Alcohol releases a neurotransmitter called GABA (gamma-aminobutyric acid), instrumental in creating a sense of euphoria. Too much GABA can impair muscle control and slow reaction times, so the brain releases a stimulating chemical called glutamate to keep it in check. When alcohol is cut off, glutamate levels remain high and can cause irritability and discomfort. To relieve those feelings, the brain craves another drink. As more GABA and glutamate are released, brain cells change their structure to accommodate the excess chemicals, making them dependent on these levels. When alcohol is withdrawn, painful emotional and physical reactions are set off.
GABA may be the reason people drink, but glutamate is the reason they can't stop. This powerful neurotransmitter is a key player in the brain's learning centers, and excess amounts create deeply embedded memories of drinking. Years after a person quits, these memories can be triggered by a place, person, or even smell associated with drinking, setting off intense cravings. Such cue-induced cravings are the main reason for relapse. "They're why it can be easy to get off a drug, but it's very hard to stay off," says Dr. Herbert D. Kleber, director of the division on substance abuse at Columbia University.
Campral helps alcoholics resist these cravings by checking production of glutamate, bringing the brain's chemistry back into balance. Clinical studies of Campral have shown that after six months of treatment, 36% of patients were still abstinent, compared with 23.4% on placebo. Vivitrex dampens cravings by a slightly different mechanism, calming opioid receptors in the neurons that are overstimulated by alcohol. A recent study showed that Vivitrex can help people cut way down on alcohol bingeing. That's not the same as abstinence, but Dr. James C. Garbutt, an alcoholism researcher at the University of North Carolina at Chapel Hill, says reduced drinking is still meaningful in a disease that is remarkably resistant to treatment. "If you significantly reduce the number of heavy drinking days, you've made a big impact." Treatment specialists believe that Campral and Vivitrex may be most effective when used in combination.
INDIFFERENCE AT LAST
Existing drugs approved for other purposes may end up being part of that combination. The field got a jolt last August from a study in The Lancet that showed that Topamax, an anti-seizure medicine from Johnson & Johnson (JNJ ), helped 13 of 55 patients abstain from drinking for a month. Dr. Bankole A. Johnson of the University of Texas Health Science Center at San Antonio, who headed the study, said the patients all started on the drug while still drinking, a significant breakthrough. Campral is taken after the patient quits.
Still, no drug is recommended in a vacuum. "We are developing better and better medications, but they need to be taken in a therapeutic context," says Kleber -- which may include AA and other types of behavioral therapies. Dr. Ameisen, for one, found it much easier to use the techniques he learned at AA while on baclofen. But it was the drug that changed his life. "At the end of my ninth month of complete liberation from symptoms of alcohol dependence, I remain indifferent to alcohol," he writes. "Abstinence has become natural to me."
By Catherine Arnst in New York