Gamma-Hydroxybutyrate (GHB, "G", Liquid X, Liquid E, Juice, Mils, Fantasy) Toxicity


Article Author:
Jacqueline Le


Article Editor:
John Richards


Editors In Chief:
Rodrigo Kuljis
Oleg Chernyshev
Aninda Acharya


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes


Updated:
6/4/2019 2:30:00 PM

Introduction

First synthesized in 1960, gamma hydroxybutyrate (GHB) was originally used as an anesthetic. While it did not gain much esteem in health care due to poor analgesia and adverse effects, including seizure-like activity, GHB gained significant popularity as a sleep aid, bodybuilding, and weight loss supplement. GHB was prohibited by the United States Food and Drug Administration in 1990 and is currently a Schedule I drug in the United States. It has been labeled a date rape drug and is also illicitly used for recreational purposes, particularly at dance clubs and raves. Street names include G, Gamma OH, Georgia Home Boy, Liquid Ecstasy, and Liquid X.[1][2][3][4]

Etiology

Clandestine production of GHB contributes to its abuse. GHB is easily manufactured and available on the street as a powder or more often, a clear, odorless liquid sold in mini shampoo bottles. It has a salty or soapy taste, but only a small capful is needed for the immediate euphoric high that users seek. Alcohol or other coingestants may mask the taste. Strength and purity vary widely, which makes it difficult to determine the toxic dose that a user ingests accurately. Furthermore, misinformation on the internet downplays the potentially lethal effects of GHB toxicity and boosts its popularity as a bodybuilding or club drug.

Epidemiology

The prevalence of GHB use in the United States is not well known due to limited data. Mortality and morbidity data is also limited partly because GHB is easily mistaken for other drugs and not tested on routine drug screens. The available data reveals that the majority of GHB users are young adult white, middle-class males. User subgroups include recreational party drug users and homosexual males. Reports indicate that concurrent use of other drugs such as alcohol (76%), cocaine, marijuana, ketamine, MDMA (ecstasy) and methamphetamines is common in GHB-related emergency department visits.[5][6][7]

Pathophysiology

GHB is endogenously found in the brain and is a precursor of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). It acts on both GABA-B and GHB receptors. GHB has a biphasic effect on dopamine. Lower doses stimulate dopamine release by binding GHB receptors. Higher doses initially inhibit dopamine release via agonist effects on GABA-B receptors, leading to neuro-inhibition and central nervous system (CNS) depression, but after that increase dopamine release via the GHB receptor. While this accounts for both the sedative and excitatory effects of GHB, the mainstay of GHB toxicity is central nervous system and respiratory depression.

Gamma-butyrolactone and 1,4-butanediol, previously sold as industrial solvents or dietary supplements, are GHB substitutes that rapidly convert to GHB following oral ingestion, thereby producing the same clinical effects of GHB toxicity.

Toxicokinetics

GHB is rapidly absorbed in the body with a quick onset of action between five minutes to 15 minutes, with users often reporting an initial period of euphoria. The clinical symptoms and duration of GHB toxicity are dose-dependent; peak plasma concentrations and clinical effects are reached between 30 minutes to 60 minutes, and duration of action is two to four hours. The elimination half-life ranges from 20 minutes to 60 minutes. Lower doses of GHB (10 mg/kg) have amnestic and variable sedative effects. Doses of 20 mg/kg to 30 mg/kg lead to cycles of rapid eye movement (REM) sleep. Higher doses (50 mg/kg) result in bradycardia, respiratory depression, and coma. Co-intoxicants, especially alcohol, can further augment the effects and duration of symptoms.

History and Physical

GHB users often experience an initial disinhibition and euphoria as quickly as 15 minutes following ingestion. The classic presentation of GHB toxicity is a sudden onset of coma followed by an abrupt awakening within several hours. Symptoms are dose-related with higher doses causing more severe respiratory and CNS depression. It is not unusual for users to become agitated or combative before, during, or after a prolonged period of somnolence or coma. Additional CNS findings include amnesia, myoclonic activity, and seizure-like effects. Bradycardia, hypotension, apnea, vomiting, and hypothermia may also occur.

It is often difficult to obtain a reliable history due to patients’ altered mental status. Clues to GHB toxicity may include empty mini shampoo bottles in their possession, attendance at a party or nightclub, or possible sexual assault.

Evaluation

GHB toxicity is a clinical diagnosis. Blood or urine testing for GHB is not routinely available in the hospital setting. Diagnostic confirmation via gas chromatography and mass spectrometry is possible but may take up to seven to 14 days for results. A urine drug screen may aid in identifying or excluding coingestants. As with any potential intoxicated patient, a fingerstick glucose, blood alcohol level, acetaminophen level, and salicylate level should be obtained. A CT scan of the head or other radiological tests may be indicated if any injury or trauma is suspected.[8][9][10]

Treatment / Management

There is no antidote for GHB toxicity. The mainstay of treatment is airway protection and monitoring. Management should also include cardiorespiratory monitoring, pulse oximetry, and capnography if available. Patients may develop severe respiratory depression or apnea, and therefore immediate evaluation of the airway is paramount. In milder cases, supplemental oxygen with or without a nasopharyngeal airway is sufficient until the patient awakens. In more severe cases, endotracheal intubation may be necessary. GHB-intoxicated patients usually do not require any sedation while mechanically ventilated and will precipitously awaken and potentially extubate themselves or require sudden extubation. Severe bradycardia can be treated with atropine, and hypotension is often sufficiently managed with intravenous (IV) fluids. If there is any concern for opioid co-ingestion and toxicity, IV naloxone should be strongly considered. Patients can often be safely discharged home once they are awake, symptom-free, and all other co-intoxications or injuries are ruled out.

Pearls and Other Issues

GHB is pharmaceutically manufactured as sodium oxybate for the treatment of narcolepsy. This formulation is considered a Schedule III drug in the United States. In Europe, GHB is also still therapeutically used as an anesthetic and for the treatment of alcohol and opiate dependence.

Withdrawal symptoms have been reported in chronic or dependent users after cessation of the drug. Early or mild symptoms of anxiety, tremors, tachycardia, and insomnia can quickly progress within 24 hours to severe and refractory agitation with autonomic instability. Severe withdrawal symptoms are life threatening and can last up to 15 days. Patients should be treated with benzodiazepines and managed in the intensive care unit.

Enhancing Healthcare Team Outcomes

GHB is pharmaceutically manufactured as sodium oxybate for the treatment of narcolepsy. This formulation is considered a Schedule III drug in the United States. In Europe, GHB is also still therapeutically used as an anesthetic and for the treatment of alcohol and opiate dependence. The agent is often misused. After prolonged used and sudden cessation, withdrawal symptoms have been reported in chronic or dependent users after cessation of the drug. The management of GHB overdose is by a multidisciplinary team. Since there is no specific antidote to reverse the toxicity, aggressive supportive care including mechanical ventilation may be required.  Severe withdrawal symptoms are life threatening and can last up to 15 days. Patients should be treated with benzodiazepines and managed in the intensive care unit. Parents should be educated about safe storage of this agent to prevent accidental poisoning in children.

 

 


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Gamma-Hydroxybutyrate (GHB, "G", Liquid X, Liquid E, Juice, Mils, Fantasy) Toxicity - Questions

Take a quiz of the questions on this article.

Take Quiz
A 17-year old male is brought in by ambulance to the emergency department. He was found unconscious at a dance nightclub. Paramedics report he has a Glasgow Coma Scale of 10. Vital signs include a temperature of 36.3 degrees Celsius, blood pressure of 110/80, heart rate of 48 beats per minute, respiratory rate of 6 breaths per minute, and oxygen saturation of 95% on room air. Fingerstick glucose was 97 mg/dl. The patient is intubated and abruptly awakens 2 hours later. He extubates himself and demands to go home. Which of the following drugs did the patient most likely accidentally overdose on?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
An 18-year-old female presents to the emergency department unresponsive after drinking an unknown substance given to her at an electronic dance music festival. As the physician prepares to intubate her for respiratory depression and airway protection, she awakes suddenly and asks, "Where am I?" Which of the following substance did she most likely ingest?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 17-year-old male is brought into the emergency department with altered mental status. He is somnolent with a respiratory rate of 8 breaths per minute. The rest of his vital signs are normal. His friends state that he ingested a colorless liquid an hour ago. Which of the following tests is necessary to diagnose gamma hydroxybutyrate (GHB) ingestion?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 17-year old male bodybuilder who uses gamma hydroxybutyrate (GHB) daily now presents to the emergency department with anxiety, tremors, and severe agitation. His temperature is 40.5 degrees Celsius and heart rate is 140 beats per minute. Urine drug screen and alcohol blood testing are both negative. Laboratory testing reveals a creatine kinase level of 70,000 U/L. What is the most likely clinical scenario?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is not a therapeutic use of gamma hydroxybutyrate (GHB)?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 20-year-old female presents to the emergency department feeling sleepy after sipping a drink at a club 8 hours earlier. She and her friend are concerned someone may have surreptitiously put Gamma-Hydroxybutyrate (GHB) in the drink. Which of the following statements is correct about GHB ingestion?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which is true of toxicology testing for gamma-hydroxybutyrate (GHB) in the emergency department?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 17-year-old male presents to the emergency department via EMS for evaluation of altered mental status. He was found outside of a college party, intermittently shouting at passersby. In the emergency department, he is arousable to voice, but when he wakes he is aggressive towards staff. After several hours of observation, he wakes up and is calm, cooperative, and at his baseline mental status. He has no recollection of the past several hours. What is the cause of the patient's symptoms?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Gamma-Hydroxybutyrate (GHB, "G", Liquid X, Liquid E, Juice, Mils, Fantasy) Toxicity - References

References

Cappetta M,Murnion BP, Inpatient management of gamma-hydroxybutyrate withdrawal. Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists. 2019 Jan 17;     [PubMed]
Morse AM,Kelly-Pieper K,Kothare SV, Management of Excessive Daytime Sleepiness in Narcolepsy With Baclofen. Pediatric neurology. 2018 Nov 22;     [PubMed]
de Biase S,Gigli GL,Valente M, Important decisions in choosing the pharmacotherapy for narcoleptics. Expert opinion on pharmacotherapy. 2018 Dec 28;     [PubMed]
Simonyan K,Frucht SJ,Blitzer A,Sichani AH,Rumbach AF, A novel therapeutic agent, sodium oxybate, improves dystonic symptoms via reduced network-wide activity. Scientific reports. 2018 Oct 31;     [PubMed]
Busardò FP,Jones AW, Interpreting γ-hydroxybutyrate concentrations for clinical and forensic purposes. Clinical toxicology (Philadelphia, Pa.). 2018 Oct 11;     [PubMed]
Grela A,Gautam L,Cole MD, A multifactorial critical appraisal of substances found in drug facilitated sexual assault cases. Forensic science international. 2018 Nov;     [PubMed]
Sodium Oxybate 2006;     [PubMed]
Mannucci C,Pichini S,Spagnolo EV,Calapai F,Gangemi S,Navarra M,Calapai G, Sodium Oxybate Therapy for Alcohol Withdrawal Syndrome and Keeping of Alcohol Abstinence. Current drug metabolism. 2018;     [PubMed]
Tomkins A,Ahmad S,Cannon L,Higgins SP,Kliner M,Kolyva A,Ward C,Vivancos R, Prevalence of recreational drug use reported by men who have sex with men attending sexual health clinics in Manchester, UK. International journal of STD     [PubMed]
Centola C,Giorgetti A,Zaami S,Giorgetti R, Effects of GHB On Psychomotor and Driving Performance. Current drug metabolism. 2018;     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Neurology. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Neurology, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Neurology, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Neurology. When it is time for the Neurology board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Neurology.