γ-Hydroxybutyric Acid: A GABAB/GHB Receptor Agonist with a Unique Neuropharmacological and Therapeutic Profile

γ-Hydroxybutyric acid (GHB) is a GABAB/GHB receptor agonist which naturally occurs in the human brain. As a pharmaceutical agent, GHB was first synthesized by Henri Laborit in 1960 and was soon recognized to have unique pharmacological and therapeutic properties. While physiological GHB concentrations seem to be insufficient to stimulate GABAB receptor, the stimulation of this receptor appears to be responsible for most of its psychotropic effects when exogenously administered. The complex pattern of neuropharmacological, behavioral, and clinical effects induced by GHB administration is a paradigmatic example of the crucial role of the GABAB receptor in modulating brain functioning and human behavior. This chapter will briefly introduce the neuropharmacological properties of GHB and give an insight into current human research addressing both neurobiological mechanisms of GHB and its clinical application. GHB represents both a powerful pharmacological model and a promising therapeutic approach to manipulate GABAB/GHB receptor activity in humans. Safety aspects and addictive liability are discussed as limiting factors for future human research.