Gamma hydroxybutiric acid (GHB): a valid pharmacological opportunity for the treatment of alcohol dependence.

Gamma-hydroxybutyric acid (GHB) is a short-chain fatty acid structurally similar to the inhibitory neurotransmitter gamma-amino-butyric acid that exerts an ethanol-mimicking effect on the central nervous system, by acting on its own receptor and on the GABAB receptor. In Anglo-Saxon Countries, GHB has emerged as a recreational drug of abuse due to its euphoric effects, and several episodes of drug intoxication and withdrawal syndrome due to its non-clinical self-administration have been described in the last 10 years. However, in the United States, GHB has been employed since 2002 for the treatment of cataplexy, a symptom often manifested by patients with narcolepsy. In some European Countries, where GHB is not so widespread as a drug of abuse, this medication is currently used for the treatment of alcohol dependence with encouraging results. Indeed, clinical trials have demonstrated that 50-100 mg/kg of GHB fractioned into three or six daily doses is able to suppress alcohol withdrawal symptoms and to favor the maintenance of abstinence from alcohol. GHB has also proved to be more efficient than naltrexone in maintaining sustained abstinence from alcohol. In addition, as far as combined treatments are concerned, the combination of GHB with naltrexone is more effective than either drug alone in maintaining alcohol abstinence and, likely, in avoiding craving for GHB. As a whole, these studies have shown that episodes of craving for GHB are a very limited phenomenon (about 10-15%) in pure alcoholics, rare episodes of sedation due to GHB abuse have been reported, no cases of intoxication, coma or deaths have occurred and a withdrawal syndrome has not been observed when this drug was discontinued. On the other hand, 40-90% of alcoholics with previous heroin or cocaine dependence develop craving for and abuse of GHB during the administration of this drug. In conclusion, physicians should attribute more importance to the clinical efficacy of GHB as a valid pharmacological tool for the treatment of alcohol addiction following some simple rules of administration: GHB should be indicated in alcoholics who do not present a poly-drug dependence, its dosage should not exceed 50-100 mg/kg fractioned into three to six daily administrations, strict medical surveillance has to be planned, and, when necessary, a family member to be entrusted with the drug should be designated