Int. J. Environ. Res. Public Health 2010, 7 1884 GABA and glutamate systems are particularly sensitive to alcohol effects, showing adaptation during the course of long-term alcohol exposure [46], for this reason receptor agonists have been studied as therapy targets for alcoholism. The limitations using these drugs lay on the changes in the gabaergic system, more specifically in the GABA A receptors in rats after chronic alcohol feeding. Among the new promising drugs for alcoholism we point to topiramate. It facilitates inhibitory GABA A-mediated currents at non-benzodiazepine sites on the GABA A receptor [43]. Baclofen is a GABA B receptor agonist which has demonstrated good outcome in small clinical trials, however further research is needed. Although neither topiramate nor baclofen have been approved by the FDA, these are among the most promising drugs, with a medium effect size in clinical trials. Furthermore serotonergic agents such as selective serotonin reuptake inhibitors and the serotonin-3 receptor antagonist, ondansetron, appear to be efficacious only among certain genetic subtypes of alcoholics [43]. Biological pathway of GABA is probably involved in AD, a key area for proteomics which consists in a biomarker discovery that could correlate protein expression with the treatment outcome or global prognosis of the disease [47]. Duloxetine is a selective serotonin/norepineprhine reuptake inhibitor (SSNRI) and has been proposed as a new therapy for alcohol use disorders. The results in rats treated with duloxetine showed robust reductions in alcohol consumption. Post-hoc analysis indicated that all doses of duloxetine significantly suppressed binge-like alcohol intake (P < 0.05) in all cases [44]. Nonetheless relapse in drinking and craving in the postdetoxification period is noticed, more than if treated with gabapentin. Disulfiram inhibits aldehyde dehydrogenase and prevents the metabolism of alcohol’s primary metabolite, acetaldehyde. The accumulation of acetaldehyde in the blood causes unpleasant effects. This drug has been accepted by the FDA since 1940 for treating AD, although craving for alcohol is not reduced and it has been related to toxicity and severe adverse effects. However it is still widely used for the treatment of alcoholism. Johnson et al. report that acamprosate has demonstrated efficacy for treating AD in European trials, but not so in the United States, with up to 70% of patients resuming drinking within one year. The use of acamprosate thus presents inconclusive results. It has been approved by the FDA, however it hasn’t shown positive results when comparing its effects with placebo. Unlike in the U.S., European studies show some efficacy in the use of acamprosate [43]. In the COMBINE study, data show that patients receiving treatment with naltrexone, combined behavioral intervention or both, fared better on drinking outcomes, whereas acamprosate showed no evidence of efficacy, with or without combined behavioral intervention [48]. New pharmacological agents that inhibit 5-HT reuptake from the synapse, reduce the voluntary consumption of ethanol. 7.2.2. Alcoholics anonymous Alcoholics Anonymous (AA) is the most commonly used program for substance abuse recovery and one of the few models to demonstrate positive abstinence outcomes. Social support is a mechanism in the effectiveness of AA in promoting a sober lifestyle and worldwide membership is estimated at over 2,000,000 in 150 countries. Some studies reported that the participation of AA was linked to positive drinking outcomes and modestly related to better psychological health, social functioning, employment situation, and legal situation [49].