Selected topics: toxicology
A case of withdrawal from the GHB precursors gamma-butyrolactone and 1,4-butanediol

https://doi.org/10.1016/S0736-4679(01)00324-9Get rights and content

Abstract

We describe a case of withdrawal from the gamma hydroxybutyric acid (GHB) precursors gamma butyrolactone and 1,4-butanediol. Symptoms included visual hallucinations, tachycardia, tremor, nystagmus, and diaphoresis. Administration of benzodiazepines and phenobarbital successfully treated the withdrawal symptoms. As predicted from the metabolism of gamma butyrolactone and 1,4-butanediol to GHB, the symptoms were nearly identical to those reported from GHB withdrawal. Because GHB is now illegal in the United States, individuals have begun abusing the legal and easier to acquire GHB precursors. More frequent cases of both abuse and withdrawal from these GHB precursors can be expected.

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)

  • Anonymous. GHB added to the list of schedule I controlled substances. Drug Enforcement Agency Press Release, March 13,...
  • Adverse events associated with ingestion of γ-butyrolactone

    MMWR

    (1999)
  • Cited by (53)

    • Detoxification with titration and tapering in gamma-hydroxybutyrate (GHB) dependent patients: The Dutch GHB monitor project

      2017, Drug and Alcohol Dependence
      Citation 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 Dependence
      Citation 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 Edition
    View all citing articles on Scopus
    View full text