Reply to the Letter “Are the Effects of Gamma-Hydroxybutyrate (GHB) Treatment Partly Physiological in Alcohol Dependence?” by Olivier Ameisen

Abstract

We find Dr. Ameisen’s comment appealing. The Gamma-hydroxybutyrate (GHB) antialcohol molecular effects are yet largely obscure. Clinically speaking, the GHB seems to act as a true “substitute” of alcohol (1) and this aspect may explain two of the major effects of GHB for the treatment of alcoholism: the suppression of both withdrawal syndrome and craving (2, 3). We know that several of the pharmacological effects induced by GHB are due to a potentiation of GABAergic transmission (4). This effect may be due to a simple brain conversion of exogenous GHB in Gamma-aminobutyric acid (GABA) and/or to a direct GHB activation of own receptors, that have been recently identified in the human brain (5). Moreover, since some of the most important central effects of GHB, that is also a naturally occurring GABA(B) receptor agonist, are shared with the GABA(B) agonist baclofen, we may suppose that several of the GHB actions may be also mediated through the activation of GABA(B) receptors (4). In light of the above evidence and considering our recent work (3), Dr. Ameisen is correct in pointing out that alcoholism may be a disease characterized by a GHB-deficiency in the brain. In accord with this hypothesis, in alcoholics the ethanol would act as a “substitute” for the insufficient effects of GHB. In other words, it is the alcohol that may act as a “substitute” for GHB and not the contrary. Furthermore, since baclofen has been demonstrated to suppress both in animals and humans the intake of several drugs including alcohol (6–9), we may suppose a key role of the endogenous GHB not only in the alcoholism but also in several other forms of drug dependence. If the previous hypothesis will be demonstrated, the role of endogenous GHB will