Pharmacotoxicology and analytical issues of gamma-hydroxybutyric acid in clinical and forensic laboratory

Gamma-hydroxybutyric acid (GHB) can be considered both an endogenous metabolite and a precursor of the neurotransmitter gamma-aminobutyric acid (GABA) acting within the central nervous system as a neuromodulator. Pharmacologically, GHB is classified as a central nervous system depressant and its mechanism of action involves interaction and binding with GABA-B receptors. With the generic name of sodium oxybate, the sodium salt of GHB, is sold as a pharmaceutical product under the trade name of Xyrem® when prescribed for the treatment of people with narcolepsy and with the name of Alcover® when used to relieve alcohol withdrawal syndrome and treat alcohol dependence. Between the end of the 90s of the twentieth century and the beginning of the twenty-first one, the abuse of GHB became increasingly widespread in the recreational field. The substance, often consumed in combination with alcohol, cannabis, ecstasy (3,4-Methylenedioxymethamphetamine, MDMA), ketamine, has been converted in one of the most used "club drugs", becoming one of the most serious health issues in the emergency department of many European and extra-European Countries because of the initial difficult clinical management of the growing number of cases of intoxication. At the same time, there was an increase of cases of sexual assaults of victims who were unaware they had been given GHB as odourless and colourless sedative substance. In this narrative review, the three different aspects of GHB as endogenous neuromodulator, as prescription drug and as substance of abuse are illustrated. The main methods for qualitative and quantitative analysis in conventional and non-conventional biological matrices for clinical and forensic purposes are also described