"One Day at a Time"
New drugs may smooth
alcoholics' road to recovery
An
Scientific American Article
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 serotonin 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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