Gamma hydroxybutyrate (GHB), gamma butyrolactone (GBL) and 1,4-butanediol (1,4-BD; BDO): A literature review with a focus on UK fatalities related to non-medical use

Abstract

Misuse of gamma hydroxybutrate (GHB) and gamma butyrolactone (GBL) has increased greatly since the early 1990s, being implicated in a rising number of deaths. This paper reviews knowledge on GHB and derivatives, and explores the largest series of deaths associated with their non-medical use. Descriptive analyses of cases associated with GHB/GBL and 1,4-butanediol (1,4-BD) use extracted from the UK's National Programme on Substance Abuse Deaths database. From 1995 to September 2013, 159 GHB/GBL-associated fatalities were reported. Typical victims: White (92%); young (mean age 32 years); male (82%); with a drug misuse history (70%). Most deaths (79%) were accidental or related to drug use, the remainder (potential) suicides. GHB/GBL alone was implicated in 37%; alcohol 14%; other drugs 28%; other drugs and alcohol 15%. Its endogenous nature and rapid elimination limit toxicological detection. Post-mortem blood levels: mean 482 (range 0-6500; SD 758)mg/L. Results suggest significant caution is needed when ingesting GHB/GBL, particularly with alcohol, benzodiazepines, opiates, stimulants, and ketamine. More awareness is needed about risks associated with consumption.

Presentations to an urban emergency department in Switzerland due to acute γ-hydroxybutyrate toxicity

“…Toxicological analysis in nonfatal cases showed a mean GHB concentration of 245 mg/L (range, 86–551 mg/L; n  = 20) in one small study [35], a median GHB concentration of 180 mg/L (range, 45–295 mg/L; n  = 15) in another study [36], and a mean GHB concentration of 137 mg/L (median, 103 mg/L; range, 29–490 mg/L; n  = 54) in a larger study [18]. Published reports of GHB-related fatalities show a wide range of concentrations that are measured in postmortem blood (0-6500 mg/L) [17, 33, 37, 38], with a median concentration of 190–347 mg/L [17, 33, 37], mean ± SD concentration of 482 ± 758 mg/L [38], and concentration of 300 mg/L that is suggested to be sufficient to cause death [37]. Thus, the concentrations of GHB in survivors and non-survivors seem to overlap.…”

“…Thus, the concentrations of GHB in survivors and non-survivors seem to overlap. However, the possible production and redistribution of GHB after death (depending on the methodology, concentrations up to 197 mg/L even in cases without GHB ingestion [38]) and several other factors (e.g., elapsed time from ingestion to death and from death to sample collection and testing; methods of sample storage and analysis; different levels based on sampling site; the occurrence of delayed death at low GHB concentrations because of loss of consciousness, hypoventilation, and hypoxia [1, 33, 38]; and the possibility that other substances are the cause of death in polyintoxication cases) make the interpretation of postmortem GHB concentrations difficult, with no clearly defined “lethal” concentration [33]. The measured concentrations in our study (median, 240 mg/L; range, 8.3–373 mg/L) were similar to those reported in the other non-fatal GHB intoxication cases.…”

Mechanisms for the Specific Properties of γ‐Hydroxybutyrate in Brain

“…However, when given under medical supervision in specific indications like narcolepsy, alcohol dependence and withdrawal, but also in experimental animals for more than 8 months daily, GHB exhibited no chronic toxicity except dependence and withdrawal disturbances in some patients or animals . GHB is also a recreational drug of abuse because of its easy availability, synthesis, and low cost with a reported high acute toxicity and mortality rate in medical and forensic publications . It is also considered as a “date‐rape” substance, like many sedative‐hypnotics compounds that target GABA receptors (especially GABA‐A receptors).…”

A fatal chemsex case involving γ‐butyrolactone and 4‐methylethcathinone

“…GHB, a potent central nervous system neuromodulator with a biphasic pharmacological profile of stimulant in lower doses and depressant in higher ones, is quite commonly encountered during forensic examination of living and deceased subjects in music and sex settings . In addition, not only GHB, but also its two precursors GBL and 1,4‐butanediol (1,4‐BD) have been implicated in a rising number of severe intoxications and deaths …”