GHB Pharmacology and Toxicology: Acute Intoxication ...

GHB Pharmacology and Toxicology: Acute Intoxication

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The illicit drug γ-hydroxybutyrate (GHB) is a potent central nervous system depressant commonly seen in forensic investigations of both living and deceased individuals. Its sodium salt has therapeutic applications in treating narcolepsy-associated cataplexy and assisting in alcohol detoxification and withdrawal. GHB naturally occurs in trace amounts within the human body and functions within the GABAergic system by binding to GABA-B receptors.

Despite GHB being a controlled substance, abuse persists due to the unregulated availability of precursor drugs like γ-butyrolactone (GBL) and 1,4-Butanediol (BD), both of which are swiftly converted into GHB post-ingestion. Detection windows for GHB are short, necessitating rapid sampling in forensic cases. Recreational doses of GHB vary widely in effect, with plasma concentrations around 100 mg/L inducing euphoria, while 500 mg/L can be fatal.

No effective antidotes exist for GHB overdoses, requiring supportive care and monitoring of vital signs. Long-term use leads to tolerance and dependence, with abrupt cessation resulting in withdrawal symptoms managed typically with benzodiazepines.

Abstract

GHB (γ-hydroxybutyrate) is an illegal recreational drug known for its central nervous system depressant effects. It is commonly encountered during forensic investigations. The sodium salt of GHB is used therapeutically. Trace amounts are produced naturally in the body and function within the GABAergic system. Despite being a controlled substance, GHB abuse continues due to the availability of precursors. Rapid metabolism means short detection windows, necessitating swift sampling. No effective antidotes exist for GHB overdoses, requiring supportive care. Chronic use leads to tolerance and dependence with significant withdrawal symptoms.

Introduction

Among commonly abused recreational drugs, GHB presents significant challenges due to its availability, low cost, and potential for adverse interactions with other sedatives. Accidental poisonings are common, leading to high emergency room admissions and forensic cases. GHB gained attention in the 1990s for its use in drug-facilitated sexual assault (DFSA). Though GHB is now controlled in many regions, precursors like GBL and BD remain available, complicating regulation.

Pharmacology

GHB acts as a central nervous system depressant, mainly interacting with GABA-B receptors. Therapeutically, it is used to treat narcolepsy-associated cataplexy under the name Xyrem and as an adjuvant for alcohol withdrawal under Alcover. GHB’s rapid absorption and short half-life necessitate prompt sampling for forensic investigations.

Pharmacokinetics

GHB shows rapid absorption and distribution throughout body water, with peak plasma levels occurring within 20-40 minutes and a short half-life of 30-50 minutes. Only minimal amounts are excreted unchanged in urine, highlighting the importance of timely sampling for forensic purposes. The pharmacokinetics are dose-dependent, exhibiting non-linear kinetics at higher concentrations.

Toxicology and Detection

Managing acute GHB intoxication primarily involves supportive care. The lack of effective antidotes means healthcare providers focus on stabilizing vital signs and preventing complications like aspiration. Laboratory analysis techniques include gas chromatography and liquid chromatography-mass spectrometry to detect GHB and its metabolites.

Endogenous Levels and Legal Implications

Endogenous concentrations of GHB exist in healthy individuals, necessitating careful interpretation of forensic results to distinguish between endogenous production and exogenous intake. Cut-off levels are established to aid this differentiation, usually 3-5 mg/L in blood and 5-10 mg/L in urine.

Conclusion

GHB continues to be a significant public health issue due to its abuse potential and involvement in impaired driving and DFSA cases. Effective forensic investigation and medical treatment are critical, despite the challenges posed by its rapid metabolism and the complexities of differentiating endogenous from exogenous sources. For further information, please visit hait.

Conflict of Interest

The authors confirm no conflicts of interest in publishing the findings of this review.

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