A multicentre case series of analytically confirmed gamma-hydroxybutyrate intoxications in Western Australian emergency departments: Pre-hospital circumstances, co-detections and clinical outcomes.

INTRODUCTION: Gamma-hydroxybutyrate (GHB) use is associated with high risk of accidental overdose. This study examined the pre-hospital circumstances, demographic characteristics and clinical outcomes of analytically confirmed GHB emergency department (ED) presentations in Western Australia (WA). METHODS: This case series was conducted across three WA EDs involved in the Emerging Drugs Network of Australia, from April 2020 to July 2022. Patient demographics, pre-hospital drug exposure circumstances and ED presentation and outcome characteristics were collected from ambulance and hospital medical records of GHB-confirmed cases. RESULTS: GHB was detected in 45 ED presentations. The median age was 34 years and 53.3% (n = 24) were female. Most patients arrived at the ED by ambulance (n = 37, 85.7%) and required immediate emergency care (Australasian Triage Score 1 or 2 = 97.8%). One-third of patients were admitted to intensive care (n = 14, 31.1%). Methylamphetamine was co-detected in 37 (82.2%) GHB-confirmed cases. Reduced conscious state was indicated by first recorded Glasgow Coma Scale of ≤8 (n = 29, 64.4%) and observations of patients becoming, or being found, 'unresponsive' and 'unconscious' in various pre-hospital settings (n = 28, 62.2%). 'Agitated' and/or 'erratic' mental state and behavioural observations were recorded in 20 (44.4%) cases. DISCUSSION AND CONCLUSIONS: Analytically verified data from ED presentations with acute toxicity provides an objective information source on drug use trends and emerging public health threats. In our study, patients presenting to WA EDs with GHB intoxication were acutely unwell, often requiring intensive care treatment. The unexpectedly high proportion of female GHB intoxications and methylamphetamine co-ingestion warrants further exploration.

GHB related acids are useful in routine casework of suspected GHB intoxication cases.

GHB related acids (3,4-dihydroxy butyric acid, 2,4-dihydroxy butyric acid and glycolic acid) are produced through oxidative GHB metabolism. These analytes could be potential biomarkers to ensure the diagnosis of a GHB intoxication and even prolong the detection window. Within this study, forensic routine cases were measured to consider the potential of additional gas chromatographic mass spectrometric analysis on these acids. 17 GHB positive real cases (10 serum samples and 7 urine samples) and 40 cases with suspicion of drugging in DFC cases and negative GHB results (21 serum samples and 19 urine samples) were evaluated. Increased GHB related acid concentrations were detected in all serum and most urine samples positive on GHB. In some GHB negative cases, especially in serum samples, concentrations of GHB related acids gave hints that GHB actually was taken. We recommend to use the following cut-offs for a more reliable interpretation of potential GHB intoxication cases: 3,4-OH-BA:>3 mg/L in serum and>50 mg/L in urine; 2,4-OH-BA:>2 mg/L in serum and>25 mg/L in urine; GA:>5 mg/L in serum and>400 mg/L in urine.

Violence against women and drug-facilitated sexual assault (DFSA): A review of the main drugs.

Sexual violence is a universal phenomenon without restriction to sex, age, ethnicity or social class that causes devastating effects in the physical and mental health spheres, in the short-term and long-term, such as pregnancy, sexually transmitted infections (STI) and greater susceptibility to psychiatric symptoms, especially depression. Some cases of sexual assault and rape are based on the use of so-called drug-facilitated sexual assault (DFSA), which cause victims' loss of consciousness and inability to defend, making them vulnerable to violence. Thus, this article aimed to review the literature on gender violence and the drugs used to facilitate sexual assault, addressing their mechanism of action and pharmacokinetics, as well as drug detection times in human body and types of forensic identification. It is understood that the knowledge of these drugs and their pharmacological and diagnostic mechanisms should be widely disseminated, especially about sensitivity tests and the time the drug remains in the body, which would validate the promotion of evidence to prove abuse, and, thus, being able to give a promising outcome to cases of aggression, which is extremely beneficial for women.

Gamma-hydroxybutyrate abuse: pharmacology and poisoning and withdrawal management.

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 and as an adjuvant for control of alcohol withdrawal syndrome. The main aim of this review is to summarise updated knowledge about GHB pharmacokinetics and pharmacodynamics, acute poisoning, and clinical features of GHB withdrawal syndrome, its diagnosis and medical treatment. The most common clinical signs and symptoms of acute poisoning include sleepiness to deep coma, bradycardia, hypotension, and respiratory failure. Therapy is essentially supportive and based on continuous monitoring of vital signs. GHB withdrawal syndrome shares patterns with other withdrawal syndromes such as alcohol withdrawal and is sometimes difficult to distinguish, especially if toxicological tests are GHB-negative or cannot be performed. There are no official detoxification protocols for GHB withdrawal syndrome, but its therapy is based on benzodiazepine. When benzodiazepine alone is not effective, it can be combined with barbiturates or antipsychotics. Information about abuse and distribution of GHB and its precursors/analogues among the general population is still limited. Their prompt identification is therefore crucial in conventional and non-conventional biological matrices, the latter in particular, to clarify all the issues around this complex molecule.

GHB concentration in a related post-mortem case.

Gamma-hydroxybutyrate (GHB) is a central nervous system depressant, primarily used as a recreational drug of abuse and as a therapeutic substance both in U.S.A. and Europe for the treatment of narcolepsy with cataplexy in adult patients and as adjuvant in the control of alcohol withdrawal syndrome. Several cases of GHB related deaths have been reported in the literature and GHB was found alone or in association to other drugs of abuse. However, only few biological matrices are often analyzed, therefore data on GHB distribution are lacking. Here we report a case involving a 45-year-old man, who was found dead in his bedroom.

Trends in gamma-hydroxybutyrate-related harms based on ambulance attendances from 2012 to 2018 in Victoria, Australia.

BACKGROUND AND AIMS: Although the prevalence of gamma-hydroxybutyrate (GHB) use is relatively low globally, harms related to the drug appear to be increasing. Few existing studies present reliable, representative, population-level data on GHB-related harms. The aim of this study was to investigate trends in acute GHB-related harms within an ambulance database in Australia. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional, retrospective analysis of data on all GHB-related ambulance attendances in the state of Victoria, Australia during a 7-year period (January 2012-December 2018) MEASUREMENTS: Presentations were characterized based on patient demographics, transport to hospital, co-occurring substance use (i.e. GHB only, alcohol, methamphetamine, heroin, benzodiazepine and cannabis) and clinical presentation (e.g. symptoms of anxiety, psychosis, depression). FINDINGS: There were 5866 GHB-related ambulance attendances between 2012 and 2018, with the prevalence rate increasing from 8.8 per 100 000 population in 2012 to a maximum of 21.7 per 100 000 population in 2017. Methamphetamine [odds ratio (OR) = 6.23, P < 0.001] and benzodiazepine-related (OR = 1.43, P < 0.001) co-occurrences; ages between 18-29 (OR = 6.58, P < 0.001) and 30-39 years (OR = 2.02, P < 0.001); and male gender (OR = 1.23, P < 0.001) were significant predictors of GHB-related attendances. CONCLUSIONS: There has been a 147% increase in the prevalence of GHB-related ambulance attendances in Victoria, Australia between 2012 and 2019, largely attributable to a growth in the proportions of people using gamma-hydroxybutyrate alone or concurrently with methamphetamine.

Gender differences in acute recreational drug toxicity: a case series from Oslo, Norway.

BACKGROUND: Female drug users report poorer physical and mental health than male drug users. We describe female and male patients treated for acute recreational drug toxicity, and look for gender differences in clinical state, treatment, and toxic agents taken. METHODS: Retrospective case series from a primary care emergency outpatient clinic and a hospital emergency department in Oslo, Norway. All patients treated for acute recreational drug toxicity from October 2013 through March 2015 were included, except patients with lone alcohol intoxication. Patients were grouped according to whether they had taken opioids or not, as a proxy differentiation between heavy drug users and party drug users. Data from the two clinical settings were analysed separately. RESULTS: In total, 2495 cases were included, 567 (22.7%) were women. Female patients were younger than males, median 31 vs 34 years (p < 0.001). On most comparisons of clinical variables there were no significant differences between genders. A larger proportion of females in the outpatient opioid group were hypotensive, 10.9% vs 3.9% (p < 0.001). Fewer females were intubated, none vs 21.1% (p = 0.019) in the hospital opioid group, and 6.4% vs 21.0% (p = 0.039) in the hospital non-opioid group. The proportion of gamma-hydroxybutyrate (GHB) poisoning was larger among females both at the outpatient clinic (14.4% vs 8.6%, p < 0.001) and at the hospital (60.3% vs 36.4%, p = 0.001), while the proportion of heroin poisoning was smaller among females at the outpatient clinic (37.1% vs 47.0%, p < 0.001). CONCLUSION: One in four patients treated for acute recreational drug toxicity were women. Female patients were younger, had more frequently taken GHB and were less frequently intubated. Otherwise, the gender differences regarding clinical state and treatment were small. Although female drug users are known to report poorer health than males, we did not find that women had a more severe clinical course than men when presenting with overdose.

Somnophilia and Sexual Abuse through the Administration of GHB and GBL.

Somnophilia, the desire to have sex with an unconscious, sleeping, or comatose person who is unable to respond, is a sexual paraphilia that is seldom reported. The underlying desire is often overshadowed by the act of sexual violation and when using GHB or GBL to induce unconsciousness, as in the case presented here, the victim might not even be able to recall, for certain, that they have been sexually violated. A case study is offered of a somnophile who adulterated drinks to render young men unconscious, so he could rape them in that state, before progressing to administering drugs anally on the pretext of applying lubrication to the anus to facilitate sexual intercourse. The offender's fetishistic compulsion to have sex with unconscious men propelled him to experiment with the means by which he surreptitiously administered drugs to his victims in order to deepen their comatose state.

Relationship Between Postmortem Urine and Blood Concentrations of GHB Furnishes Useful Information to Help Interpret Drug Intoxication Deaths.

This article reports the concentrations of gamma-hydroxybutyrate (GHB) in femoral blood and bladder urine in a case series of drug intoxication deaths (N = 37). GHB was determined in blood (B-GHB) and urine (U-GHB) by a GC-FID-GBL method and 30 mg/L was used as a cut-off concentration for reporting positive results. The mean (median) and range of GHB concentrations in bladder urine were 2,818 mg/L (1,900 mg/L) and 120-13,000 mg/L, respectively. These concentrations were appreciably higher than those in femoral blood, 637 mg/L (260 mg/L) and 30-9,200 mg/L, respectively. Urine/blood ratios of GHB were highly variable (mean 8.99, median 5.33 and range 0.16-29.3). GHB is rapidly metabolized and cleared from the bloodstream, whereas there is no metabolism occurring in the urinary bladder. In five autopsy cases, U-GHB was lower than B-GHB, which suggests that these individuals died before equilibration of the drug in all body fluids and tissues. In the other 32 deaths, U-GHB was higher than B-GHB, sometimes appreciably higher, which points towards a longer survival time after intake or administration of GHB. The analysis of urine extends the window of detection of GHB by several hours compared with blood samples, depending in part on when the bladder was last voided before death. Furthermore, the urinary concentration of GHB gives a hint about the concentration in blood during the time that the urine was produced in the kidney and stored in the bladder since the previous void.

Gamma-hydroxybutyrate (GHB), an unusual cause of high anion gap metabolic acidosis.

The causes of high anion gap metabolic acidosis (HAGMA) are well described in the literature. However, sometimes more frequent causes of HAGMA cannot explain its occurrence.In the case of HAGMA and severe neurological depression in the absence of other causes of HAGMA, clinicians should consider an intoxication with gamma-hydroxybutyrate (GHB) as a possible cause.GHB is endogenous to the mammalian central nervous system (CNS). Synthetic GHB was initially used as an anesthetic but is now only licensed for medical use in a limited number of indications such as the treatment of narcolepsy. Because of its euphoric effects, it became popular for recreational use under the street names: Liquid Ecstasy, Georgia Home Boy, and Liquid G.We describe the clinical case of a patient who suffered from severe neurological depression and HAGMA.

Fatal Overdose of Gamma-hydroxybutyrate Acid After Ingestion of 1,4-Butanediol.

We report a case of fatal intoxication from 1,4-butanediol (1,4-BD), which was ingested by a young and "naïve" gamma-hydroxybutyrate (GHB) consumer during a party with the co-ingestion of alcohol, cannabis, and methylene-dioxy-methamphetamine. The following drug concentrations were found using gas chromatography coupled with mass spectrometry on autopsy samples and on a cup and a glass found at the scene: 20,350 mg/L (bottle) for 1,4-BD; 1020 mg/L (femoral blood), 3380 mg/L (cardiac blood), 47,280 mg/L (gastric content), and 570 mg/L (vitreous humor) for GHB. The concentration of GHB is difficult to interpret in forensic cases due to the possibility of an endogenous production of GHB. The variable tolerance of the user may also modify the peri- and postmortem GHB concentrations. This case underscores the need to have many different sources of toxicology samples analyzed to avoid the hypothesis of endogenous production of GHB.

Intoxication by gamma hydroxybutyrate and related analogues: Clinical characteristics and comparison between pure intoxication and that combined with other substances of abuse.

OBJECTIVE: 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. METHOD: 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. RESULTS: 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 >12h, p<0.01). CONCLUSIONS: 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.

INTRODUCTION: 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. MEASURES: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSION: 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.

Postmortem concentrations of gamma-hydroxybutyrate (GHB) in peripheral blood and brain tissue - Differentiating between postmortem formation and antemortem intake.

Gamma-hydroxybutyrate (GHB) is a recreational drug, a drug of abuse, as well as an endogenous molecule in mammals. The drug has become infamous as a tool for drug-facilitated sexual assault. GHB is found in low concentrations in living humans, while at postmortem the concentration of GHB rises due to fermentation processes. The endogenous nature of GHB leads to difficulty in interpretation of concentrations, as the source of GHB is not obvious. Postmortem brain and blood samples were collected from 221 individuals at autopsy. Of these, 218 were not suspected of having ingested GHB, while GHB intake was reported for the last three (cases A-C). Decomposition level was estimated and cases classified into no/minor and advanced decomposition. Brain samples were extracted from the frontal lobe; only gray matter from the cerebral cortex was used. Blood was drawn from the femoral vein. Brain samples were homogenized and diluted with water. Brain homogenates or femoral blood were then prepared using protein precipitation and GHB was quantified with UHPLC-MS/MS. For 189 cases where ingestion of GHB was not suspected and where no/minor decomposition had occurred the concentrations were in the range 4.8-45.4mg/kg (median 15.3mg/kg) in blood and not-detected to 9.8mg/kg (median 4.8mg/kg) in brain tissue. For case A, where intoxication with GHB was deemed to be the sole cause of death, the concentrations were 199 and 166mg/kg in blood and brain, respectively. For case B, where intoxication with GHB was a contributing factor of death, the respective concentrations were 142 and 78.4mg/kg. For case C, where GHB was ingested but the cause of death was opioid poisoning, the concentrations were 40.3 and 12.7mg/kg. The results demonstrate that postmortem-formed levels of GHB are much lower in brain than peripheral blood. Analysis of GHB in brain tissue thus provides for an improved capability to identify an exogenous source of GHB. By measuring GHB in brain tissue and employing a cut-off concentration of 10mg/kg, a tentative distinction can be made between an endo- and exogenous source of GHB. An exception to this strategy is for extensively decomposed corpses, where endogenous GHB concentrations can be high even in brain.

An observed rise in γ-hydroxybutyrate-associated deaths in London: Evidence to suggest a possible link with concomitant rise in chemsex.

BACKGROUND: Gamma-hydroxybutyrate (GHB) is the drug most linked to acute harm out of those used in chemsex, the incidence of which is reported to be increasing. However, there have been few systematic studies of the harms associated with GHB use. We investigated GHB-associated deaths from London coroners' jurisdictions between 2011 and 2015. METHODS: Blood and urine samples were collected by pathologists and submitted for toxicological analysis at the request of coroners. Data from the Toxicology Unit, Imperial College London was retrospectively analysed. This comprised of 6633 cases from seven out of eight coroners' jurisdictions in London that underwent toxicological analysis between January 2011 and December 2015. RESULTS: A total of 61 GHB-associated deaths (0.92% of total cases), 184 cocaine-associated deaths (2.8% of total cases) and 83 MDMA-associated deaths (1.3% of total cases) were identified. There was a 119% increase in the proportion of GHB-associated deaths detected in 2015 compared to 2014. Over the same time period there was a 25% increase in cocaine-associated deaths and a 10% decrease in MDMA-associated deaths. CONCLUSIONS: Our data suggest that GHB-associated deaths are increasing in London, and that this is likely at least in part due to increasing use of GHB for chemsex. Further studies on the use of GHB are urgently required to understand the extent of its use, whether this is as prevalent in other major urban areas in the UK, and the full extent of the harms it causes.