Alcohol Abuse and Dependence: Update on Etiology and Treatment

Alcohol is unique in the pantheon of abusable substances. In addition to the association between chronic, heavy drinking and cirrhosis of the liver, peripheral neuropathies, dementia, and other medical and behavioral problems (eg, those that lead to traffic fatalities), there is also an association between moderate use and lowered rates of coronary artery disease and stroke--as the following articles describe.

While alcohol shares a common mesolimbic dopamine-based reinforcement process with almost all abusable substances, chronic alcohol use also alters opioid, serotonergic, and cannabinoid systems, as well as the brain's 2 most common receptor systems: the g-aminobutyric acid (GABA) receptors and glutamate receptors. The GABA and glutaminergic systems regulate, respectively, inhibitory and excitatory mechanisms for the CNS. Chronic, heavy alcohol use appears to reduce activity of the GABA_A subtype (ie, inhibiting the inhibitor) and increase the glutamate-mediated excitatory system (above a certain threshold, this excitation can lead to cell death). Indeed, it is the study of alcohol's underlying biologic mechanisms that has produced the most effective pharmacotherapeutic agents to date: naltrexone (ReVia), a mixed opioid receptor antagonist, and acamprosate (Campral), a GABA analog. These agents are also discussed in the following pages.

Additional pharmacotherapies for alcohol dependence are on the way, and new ones will likely be discovered as research moves forward. *

Dr Wilkins is vice chair in the department of psychiatry and director of addiction medicine at Cedars-Sinai Medical Center. He is also adjunct professor of psychiatry at the University of California, Los Angeles, School of Medicine.