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"One Day at a Time"

New drugs may smooth alcoholics' road to recovery
As many as 1.5 million alcoholics in the U.S. seek help each year, the National Institute of Alcohol and Alcoholism estimates. Unfortunately, rehabilitation programs often fail them. Most treatments address only the physical symptoms of withdrawl. Indeed, alcoholics trying to dry out typically receive little more than tranquilizers to minimize anxiety and tremors, and vitamins to restore nutritional deficiencies.

The truly desperate, who need added incentive to stay sober, sometimes take disulfiram (Antabuse)--a medication that, in combination with alcohol, almost immediately causes the worst hangover any drinker can remember: throbbing headache, nausea, vomiting, increased blood pressure and a racing heart beat. But the fear of a bit of liqueur in an expensive chocolate makes it a risky bet for even the most determined drinker. Most recovering alcoholics continue to want to drink--and must choose not to, as the phrase made famous by the support group Alcoholics Anonymous goes, one day at a time.

Several new remedies, however, promise to make this daily choice easier by lessening an addict's actual craving for alcohol. These drugs, now in preliminary testing, seem to target the brain systems responsible for addiction One such medication, isradipine (Dynacirc), is a calcium-channel blocker most often prescribed for hypertension. The drug lowers blood pressure by altering the flow of calcium molecules in and out of cells. In alcoholics, isradipine also appears to alter the effects of the neurotransmitter dopamine.

"Animal studies have shown that alcohol and cocaine stimulate the release of dopamine in the nucleus accumbans, and that isradipine blocks this release," says Edward De Met, a professor and clinician at the University of California at Irvine. "Because this circuit is involved in reward reinforcement and goal-seeking behavior, we believe that isradipine blocks the reinforcing aspects of drinking behavior." Isradipine also has some activity as a seratonin re-uptake inhibitor, as do certain antidepressants--some of which help the recovery of alcoholics who are also depressed. But DeMet doubts that isradipine works primarily through this mechanism. He has found in his studies that better seratonin uptake blockers, such as paroxetine (Paxil), do not seem to supress cravings as effectively.

Indeed, DeMet recently studied 12 alcoholic men for 12 weeks at the Long Beach Veteran's Hospital. All had tried to sober up on several occasions and failed. Five patients received isradipine, and three took naltrexone (ReVia), a drug that acts on the opioid receptor in the brain. It is often prescribed for heroin craving, but was also approved by the Food and Drug Administration for treating alcoholism in December 1994. Four more subjects received paroxetine.

In addition to the drug treatment, all of the men enrolled in an outpatient program, consisting of group therapy and 12 step programs, such as AA. They were asked to record how much they drank, and how much they wanted to drink over time.

"Craving ratings in the five subjects given isradipine for 12 weeks decreased rapidly," DeMet says. None reported drinking during the three months, and none failed urine tests for alcohol or any other drug. More important still, these men reported that their craving for alcohol fell off steadily as long as they were being treated. In contrast, the groups receiving naltrexone and paroxetine said they experienced unchanged or slighted elevated cravings after finishing treatment. "The next step is to increase our sample size, and to examine the effects of isradipine on cocaine craving," DeMet adds.

The Substance Abuse and Mental Health Services Administration reports that, in fact, many alcoholics abuse cocaine and other drugs. Larry Reid and his colleagues at the Rensslaer Polytechnic Institute have observed that many alcoholics who come in for treatment are also using cocaine.

Reid's research has focused on using isradipine and naltrexone for cocaine abuse. He has found that this mix successfully blocks cocaine's rewarding effects in rats, and also reduces the animals' intake of alcohol. "When used alone, in safe doses, the drugs have no effect on cocaine-induced behavior in rats," Reid adds. "The effectiveness of the two drugs together, however, is impressive. These promising results lead to the suggestion that this combination of drugs should be tested in humans." Given how many people battle addiction daily, Reid and his co-workers hope these tests happen sooner rather than later.


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