Selected topics: toxicologyA case of withdrawal from the GHB precursors gamma-butyrolactone and 1,4-butanediol
Introduction
In 1992, the Food and Drug Administration began aggressive enforcement actions against the manufacture and interstate distribution of gamma-hydroxybutyric acid (GHB) after serious adverse effects and increasing cases of abuse became evident (1). On March 13, 2000, GHB was made a schedule I drug by the Drug Enforcement Agency (2). Two chemical precursors of GHB, gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD), have been marketed as legal alternatives to GHB. Toxicity from ingestion of these precursors has been previously reported, with the manifestations being identical to those seen with GHB 3, 4, 5. This is predicted based on the in vivo metabolism of these compounds to GHB. Gamma hydroxybutyric acid withdrawal has been documented in patients who chronically abuse the drug 6, 7, 8, 9, 10, 11, 12. Two abstracts document withdrawal from GBL 13, 14. We report a case of withdrawal from chronic abuse of GHB precursors.
Section snippets
Case report
A 36-year-old man presented to the Emergency Department (ED) from jail with altered mental status. The police who accompanied the patient informed us that he might have been suffering from GBL withdrawal. When arrested approximately 10 h before ED presentation, he had warned the arresting officers that without consumption of GBL he would likely soon suffer withdrawal. During custody he had developed worsening agitation, hallucinations, and delirium. On arrival at the ED, he had the following
Discussion
We report a patient who suffered significant withdrawal symptoms from GBL and 1,4-BD. He described in detail the dose and frequency of GBL ingestion and repeatedly denied abusing ethanol. The withdrawal symptoms that he suffered, including agitation, hallucinations, tachycardia, nystagmus, tremor, and diaphoresis, are identical to those reported from GHB withdrawal. 6, 7, 8, 9, 10, 11, 12 The symptoms are also identical to those observed in two of the three reported patients suffering from GBL
References (24)
- et al.
Coma and respiratory depression following the ingestion of GHB and its precursorsthree cases
J Emerg Med
(2000) - et al.
Severe γ-hydroxybutyrate withdrawala case report and literature review
J Emerg Med
(2000) - et al.
Physical dependence on sodium oxybate
Lancet
(1994) - et al.
Preliminary report on the metabolism of γ-butyrolactone and γ-hydroxybutyric acid
Biochem Pharmacol
(1965) - et al.
1,4 Butanediol, γ-hydroxybutyric acid and ethanolrelationships and interactions
Neuropharmacology
(1984) - et al.
Cross-tolerance to ethanol and γ-hydroxybutyric acid
Eur J Pharmacol
(1995) Gammahydroxybutyratean overview of the pros and cons for it being a neurotransmitter and/or a useful therapeutic agent
Neurosci Behav Rev
(1994)- et al.
γ-butyrolactone and γ-hydroxybutyric acid-II. The pharmacologically active form
Int J Neuropharmacol
(1966) - et al.
Absorption of sodium γ-hydroxybutyrate and its prodrug γ-butyrolactonerelationship between in vitro transport and in vivo absorption
J Pharmaceut Sci
(1980) - Reuter, N. Statement on behalf of U. S. Food and Drug Administration before the Subcommittee on Commerce—U. S. House of...
Adverse events associated with ingestion of γ-butyrolactone
MMWR
Cited by (53)
Detoxification with titration and tapering in gamma-hydroxybutyrate (GHB) dependent patients: The Dutch GHB monitor project
2017, Drug and Alcohol DependenceCitation Excerpt :Some case studies showed successful treatment of GHB withdrawal symptoms with low doses of benzodiazepines (Addolorato et al., 1999; Price, 2000). In contrast, other patients developed severe GHB withdrawal symptoms upon cessation, including delirium, psychosis, autonomic instability, rhabdomyolysis, seizures, and agitation, despite high-dose benzodiazepine treatment and/or additional pentobarbital (Chin, 2001; Craig et al., 2000; Dyer et al., 2001; Schneir et al., 2001; Sivilotti et al., 2001; van Noorden et al., 2015). Nevertheless, benzodiazepines are still considered first choice agents in GHB withdrawal, according to reviews and case reports (Schep et al., 2012).
Physical dependence on gamma-hydroxybutrate (GHB) prodrug 1,4-butanediol (1,4-BD): Time course and severity of withdrawal in baboons
2013, Drug and Alcohol DependenceCitation Excerpt :In rats, precipitated (via GABA-B antagonist) and spontaneous withdrawal syndromes (i.e., occurrence of audiogenic seizures) from 1,4-BD (administered for 6–9 days) occurred only in selectively bred Sardinian alcohol-preferring rats but was not detected in other rat lines (Carai et al., 2005; Quang et al., 2006). Human case studies suggest that the withdrawal syndrome produced by cessation of 1,4-BD use is similar to that for GHB (Schep et al., 2012; Schneir et al., 2001; Wojtowicz et al., 2008; Wood et al., 2011; Zvosec et al., 2001). Case studies, however, rely on self-report of drug use by patients.
GHB and Related Compounds
2007, Haddad and Winchester's Clinical Management of Poisoning and Drug Overdose, Fourth EditionPharmacological Treatment of GHB Withdrawal Syndrome
2024, Current Addiction ReportsPhenobarbital to manage severe gamma-hydroxybutyrate withdrawal: A case series
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