Trends in γ-Hydroxybutyrate (GHB) and Related Drug Intoxication: 1999 to 2003

doi:10.1016/j.annemergmed.2005.10.012

Annals of Emergency Medicine

Volume 47, Issue 2, February 2006, Pages 177-183

Presented as a poster at the European Association of Poison Centres and Clinical Toxicologists (EAPCCT) international conference, May 2005, Berlin, Germany. In conjunction with this meeting, it was published in abstract form in Clinical Toxicology. [Dyer JE, Anderson IB, Kim SY, et al. Reports of GHB and related drug exposures in California: A 5 year review of Poison Control Center Data. [abstract]. Clinical Toxicology. 2005;43:520.]

https://doi.org/10.1016/j.annemergmed.2005.10.012 Get rights and content

Study objective

To analyze changes in γ-hydroxybutyrate (GHB) case reporting, we review GHB or congener drug cases reported to the California Poison Control System, comparing these to other data sets.

Methods

We identified cases from the California Poison Control System computerized database using standardized codes and key terms for GHB and congener drugs (“gamma butyrolactone,” “1,4-butanediol,” “gamma valerolactone”). We noted California Poison Control System date, caller and exposure site, patient age and sex, reported coingestions, and outcomes. We compared California Poison Control System data to case incidence from American Association of Poison Control Centers and Drug Abuse Warning Network data and drug use prevalence from National Institute for Drug Abuse survey data.

Results

A total of 1,331 patients were included over the 5-year period (1999-2003). California Poison Control System–reported GHB exposures decreased by 76% from baseline (n=426) to the final study year (n=101). The absolute decrease was present across all case types, although there was a significant proportional decrease in routine drug abuse cases and an increase in malicious events, including GHB-facilitated sexual assault (P=.002). American Association of Poison Control Centers data showed a similar decrease from 2001 to 2003. Drug Abuse Warning Network incidence flattened from 2001 to 2002 and decreased sharply in 2003. National Institute for Drug Abuse survey time trends were inconsistent across age groups.

Conclusion

Based on the precipitous decrease in California Poison Control System case incidence for GHB during 5 years, the parallel trend in American Association of Poison Control Centers data, and a more recent decrease in Drug Abuse Warning Network cases, a true decrease in case incidence is likely. This could be due to decreased abuse rates or because fewer abusers seek emergency medical care. Case reporting may account for part of the decrease in the incidence of poison center contacts involving GHB.

Introduction

Since the first reports of γ-hydroxybutyrate (GHB) abuse appeared in the early 1990s, this illicit drug has manifested changing use patterns marked by differing at-risk populations, forms of administration (including substitution of chemical congener precursors and analogs), and types of associated adverse effects. GHB was initially marketed as a dietary supplement in health food stores and later was promoted on the Internet as a safe agent for use by bodybuilders. It has also been touted for treating a variety of medical disorders, including insomnia, obesity, depression, alcohol addiction, and sexual dysfunction.¹ GHB use in the general population broadened greatly as it became known as a party drug.² It also gained a reputation as a date rape drug and has been implicated in a number of criminal drug-facilitated sexual assault cases.³

Editor’s Capsule Summary

What is already known on this topic

Initially marketed as a dietary supplement, γ-hydroxybutyrate (GHB) is a popular party drug. It is also available under strict controls as a US Food and Drug Administration–approved treatment for narcolepsy.

What question this study addressed

A rapid and marked decrease in the number of cases involving GHB managed by the California Poison Control System was noted. The cause of this decrease was sought by analyzing national poisoning data, as well as other sources about the use of GHB.

What this study adds to our knowledge

The incidence of GHB use as reflected by these signal detection systems suggests that the misuse and abuse of GHB may be decreasing. Although the number of cases reported by these mechanisms has decreased dramatically, the proportion of cases involving malicious intent (attempted rape) increased.

How this might change clinical practice

When GHB intoxication occurs, specifically soliciting information about malicious events may be prudent. Involvement of law enforcement and maintenance of chain of custody may be prudent.

The heterogeneous acute and chronic effects (including drug withdrawal) associated with GHB and its principal congeners, γ-butyrolactone and 1,4-butanediol, are well described in the literature.4, 5 Fewer data are available concerning a more recently introduced GHB congener, γ-valerolactone. We noted empirically a steep decrease in GHB-related calls to the California Poison Control System. Systematically confirming this potential change is important for the purposes of emergency medical care planning and delivery. In addition, the patterns of incidence among specific subgroups of GHB users could be relevant for targeting prevention and treatment interventions (eg, GHB-dependent users presenting to the emergency department [ED] in need of drug withdrawal management).

Patterns of GHB abuse have not been systematically analyzed. This study of GHB and related drug cases reported to the California Poison Control System was conducted in order to test the hypothesis that the incidence of GHB was changing over the study period. Specifically, we hypothesized that key demographic and clinical characteristics of the cases would demonstrate a systematic (nonrandom) pattern of decreasing incidence that might affect certain subgroups more than others (for example, by sex, by case severity, or by calls originating from health care centers compared to the general public). We further hypothesized that specific subsets of GHB California Poison Control System reports (such as those experiencing a GHB withdrawal syndrome or patients maliciously poisoned) would have differing characteristics potentially related to changing case incidence.

Section snippets

Study Design and Setting

We retrospectively reviewed case records reported to the California Poison Control System involving suspected exposures to GHB or its congeners (precursors and analogs), principally γ-butyrolactone, 1,4-butanediol, and γ-valerolactone. Throughout this paper, the term GHB will refer to gamma hydroxybutyrate as well as these congeners, because in clinical practice it is not typically possible to identify with precision the specific compound that has been ingested. We also separately enumerated

Characteristics of Study Subjects

Table 1 summarizes case record identification, ineligible cases, and exclusions. In total, 589 cases were excluded. Of these exclusions, 484 (82%) were case records that involved no apparent exposure (information requests only; analyzed separately). In total, 1,331 exposure case records were ultimately included in the analysis of exposure-related cases (Table 1). Only 6 (0.45%) case records included were identified using an assault history and narrative descriptive alone, rather than from the

Limitations

The majority of cases lacked laboratory confirmation of GHB. GHB analysis is not routinely available at hospitals. Exogenous GHB administration undergoes rapid elimination, resulting in levels that cannot be differentiated from “background” blood and urine levels within 6 to 12 hours, respectively, severely limiting analysis in delayed presentation. Because of limitations in toxicologic confirmation, the cases tallied in this study may underestimate the true case incidence. The lag time before

Discussion

We observed a precipitous decrease in GHB exposures reported to the California Poison Control System for 1999 through 2003, which parallels decreasing GHB exposures reported nationally through the American Association of Poison Control Centers during 2001 to 2003 and is consistent with the overall trend in Drug Abuse Warning Network data in 2002 to 2003, although not from earlier years. In contrast, National Institute for Drug Abuse survey data on GHB use among high school students did not

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Cited by (68)

Determination of endogenous GHB levels in chest and pubic hair
2021, Forensic Science International
Citation Excerpt :
Since its synthesis in 1960, GHB has been used as anaesthetic agent and later it found application in treatment of narcolepsy with cataplexy, alcohol withdrawal syndrome and alcohol dependence [10,11]. GHB is also used out of medical prescription as enhancer of muscle mass in body building practices and as psychoactive drug for recreational purposes [12–14]. Besides these uses, GHB can be also employed as date rape drug in DFSA for its organoleptic features and psychoactive effects [12,15,16].
Endogenous nature of GHB represents a critical issue for forensic toxicologists, especially in alleged sexual assaults. Therefore, discrimination between physiologically and additional amounts from exogenous sources of such a substance must be effective and reliable in order to avoid severe misinterpretation. This study aimed to quantify the GHB baseline concentrations in chest and pubic hairs collected from 105 healthy volunteers, non-consumers of any drugs of abuse. The final scope was to investigate if these keratin matrices could represent valid alternative to scalp hair when not available. Moreover, we also evaluated the age and gender influences on the GHB baseline levels. 25 mg of hair were incubated overnight with NaOH at 56 °C. After acidification with H₂SO₄, the solution was liquid-liquid extracted with ethyl acetate and a trimethylsilyl derivatization was then achieved. Analysis was performed in gas chromatography-mass spectrometry in single ion monitoring mode (m/z 233, 234, 147 for GHB; m/z 239, 240 and 147 for GHB-d6). The endogenous amount in “blank” hair was estimated by the standard addition method (0.301 for chest hair and 0.235 ng/mg for pubic hair). GHB concentration ranged from 0.205 to 1.511 ng/mg for chest hair and from 0.310 to 1.913 ng/mg for pubic hair. These values were consistent with previous studies on scalp hair and on pubic hair. Unfortunately, research on chest hair is not available in literature. T-Test and Linear Regression highlighted no statistically significant differences for the two matrices and for all age/gender sub-groups. However, further studies are required to estimate a reliable cut-off value for these keratin matrices. For the first time, we demonstrated the suitability of chest and pubic hair to detect endogenous levels of GHB.
Unity in diversity: A systematic review on the GHB using population
2021, International Journal of Drug Policy
Citation Excerpt :
The findings of this study have to be seen in light of some limitations, resulting in knowledge gaps and related recommendations for future studies. First, about half of the studies included less than a hundred subjects (45%), and the range between studies is large: between 7 (Boyce et al., 2000) and 1331 subjects (Anderson et al., 2006). We did not correct for these differences and this could have biased our results.
Over the past decades gamma-hydroxybutyrate (GHB) has emerged as a popular drug with high potential of (ab)use due to its euphoric and relaxing effects. An overview of different populations using GHB is urgently needed, since this would enable development of adequate prevention and treatment policies to diminish the risks associated with GHB use. We systematically reviewed literature on different GHB using populations, comparing demographic characteristics, GHB use patterns, psychosocial aspects and psychiatric comorbidity.
We conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using Rayyan software. Original studies published from January 1997 up to October 2019 on GHB use were included. Out of 80 full-text articles, 60 articles of 51 unique studies were included. Most studies included people using GHB 1) presenting at emergency departments (n = 22), 2) recruited from the general population (n = 11), or 3) presenting at addiction care (n = 8).
Three main sub-populations of people using GHB are described in the literature: people using GHB recreationally without adverse effects; people using GHB recreationally with adverse effects, and people with dependence on GHB. These groups show considerable overlap in gender, age range, and comorbid substance use, as well as amount of GHB use per occasion. Differences are related to frequency and function of GHB use, the number of comas experienced, as well as work status, and psychiatric comorbidity.
Policy interventions should aim at preventing the transition from recreational substance use to GHB use, as most users are experienced recreational substance users prior to starting GHB use. When people use GHB regularly, interventions should aim at reducing the level of GHB use and preventing GHB use-related harm. Longitudinal studies and population-based probability sampling are required for more insight in the dynamics of GHB use in different sub-populations, and the transition from one group to the other, ultimately leading to dependence on GHB.
Intoxication by gamma hydroxybutyrate and related analogues: Clinical characteristics and comparison between pure intoxication and that combined with other substances of abuse
2017, Toxicology Letters
To study the profile of European gamma-hydroxybutyrate (GHB) and gammabutyrolactone (GBL) intoxication and analyse the differences in the clinical manifestations produced by intoxication by GHB/GBL alone and in combination with other substances of abuse.
We prospectively collected data on all the patients attended in the Emergency Departments (ED) of the centres participating in the Euro-DEN network over 12 months (October 2013 to September 2014) with a primary presenting complaint of drug intoxication (excluding ethanol alone) and registered the epidemiological and clinical data and outcomes.
We included 710 cases (83% males, mean age 31 years), representing 12.6% of the total cases attended for drug intoxication. Of these, 73.5% arrived at the ED by ambulance, predominantly during weekend, and 71.7% consumed GHB/GBL in combination with other substances of abuse, the most frequent additional agents being ethanol (50%), amphetamine derivatives (36%), cocaine (12%) and cannabis (8%). Among 15 clinical features pre-defined in the project database, the 3 most frequently identified were altered behaviour (39%), reduced consciousness (34%) and anxiety (14%). The severity ranged from mild cases requiring no treatment (308 cases, 43.4%) to severe cases requiring admission to intensive care (103 cases, 14.6%) and mechanical ventilation (49 cases, 6.9%). No deaths were reported. In comparison with only GHB/GBL consumption, patients consuming GHB/GBL with co-intoxicants presented more vomiting (15% vs. 3%, p < 0.001) and cardiovascular symptoms (5.3% vs. 1.5%, p < 0.05), a greater need for treatment (59.8% vs. 48.3%, p < 0.01) and a longer ED stay (11.3% vs. 3.6% patients with ED stay >12 h, p < 0.01).
The profile of the typical GHB/GBL-intoxicated European is a young male, requiring care for altered behaviour and reduced level of consciousness, mainly during the weekend. The clinical features are more severe when GHB is consumed in combination with other substances of abuse.
GHB-involved crimes among intoxicated patients
2017, Forensic Science International
Citation Excerpt :
Demographic characteristics of the assessed cases showed that the sex ratio of GHB-intoxicated patients is rather balanced, except for the cases of unintentional GHB intake, where the rate of female patients was significantly higher than that of males. We found a similar mean age than other studies that assessed samples of GHB users [24–28], however our sample consisted of not only voluntary GHB users, but victims of GHB-involved sexual assaults and acquisitory crimes as well. Therefore the result that the majority of the patients were in their twenties can also be explained by the fact that this is also the typical mean age of party-goers who consume psychoactive substances during these recreational events [29,30], which can be interpret as a risk factor for enduring the above mentioned GHB-involved offences as well.
In recent years, the involvement of GHB in drug facilitated sexual assaults has been one of the most frequently studied aspects of GHB in both clinical and non-clinical settings. GHB-involved acquisitory crimes, however, can be mentioned as understudied research topics, as well as the poisoning severity properties of GHB.
The medical reports of Péterfy Sándor Street Hospital Clinic and Casualty Centre’s 408 GHB-intoxication cases (352 patients) were reviewed and registered. Analyzed data consisted of epicrisis, serum and urine concentration of various substances (including GHB), scores of Glasgow Coma Scale and Poisoning Severity Score.
Majority of the patients were males, in their twenties. GHB was detected in 34.1% and it was solely consumed in 27.7% of all the cases. Ethanol was found to be the most frequently co-ingested substance. A higher rate of severe poisonings was observed among males. We found significant difference in the frequency of enduring sexual assaults and acquisitory crimes between intentional and unintentional GHB intake cases. Among unintentional GHB intake cases, 6.5% endured GHB-involved sexual assaults, whereas 21.7% endured an acquisitory crime. Among recurrent GHB intoxication cases generated by the same patients, voluntary and sole GHB consumptions were more frequently observed, however, enduring any crime was less characteristic.
Our results regarding demographic and substance use characteristics and the frequency of GHB-facilitated sexual assaults are in line with former findings. Enduring acquisitory crimes due to unintentional GHB intake was found to be more inherent than enduring sexual assaults. Authors emphasise that the victims of these acquisitory crimes were typically males.
GHB’s role in drug facilitated acquisitory crimes seems to be significant, although the decrease in GHB’s popularity is observed among intoxicated patients as well. The need for further research on GHB’s impact on cognitive impairment and on sexual correlates of intentional GHB use is addressed by the authors.
Determination of endogenous concentration of γ-hydroxybutyric acid (GHB) in hair through an ad hoc GC-MS analysis: A study on a wide population and influence of gender and age
2016, Journal of Pharmaceutical and Biomedical Analysis
γ-Hydroxybutyric acid (GHB) spread for recreational purposes or as “rape drug” represents a hard issue for forensic toxicologists due to its endogenous nature. It is clear that an actual and reliable discrimination between basal and exogenous levels is mandatory to achieve a correct evaluation of conscious/unconscious administration. This research aimed to study the GHB baseline in hair samples, collected from 150 volunteers, non-consumers of any drugs of abuse, in order to evaluate if a generic cut-off value could be accepted, also focusing on potential influences of gender and age. The analysis consisted of an overnight incubation with NaOH at 56 °C, liquid–liquid extraction with ethylacetate and trimethylsylil derivatization. Detection was carried out through gas chromatography-mass spectrometry in single ion monitoring (m/z 233, 234, 147 for GHB; m/z 239, 240 and 147 for GHB-d6). The endogenous amount in “blank” hair was estimated by the standard addition method. Concentration range was 0.279–2.839 ng/mg. In males, the average GHB levels were higher than in females (0.829 vs 0.596 ng/mg, respectively), especially in the first age category (<30 years, 1.008 vs 0.606 ng/mg, respectively). Age influences on GHB levels seemed to be different among the two sexes: in male population concentrations were higher <30 (1.008 ng/mg) and similar in the other age ranges (0.762 ng/mg, 30–50; 0.763 ng/mg, >50); in female, quite similar levels were registered throughout all the age categories (0.606 ng/mg, <30; 0.536 ng/mg, 30–50; 0.691 ng/mg, >50). Further study should be performed on GHB physiology in order to better understand these differences among ages and genders. Moreover, we demonstrated that for hair analysis a cut-off reference value is not strictly mandatory, underlining the great interpretative valence of segmental analysis.
Accidental gamma-hydroxybutyrate poisoning in an infant
2016, Archives de Pediatrie

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: Supervising editor: Richard C. Dart, MD, PhD

: Author contributions: IBA, SYK, JED, and PDB conceived the study and obtained research funding. IBA coordinated and supervised all aspects of the project and, along with SYK, drafted the manuscript. SYK, JED, CBB, and JCI assisted in study design and data collection. SYK and CBB assisted in data analysis. SYK led the writing of the manuscript. JED conceptualized ideas and edited the manuscript. MJW assisted with data collection and manuscript review; PDB was the overall medical advisor for the project, analyzed data, and played a vital role in editing the manuscript. IBA takes responsibility for the paper as a whole.

: Funding and support: The research is funded by a grant from the National Institute on Drug Abuse. Approval NIDA 1 RO1 DA 14935-02A. The University of California, San Francisco, Committee on Human Research approved the study.

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Toxicology/original researchTrends in γ-Hydroxybutyrate (GHB) and Related Drug Intoxication: 1999 to 2003

Study objective

Methods

Results

Conclusion

Introduction

Editor’s Capsule Summary

Section snippets

Study Design and Setting

Characteristics of Study Subjects

Limitations

Discussion

Ann Emerg Med

Ann Emerg Med

Am J Emerg Med

Am J Emerg Med

Am J Emerg Med

Alcohol

Adverse events associated with ingestion of gamma-butyrolactoneMinnesota, New Mexico, and Texas, 1998-1999

MMWR Morb Mortal Wkly Rep

The Dawn ReportClub Drugs, 2002 Update.

Toxicology/original research
Trends in γ-Hydroxybutyrate (GHB) and Related Drug Intoxication: 1999 to 2003