158 results match your criteria Toxicity Gamma-Hydroxybutyrate

Treatment of γ-Hydroxybutyrate (GHB) Overdose with the GABA Antagonist SGS742.

J Pharmacol Exp Ther 2022 May 3. Epub 2022 May 3.

Pharmaceutical Sciences, University at Buffalo, United States

High doses of the partial agonist of the GABA receptor, γ-hydroxybutyric acid (GHB), causes respiratory depression that can lead to death. Previously, it has been shown that GABA receptor antagonism is able to prevent respiratory depression and sedation when inhibitors are pre-administered. In order to treat GHB overdoses, safety and efficacy of a treatment strategy at various times after GHB administration is necessary, in order to more closely replicate a true overdose situation. Read More

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Amphetamine toxicity masked by concomitant γ-hydroxybutyrate (GHB) ingestion.

Am J Emerg Med 2022 Mar 31. Epub 2022 Mar 31.

Department of Critical Care Medicine, Taipei Medical University Hospital, Taipei City, Taiwan; Department of Emergency Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan; Graduate Institute of Injury Prevention and Control, College of Public Health, Taipei Medical University, Taipei City, Taiwan. Electronic address:

We report a case of a young male with amphetamine toxicity initially obscured by concomitant use of gamma-hydroxybutyrate (GHB), and the sympathomimetic symptoms emerged after GHB's effects receded. A 24-year-old unconscious man presented to emergency department showed the following vital signs upon admission: blood pressure 136/58 mmHg; heart rate 79 bpm; SpO2 87% under ambient air; body temperature 36.1 °C; Glasgow Coma Scale score 3. Read More

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Clinical effect of ethanol co-use in patients with acute drug toxicity involving the use of central nervous system depressant recreational drugs.

Eur J Emerg Med 2022 Apr 8. Epub 2022 Apr 8.

Division of Clinical Toxicology and Poison Control Centre Munich, Department of Internal Medicine II, TUM School of Medicine, Technical University of Munich, Germany.

Background And Importance: Patients who use recreational drugs frequently co-ingest ethanol, which is considered a central nervous system (CNS) depressant. The clinical relevance of this in acute toxicity involving other CNS depressants is not well described.

Objective: To assess the clinical impact of ethanol co-use in patients presenting to the emergency department (ED) with acute toxicity involving the use of CNS depressant drugs. Read More

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Current Insights on the Impact of Gamma-Hydroxybutyrate (GHB) Abuse.

Subst Abuse Rehabil 2022 9;13:13-23. Epub 2022 Feb 9.

Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.

Recreational gamma-hydroxybutyrate (GHB) use, although less common than other substance use, is increasingly recognised and is over-represented in emergency toxicology presentations. This narrative review summarizes GHB pharmacology, current patterns of use, potential harms and management of GHB toxicity and withdrawal. There is a complex interplay between GHB and GABA as GHB is both a prodrug and metabolite of GABA and GHB activates both GHB and GABA receptors. Read More

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February 2022

Evaluating the risk of toxicity and adverse drug interactions involving recreational GHB use and prescribed drugs.

Expert Opin Drug Metab Toxicol 2021 Dec 20;17(12):1445-1454. Epub 2022 Jan 20.

Unit of Forensic Toxicology, Section of Legal Medicine, Department of Excellence of Biomedical Sciences and Public Health, Marche Polytechnic University of Ancona, Ancona, Italy.

Introduction: GHB is a small molecule and is present in the human CNS. Exogenously, GHB is administered orally in the form of sodium oxybate to treat cataplexy and excessive daytime sleepiness in patients with narcolepsy, and to manage alcohol withdrawal and detoxification in alcoholics. GHB shows a biphasic effect and dose-dependent pharmacokinetics and may interact with neuronal systems different from GABAergic one. Read More

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December 2021

Increasing emergency department attendances in central London with methamphetamine toxicity and associated harms.

Emerg Med J 2021 Oct 14. Epub 2021 Oct 14.

Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust, London, UK.

Background: Methamphetamine is a stimulant drug of abuse with increasing prevalence of use worldwide leading to public health concern. While previous research by our group a decade ago found no evidence of increasing harms associated with methamphetamine use in the UK, there are conflicting data on whether or not this is still the case. This paper aims to identify trends in methamphetamine-related harms and characterise the clinical features of ED presentations involving methamphetamine with gamma-hydroxybutyrate/gamma-butyrolactone (GHB/GBL). Read More

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October 2021

Is impaired energy production a novel insight into the pathogenesis of pyridoxine-dependent epilepsy due to biallelic variants in ALDH7A1?

PLoS One 2021 8;16(9):e0257073. Epub 2021 Sep 8.

Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada.

Background: Pyridoxine-dependent epilepsy (PDE) is due to biallelic variants in ALDH7A1 (PDE-ALDH7A1). ALDH7A1 encodes α-aminoadipic semialdehyde dehydrogenase in lysine catabolism. We investigated the gamma aminobutyric acid (GABA) metabolism and energy production pathways in human PDE-ALDH7A1 and its knock-out aldh7a1 zebrafish model. Read More

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November 2021

Drug-drug interaction between diclofenac and gamma-hydroxybutyric acid.

Biopharm Drug Dispos 2021 Sep 8;42(8):351-358. Epub 2021 Jul 8.

Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA.

Gamma hydroxybutyric acid (GHB) has been approved clinically to treat excessive daytime sleepiness and cataplexy in patients with narcolepsy, alcohol and opioid withdrawal, and as an anesthetic. The use of GHB clinically is limited due to its high abuse potential. The absorption, clearance and tissue uptake of GHB is mediated by proton-dependent and sodium-coupled monocarboxylate transporters (MCTs and SMCTs) and inhibition of these transporters may result in a change in GHB pharmacokinetics and pharmacodynamics. Read More

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September 2021

Comparison of N-methyl-2-pyrrolidone (NMP) and the "date rape" drug GHB: behavioral toxicology in the mouse model.

Psychopharmacology (Berl) 2021 Aug 21;238(8):2275-2295. Epub 2021 Apr 21.

Department of Translational Medicine, Section of Legal Medicine and LTTA Centre, University of Ferrara, Ferrara, Italy.

N-methyl-2-pyrrolidone (NMP) and γ-hydroxybutyrate acid (GHB) are synthetic solvents detected in the recreational drug market. GHB has sedative/hypnotic properties and is used for criminal purposes to compromise reaction ability and commit drug-facilitated sexual assaults and other crimes. NMP is a strong solubilizing solvent that has been used alone or mixed with GHB in case of abuse and robberies. Read More

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Variation of drugs involved in acute drug toxicity presentations based on age and sex: an epidemiological approach based on European emergency departments.

Clin Toxicol (Phila) 2021 Oct 16;59(10):896-904. Epub 2021 Mar 16.

Emergency Department, Hospital Clínic, IDIBAPS, Barcelona, Spain.

Objective: To analyse the relative percentage of acute recreational drug toxicity emergency department (ED) presentations involving the main drug groups according to age and sex and investigate different patterns based on sex and age strata.

Methods: We analysed all patients with acute recreational drug toxicity included by the Euro-DEN Plus dataset (22 EDs in 14 European countries) between October 2013 and December 2016 (39 months). Drugs were grouped as: opioids, cocaine, cannabis, amphetamines, gamma-hydroxybutyrate (GHB), hallucinogens, new psychoactive substances (NPS), benzodiazepines and ketamine. Read More

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October 2021

γ-Hydroxybutyric Acid: Pharmacokinetics, Pharmacodynamics, and Toxicology.

AAPS J 2021 01 8;23(1):22. Epub 2021 Jan 8.

Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, 304 Pharmacy Building, Buffalo, New York, 14214, USA.

Gamma-hydroxybutyrate (GHB) is a short-chain fatty acid present endogenously in the brain and used therapeutically for the treatment of narcolepsy, as sodium oxybate, and for alcohol abuse/withdrawal. GHB is better known however as a drug of abuse and is commonly referred to as the "date-rape drug"; current use in popular culture includes recreational "chemsex," due to its properties of euphoria, loss of inhibition, amnesia, and drowsiness. Due to the steep concentration-effect curve for GHB, overdoses occur commonly and symptoms include sedation, respiratory depression, coma, and death. Read More

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January 2021

High prevalence of recreational and illicit drug use in German people living with HIV with a potential for drug-drug interactions with antiretroviral therapy.

Int J STD AIDS 2021 01 25;32(1):75-82. Epub 2020 Nov 25.

MSD Sharp & Dohme GmbH, Medical Affairs, Haar, Germany.

Recreational drug use is higher in people living with HIV (PLHIV) than in the general population in Europe. This use increases the risk for drug-drug interactions (DDIs) and adverse events. We assessed the prevalence and clinical consequences of substance abuse among PLHIV. Read More

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January 2021

Perceived harm, motivations for use and subjective experiences of recreational psychedelic 'magic' mushroom use.

J Psychopharmacol 2020 09 17;34(9):999-1007. Epub 2020 Jul 17.

Department of Psychological Sciences, University of Liverpool, UK.

Background: Data on actual harm of magic mushrooms suggest that toxicity and abuse potential is low, however, their legal status suggests otherwise. We aimed to gauge perception of harm of magic mushrooms in both users and mushroom-naïve participants. We also aimed to observe differences in expectations of effects between users and mushroom-naïve participants, and whether motivations for use predicted their expected effects. Read More

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September 2020

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

Arh Hig Rada Toksikol 2020 03;71(1):19-26

Department of Anatomical, Histological, Forensic, and Orthopaedic Sciences,Sapienza University of Rome, Rome, Italy.

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. Read More

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Characteristics and circumstances of death related to gamma hydroxybutyrate (GHB).

Clin Toxicol (Phila) 2020 11 18;58(11):1028-1033. Epub 2020 Feb 18.

National Drug & Alcohol Research Centre, University of New South Wales, Kensington, Australia.

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. Retrospective study of all Australian cases in which GHB was a mechanism contributory to death retrieved from the National Coronial Information System ( = 74). Read More

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November 2020

When fantasy fades: A case of severe delirium due to GHB withdrawal.

Emerg Med Australas 2020 02 11;32(1):169-170. Epub 2020 Jan 11.

Clinical Toxicology Unit, Princess Alexandra Hospital, Brisbane, Queensland, Australia.

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February 2020

Focus on Adolescent Use of Club Drugs and "Other" Substances.

Pediatr Clin North Am 2019 12;66(6):1121-1134

Substance Abuse Research Division, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, 3901 Chrysler Service Drive, Suite 2A, Detroit, MI 48201, USA.

Club drugs and "other" abusable substances are briefly overviewed as a reminder about the wide variety of known and unknown substances used by adolescents, the high potential for direct and interactive substance use effects to manifest acutely and chronically, and the vigilance needed to anticipate and recognize the new effects and drug-drug interactions arising as novel substances continue to be custom "designed," manufactured, and marketed to meet substance use trends. This article discusses dextromethorphan, flunitrazepam (Rohypnol), gamma-hydroxybutyrate, inhalants, ketamine, lysergic acid diethylamide, methylenedioxymethamphetamine, phencyclidine, Salvia divinorum (salvia), synthetic cannabinoids, and synthetic cathinones (bath salts). Read More

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December 2019

Clinical relevance of ethanol coingestion in patients with GHB/GBL intoxication.

Toxicol Lett 2019 Oct 10;314:37-42. Epub 2019 Jul 10.

Emergency Department, Hospital Clínic, Barcelona, IDIBAPS, Barcelona, Spain; Medical School, University of Barcelona, Spain.

Objective: Ethanol intake can increase the sedative effects of gamma-hydroxybutyrate/gamma-butyrolactone (GHB/GBL), although the real clinical impact is unknown. We studied the clinical impact of the co-ingestion of ethanol in patients presenting to the Emergency Department (ED) with acute toxicity related to GHB/GBL use.

Method: We performed a secondary analysis of the Euro-DEN Plus Registry (14 countries, 22 EDs) which includes 17,371 consecutive patients presenting to the ED with acute recreational drug toxicity over 39 consecutive months (October 2013 - December 2016). Read More

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October 2019

1,4-Butanediol overdose mimicking toxic alcohol exposure.

Clin Toxicol (Phila) 2020 03 20;58(3):204-207. Epub 2019 Jun 20.

Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Sydney, Australia.

1,4-butanediol (1,4-BD) is a gamma-hydroxybutyrate (GHB) analogue with a similarly narrow therapeutic window that is becoming a more common cause of recreational overdose. Reports of confirmed exposures are limited. A 44 year-old man who had consumed alcohol subsequently became unconscious after ingesting what was thought to be GHB. Read More

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

BMC Emerg Med 2019 04 29;19(1):29. Epub 2019 Apr 29.

Oslo Accident and Emergency Outpatient Clinic, Department of Emergency General Practice, City of Oslo Health Agency, 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. Read More

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The effect of diet and exercise on tobacco carcinogen-induced lung cancer.

Carcinogenesis 2019 05;40(3):448-460

The Terry Fox Laboratory, British Columbia Cancer Center, Vancouver, British Columbia, Canada.

In previous studies, we found that low-carbohydrate (CHO) diets reduced the incidence of tumors in mice genetically predisposed to cancer. However, because >90% of human cancers arise via carcinogen-induced somatic mutations, we investigated, herein, the role that different types and levels of CHO, protein and lipid play in lung cancer induced by the tobacco-specific carcinogen, nicotine-derived nitrosamine ketone (NNK) in A/J mice. We found lowering CHO levels significantly reduced lung nodules and blood glucose levels. Read More

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GHB Pharmacology and Toxicology: From Metabolism and Pharmacokinetics to Applications: In Clinical and Forensic Toxicology.

Curr Drug Metab 2018 ;19(13):1054-1055

Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche, Bologna, Italy.

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February 2019

[The chemical toxicological investigation of gamma-hydroxybutyric acid in biological objects and the interpretation of the results of the analysis].

Sud Med Ekspert 2018;61(5):21-24

Saint-Petersburg state budgetary institution 'Bureau of Forensic Medical Expertise', Saint-Petersburg, Russia, 195067.

The authors propose a method for the quantitative determination of gamma-hydroxybutyric acid (GHBA) in biological objects including biological fluids (blood, urine) and tissues with the use of gas chromatography with mass-selective detector. The samples for the analysis were prepared by liquid-liquid extraction by butyl acetate with subsequent derivatization using a N,O-Bis(trimethylsilyl)trifluoroacetamide/Trimethylchlorosilane mixture (BSTFA + 1%TMCS). The graded graphs were linear in the range of GHBA concentrations from 26. Read More

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Replacing GHB with GBL in Recreational Settings: A New Trend in Chemsex.

Curr Drug Metab 2018 ;19(13):1080-1085

Unit of Forensic Toxicology (UoFT), Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Sapienza University of Rome, V.Le Regina Elena 336, 00161, Rome, Italy.

Background: Recently, Gamma-hydroxybutyrate (GHB) consumption in the recreational setting has been replaced by that of its prodrug Gamma-butyrolactone (GBL), cheaper and easier to obtain due to several legal industrial applications.

Objective: The aim of the present paper was to report the most authoritative literature on the pharmacology and toxicology of GBL, dependence and abuse potential and the related public health issues together with the results of the analyses of several illicit liquid preparations containing GHB/GBL generally sold as "G".

Method: International literature concerning "Gamma-butyrolactone", "GBL" "toxicology", "pharmacology", "abuse", "dependence" and "GHB has been reviewed and liquid preparations containing GHB/GBL analysed by ultra-high performance liquid chromatography coupled to the tandem mass spectrometry validated methodology. Read More

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February 2019

Production of high molecular weight poly(3-hydroxybutyrate-co-4-hydroxybutyrate) copolymer by Cupriavidus malaysiensis USMAA1020 utilising substrate with longer carbon chain.

Int J Biol Macromol 2018 Sep 1;116:217-223. Epub 2018 May 1.

School of Biological Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia; Malaysian Institute of Pharmaceuticals and Nutraceuticals, NIBM, 11700 Gelugor, Penang, Malaysia; Centre for Chemical Biology, Universiti Sains Malaysia, 11900 Bayan Lepas, Penang, Malaysia. Electronic address:

Long carbon chain alkanediols are used in the production of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)], however these substrates possess high toxicity towards bacterial cells. This study demonstrated the effective utilisation of a long carbon chain alkanediol, namely 1,8-octanediol, to enhance the yield and production of a copolymer with a high molecular weight of over 1000 kDa, which is desirable for novel applications in medical and biopharmaceuticals. The increased PHA content (47-61 wt%) and concentration (1. Read More

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September 2018

An index of fatal toxicity for new psychoactive substances.

J Psychopharmacol 2018 07 27;32(7):793-801. Epub 2018 Feb 27.

2 Psychopharmacology, Drug Misuse & Novel Psychoactive Substances Research Unit, Department of Pharmacy, Pharmacology & Post-graduate Medicine, University of Hertfordshire, Hatfield, UK.

An index of fatal toxicity for new psychoactive substances has been developed based solely on information provided on death certificates. An updated index of fatal toxicity (T), as first described in 2010, was calculated based on the ratio of deaths to prevalence and seizures for the original five substances (amphetamine, cannabis, cocaine/crack, heroin and 3,4-methylenedioxymethylamphetamine). These correlated well with the 2010 index. Read More

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Baclofen in gamma-hydroxybutyrate withdrawal: patterns of use and online availability.

Eur J Clin Pharmacol 2018 Mar 3;74(3):349-356. Epub 2017 Dec 3.

Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners, London, UK.

Purpose: Gamma-hydroxybutyrate (GHB) withdrawal is a life-threatening condition that does not always respond to standard treatment with benzodiazepines. Baclofen has potential utility as a pharmacological adjunct and anecdotal reports suggest that it is being used by drug users to self-manage GHB withdrawal symptoms. Here, we investigate current patterns of use and the online availably of baclofen. Read More

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Deaths in the Lesbian, Gay, Bisexual and Transgender United Kingdom Communities Associated with GHB and Precursors.

Curr Drug Metab 2018 ;19(13):1086-1099

Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, Department of Pharmacy, Pharmacology and Postgraduate Medicine, University of Hertfordshire, Hertfordshire, United Kingdom.

Background: Misuse of gammahydroxybutrate (GHB) and its prodrugs gammabutyrolactone (GBL) and 1,4 butanediol (1,4-BD) has increased greatly since the early 1990s, particularly amongst lesbian, gay, bisexual and transgender (LGBT) individuals in recreational and sexual settings, e.g. 'chemsex'. Read More

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February 2019

Toxicologic/transport properties of NCS-382, a γ-hydroxybutyrate (GHB) receptor ligand, in neuronal and epithelial cells: Therapeutic implications for SSADH deficiency, a GABA metabolic disorder.

Toxicol In Vitro 2018 Feb 12;46:203-212. Epub 2017 Oct 12.

Department of Pharmacotherapy, College of Pharmacy, Washington State University, Spokane, WA, United States. Electronic address:

We report the in vitro assessment of pharmacotoxicity for the high-affinity GHB receptor ligand, NCS-382, using neuronal stem cells derived from mice with a targeted deletion of the aldehyde dehydrogenase 5a1 gene (succinic semialdehyde dehydrogenase(SSADH)-deficient mice). These animals represent a phenocopy of the human disorder of GABA metabolism, SSADH deficiency, that metabolically features accumulation of both GABA and the GABA-analog γ-hydroxybutyric acid in conjunction with a nonspecific neurological phenotype. We demonstrate for the first time using MDCK cells that NCS-382 is actively transported and capable of inhibiting GHB transport. Read More

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February 2018