Alcoholism treatment under scrutiny.

Alcoholism treatment under scrutiny

For several years, researchers and physicians have pondered the effectiveness of treating alcoholics with disulfiram (Antabuse), a drug that counteracts alcohol craving by causing such ill effects as nausea and flushing whenever a person takes an alcoholic drink. A study in rats added to the complexity of the issue by showing that disulfiram interacts with the neurotransmitter serotonin to boost brain levels of a chemical that enhances alcohol craving in animals. Building on that work, a new study in humans suggests that people who take disulfiram may need to avoid serotonin-rich foods.

Disulfiram works by inhibiting enzymes that normally convert acetaldehyde, an intermediate metabolite of alcohol, into acetate. The toxic acetaldehyde accumulates, creating extreme discomfort in people who drink alcohol while on the drug.

But disulfiram can also increase the accumulation of other, potentially addictive compounds. Among these are the intermediate breakdown products of certain neurotransmitters, including a seortonin metabolite called 5-hydroxytryptophol (5-HTOL). The rat study showed that elevated brain levels of 5-HTOL boost the animals' consumption of alcohol. Researchers have yet to conduct similar tests in human alcoholics says nutritionist U.D. Register of Loma Linda (Calif.) University.

Register and his colleagues have now applied the rat findings to a study of 12 nonalcoholic men, gauging the effects of two serotonin-rich foods on 5-HTOL production. The researchers added three bananas and 3.5 ounces of walnuts to the men's daily diets. Taken without disulfiram, these foods did not alter the production of 5-HTOL as measured in urine. Adding disulfiram to the supplemented diets did not intensify alcohol craving, but it did cause the men to excrete 10 to 40 times the normal level of 5-HTOL, indicating excess production.

Register told SCIENCE NEWS he plans to repeat the study with a group of alcoholics to determine whether the combination of disulfiram and a serotonin-rich diet increases their alcohol craving. But on the basis of the existing findings, he advises alcoholics to avoid serotonin-rich foods while using the drug.

More generally, he asserts that physicians should consider disulfram a "second-line therapy" for alcoholics rather than a primary treatment, in light of its interaction with neurotransmitters and other chemicals in the body. This is not the first time researchers have questioned the drug's use, he notes, although several physicians have reported that neither they nor their colleagues have ever found that the compound increases alcoholics' urge to drink. In 1983, a tema led by Ted D. Nirenberg of Brown University in Providence, R.I., attempted to determine whether disulfiram could increase an alcoholic's cravings. To gauge the degree of craving, the study relied on self-reports from alcoholics, some taking disulfiram and others maintaining abstinence without it. But the results, published in ADDICTIVE BEHAVIORS, proved inconclusive and were never followed up with a controlled study, Nirenberg says.

In 1986, a large, controlled study led by Richard K. Fuller at the Cleveland Veterans Affairs Medical Center showed no significant differences in abstinence among alcoholics on three different regimens: a therapeutic dose of disulfiram; a dose too small to be effective; or a placebo. Nonetheless, clinical observations have indicated that many alcoholics who are motivated to stop drinking, yet have difficulty quitting, do well on the drug, notes Fuller, now at the National Institute on Alcohol Abuse and Alcoholism in Rockville, Md. A report on alcoholism treatment, scheduled for public release next month by the Institute of Medicine in Washington, D.C., stresses the need for more research on disulfiram and other drugs that use negative reinforcement to combat alcohol abuse.