Gamma-hydroxybutyrate (GHB), 1,4-butanediol (1,4BD), and gamma-butyrolactone (GBL) intoxication: A state-of-the-art review

γ-hydroxybutyrate (GHB) is synthesized endogenously from γ-aminobutyric acid (GABA) or exogenously from 1,4-butanediol (butane-1,4-diol; 1,4-BD) or γ-butyrolactone (GBL). GBL, and 1,4-BD are rapidly converted to GHB. The gastric absorption time, volume of distribution, and half-life of GHB are betwe...

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Published in:Regulatory toxicology and pharmacology 2023-08, Vol.142, p.105435-105435, Article 105435
Main Authors: Dufayet, Laurene, Bargel, Sophie, Bonnet, Anastasia, Boukerma, Arezki Khaled, Chevallier, Cécile, Evrard, Marion, Guillotin, Sophie, Loeuillet, Elodie, Paradis, Camille, Pouget, Alix Marie, Reynoard, Julien, Vaucel, Jules-Antoine
Format: Article
Language:English
Subjects:
4-Butyrolactone - toxicity
Drug facilitated sexual assault
Drug overdose
Forensic toxicology
GABA-B receptor agonists
gamma-Aminobutyric Acid
Humans
Sexual assault
Sodium Oxybate - toxicity
Substance Withdrawal Syndrome
Substance-related disorders
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Summary:γ-hydroxybutyrate (GHB) is synthesized endogenously from γ-aminobutyric acid (GABA) or exogenously from 1,4-butanediol (butane-1,4-diol; 1,4-BD) or γ-butyrolactone (GBL). GBL, and 1,4-BD are rapidly converted to GHB. The gastric absorption time, volume of distribution, and half-life of GHB are between 5 and 45 min, 0.49 ± 0.9 L/kg, and between 20 and 60 min, respectively. GHB and its analogues have a dose-dependent effect on the activation of GHB receptor, GABA-B, and GABA localized to the central nervous system. After ingestion, most patients present transient neurological disorders (lethal dose: 60 mg/kg). Chronic GHB consumption is associated with disorders of use and a withdrawal syndrome when the consumption is discontinued. GHB, GBL, and 1,4-BD are classified as narcotics but only the use of GHB is controlled internationally. They are used for drug facilitated (sexual) assault, recreational purposes, slamsex, and chemsex. To confirm an exogenous intake or administration of GHB, GBL, or 1-4-BD, the pre-analytical conservation is crucial. The antemortem cutoff doses for detection are 5 and 5–15 mg/L, with detection windows of 6 and 10 h in the blood and urine, respectively Control of GHB is essential to limit the number of users, abuse, associated risks, and death related to their consumption. •GHB is synthesized endogenously from GABA or exogenously from 1,4-BD or GBL.•GHB and its analogues have a dose-dependent effect on central nervous system.•Transient neurological disorders are common symptoms with a lethal dose at 60 mg/kg.•Antemortem detection windows are 6 and 10 h in the blood and urine, respectively.•Recreational use and drug facilitated (sexual) assault are major problems.
ISSN:0273-2300
1096-0295
DOI:10.1016/j.yrtph.2023.105435