Acamprosate: potential medication for treating alcoholism

July 14, 2004

As scientists and clinicians learn more about the changes in brain chemistry that chronic alcohol use can cause, the pharmacotherapy of alcoholism has become increasingly relevant for the treatment of alcohol craving, abstinence, and relapse. A study in the July issue of Alcoholism: Clinical & Experimental Research examines the effects of acamprosate (calcium acetyl homotaurinate), a medication used in Europe and elsewhere to prevent relapse in alcoholics, and currently under review for use by the U.S. Food and Drug Administration. The study's findings, in conjunction with previous research, indicate that acamprosate should be safe to take when people are drinking, and should not make them want to drink more or behave differently over and above the effects of alcohol alone.

"To our knowledge, this is the first published report that examines potential interactions between acamprosate and alcohol in humans," said Elisabeth J. Houtsmuller, assistant professor of behavioral biology at Johns Hopkins University School of Medicine and corresponding author for the study. "Other studies have shown that acamprosate helps people abstain from drinking, and our study examined what may underlie this. Because acamprosate acts on a neurotransmitter system - the glutamate system - that alcohol also has many effects on, we thought it was possible that acamprosate might change some of alcohol's effects, and this might be part of why it helps people to abstain. We therefore examined whether acamprosate alters the way alcohol makes people feel."

The findings suggest that acamprosate does not alter the rate of absorption or elimination of alcohol by the body, the disrupting effects of alcohol on performance tasks, or most of alcohol's mood effects, she said.

"The glutamate system is one of the most strongly affected by chronic alcohol use," added Raymond Anton, Distinguished Professor and director of the Center for Drug and Alcohol Programs at the Medical University of South Carolina. "Following the initiation of abstinence, it takes considerable time for the brain chemistry of this system to become 'normal' again. It is thought that acamprosate helps speed this process so that the person has a greater chance of staying abstinent by not 'turning to the bottle' to feel normal. Acamprosate is well tolerated but needs to be taken a few times per day, unlike disulfiram and naltrexone, which can be taken once per day."

Disulfiram (Antabuse®) and naltrexone (ReVia®) are the only two medications currently approved for use in the United States for treating alcoholism. Disulfiram blocks the breakdown in the liver of an alcohol metabolite called acetaldehyde. The resulting buildup leads to flushing, nausea, vomiting, headache and a general feeling of lousiness. The underlying rationale is that a person will begin to associate unpleasant consequences with drinking alcohol. However, it is unclear if craving or the desire to drink are reduced, and many people simply stop taking the medication. Studies have shown that disulfiram works best when its ingestion is monitored/observed on a daily basis.

Naltrexone has been shown to indirectly hinder the elevation of dopamine, referred to as the "feel-good" molecule. It does so by hindering the alcohol-generated release of natural brain opiate or heroin-like molecules - which increases other brain chemicals like dopamine - by blocking the brain-cell receptors to which they bind. Naltrexone can also block alcohol craving (especially the type of craving generated by people, places and things associated with alcohol) and reduce alcohol consumption, leading to less relapse drinking and more abstinent days. Although it is well tolerated and does not produce many adverse effects, naltrexone does not work for everyone, leading some scientists to think there are genetic differences behind the treatment response.

For this study, adult participants (7 males, 3 females) were recruited through local advertising. All of the participants were classified as heavy drinkers, having reported alcohol consumption a minimum of eight days per month; with five or more drinks per occasion at least three times a month for the men, and four or more drinks per occasion at least three times a month for the women. During the six-week study, subjects received three different doses of oral acamprosate (0, 2 and 4 g.) for 11 days on each dose. Physiological, subjective and psychomotor measures were collected daily during each dosing cycle. During each of the acamprosate dose conditions, subjects also received three different doses of alcohol (0, 0.5 and 1.0 g/kg) during three separate laboratory sessions. Researchers collected the subjective, physiological and psychomotor effects of the alcohol as well as breath-alcohol levels at baseline and at 30-minute intervals for three hours following administration.

Results indicate that acamprosate does not appear to alter alcohol's pharmacokinetics (the way it moves through the body), acute physiological or psychomotor alcohol effects, or most subjective alcohol effects.

"While the results of this study are rather clear and straightforward, namely, that acamprosate has minimal effects on the alcohol experience, the findings should be interpreted cautiously because only a few subjects were studied and those subjects were not alcoholics," said Anton. "Since people vary in medication response, generalizing from a study of only a few people is difficult. Also, we know that chronic alcohol use changes brain chemistry in ways that might make medications and alcohol-response interactions different. However, given these cautions, the study is consistent with a growing body of literature and clinical experience that acamprosate should be safe to take when people are drinking and it should not make them want to drink more, or behave differently over and above the effects of alcohol alone."

Anton added that it is always useful and important to investigate interactions between alcohol and medications.

"In fact," he said, " not enough of this is done during drug development. This is especially true of medications that work on the brain and liver, where alcohol has its major effects. It is important to know whether a medication can alter the metabolism of alcohol, for example, increasing blood alcohol levels that would make the person more intoxicated per unit of drink consumed, or increase levels of intoxication by direct brain interaction with alcohol. This type of research also relates to how safely a medication can be used when a person drinks. For instance, if a medication makes a person slower in movement or coordination when they drink, then it may put them in increased danger while driving, boating, or operating machinery. Or it may cause more falls in the elderly, for instance."

Anton added that a "new era of advancement in the treatment of alcoholism" is imminent. "There are a number of emerging possibilities," he said, "ranging from acamprosate, naltrexone and disulfiram to anticonvulsants and novel compounds working on heretofore untested neurochemical systems. The neuroscience of addiction is rapidly advancing, and the future is brighter than it has ever been."
Alcoholism: Clinical & Experimental Research (ACER) is the official journal of the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism. Co-authors of the ACER paper, "Alcohol effects during acamprosate treatment: A dose response study in humans" were Susan M. Brasser and Mary E. McCaul of the Department of Psychiatry and Behavioral Sciences at Johns Hopkins University School of Medicine. The study was funded by the National Institute on Alcohol Abuse and Alcoholism.

Alcoholism: Clinical & Experimental Research

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