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Elise M. Weerts - One of the best experts on this subject based on the ideXlab platform.
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Behavioral effects and pharmacokinetics of Gamma-hydroxybutyrate (GHB) precursors Gamma-Butyrolactone (GBL) and 1,4-butanediol (1,4-BD) in baboons
2020Co-Authors: Amy K. Goodwin, P.r. Brown, Erwin E.w. Jansen, C. Jakobs, K.m. Gibson, Elise M. WeertsAbstract:Abstract Rationale Gamma-Butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are prodrugs for Gamma-hydroxybutyrate (GHB). Like GHB, GBL and 1,4-BD are drugs of abuse, but their behavioral effects may differ from GHB under some conditions. Objectives The first study compared the behavioral effects of GBL (32-240 mg/kg) and 1,4-BD (32-240 mg/kg) with each other and to effects previously reported for GHB (32-420 mg/kg). A second study determined GHB pharmacokinetics following intragastric administration of GHB, GBL, and 1,4-BD. Methods Operant responding for food, observed behavioral effects, and a fine-motor task occurred at multiple time intervals after administration of drug or vehicle. In a separate pharmacokinetics study, blood samples were collected across multiple time points after administration of GHB, GBL, and 1,4-BD. Results Like GHB, GBL, and 1,4-BD impaired performance on the fine-motor task, but the onset of motor impairment differed across drugs. GBL and 1,4-BD dose dependently decreased the number of food pellets earned, but at lower doses than previously observed for GHB. Similar to GHB, both GBL and 1,4-BD produced sedation, muscle relaxation, gastrointestinal symptoms, and tremors/jerks. Administration of GBL and 1,4-BD produced higher maximum concentrations of GHB with shorter times to maximum concentrations of GHB in plasma when compared to GHB administration. Conclusions GBL and 1,4-BD produced behavioral effects similar to those previously reported with GHB and the time course of effects were related to blood levels of GHB. Given their higher potency and faster onset of effects, the abuse liability of GBL and 1,4-BD may be greater than GHB. Keywords GABA . Behavior . Drug abuse . Operant Gamma-hydroxybutyrate (GHB) is a drug of abuse and a prescribed treatment for narcolepsy under the name Xyrem (sodium oxybate). Gamma-Butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are GHB precursors that are metabolized into GHB after ingestion, although via differen
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self administration of Gamma hydroxybutyric acid ghb precursors Gamma Butyrolactone gbl and 1 4 butanediol 1 4 bd in baboons
Psychopharmacology, 2013Co-Authors: Amy K. Goodwin, Barbara J Kaminski, Elise M. WeertsAbstract:Rationale Gamma-Butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are Gamma-hydroxybutyrate (GHB) pro-drugs and drugs of abuse.
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Behavioral effects and pharmacokinetics of Gamma-hydroxybutyrate (GHB) precursors Gamma-Butyrolactone (GBL) and 1,4-butanediol (1,4-BD) in baboons
Psychopharmacology, 2009Co-Authors: Amy K. Goodwin, P.r. Brown, Erwin E.w. Jansen, C. Jakobs, K.m. Gibson, Elise M. WeertsAbstract:Rationale Gamma-Butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are prodrugs for Gamma-hydroxybutyrate (GHB). Like GHB, GBL and 1,4-BD are drugs of abuse, but their behavioral effects may differ from GHB under some conditions.
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Chronic intragastric administration of Gamma-Butyrolactone produces physical dependence in baboons
Psychopharmacology, 2006Co-Authors: Amy K. Goodwin, Roland R. Griffiths, P. Rand Brown, Wolfgang Froestl, Cornelis Jakobs, K. Michael Gibson, Elise M. WeertsAbstract:Rationale Abuse of Gamma-hydroxybutyrate (GHB) and its precursors is a public health concern. Gamma-Butyrolactone (GBL) is found in commercially available products and, when ingested, is metabolized to GHB.
Paul I. Dargan - One of the best experts on this subject based on the ideXlab platform.
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psychiatric aspects of acute withdrawal from Gamma hydroxybutyrate ghb and its analogue Gamma Butyrolactone gbl implications for psychiatry services in the general hospital
International Journal of Psychiatry in Clinical Practice, 2013Co-Authors: Debajeet Choudhuri, David M. Wood, Paul I. Dargan, Sean Cross, Gopinath RanjithAbstract:AbstractObjective. The objective of this study was to describe the psychiatric symptoms, management and outcomes in a consecutive series of patients being managed medically for symptoms of withdrawal from Gamma-hydroxybutyrate (GHB) and its analogue Gamma-Butyrolactone (GBL) in a general hospital setting. Methods. A toxicology database was used to identify patients presenting with a history suggestive of withdrawal from GHB and analogues. Electronic and paper medical records were searched for demographic features, neuropsychiatric symptoms, psychiatric management while in hospital and overall outcome. Results. There were 31 presentations with withdrawal from the drugs involving 20 patients. Of these 17 (54%) were referred to and seen by the liaison psychiatry team. Anxiety (61.3%) and agitation (48.4%) were the most common symptoms. Of the 17 cases seen by the liaison psychiatry team, 52.9% required close constant observation by a mental health nurse and 29.4% required to be detained in hospital under men...
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acute toxicity and withdrawal syndromes related to Gamma hydroxybutyrate ghb and its analogues Gamma Butyrolactone gbl and 1 4 butanediol 1 4 bd
Drug Testing and Analysis, 2011Co-Authors: David M. Wood, Alan D. Brailsford, Paul I. DarganAbstract:Gamma-hydroxybutyrate (GHB) has been used as a recreational drug since the 1990s and over the last few years there has been increasing use of its analogues Gamma-Butyrolactone (GBL) and to a lesser extent 1,4-butanediol (1,4BD). This review will summarize the literature on the pharmacology of these compounds; the patterns and management of acute toxicity associated with their use; and the clinical patterns of presentation and management of chronic dependency associated with GHB and its analogues. Copyright © 2011 John Wiley & Sons, Ltd.
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acute toxicity and withdrawal syndromes related to Gamma hydroxybutyrate ghb and its analogues Gamma Butyrolactone gbl and 1 4 butanediol 1 4 bd
Drug Testing and Analysis, 2011Co-Authors: David M. Wood, Alan D. Brailsford, Paul I. DarganAbstract:Gamma-hydroxybutyrate (GHB) has been used as a recreational drug since the 1990s and over the last few years there has been increasing use of its analogues Gamma-Butyrolactone (GBL) and to a lesser extent 1,4-butanediol (1,4BD). This review will summarize the literature on the pharmacology of these compounds; the patterns and management of acute toxicity associated with their use; and the clinical patterns of presentation and management of chronic dependency associated with GHB and its analogues.
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The first reported UK fatality related to Gamma-Butyrolactone (GBL) ingestion.
Journal of the Royal Society of Medicine, 2009Co-Authors: Paul I. Dargan, Jenny Button, Susie Davies, John Ramsey, Simi George, David W. Holt, David M. WoodAbstract:Gamma-Butyrolactone (GBL) is rapidly metabolized to Gamma-hydroxybutyrate (GHB) in vivo following ingestion. GBL and GHB cause similar clinical features in users, and both of these agents are widely used as recreational drugs due to their mood-enhancing, stimulant and prosexual effects, particularly on the nightclub scene.1,2 In 2003, GHB was classified in the UK as a Class C controlled substance under the Home Office Misuse of Drugs Act (1971). GBL is currently not classified in the UK and many other countries in the world; the UK Home Office Advisory Council on the Misuse of Drugs is currently consulting on proposed changes to the legal status of GBL, and the related compound 1,4-butanediol (1,4BD). There are numerous reported fatalities related to GHB ingestion.3 However, although there has been media coverage in the lay press of potential GBL-related fatalities in the UK,4,5 there have only been three previous reports of GBL-related fatality, two in Germany and one in the USA.6,7 We report here the first case of a fatality related to isolated GBL toxicity in the UK, which we feel supports the case for classifying GBL similar to that of GHB.
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medical and legal confusion surrounding Gamma hydroxybutyrate ghb and its precursors Gamma Butyrolactone gbl and 1 4 butanediol 1 4bd
QJM: An International Journal of Medicine, 2007Co-Authors: David M. Wood, John Ramsey, David W. Holt, Charlotte Warrengash, T Ashraf, S L Greene, Z Shather, C Trivedy, S Clarke, Paul I. DarganAbstract:Background: Gamma-hydroxybutyrate (GHB) is used as a recreational drug, with significant associated morbidity and mortality; it is therefore a class C drug under the Misuse of Drugs Act (1971). However, its precursors Gamma-Butyrolactone (GBL) and 1,4-butanediol (1,4BD) remain legally available despite having similar clinical effects. Aim: The aim of this study was to determine whether the relative proportions of self-reported ingestions of GHB or its precursors GBL and 1,4BD were similar to those seen in analysis of seized drugs. Design and methods: Retrospective review of our clinical toxicology database to identify all cases of self-reported recreational GHB, GBL and 1,4BD use associated with ED presentation in 2006. Additionally all seized substances on people attending local club venues were analysed by a Home Office approved laboratory to identify any illicit substances present. Results: In 2006, there were a total of 158 ED presentations, of which 150 (94.9%) and 8 (5.1%) were GHB and GBL self-reported ingestions respectively; 96.8% (153) were recreational use. Of the 418 samples seized, 225 (53.8%) were in liquid form; 85 (37.8%) contained GHB and 140 (62.2%) contained GBL. None of the seized samples contained 1,4BD and there were no self-reported 1,4BD ingestions. Conclusions: Self-reported GHB ingestion was much more common than GBL ingestion, whereas GBL was more commonly found in the seized samples. These differences suggest that GBL use may be more common than previously thought and we suggest that there should be further debate about the legal status of the precursors of GHB.
Amy K. Goodwin - One of the best experts on this subject based on the ideXlab platform.
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Behavioral effects and pharmacokinetics of Gamma-hydroxybutyrate (GHB) precursors Gamma-Butyrolactone (GBL) and 1,4-butanediol (1,4-BD) in baboons
2020Co-Authors: Amy K. Goodwin, P.r. Brown, Erwin E.w. Jansen, C. Jakobs, K.m. Gibson, Elise M. WeertsAbstract:Abstract Rationale Gamma-Butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are prodrugs for Gamma-hydroxybutyrate (GHB). Like GHB, GBL and 1,4-BD are drugs of abuse, but their behavioral effects may differ from GHB under some conditions. Objectives The first study compared the behavioral effects of GBL (32-240 mg/kg) and 1,4-BD (32-240 mg/kg) with each other and to effects previously reported for GHB (32-420 mg/kg). A second study determined GHB pharmacokinetics following intragastric administration of GHB, GBL, and 1,4-BD. Methods Operant responding for food, observed behavioral effects, and a fine-motor task occurred at multiple time intervals after administration of drug or vehicle. In a separate pharmacokinetics study, blood samples were collected across multiple time points after administration of GHB, GBL, and 1,4-BD. Results Like GHB, GBL, and 1,4-BD impaired performance on the fine-motor task, but the onset of motor impairment differed across drugs. GBL and 1,4-BD dose dependently decreased the number of food pellets earned, but at lower doses than previously observed for GHB. Similar to GHB, both GBL and 1,4-BD produced sedation, muscle relaxation, gastrointestinal symptoms, and tremors/jerks. Administration of GBL and 1,4-BD produced higher maximum concentrations of GHB with shorter times to maximum concentrations of GHB in plasma when compared to GHB administration. Conclusions GBL and 1,4-BD produced behavioral effects similar to those previously reported with GHB and the time course of effects were related to blood levels of GHB. Given their higher potency and faster onset of effects, the abuse liability of GBL and 1,4-BD may be greater than GHB. Keywords GABA . Behavior . Drug abuse . Operant Gamma-hydroxybutyrate (GHB) is a drug of abuse and a prescribed treatment for narcolepsy under the name Xyrem (sodium oxybate). Gamma-Butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are GHB precursors that are metabolized into GHB after ingestion, although via differen
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self administration of Gamma hydroxybutyric acid ghb precursors Gamma Butyrolactone gbl and 1 4 butanediol 1 4 bd in baboons
Psychopharmacology, 2013Co-Authors: Amy K. Goodwin, Barbara J Kaminski, Elise M. WeertsAbstract:Rationale Gamma-Butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are Gamma-hydroxybutyrate (GHB) pro-drugs and drugs of abuse.
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Behavioral effects and pharmacokinetics of Gamma-hydroxybutyrate (GHB) precursors Gamma-Butyrolactone (GBL) and 1,4-butanediol (1,4-BD) in baboons
Psychopharmacology, 2009Co-Authors: Amy K. Goodwin, P.r. Brown, Erwin E.w. Jansen, C. Jakobs, K.m. Gibson, Elise M. WeertsAbstract:Rationale Gamma-Butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are prodrugs for Gamma-hydroxybutyrate (GHB). Like GHB, GBL and 1,4-BD are drugs of abuse, but their behavioral effects may differ from GHB under some conditions.
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Chronic intragastric administration of Gamma-Butyrolactone produces physical dependence in baboons
Psychopharmacology, 2006Co-Authors: Amy K. Goodwin, Roland R. Griffiths, P. Rand Brown, Wolfgang Froestl, Cornelis Jakobs, K. Michael Gibson, Elise M. WeertsAbstract:Rationale Abuse of Gamma-hydroxybutyrate (GHB) and its precursors is a public health concern. Gamma-Butyrolactone (GBL) is found in commercially available products and, when ingested, is metabolized to GHB.
David M. Wood - One of the best experts on this subject based on the ideXlab platform.
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psychiatric aspects of acute withdrawal from Gamma hydroxybutyrate ghb and its analogue Gamma Butyrolactone gbl implications for psychiatry services in the general hospital
International Journal of Psychiatry in Clinical Practice, 2013Co-Authors: Debajeet Choudhuri, David M. Wood, Paul I. Dargan, Sean Cross, Gopinath RanjithAbstract:AbstractObjective. The objective of this study was to describe the psychiatric symptoms, management and outcomes in a consecutive series of patients being managed medically for symptoms of withdrawal from Gamma-hydroxybutyrate (GHB) and its analogue Gamma-Butyrolactone (GBL) in a general hospital setting. Methods. A toxicology database was used to identify patients presenting with a history suggestive of withdrawal from GHB and analogues. Electronic and paper medical records were searched for demographic features, neuropsychiatric symptoms, psychiatric management while in hospital and overall outcome. Results. There were 31 presentations with withdrawal from the drugs involving 20 patients. Of these 17 (54%) were referred to and seen by the liaison psychiatry team. Anxiety (61.3%) and agitation (48.4%) were the most common symptoms. Of the 17 cases seen by the liaison psychiatry team, 52.9% required close constant observation by a mental health nurse and 29.4% required to be detained in hospital under men...
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acute toxicity and withdrawal syndromes related to Gamma hydroxybutyrate ghb and its analogues Gamma Butyrolactone gbl and 1 4 butanediol 1 4 bd
Drug Testing and Analysis, 2011Co-Authors: David M. Wood, Alan D. Brailsford, Paul I. DarganAbstract:Gamma-hydroxybutyrate (GHB) has been used as a recreational drug since the 1990s and over the last few years there has been increasing use of its analogues Gamma-Butyrolactone (GBL) and to a lesser extent 1,4-butanediol (1,4BD). This review will summarize the literature on the pharmacology of these compounds; the patterns and management of acute toxicity associated with their use; and the clinical patterns of presentation and management of chronic dependency associated with GHB and its analogues. Copyright © 2011 John Wiley & Sons, Ltd.
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acute toxicity and withdrawal syndromes related to Gamma hydroxybutyrate ghb and its analogues Gamma Butyrolactone gbl and 1 4 butanediol 1 4 bd
Drug Testing and Analysis, 2011Co-Authors: David M. Wood, Alan D. Brailsford, Paul I. DarganAbstract:Gamma-hydroxybutyrate (GHB) has been used as a recreational drug since the 1990s and over the last few years there has been increasing use of its analogues Gamma-Butyrolactone (GBL) and to a lesser extent 1,4-butanediol (1,4BD). This review will summarize the literature on the pharmacology of these compounds; the patterns and management of acute toxicity associated with their use; and the clinical patterns of presentation and management of chronic dependency associated with GHB and its analogues.
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The first reported UK fatality related to Gamma-Butyrolactone (GBL) ingestion.
Journal of the Royal Society of Medicine, 2009Co-Authors: Paul I. Dargan, Jenny Button, Susie Davies, John Ramsey, Simi George, David W. Holt, David M. WoodAbstract:Gamma-Butyrolactone (GBL) is rapidly metabolized to Gamma-hydroxybutyrate (GHB) in vivo following ingestion. GBL and GHB cause similar clinical features in users, and both of these agents are widely used as recreational drugs due to their mood-enhancing, stimulant and prosexual effects, particularly on the nightclub scene.1,2 In 2003, GHB was classified in the UK as a Class C controlled substance under the Home Office Misuse of Drugs Act (1971). GBL is currently not classified in the UK and many other countries in the world; the UK Home Office Advisory Council on the Misuse of Drugs is currently consulting on proposed changes to the legal status of GBL, and the related compound 1,4-butanediol (1,4BD). There are numerous reported fatalities related to GHB ingestion.3 However, although there has been media coverage in the lay press of potential GBL-related fatalities in the UK,4,5 there have only been three previous reports of GBL-related fatality, two in Germany and one in the USA.6,7 We report here the first case of a fatality related to isolated GBL toxicity in the UK, which we feel supports the case for classifying GBL similar to that of GHB.
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medical and legal confusion surrounding Gamma hydroxybutyrate ghb and its precursors Gamma Butyrolactone gbl and 1 4 butanediol 1 4bd
QJM: An International Journal of Medicine, 2007Co-Authors: David M. Wood, John Ramsey, David W. Holt, Charlotte Warrengash, T Ashraf, S L Greene, Z Shather, C Trivedy, S Clarke, Paul I. DarganAbstract:Background: Gamma-hydroxybutyrate (GHB) is used as a recreational drug, with significant associated morbidity and mortality; it is therefore a class C drug under the Misuse of Drugs Act (1971). However, its precursors Gamma-Butyrolactone (GBL) and 1,4-butanediol (1,4BD) remain legally available despite having similar clinical effects. Aim: The aim of this study was to determine whether the relative proportions of self-reported ingestions of GHB or its precursors GBL and 1,4BD were similar to those seen in analysis of seized drugs. Design and methods: Retrospective review of our clinical toxicology database to identify all cases of self-reported recreational GHB, GBL and 1,4BD use associated with ED presentation in 2006. Additionally all seized substances on people attending local club venues were analysed by a Home Office approved laboratory to identify any illicit substances present. Results: In 2006, there were a total of 158 ED presentations, of which 150 (94.9%) and 8 (5.1%) were GHB and GBL self-reported ingestions respectively; 96.8% (153) were recreational use. Of the 418 samples seized, 225 (53.8%) were in liquid form; 85 (37.8%) contained GHB and 140 (62.2%) contained GBL. None of the seized samples contained 1,4BD and there were no self-reported 1,4BD ingestions. Conclusions: Self-reported GHB ingestion was much more common than GBL ingestion, whereas GBL was more commonly found in the seized samples. These differences suggest that GBL use may be more common than previously thought and we suggest that there should be further debate about the legal status of the precursors of GHB.
Bruno Megarbane - One of the best experts on this subject based on the ideXlab platform.
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the clinical toxicology of Gamma hydroxybutyrate Gamma Butyrolactone and 1 4 butanediol
Clinical Toxicology, 2012Co-Authors: Leo J Schep, Kai Knudsen, Robin J Slaughter, Allister J Vale, Bruno MegarbaneAbstract:Introduction. Gamma-hydroxybutyrate (GHB) and its precursors, Gamma-Butyrolactone (GBL) and 1,4-butanediol (1,4-BD), are drugs of abuse which act primarily as central nervous system (CNS) depressants. In recent years, the rising recreational use of these drugs has led to an increasing burden upon health care providers. Understanding their toxicity is therefore essential for the successful management of intoxicated patients. We review the epidemiology, mechanisms of toxicity, toxicokinetics, clinical features, diagnosis, and management of poisoning due to GHB and its analogs and discuss the features and management of GHB withdrawal. Methods. OVID MEDLINE and ISI Web of Science databases were searched using the terms “GHB,” “Gamma-hydroxybutyrate,” “Gamma-hydroxybutyric acid,” “4-hydroxybutanoic acid,” “sodium oxybate,” “Gamma-Butyrolactone,” “GBL,” “1,4-butanediol,” and “1,4-BD” alone and in combination with the keywords “pharmacokinetics,” “kinetics,” “poisoning,” “poison,” “toxicity,” “ingestion,” “adver...
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the clinical toxicology of Gamma hydroxybutyrate Gamma Butyrolactone and 1 4 butanediol
Clinical Toxicology, 2012Co-Authors: Leo J Schep, Kai Knudsen, Robin J Slaughter, Allister J Vale, Bruno MegarbaneAbstract:Introduction. Gamma-hydroxybutyrate (GHB) and its precursors, Gamma-Butyrolactone (GBL) and 1,4-butanediol (1,4-BD), are drugs of abuse which act primarily as central nervous system (CNS) depressan...
