γ-Hydroxybutyric acid (GHB), γ-butyrolactone (GBL), and 1,4-butanediol (1,4-BD): A literature review of pharmacological, clinical, analytical, and medico-legal aspects

Introduction. - y-hydroxybutyric acid (GHB) is produced endogenously from y-aminobutyric acid (GABA) or formed after the absorption of y-butyrolactone (GBL) or 1,4-butanediol (1,4 -BD). Because of their psychotropic properties, these molecules are diverted, in particular in festive contexts. The objective of this article is to summarize the state of knowledge concerning GHB.Pharmacology. - GBL and 1,4-BD are rapidly converted to GHB. The Tmax of GHB is about 20 minutes. GHB dehydrogenase (liver) and GABA transaminase (brain) metabolize it to succinic acid. Its elimination half-life is about 40 minutes. Its action on three central nervous system receptors (GHB-R, GABA-B, and GABA-A) is dose-dependent.Clinical aspects. - Acute intoxication induces neurological symptoms. The lethal dose is above 60 mg/kg. Symptoms disappear within a few hours. Chronic consumption can lead to a use disorder, and a withdrawal syndrome when stopped.Medico-legal aspects. - Although this substance is much discussed in the media, analytical confirmations of GHB in drug-facilitated crimes are rare.Analytical aspects. - GHB is difficult to isolate in biological matrices. Pre-analytical conditions are crucial for interpretation. The ante-mortem cut-offs of an exogenous administration are 5 mg/L in blood and 15 mg/L in urine with a detection window of 6 hours in blood and 10 hours in urine.Conclusion. - A better control of these substances would limit their abuse and the risks asso-ciated with substance use disorder. Further studies in alternative matrices (hair, sweat) would help better characterize the actual proportion of GHB used in drug-facilitated crimes.(c) 2022 Societe Francaise de Toxicologie Analytique. Published by Elsevier Masson SAS. All rights reserved.