Gamma-Hydroxybutyric (GHB) Acid

Abstract

This new agent became known as “Liquid Ecstasy, Liquid E, Liquid X, or Fantasy”. It is a central nervous system depressant, and has been used as an anxiolytic, anesthetic and sedative/hypnotic, inducing a sleep-like state in experimental animals in doses ranging from 0.1 to 1.5 g/kg [5]. GHB is also a putative neurotransmitter [6]. Treatment with GHB has been shown to affect many neurotransmitter systems, most notably, dopamine, glutamate and acetylcholine [7]. A number of early studies focused on GHB’s action at dopaminergic synapses and showed that GHB initially inhibits dopamine release and then, time-dependently, causes its release [8]. Importantly, GHB exhibits an extremely high affinity for a specific GHB receptor [9]. This GHB receptor is a novel G-protein coupled receptor [10], which is widely distributed throughout the cortex and certain subcortical locations, most notably the hippocampus, amygdala, septum, basal ganglia and substantia nigra [11]. It is obvious that GHB receptors mediate some of GHB’s action because cortical neurons, which are normally activated by GHB revert to their normal activity levels when GHB is added, along with its selective receptor antagonist NCS-3827 [11a]. The recent development of truly selective GHB receptor agonists has allowed scientists to finally understand GHB’s mechanism. At low doses, GHB is binding almost exclusively to the GHB receptor, a receptor, which through pathways not yet understood, stimulates the release of glutamate, the major excitatory neurotransmitter in the cortex. As the dose of GHB increases, more and more GHB binds to, and activates the inhibitory GABAB receptor. This leads to the sedative/hypnotic effect of GHB. GHB’s dose-response curve is similar to that of alcohol. At higher doses, users fall unconscious and are temporarily unable to be awakened (coma). It also may dangerously depress breathing, therefore mixing with alcohol should be avoided.