Sites of Action of Gamma-Hydroxybutyrate (GHB)–A Neuroactive Drug with Abuse Potential

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Abstract
Objective: This review highlights the biochemistry, pharmacology, and toxicology of the naturally-occurring fatty acid derivative, gamma-hydroxy-butyrate (GHB). GHB is derived from gamma-aminobutyric acid (GABA) and is proposed to function as an inhibitory chemical transmitter in the central nervous system. Content: When administered in pharmacological doses, its powerful central nervous system depressant effects are readily observed. Although some of the neurophysiological actions of GHB could involve alterations in dopaminergic transmission in the basal ganglia, both its physiological and pharmacological actions are probably mediated through specific brain receptors for GHB. In addition, GHB might mediate some of its effects through interaction with the GABAB receptor. Experimentally, GHB has been used as a model for petit mal epilepsy; clinically, it has been used as a general anesthetic and as a drug to treat certain sleep disorders and related conditions. Owing to the purported ability of GHB to induce a state of euphoria, recreational use of this substance is popular. Although no deaths or long-term problems have been associated with GHB abuse, symptoms of GHB intoxication can be severe. The continued potential for GHB abuse makes it imperative for clinical toxicologists to be aware of the effects of this agent. Future research on the mechanism of action of GHB is needed to elucidate both its central nervous system depressant properties and its ability to effect a state of well-being.