The clinical toxicology of gamma-hydroxybutyrate, gamma-butyrolactone and 1,4-butanediol

  title={The clinical toxicology of gamma-hydroxybutyrate, gamma-butyrolactone and 1,4-butanediol},
  author={Leo J. Schep and Kai Knudsen and Robin J Slaughter and J Allister Vale and Bruno M{\'e}garbane},
  journal={Clinical Toxicology},
  pages={458 - 470}
Introduction. Gamma-hydroxybutyrate (GHB) and its precursors, gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD), are drugs of abuse which act primarily as central nervous system (CNS) depressants. In recent years, the rising recreational use of these drugs has led to an increasing burden upon health care providers. Understanding their toxicity is therefore essential for the successful management of intoxicated patients. We review the epidemiology, mechanisms of toxicity, toxicokinetics… 

Gamma-Butyrolactone Overdose Potentially Complicated by Co-Ingestion of Industrial Solvent N-Methyl-2-pyrrolidone.

A case of a 50-year-old-man with a history of polysubstance misuse who experienced an overdose of GHB from gamma-butyrolactone ingestion is described, underscoring that the emergence of new psychoactive substance use patterns requires ongoing vigilance and toxicologic confirmation.

1,4-Butanediol overdose mimicking toxic alcohol exposure

1,4-butanediol is a gamma-hydroxybutyrate analogue with a similarly narrow therapeutic window that is becoming a more common cause of recreational overdose, including the interaction with ethanol which delays the onset of psychoactive effects from 1, 4-BD’s metabolite GHB, and dose-dependent pharmacokinetics.

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

Recreational gamma-hydroxybutyrate (GHB) use, although less common than other substance use, is increasingly recognised and is over-represented in emergency toxicology presentations and medications for longer-term management are currently being investigated.

Pharmacological Treatment in γ-Hydroxybutyrate (GHB) and γ-Butyrolactone (GBL) Dependence: Detoxification and Relapse Prevention

An overview of GHB dependence syndrome and GHB/GBL withdrawal syndrome is provided, and general recommendations are given on pharmacological treatment and preferred treatment setting.

The Use of Intravenous Baclofen as Therapy for the γ-hydroxybutyric Acid Withdrawal Syndrome

Baclofen, a γ-aminobutyric acid type B (GABA-B) receptor agonist, is introduced as treatment of the withdrawal syndrome, it has been hypothesised that a substitution for GHB on the GABA-B receptor could prevent withdrawal.

Management and treatment of gamma butyrolactone withdrawal syndrome: a case report and review.

It is suggested that barbiturates could be evaluated as first-choice agents for the treatment of GBL/gamma hydroxybutyrate (GHB) withdrawal instead of benzodiazepines.

Gamma-hydroxybutyrate Abuse: Pharmacology and Poisoning and Withdrawal Management

Abstract Gamma-hydroxybutyrate (GHB) is a central nervous system depressant primarily used as a recreational drug of abuse, but also for the treatment of narcolepsy with cataplexy in adult patients

Treat γ-hydroxybutyrate (GHB) and γ-butyrolactone (GBL) dependence with benzodiazepines first, then with other approaches if benzodiazepine-resistant

A multidisciplinary approach should be adopted to optimize treatment outcomes when treating patients with GHB/GBL dependence, and several knowledge gaps still exist for these therapeutic options.



Withdrawal from gamma-hydroxybutyrate, 1,4-butanediol and gamma-butyrolactone: a case report and systematic review.

Emergency physicians must consider withdrawal from GHB, 1,4-BD and gamma-butyrolactone when patients present with clinical features suggestive of a sedative-hypnotic withdrawal syndrome, according to source articles.

Acute toxicity and withdrawal syndromes related to γ-hydroxybutyrate (GHB) and its analogues γ-butyrolactone (GBL) and 1,4-butanediol (1,4-BD).

This review will summarize the literature on the pharmacology of these compounds; the patterns and management of acute toxicity associated with their use; and the clinical patterns of presentation andmanagement of chronic dependency associated with GHB and its analogues.

Gamma-hydroxybutyrate, gamma-butyrolactone, and 1,4-butanediol: a case report and review of the literature.

Despite repeated FDA warnings to the public about their dangers, GHB and GBL remain accessible as "club drugs" on Internet websites, as natural dietary supplements in health food stores and as illicit products manufactured at home or in clandestine laboratories.

Medical and legal confusion surrounding gamma-hydroxybutyrate (GHB) and its precursors gamma-butyrolactone (GBL) and 1,4-butanediol (1,4BD).

Self-reported GHB ingestion was much more common than GBL ingestion, whereas GBL was more commonly found in the seized samples, suggesting that GBL use may be more common in people attending local club venues than previously thought.

Treatment of a 1,4-Butanediol Poisoning with Fomepizole

Fomepizole administration appeared safe in this 1,4-butanediol-intoxicated patient and the rapid awakening observed suggests that it may have been useful in this patient, although further experience is needed to define the efficacy of this antidotal therapy.

The clinical development of gamma-hydroxybutyrate (GHB).

GHB was being developed for the treatment of narcolepsy, leading to the approval of Xyrem (sodium oxybate) oral solution in 2002, and post-marketing surveillance indicates sodium oxybates has an acceptable safety profile and presents minimal risk for the development of physical dependence.

Clinical Pharmacology of 1,4‐Butanediol and Gamma‐hydroxybutyrate After Oral 1,4‐Butanediol Administration to Healthy Volunteers

BD was extensively converted to GHB after oral administration, but significant inter‐individual variability in the rate of metabolism, possibly related to variants in ADH‐IB, was observed.

Physostigmine as a Treatment for Gamma-Hydroxybutyrate Toxicity: A Review

There is currently insufficient scientific evidence to support the routine use of physostigmine in the treatment of gamma-hydroxybutyrate toxicity, and further studies are needed to determine the role, if any, for physostIGmine in this setting.

Adverse events associated with ingestion of gamma-butyrolactone--Minnesota, New Mexico, and Texas, 1998-1999.

  • Medicine
    MMWR. Morbidity and mortality weekly report
  • 1999
This report describes seven cases of GBL toxicity involving the product "Revivarant," which is labeled as containing 1.82 g of G BL per fluid ounce, reported from two hospital emergency departments in Minnesota during October-December 1998 and summarizes an additional 34 cases of GHB toxicity reported to poison centers in New Mexico and Texas during October 1998-January 1999.