The gamma-hydroxybutyrate signalling system in brain: organization and functional implications.

GHB: a new and novel drug of abuse.

Gamma-hydroxybutyric acid.

Gamma-hydroxybutyrate (GHB) is a compound found in mammalian brain which meets many criteria of a neurotransmitter. GHB has been investigated as a tool for inducing absence (petit mal) seizures, for use as an anesthetic, and for treatment of narcolepsy, alcohol dependence and opiate dependence. Since 1990 GHB has been abused in the United States for euphoric, sedative and anabolic effects. Coma and seizures have been reported following abuse of GHB, but dependence liability has received little attention. The neuropharmacology, potential therapeutic uses and acute adverse effects of GHB are reviewed, followed by a case series of eight people using GHB. Adverse effects of GHB may include prolonged abuse, seizure activity and a withdrawal syndrome. This withdrawal syndrome includes insomnia, anxiety and tremor; withdrawal symptoms resolve in 3-12 days. GHB has the potential to cause a significant incidence of abuse and adverse effects. Prolonged use of high doses may lead to a withdrawal syndrome, which resolves without sequelae. Educational efforts should address the narrow therapeutic index, possible physical dependence and dangers of combining GHB with other drugs of abuse.

Gamma-hydroxybutyrate: An emerging drug of abuse that causes physical dependence

The Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (the Panel) is asked to advise the Commission on the implications for human health of chemically defined flavouring substances used in or on foodstuffs in the Member States. In particular, the Scientific Panel is asked to evaluate the 47 flavouring substances in this Flavouring Group Evaluation 6, Revision 1 (FGE.06Rev1), using the procedure as referred to in the Commission Regulation EC No 1565/2000. These 47 flavouring substances belong to chemical groups 1 and 4 of Annex I of the Commission Regulation (EC) No 1565/2000.

Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in contact with Food (AFC) on a request from the Commission, Flavouring Group Evaluation 22: Ring-substituted phenolic substances from chemical groups 21 and 25: Question No EFSA-Q-2003-165

— Ninhydrin decarboxylation experiments were carried out on the labelled amino acids produced following intraventricular injection of either γ-hydroxy-[1-14C]butyric acid (GHB) or [1-14C] succinate. The loss of isotope (as 14CO2) was similar for both substances. The [1-14C]GHB metabolites lost 75% of the label and the [1-14C] succinate metabolites lost 68%. This observation gives support to the hypothesis that the rat brain has the enzymatic capacity to metabolize [1-14C]GHB to succinate and to amino acids that have the isotope in the carboxylic acid group adjacent to the a-amino group. These results also indicate that the label from [1-14C]GHB does not enter the Krebs cycle as acetate. The specific activity ratio of radiolabelled glutamine to glutamic acid was determined in order to evaluate which of the two major metabolic compartments preferentially metabolize GHB. It was found that for [1-14C]GHB this ratio was 4.20 ± 0.18 (S.E. for n = 7) and for [l-14C]succinate this ratio was 7.71 (average of two trials, 7.74 and 7.69). These results suggest that the compartment thought to be associated with glial cells and synaptosomal structures is largely responsible for the metabolism of GHB. Metabolism as it might relate to the neuropharmacological action of GHB is discussed.

Metabolism of gamma-hydroxy-[1-14C] butyrate by rat brain: relationship to the Krebs cycle and metabolic compartmentation of amino acids

A sensitive method for quantitation of γ-hydroxybutyric acid and γ-butyrolactone in brain by electron capture gas chromatography

Gamma-hydroxybutyrate: a role in the regulation of central dopaminergic neurons?

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Metabolism of gamma-hydroxy-[1-14C] butyrate by rat brain: relationship to the Krebs cycle and metabolic compartmentation of amino acids

A sensitive method for quantitation of γ-hydroxybutyric acid and γ-butyrolactone in brain by electron capture gas chromatography

Gamma-hydroxybutyrate: a role in the regulation of central dopaminergic neurons?