[Update on gamma-hydroxybutyric acid]

Abstract

Aims: The article offers an updated review of the main pharmacological aspects of gamma-hydroxybutyric acid (GHB), as well as its clinical and behavioural effects.

Development: A number of pharmacological, neurochemical and electrophysiological studies have clearly shown that endogenous GHB plays a role as a neurotransmitter and/or neuromodulator in the central nervous system (CNS). GHB displays specific synthesis, release and reuptake mechanisms, as well as particular binding sites that suggest the existence of a central GHBergic system. This substance, popularly known as 'liquid ecstasy', is also a potentially abusable drug; if administered for prolonged periods of time it can lead to dependence and withdrawal symptoms after the patient stops taking it. Its chief behavioural actions include sedation/sleepiness, induction of absence seizures, catalepsy or reduced aggression, among others. Some of these effects appear to be related to an interaction that has been reported to exist between the GHBergic system and the dopaminergic and GABAergic receptors in the CNS. From the clinical point of view, its use has been approved in some countries to treat the narcoleptic syndrome, and it has also been considered for possible use in the treatment of alcohol or opiate abuse. Finally, recent studies conducted with laboratory animals suggest the existence of a possible neurotoxic effect following prolonged administration in abusable dosages.

Conclusions: GHB is an extraordinarily interesting compound. It acts as a neurotransmitter/neuromodulator in the CNS. It is also an abusable recreational drug and may also be used to treat a number of different pathological conditions, the most important of which is narcolepsy. The possible development of neurotoxicity following prolonged administration, however, imposes considerable limitations on its usefulness in clinical contexts.