Gamma hydroxybutyric acid (GHB) for the treatment of alcohol dependence: a review

Abstract

Gamma-hydroxybutyric acid (GHB) is a short-chain fatty acid structurally similar to the inhibitory neurotransmitter gamma-aminobutyric acid. 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 facilitates the maintenance of abstinence from alcohol. These studies have also shown that GHB craving episodes are a very limited phenomenon (about 10-15%). Thus, physicians with access should consider the clinical efficacy of GHB as a valid pharmacological tool for the treatment of alcohol addiction.

Keywords: alcohol withdrawal syndrome; anti-craving drug; gamma-hydroxybutyric acid.

Figure 1.

GHB metabolism in the central nervous system. GHBDH: GHB dehydrogenase; SSR: succinic semialdehyde reductase; SSA: succinic semialdehyde; GABA: gamma-aminobutyric acid; GABAT: GABA-transaminase; SSADH: succinic semialdehyde dehydrogenase.

Figure 2.

Activity of meso-corticolimbic system in physiological condition (a), and during exogenous administration of GHB (b). (a) dopaminergic neurons (DA) originate from ventral tegmental area (VTA) and project their fibres to the nucleus accumbens (NAc) and to the pre-frontal cortex; DA neurons play a relevant role in physiological reward (i.e. food, sleeping, sexual activity); this circuit is often inhibited by noradrenergic and GABA-ergic neurons originated from the locus ceruleus (LC). (b) GHB induces dis-inhibition of DA originated from VTA through DA direct activation and inhibition of GABA-ergic and noradrenergic neurons with a consequent increase in dopamine release from NAc and pre-frontal cortex; this mechanism is on the basis of the alcohol-mimicking effect of GHB.

Figure 2.

Activity of meso-corticolimbic system in physiological condition (a), and during exogenous administration of GHB (b). (a) dopaminergic neurons (DA) originate from ventral tegmental area (VTA) and project their fibres to the nucleus accumbens (NAc) and to the pre-frontal cortex; DA neurons play a relevant role in physiological reward (i.e. food, sleeping, sexual activity); this circuit is often inhibited by noradrenergic and GABA-ergic neurons originated from the locus ceruleus (LC). (b) GHB induces dis-inhibition of DA originated from VTA through DA direct activation and inhibition of GABA-ergic and noradrenergic neurons with a consequent increase in dopamine release from NAc and pre-frontal cortex; this mechanism is on the basis of the alcohol-mimicking effect of GHB.