Introduction: Gamma hydroxybutyrate (GHB) has gained substantial popularity as an illicit recreational drug. The current study aimed to: (1) determine the characteristics and circumstances of death ...of all recorded cases of GHB-related death in Australia, 2001-2019; (2) determine the toxicology of cases; and (3) determine major organ pathology.
Methods: Retrospective study of all Australian cases in which GHB was a mechanism contributory to death retrieved from the National Coronial Information System (n = 74). Information was collected on cause of death, demographics, circumstances of death, toxicology and major organ pathology.
Results: The mean age was 31.5 years and 70.3% were male. The predominant circumstance of death was accidental drug toxicity (79.7%), including five cases attributed to a combination of toxicity and natural disease. Other deaths were due to trauma (12.2%) and suicide (8.2%). The fatal incident overwhelmingly occurred in a home environment (82.4%). In all cases, GHB was consumed orally. The median GHB blood concentration was 210 mg/L (range 13-1350 mg/L), and was significantly higher in toxicity cases than others (258 vs. 98 mg/L, p < .01). Other substances were present in 92.2%, most commonly psychostimulants (64.1%), hypnosedatives (28.2%) and alcohol (20.3%). Resuscitation was attempted in 20.3% of cases. Acute pneumonia (36.7%) and aspiration of vomitus (30.6%) were common.
Conclusions: The typical case was a young male, who swallowed GHB and used it with other substances, most commonly at home. While acute drug toxicity was the most common cause of death, there was a substantial minority due to trauma or suicide.
•A new application of HILIC-Z stationary phase is presented.•A new method for GHB determination in hair is proposed.•The importance of GHB-glucuronide as a biomarker of GHB is issued.
In this work, ...the physical and chemical properties of a novel zwitterionic LC stationary phase are applied to the development, validation and application of a new fast and reliable method devoted to the analysis of GHB (gamma-hydroxybutyric acid) and its relatively new discovered glucuronide metabolite in hair. The obtained sensitivity, expressed as limit of detection (LOD) and quantification (LOQ), were 0.033 and 0.10 ng/mg for GHB and 0.11 and 0.37 ng/mg, for GHB-glucuronide respectively. Linearity was assessed between LOQ and 50 ng/mg for both compounds. GHB and GHB-glucuronide extraction from hair matrix was maintained simple and consisted in an acidified-solvent incubation. No samples purification was required before LC–MS/MS analysis. The method was finally applied to 65 real hair sample, 60 adults and 5 children below 2 years old. The obtained results highlighted that GHB concentrations were in the range 0.11–0.96 ng/mg (average 0.38 ± 0.25 ng/mg) in 44 cases (68%) while in 21 samples GHB concentrations were in the range between LOD and LOQ (0.033–0.1 ng/mg). GHB-glucuronide was detected in few samples (n. 3) at levels below LOQ. The interest on these molecules relies on the fact that GHB is both a naturally occurring inhibitory neurotransmitter in the central nervous system and an illicit drug often experienced by victims of drug-facilitated sexual assault. GHB-glucuronide was firstly identified in urine by the group of Petersen in 2013 and, as per analogy to ethyl glucuronide, it was proposed as a longer biomarker for GHB intoxication.
Display omitted
•Fluorene-containing cyanostilbenes show characteristic aggregation induced emission in aqueous media.•The emission spectra show strong wavelength shifts in emission in the presence ...of GHB due to H-bonding induced intramolecular charge transfer.•GHB detection is achieved using a chromatographic paper sensor that can detect GHB with the naked eye.
A “Turn-On” fluorescence probe based on a cyanostilbene scaffold was developed for the detection of a sedative γ- Hydroxy Butyric Acid (GHB). The cyanostilbenes show characteristic aggregation-induced emission in water except for fluorene substituted hydroxy cyanostilbene. But upon interaction with GHB in ethanol–water mixtures, the compound shows strong emission accompanied by shifts in the wavelength induced by H-bond supported intramolecular charge transfer. Also, the dye-coated chromatographic strips give visual demarcation of solution with GHB in different ethanol–water fractions. Overall, the probe design with AIE behavior provides a powerful and sensitive strategy to detect psychoactive substrates such as GHB in ethanol–water mixtures.
There are many nonopioid central nervous system depressant substances that share a gamma‐aminobutyric acid (GABA) receptor–related mechanism of action. These sedatives‐hypnotics can be indicated to ...treat anxiety, seizures, depression, and insomnia but are also used as substances of abuse and used to facilitate sexual assault. Barbiturates, methaqualone, and glutethimide were among the first type A GABA receptor–mediated sedative‐hypnotics. Their clinical use was limited for most indications by serious adverse events and strong abuse potential but continue to be used illicitly around the world. The benzodiazepines supplanted barbiturates for most indications because they were less likely to cause severe adverse events in monotherapy. Flunitrazepam is a newer benzodiazepine that is preferentially used recreationally and to facilitate sexual assault. Flunitrazepam has greater potency and higher affinity for the type A GABA receptor than most benzodiazepines. Gamma‐hydroxybutyric acid is sought illicitly for its hypnotic, euphoric and anabolic effects as well as to facilitate sexual assault. When any of these GABAergic drugs are used in high doses or with other sedative hypnotic agents, respiratory depression, coma, and death have occurred. Chronic use of these GABAergic drugs can lead to significant withdrawal syndromes. Phenibut and selank are poorly studied Russian drugs with GABAergic mechanisms that are inexplicably sold to US consumers as dietary supplements. Poison control center calls regarding phenibut have increased substantially over the past 5 years. Desired euphoriant effects account for the recreational and illicit use of many GABA‐modulating agents. However, illicit use can lead to significant toxicities related to abuse, dependence, and subsequent withdrawal syndromes. Significant evaluation of developing agents with GABA properties should be conducted to determine abuse potential before public access ensues.
GHB (gamma-hydroxybutyrate) and its pro-drugs GBL (gamma-butyrolactone) and 1,4-butanediol (1,4-BD) are central nervous system depressants whose street names include 'G' and 'liquid ecstasy'. They ...are used recreationally predominately for their stimulant and pro-sexual effects or for sedation to help with sleep and/or to 'come down' after using stimulant recreational drugs. Although overall population prevalence is low (0.1 %), in some groups such as men who have sex with men, GHB/GBL use may reach 20 %. GHB/GBL dependence may be associated with severe withdrawal with individuals presenting either acutely to emergency departments or to addiction services for support. Benzodiazepines are currently prescribed for GHB/GBL detoxification but do not prevent all complications, such as behavioural disinhibition, that may require hospitalisation or admission to a high dependency/intensive care unit. The GABA
receptor mediates most effects of GHB/GBL and the GABA
agonist, baclofen, has shown promise as an adjunct to benzodiazepines in reducing withdrawal severity when prescribed both during withdrawal and as a 2-day 'preload' prior to detoxification. The key aim of this feasibility study is provide information about recruitment and characteristics of the proposed outcome measure (symptom severity, complications including delirium and treatment escalation) to inform an application for a definitive randomised placebo controlled trial to determine the role of baclofen in the management of GHB/GBL withdrawal and whether starting baclofen 2 days earlier improves outcomes further.
This is a prospective, randomised, double-blind, placebo-controlled feasibility study that will recruit participants (aged over 18 years) who are GHB/GBL-dependent and wish to undergo planned GHB/GBL detoxification or are at risk of acute withdrawal and are inpatients requiring unplanned withdrawal. We aim to recruit 88 participants: 28 unplanned inpatients and 60 planned outpatients. During detoxification we will compare baclofen 10 mg three times a day with placebo as an adjunct to the usual benzodiazepine regimen. In the planned outpatient arm, we will also compare a 2-day preload of baclofen 10 mg three times a day with placebo. Ratings of GHB/GBL withdrawal, sleep, depression, anxiety as well as GHB/GBL use will be collected. The main data analyses will be descriptive about recruitment and characterising the impact of adding baclofen to the usual benzodiazepine regimen on measures and outcomes of GHB/GBL withdrawal to provide estimates of variability and effect size. A qualitative approach will evaluate research participant and clinician acceptability and data collected to inform cost-effectiveness.
This feasibility study will inform a randomised controlled trial to establish whether adding baclofen to a benzodiazepine regimen reduces the severity and complications of GHB/GBL withdrawal.
ISRCTN59911189 . Registered 14 October 2015.
v3.1, 1 February 2016.
•A sampler for portable capillary electrophoresis to detect GHB in situ.•Sampler based on peristaltic pumps, a check valve, and a pinch valve.•LOD with CCD for GHB 1.7 mg L−1, meets the cutoff ...testing value for GHB in saliva.
A compact, inexpensive sampler instrument for portable capillary electrophoresis was developed for monitoring illegal drugs in human body fluids and evaluated for γ-hydroxybutyric acid (GHB) in simulated saliva samples. The sampler uses peristaltic pumps and pinch and check valves to activate liquid flows. This short communication addresses aspects of CE associated with portability, open access instrumentation, and prospects of CE for citizen science. The extensive use of items provided by the electronic and computer industry contributes to this trend.
Because of its small detection window, uncovering drug-facilitated crime after gamma-hydroxybutyric acid (GHB) intake remains a problem. The aim of this experiment was to determine endogenous ...concentrations of GHB and GHB-
O
-β-glucuronide (GHB-Gluc) in plasma and urine samples and to compare them with concentrations after GHB intake in humans. Plasma and urine samples of volunteers (
n
= 50) who had never taken GHB during their lifetime (control group) were collected, and endogenous concentrations of GHB and GHB-Gluc were determined. In addition, plasma and urine samples of patients (
n
= 3) therapeutically taking sodium oxybate (GHB-sodium salt) were collected prior to and at different time points after the intake. GHB was determined via a liquid chromatography (LC)–tandem mass spectrometry system operated in multiple reaction monitoring mode. GHB-Gluc was detected by LC–quadrupole time-of-flight mass spectrometry. In plasma and urine samples of the control group (
n
= 50), endogenous concentrations of GHB-Gluc ranged from 0.011 to 0.067 mg/L and from 0.16 to 7.1 mg/L, respectively, while unconjugated GHB concentrations were less than 2 mg/L in both matrices. In contrast, after sodium oxybate administration, GHB concentrations increased markedly, and fell to below the commonly used cutoff value (plasma 4 mg/L and urine 10 mg/L) after 6–8 h in all patients. GHB-Gluc concentrations showed no significant time-dependent increase in plasma samples. In urine, GHB-Gluc concentrations increased after GHB intake, but were generally not higher than the endogenous concentrations of the control group. Therefore, it can be concluded that GHB-Gluc concentrations are not a suitable marker for extending the detection window after GHB intake.
•GHB-induced comas are associated with alterations of long-term memory network.•GHB-Coma group performed worse on the verbal memory test.•GHB-Coma group showed lower hippocampus activity while ...performing the memory task.•GHB-Coma group showed lower lingual gyrus activity while performing the memory task.•GHB-Coma group showed reduced hippocampal functional connectivity with the left STC.
Gamma-Hydroxybutyric acid (GHB) is a drug of abuse associated with increasing numbers of GHB-dependent patients and emergency attendances often related to GHB-induced coma. Animal studies suggest that GHB induces oxidative stress in the hippocampus, resulting in memory impairments. However, the consequences of chronic GHB use and GHB-induced coma on human brain function and cognition are unknown.
We recruited 27 GHB users with ≥4 GHB-induced comas (GHB-Coma), 27 GHB users without a coma (GHB-NoComa), and 27 polydrug users who never used GHB (No-GHB). Participants completed verbal and spatial memory tests and an associative memory encoding task during functional magnetic resonance imaging (fMRI) to probe hippocampus functioning.
The GHB-Coma group showed a lower premorbid IQ (p = 0.006) and performed worse on the verbal memory test (p = 0.017) compared to the GHB-NoComa group, despite exhibiting similar levels of education. Compared with the other two groups, the GHB-Coma group showed lower left hippocampus (pSVC = 0.044) and left lingual gyrus (pFWE = 0.017) activity, and a trend for lower hippocampal functional connectivity with the left superior temporal cortex during performance of the associative memory encoding task (pFWE = 0.063). No significant differences were observed between the GHB-NoComa group and the No-GHB group.
These results suggest that multiple GHB-induced comas, but not the use of GHB per se, are associated with alterations of memory performance and memory-related brain, although no causal link can be inferred from this cross-sectional study. The results highlight the need for public awareness to minimize the negative health consequences of recreational GHB use, in particular when related with GHB-induced comas.
: The short chain fatty acid gamma-hydroxybutyric acid (GHB) is a precursor, and the metabolite of gamma-aminobutyric acid is commonly used as an illegal recreational drug of abuse.
: An ...ultra-high-performance liquid chromatography tandem mass spectrometry was developed and validated for endogenous GHB and its glucuronide in nails, to complement hair in forensic contexts for a retrospective detection of psychotropic drugs consumption.
: GHB endogenous values for children and adolescents, adult females, and adult males in fingernails ranged from 0.3 to 3.0, 3.2, and 3.8 ng/mg, respectively, and toenails values ranged from 0.3 to 1.8, 2.0, and 2.4 ng/mg, respectively. In the three different groups, values of GHB in fingernails were statistically higher than those in toenails. GHB glucuronide could only be detected in finger nails with values ranging from 0.08 to 0.233, 0.252 and 0.243 in children and adolescents, adult females and adult males, respectively.
: The validated method was efficaciously applied to real finger and toe nails specimens from a population of males and females non GHB consumers. A preliminary cut-off of 5.0 ng/mg nail for endogenous GHB and 0.5 ng/mg for endogenous GHB-Gluc in the general population was proposed.
PDF
