed.

Bankole Johnson's talk dealt with the complexities of the serotonin, glutamate and opioid systems in the brain, a knotty maze of chemical interactions affecting mood, sleep and vulnerability to addiction. Therapies involving selective serotonin reuptake inhibition have been somewhat effective, he said, but he is now investigating a drug called ondansetron, an antagonist of the 5HT3 receptor. "This drug is quite expensive but is highly promising as a treatment for early onset or biological alcoholism," he said.

Johnson also suggested, with real optimism, that careful, targeted alteration of selected neurotransmitters in the brain offers the best hope for new therapies.


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