Current Insights on the Impact of Gamma-Hydroxybutyrate (GHB) Abuse

Abstract

Recreational gamma-hydroxybutyrate (GHB) use, although less common than other substance use, is increasingly recognised and is over-represented in emergency toxicology presentations. This narrative review summarizes GHB pharmacology, current patterns of use, potential harms and management of GHB toxicity and withdrawal. There is a complex interplay between GHB and GABA as GHB is both a prodrug and metabolite of GABA and GHB activates both GHB and GABA receptors. GHB is rapidly absorbed, with effects seen within minutes of ingestion. Metabolism is non-linear at higher doses. While GHB is listed as a controlled substance, its precursor's gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are easily available as both have industrial applications. National surveys indicate low rates of GHB use, with identification of high-risk populations in men who have sex with men and polysubstance users. GHB is one of the three drugs most commonly used in chemsex. GHB is often co-ingested with other interacting psychoactive substances. Acute toxicity is dose-dependent, and management is supportive care. Withdrawal management is generally with benzodiazepines with addition of baclofen for more severe withdrawal. Barbiturates may have a role. Titration and tapering of pharmaceutical GHB is commonly used in the Netherlands. Complicated withdrawal with delirium may require intensive care and treatment with intravenous sedation. There are high rates of relapse after withdrawal and medications for longerterm management are currently being investigated. Chronic use is associated with poorer mental, physical and sexual health, social dysfunction and poor work performance. Laboratory detection is complicated as GHB is an endogenous substance with a short halflife, and therefore not often routinely assayed in the clinical setting. Future research should focus on improving GHB detection and management of GHB withdrawal and dependence. Interventions specific for high-risk groups should be developed and assessed.

Forensic Toxicology of Typical Drugs in Drug-Facilitated Sexual Assault

“…GHB is also called "divine water" in China (Shen Xian Shui), and widely known in western countries as a "club drug" and subsequently a "date rape drug" because of its use in DFSA, otherwise referred to as "fantasy, liquid ecstasy" for the symptoms it may cause [4]. GHB was initially used as a CNS inhibitor and anesthetic adjuvant for clinical use, but it was also used to treat problems related to narcolepsy, alcohol dependence and withdrawal, and a supplement to increase muscle mass [4,5].…”

“…GHB modulates the activity of dopamine and serotonin, as well as opioid systems, especially in the brain. When administered through oral path, GHB is quickly absorbed and reaches its peak serum concentrations no longer than 1 hour after intake [5]. Monocarboxylate transporters may help GHB pass the blood-brain barrier more easily.…”

“…The fact that less than 2% of a therapeutic dose of GHB is eliminated in the urine indicates that metabolism is the primary route of clearance [5]. The brain has multiple pathways for GHB metabolism, but there is little or no knowledge on the role of other tissues to GHB metabolism.…”

“…GHB is widely assumed to be the pharmacologically active molecule. There are three mechanisms for GHB that may take place [5]. First, GHB is converted to γ-Aminobutyric acid (GABA) and binds to GABAA but mostly GABAB receptors.…”

“…γ-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are GHB prodrugs metabolized by a calciumdependent lactonase and two types of dehydrogenase, respectively (Fig. 1) [5,6]. Lactonase is the enzyme that catalyses GBL, and alcohol dehydrogenase breaks 1,4-BD into 4-hydroxybutyraldehyde, which is ultimately transformed to GHB.…”