Medications To Treat Alcoholism

Alcohol Research & Health,  Spring, 1999  by Bankole A. Johnson,  Nassima Ait-Daoud

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Advances in neurobiology support the development of medications to treat alcoholism by modifying the activity of specific chemical messengers (i.e., neurotransmitters) in the brain. Among the most promising new medications is acamprosate, which appears to decrease the intensity of craving after a person has stopped drinking. Naltrexone ([ReVia.sup.TM]) has been shown to decrease alcohol consumption, although its practical effectiveness may be compromised by poor patient compliance and other factors. Ondansetron shows promise for decreasing drinking and increasing abstinence rates among early onset alcoholics, who respond poorly to psychosocial treatment alone. Researchers are investigating whether the use of specific medications in combination can further enhance their effectiveness. Additional research is needed to determine how medications interact with different psychosocial factors and treatments. KEY WORDS: drug therapy; AOD (alcohol and other drug) dependence; calcium acetylhomotaurinate; naltrexone; AO D craving; AOD abstinence; drug efficacy; antagonists; opioids; glutamate; serotonin; serotonin uptake inhibitors; dopamine; serotonin receptors; buspirone; combination drug therapy; patient compliance; literature review

Although psychosocial therapies help many alcohol-dependent persons reduce alcohol consumption and maintain abstinence, 40 to 70 percent of patients resume drinking within 1 year of such treatment (Swift 1999). Advances in neuroscience research in the past decade suggest the possibility of developing medications to improve the efficacy of concurrent psychological or behavioral addiction therapies (Litten et al. 1996). These advances include research that implicates specific neurotransmitter systems (see textbox, p. 100) in the development of addiction, suggesting that medications that modify the activity of these systems may interfere with the development of alcoholism. In addition, some alcoholics may be biologically predisposed to alcohol dependence. Those persons may benefit from medications designed to correct or ameliorate the biochemical abnormalities that presumably underlie their susceptibility.

This article reviews recent efforts to develop medications to both reduce the desire to drink and promote abstinence. Each section begins with a brief explanation of the probable role played by a specific neurotransmitter system in the development of addiction to alcohol and other drugs (AODs). These neurotransmitter systems include opioids, glutamate, serotonin (5HT), and dopamine. Medications that affect the function of these neurotransmitters to influence alcoholism are discussed, focusing on those medications that have shown the most promise in clinical trials on human subjects. Finally, the article recommends areas for future research.

OPIOID ANTAGONISTS

Opioid peptides are a class of neurotransmitters that produce physiological effects similar to those of morphine and heroin. In humans, opioid peptides modulate the effects of other neurotransmitters, thereby influencing a broad range of physiological functions (Froehlich 1997). Alcohol consumption affects the production, release, and activity of opioid peptides (Herz 1997). Opioid peptides appear to increase the rewarding effects of alcohol, nicotine, and opiates, contributing to the reinforcement of their use. Research suggests that this effect results from interaction with other neurotransmitter systems, particularly dopamine. For example, alcohol consumption by laboratory animals is reduced by naltrexone (ReVia(TM)) and naloxone, antagonists of the mu receptor, one of the major subtypes of opioid receptor in the brain (Froehlich 1997). These medications have been shown to block the alcohol-induced release of dopamine in the nucleus accumbens (Swift 1999). Antagonists at the mu opioid receptor may also aff ect alcohol consumption by suppressing general consummatory behaviors without altering motivational or approach behaviors (for technical terms not defined in the text, see glossary, pp. 100) (Boyle et al. 1998). In addition, researchers (see Gianoulakis 1998) have proposed other mechanisms for the effects of opioid peptides on alcohol consumption, including modulation of the body's hormonal stress response.

Human laboratory studies exploring the effects of naltrexone on alcohol-induced mood and craving have produced equivocal results (reviewed in Litten and Allen 1998). One factor that may contribute to the discrepancy among research results is a person's genetic susceptibility to alcoholism. In a recent study (King et al. 1997), nonalcoholic social drinkers (average consumption of two drinks per day) consumed an alcoholic beverage 3 to 4 hours after raking naltrexone. Compared with subjects who did nor have any alcoholic relatives, subjects with family histories of alcoholism (i.e., high-risk subjects) experienced less of alcohol's stimulant effects but reported increased tension, fatigue, and confusion.

Consistent with the above results, persons at genetically high risk for developing alcoholism have lower levels of [beta]endorphin and demonstrate a more pronounced increase in [beta]-endorphin levels in response to alcohol administration compared with persons who do not have alcoholic relatives. Similarly, naltrexone's propensity to reduce alcohol intake in humans is greater in persons who have higher beta-endorphin levels (Gianoulakis et al. 1996).