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Gamma Hydroxybutyrate

Gamma Hydroxybutyrate
30.May.2017-Expires: 7 days - Do not archive



Gamma Hydroxybutyrate


This substance may be used either therapeutically but can also be subject to abuse.

Treatment for narcolepsy
Treatment for alcoholism
Anesthetic agent
“Date rape” agent
“Growth Hormone booster”
“Muscle builder” (although effectiveness has never been proven)


The correct identification of the substance is important. If the symptoms are inconsistent with those described in the literature, or the history is considered unreliable, other substances may need to be considered.

Intervention Level


Medical observation is recommended:
- For any suspected ingestion in children
The risks of decontamination outweigh any benefits, and should not be attempted.


Medical observation is recommended:
- For any suspected ingestion
The risks of decontamination outweigh any benefits, and should not be attempted.
History of dose ingested is not a reliable guide to management.

Observation Period

Observation at Home

All patients require medical attention.

Medical Observation

If medical observation is required the patient must be monitored for 6 hours following exposure for onset or worsening of symptoms.
If the patient is asymptomatic at the end of the observation period, and provided that appropriate assessment and investigations have been carried out, they may be:
Discharged into the care of a reliable observer, or
Referred for psychological assessment if the overdose or exposure was with intent to self-harm



Serum concentrations do not aid management.


Level of consciousness
Heart rate
Blood pressure
Seizure activity

Admission Criteria

Admission to an intensive care environment is recommended for patients who develop significant signs of toxicity including:
CNS depression requiring intubation
Respiratory depression
Aspiration pneumonitis
Hemodynamic instability



Emergency stabilization may be required for respiratory depression and/or pulmonary aspiration, immediate assessment and management of respiratory compromise is a priority. Due to fast onset of action, gastrointestinal decontamination is not recommended.
There is no proven antidote for poisoning. Extracorporeal elimination techniques would not be anticipated to be of clinical benefit in the majority of patients as most will satisfactorily recover with adequate airways management alone.
Supportive care is the mainstay of management, with primary emphasis on airway management and cardiovascular support. Airway protection including endotracheal intubation and/or assisted ventilation may be necessary due to respiratory depression and aspiration risk. Seizures may rarely occur and, in the presence of coma, indicate anoxia: manage the airway and ensure adequate ventilation. Should repetitive seizure occur in a well ventilated patient treat with a benzodiazepine, or if still refractory, a barbiturate. Myoclonic jerking is a recognized re-emergence phenomenon and single episodes do not require treatment. Other complications such as bradycardia, hypotension, hypothermia, and gastrointestinal upset should be treated along usual guidelines.
A withdrawal syndrome is recognized after chronic abuse of this compound and may last 3 to 21 days. Benzodiazepines are usually effective to relieve symptoms. Weakness, headache, fatigue and nausea lasting 3 days after ingestion may occur. However, if significant CNS depressant effects persist beyond 8 hours, alternative causes should be investigated.
Emergency Stabilization
Enhanced Elimination
Supportive Care


Ensure Adequate Cardiopulmonary Function

Ensure the airway is protected if compromised (intubation may be necessary).


Establish secure intravenous access if hypotensive.

Emergency Monitoring

Blood pressure
Heart rate/rhythm
Core body temperature
Blood oximetry



Decontamination Not Recommended

Absorption is too rapid for decontamination to be effective.

Supportive care is likely to be successful without decontamination.


There Are No Antidotes For This Substance

There are no specific antidotes for this overdose.[1]
Agents including naloxone, flumazenil, and physostigmine have been investigated as potential antidotes. None have shown consistent results in reversing intoxication.
Physostigmine is viewed as an unproven experimental antidote for this intoxication. It was initially investigated as a reversal agent in patients under GHB-induced anesthesia.[2][3] However, use following poisoning has produced differing results, with the majority of patients not showing response.[4][5][6] Reviews of the literature have shown there is not sufficient evidence to support the use of physostigmine in acute GHB overdose.[6][7] At this stage physostigmine is not recommended.[1]
Additionally, naloxone and flumazenil have been used following human poisoning, both have had limited effect on reversing toxicity.[8][9][10][11][12] Neither of these compounds can be recommended.[1]


Enhanced Elimination Not Recommended

There is limited information regarding use of hemodialysis, hemoperfusion, hemodiafiltration, or hemofiltration to enhance elimination. GHB has minimal protein binding, a low molecular weight,[13] and a relatively small volume of distribution,[14][15][16] suggesting use of extra-corporal techniques may enhance its elimination. However, it would not be anticipated to be of benefit in the majority of patients as GHB has a rapid clearance and short duration of clinical effects.



Closely monitor:
Level of consciousness
Respiratory function
Gag reflex
For signs of withdrawal


Respiratory Failure

Respiratory compromise is the most critical problem in severe poisoning. Intense respiratory support, when needed, constitutes the most vital supportive measure. Rapid sequence induction with endotracheal intubation and/or assisted ventilation may be required.[1]
Monitoring for respiratory failure should include:
Chest auscultation
Oxygen saturation
Arterial blood gases
Treat using standard protocols for respiratory failure.

Pulmonary Aspiration

Aspiration is a significant risk. Protection and careful monitoring of the airway is required if aspiration is suspected. Oxygen should be administered and artificial ventilation may be required.[1]
Pulse oximetry
Arterial blood gases
Chest x-ray



Profound coma is characteristic and generally short-term. Airway protection may be required, endo-tracheal intubation and even ventilation may on occasion be necessary.[17]
Closely monitor level of consciousness.
Follow standard protocols for the management of coma.


Myoclonic jerking is recognized as a re-emergence phenomenon (sometime mistaken for seizure activity) and does not require treatment. However, tonic-clonic seizures may occur and should be treated with standard protocols. Anoxia is an important precipitant and adequate airways and ventilation must be ensured.
Observe the patient closely for onset of seizure activity.



Bradycardia may occur in moderate to severe intoxication. Pharmacological intervention is rarely required in patients with hemodynamically stable bradycardia. Atropine may be useful in the presence of hemodynamically-unstable bradycardia.[1]
Heart rate/rhythm
Blood pressure
Manage bradycardia following standard treatment protocols.


Metabolic Acidosis

Metabolic acidosis is reported in severe cases. Acid-base abnormalities should be sought and appropriately treated. In severe, refractory acidosis, hemodialysis may be required.[18]
Arterial blood gases (pH, bicarbonate, pCO2, pO2)
Plasma lactate
Base excess
Follow standard protocols for the management of metabolic acidosis.


Withdrawal Syndrome

A withdrawal syndrome related to gamma hydroxybutyrate is recognized with symptoms resolving in some 3 to 21 days.[19][20][21][22][23][24] Treatment with benzodiazepines has been reported as being sufficient to achieve regression of symptoms.[25] The initial treatment of choice appears to be benzodiazepine administration; if necessary, second line management options include barbiturates, baclofen, or propofol.[21][23][26][27][28][29]
Monitor for:
Autonomic instability
Increased creatine phosphokinase
Follow standard protocols for the management of withdrawal.


Patients may, if initially symptomatic, be discharged following 6 hours of observation. Symptomatic patients may discharged subsequent to becoming stable and asymptomatic.[30]


Medical follow-up is unlikely to be required, as long as recovery from any complications is complete. Psychiatric intervention may be necessary depending on the circumstances of the exposure.


Following appropriate supportive care the prognosis is good.


The correct identification of the substance is important. If the symptoms are inconsistent with those described in the literature, or the history is considered unreliable, other substances may need to be considered.
Other drug/compounds are commonly co-ingested with this substance and may significantly influence the clinical picture.[1]
With mild toxicity, gastrointestinal upset may occur and CNS effects predominate including CNS depression, euphoria, ataxia, disorientation, dizziness, and occasionally miosis and nystagmus. Sudden drowsiness followed by profound coma is a characteristic presentation; a GCS of 3 is not uncommon. Recovery is sometimes accompanied by emergence phenomena including myoclonic jerking, transient confusion, and agitation and combativeness.[1]
With severe toxicity, sudden, profound coma, seizures, and respiratory arrest may occur. Further complications may include bradycardia, hypotension, and hypothermia. Deaths are reported.[1][31][32][33]
Persistent symptoms of weakness, headache, fatigue, and nausea lasting three days after ingestion has been noted,[34] and a withdrawal syndrome is described.[19][20]

Onset/Duration of Symptoms

In the majority of cases signs and symptoms develop within 1 hour of ingestion and resolve within 4 to 8 hours of onset.[8][35][36][37][38][39] Recovery from coma, if it occurs, is typically rapid, and may be indicated by initial GCS score.[35] Weakness, headache, fatigue, and nausea lasting three days after ingestion has been noted.[34]
A withdrawal syndrome which may begin within 1 to 12 hours of the last dose and may continue for 3 to 21 days is described.[19][20][21][22][23][24]

Severity of Poisoning

Mild Gamma-Hydroxybutyrate ToxicityModerate Gamma-Hydroxybutyrate ToxicitySevere Gamma-Hydroxybutyrate Toxicity
Myoclonic jerking
Hypothermia (mild)
Respiratory depression
Profound coma
Respiratory arrest



Slurred speech[56][62][65]
Bruxism (teeth grinding)[5]
Extrapyramidal side effects[65]
Athetoid posturing[5]


Chest tightness[60][63]
ECG changes
U waves[10]
Transient P-wave inversion[83]
Elevation of the ST segments[69]
QTc prolongation[69]
Right bundle-branch block[10][69]
First-degree atrioventricular block[10]
Atrial fibrillation[5][35]





Fluid and Electrolytes

Hypernatremia (if large doses of the sodium salt ingested)[92]





Withdrawal Syndrome

Nausea and vomiting[21][25]
Abdominal pain[94]
Cardiac palpitations[94][107][113]


The correct identification of the substance is important. If the symptoms are inconsistent with those described in the literature, or the history is considered unreliable, other substances may need to be considered.



The acute toxic dose in children has not been determined.


Toxicity of gamma hydroxybutyrate:[17][20][26][30][92]
10 mg/kg
Anterograde amnesia, hyptonia, and euphoria
20 to 30 mg/kg
Drowsiness, a normal sequence of REM and non-REM sleep, and myoclonus
50 mg/kg
Anesthesia and unconsciousness
>50 mg/kg
Decreased cardiac output, severe respiratory depression, seizure-like activity, coma
Other substances may be abused concomitantly with this compound greatly increasing toxicity.[1][116][117]
Sodium hydroxide may be inappropriately used in the preparation of gamma hydroxybutyrate forming a caustic mixture.[32]


Sodium Gamma Hydroxybutyrate:
LD50 Oral, Rat
9,690 mg/kg9,690 mg/kg/[118]
LD50 IP, Rat
1,650 mg/kg1,650 mg/kg/[118]
LD50 IP, Mouse
3,330 mg/kg3,330 mg/kg/[118]


Blood concentrations do not aid patient management.



GHB crosses the placenta.[119] Therapeutic GHB/sodium oxybate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.[120]
There are no adequate and well-controlled studies in pregnant women. Animal studies in rats and rabbits have shown no clear evidence of developmental toxicity. In rats administration of 150, 350, or 1,000 mg/kg/day throughout pregnancy and lactation resulted in increased stillbirths and decreased offspring postnatal viability and body weight gain at the highest dose tested.[120]Gamma hydroxybutyrate is not reported as teratogenic when injected into fertile chicken eggs.[121]


GHB is excreted into human breast milk.[122] GHB may affect the infant. Taking GHB is not considered acceptable when breastfeeding. The manufacturers of therapeutic GHB/sodium oxybate only recommend use while breast feeding when the potential benefit out weighs the risk.[120]


Gamma hydroxybutyrate (GHB) is a water-soluble four carbon molecule normally found in the human body. It is formed from the precursor molecule gamma butyrolactone (GBL) and is metabolized to succinic semialdehyde and the neurotransmitter gamma-aminobutyric acid (GABA).[30] The greatest concentration of GHB in humans is in the basal ganglia.
Mechanism of Action
Gamma hydroxybutyrate (GHB) acts as:
- An inhibitory neurotransmitter regulating dopaminergic neurons
- A central nervous system depressant with euphoria-inducing capabilities
Has a general anesthetic effect caused via:
- Suppression of the entire cerebrospinal axis, and
- Muscular relaxation by direct action on the spinal cord, rather than neuromuscular junction.[123]
GHB alters dopaminergic activity:
Either by reducing dopaminergic activity in the basal ganglia
- Possibly due to the inhibition of dopamine-releasing nerve cells
Or by stimulating dopamine release
However, the direction is dependent on several undefined variables.
GHB has binding affinity for two receptor sites in the central nervous system
- GHB-specific receptor
- The GABAB receptor
GHB might mediate some of its effects (alteration in dopaminergic activity) through interaction with the GABAB receptor.[124]




Oral Absorption
Yes, rapidly
Effect of Food
Reduces mean peak plasma concentrations, increases median time to peak concentration, and decreases the area under the plasma concentration-time curve[125]
First Pass Metabolism
Onset of Action
15 to 45 minutes[38][59][66]
Effects typically peak at 30 to 60 minutes post ingestion[13][128][129]
Duration of Action
~ 1 to 8 hours[30][35][38][39][57]
Time to Peak Plasma Levels


  1. Rapid[135]
Volume of Distribution
  1. 192 to 741 mL/kg[14][16][130]
Plasma Protein Binding
  1. Limited[13]
Lipid Solubility
Crosses the blood brain barrier[136][137][138]
Crosses the placenta[119]
Is excreted in breast milk[120]


  1. Hepatic[1]
Major Metabolic Pathways
  1. Following oxidation to succinate and entry into the Krebs cycle, gamma hydroxybutyrate is almost completely metabolized to water and carbon dioxide.[92][123]
First Pass Metabolism
  1. Significant[127]


  1. 2 to 5% excreted unchanged[37][128]
  1. Excreted as carbon dioxide
Clearance Rate
  1. 3.7 to 15.8 mL/min/kg[13][14][125]
Time to Completion
  1. 4 to 8 hours[133][134]



This substance may be available in a stated dosage, however this should be treated with some caution particularly if obtained illicitly, due to variables such as uncontrolled manufacturing process, inappropriate packaging, and product bulking.


Chemical Name

Gamma hydroxybutyric acid:
4-hydroxy butyrate

Common Names

4-hydroxy butyrate4-hydroxybutanoic acid
Gamma-hydroxybutyric acidGBH
GHB Sodium oxybate
Sodium oxybutyrate

“Street” Names

Alcover Aminos Blue Thunder
Cherry Menth Cherry Meth Date Rape Drug
Easy LayEverclearFantasy
Fingernail Polish Remover Flower Power G
G caps G juice Gamma 10
Gamma Date Rape Drug Gamma-OH GBH
Georgia Home BoyGH Buddy GHB
GHBees (GHB & 2C-B)Ghbers GHGold
Gina Goop Great Hormones
Great Hormones at BedtimeGrevious Bodily HarmGrievous Bodily Harm
G-Riffick H2O Ink Jet Cartridge Cleaner
Jib Liquid E Liquid Ecstasy
Liquid Fantasy Liquid G Liquid X
Max (GHB & Amphetamines)Nail Polish Remover Natural Sleep 500
Nectar Organic Quaalude Oxy-Sleep
Paint Stripper Phantasy Plant Food
PMSomax Puritech Rejoov
Salty water Scoop Sleep-500
Soap Somatomax Somsanit
Swirl Thundar Tranquili G
Vita-G Water White Magic Cleaner
Womans Viagra



Anesthetics, General - Other General AnestheticsAnesthetics, General
N01A X11
Sodium Oxybate
N01A X
Other Nervous System Drugs - Other Nervous System DrugsOther Nervous System Drugs
N07X X04
Sodium Oxybate
N07X X


Gamma Hydroxybutyrate:
Sodium Gamma Hydroxybutyrate:




Molecular Weight
104.10 104.10% degrees C[139]
Molecular Weight
127.09 127.09% degrees C[139]
Water: highly soluble[139]
Attempts to avoid detection:
Artificial flavoring
Artificial coloring
Mixed in:
Fruit drinks
Bottled water
Sold as cleaning products, e.g. CD cleaner
Gamma butyrolactone (GBL) and 1,4 butanediol are rapidly metabolized to gamma hydroxybutyrate (GHB), therefore:
Routine drug screen will not detect GHB
Tests must be targeted specifically for GHB
Urine testing should be used


[1] Schep LJ, Knudsen K, Slaughter RJ, Vale JA, Mégarbane B. The clinical toxicology of gamma-hydroxybutyrate, gamma-butyrolactone and 1,4-butanediol. Clin Toxicol (Phila) 2012 Jul; 50 (6): 458-70.
[2] Holmes CM, Henderson RS. The elimination of pollution by a non inhalational technique. Anaesth Intensive Care 1978 May; 6 (2): 120-4.
[3] Henderson RS, Holmes CM. Reversal of the anaesthetic action of sodium gamma-hydroxybutyrate. Anaesth Intensive Care 1976 Nov; 4 (4): 351-4.
[4] Yates SW, Viera AJ. Physostigmine in the treatment of gamma-hydroxybutyric acid overdose. Mayo Clin Proc 2000 Apr; 75 (4): 401-2.
[5] Caldicott DG, Kuhn M. Gamma-hydroxybutyrate overdose and physostigmine: teaching new tricks to an old drug? Ann Emerg Med 2001 Jan; 37 (1): 99-102.
[6] Zvosec DL, Smith SW, Litonjua R, Westfal RE. Physostigmine for gamma-hydroxybutyrate coma: inefficacy, adverse events, and review. Clin Toxicol (Phila) 2007; 45 (3): 261-5.
[7] Traub SJ, Nelson LS, Hoffman RS. Physostigmine as a treatment for gamma-hydroxybutyrate toxicity: a review. J Toxicol Clin Toxicol 2002; 40 (6): 781-7.
[8] Ross TM. Gamma hydroxybutyrate overdose: two cases illustrate the unique aspects of this dangerous recreational drug. J Emerg Nurs 1995 Oct; 21 (5): 374-6.
[9] Thomas G, Bonner S, Gascoigne A. Coma induced by abuse of gamma-hydroxybutyrate (GBH or liquid ecstasy): a case report. BMJ 1997 Jan 4; 314 (7073): 35-6.
[10] Li J, Stokes SA, Woeckener A. A tale of novel intoxication: seven cases of gamma-hydroxybutyric acid overdose. Ann Emerg Med 1998 Jun; 31 (6): 723-8.
[11] Libetta C. Gamma hydroxybutyrate poisoning. [Letter] J Accid Emerg Med 1997 Nov; 14 (6): 411.
[12] Williams H, Taylor R, Roberts M. Gamma-hydroxybutyrate (GHB): a new drug of misuse. Ir Med J 1998 Mar-Apr; 91 (2): 56-7.
[13] Palatini P, Tedeschi L, Frison G, Padrini R, Zordan R, Orlando R, Gallimberti L, Gessa GL, Ferrara SD. Dose-dependent absorption and elimination of gamma-hydroxybutyric acid in healthy volunteers. Eur J Clin Pharmacol 1993; 45 (4): 353-6.
[14] Brenneisen R, Elsohly MA, Murphy TP, Passarelli J, Russmann S, Salamone SJ, Watson DE. Pharmacokinetics and excretion of gamma-hydroxybutyrate (GHB) in healthy subjects. J Anal Toxicol 2004 Nov-Dec; 28 (8): 625-30.
[15] Ferrara SD, Tedeschi L, Frison G, Orlando R, Mazzo M, Zordan R, Padrini R, Palatini P. Effect of moderate or severe liver dysfunction on the pharmacokinetics of gamma-hydroxybutyric acid. Eur J Clin Pharmacol 1996; 50 (4): 305-10.
[16] Thai D, Dyer JE, Jacob P, Haller CA. Clinical pharmacology of 1,4-butanediol and gamma-hydroxybutyrate after oral 1,4-butanediol administration to healthy volunteers. Clin Pharmacol Ther 2007 Feb; 81 (2): 178-84.
[17] Multistate outbreak of poisonings associated with illicit use of gamma hydroxy butyrate. MMWR Morb Mortal Wkly Rep 1990 Nov 30; 39 (47): 861-3.
[18] Roberts DM, Smith MW, Gopalakrishnan M, Whittaker G, Day RO. Extreme ?-butyrolactone overdose with severe metabolic acidosis requiring hemodialysis. Ann Emerg Med 2011 Jul; 58 (1): 83-5.
[19] Craig K, Gomez HF, McManus JL, Bania TC. Severe gamma-hydroxybutyrate withdrawal: a case report and literature review. J Emerg Med 2000 Jan; 18 (1): 65-70.
[20] Galloway GP, Frederick SL, Staggers FE Jr, Gonzales M, Stalcup SA, Smith DE. Gamma-hydroxybutyrate: an emerging drug of abuse that causes physical dependence. Addiction 1997 Jan; 92 (1): 89-96.
[21] Dyer JE, Roth B, Hyma BA. Gamma-hydroxybutyrate withdrawal syndrome. Ann Emerg Med 2001 Feb; 37 (2): 147-53.
[22] van Noorden MS, van Dongen LC, Zitman FG, Vergouwen TA. Gamma-hydroxybutyrate withdrawal syndrome: dangerous but not well-known. Gen Hosp Psychiatry 2009 Jul-Aug; 31 (4): 394-6.
[23] Wojtowicz JM, Yarema MC, Wax PM. Withdrawal from gamma-hydroxybutyrate, 1,4-butanediol and gamma-butyrolactone: a case report and systematic review. CJEM 2008 Jan; 10 (1): 69-74.
[24] Galloway GP, Frederick SL, Staggers F Jr. Physical dependence on sodium oxybate. [Letter] Lancet 1994 Jan 1; 343 (8888): 57.
[25] Addolorato G, Caputo F, Capristo E, Bernardi M, Stefanini GF, Gasbarrini G. A case of gamma-hydroxybutyric acid withdrawal syndrome during alcohol addiction treatment: utility of diazepam administration. Clin Neuropharmacol 1999 Jan-Feb; 22 (1): 60-2.
[26] Snead OC 3rd, Gibson KM. Gamma-hydroxybutyric acid. N Engl J Med 2005 Jun 30; 352 (26): 2721-32.
[27] Wood DM, Brailsford AD, Dargan PI. Acute toxicity and withdrawal syndromes related to gamma-hydroxybutyrate (GHB) and its analogues gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD). Drug Test Anal 2011 Jul-Aug; 3 (7-8): 417-25.
[28] McDonough M, Kennedy N, Glasper A, Bearn J. Clinical features and management of gamma-hydroxybutyrate (GHB) withdrawal: a review. Drug Alcohol Depend 2004 Jul 15; 75 (1): 3-9.
[29] Sivilotti ML, Burns MJ, Aaron CK, Greenberg MJ. Pentobarbital for severe gamma-butyrolactone withdrawal. Ann Emerg Med 2001 Dec; 38 (6): 660-5.
[30] Li J, Stokes SA, Woeckener A. A tale of novel intoxication: a review of the effects of gamma-hydroxybutyric acid with recommendations for management. Ann Emerg Med 1998 Jun; 31 (6): 729-36.
[31] Kraner J, Plassard J, McCoy D, Roraback J, Witeck M, Evans M. Fatal overdose from ingestion of 1,4-butanediol, a GHB precursor [abstract]. J Toxicol Clin Toxicol 2000; 38 (5): 534-5.
[32] Gamma hydroxy butyrate use--New York and Texas, 1995-1996. MMWR Morb Mortal Wkly Rep 1997 Apr 4; 46 (13): 281-3.
[33] Zvosec DL, Smith SW, McCutcheon JR, Spillane J, Hall BJ, Peacock EA. Adverse events, including death, associated with the use of 1,4-butanediol. N Engl J Med 2001 Jan 11; 344 (2): 87-94.
[34] Gilmore DA, Freed CR. Central nervous system depression and weakness following ingestion of gamma hydroxybutyrate [abstract]. Vet Hum Toxicol 1991; 33: 366.
[35] Chin RL, Sporer KA, Cullison B, Dyer JE, Wu TD. Clinical course of gamma-hydroxybutyrate overdose. Ann Emerg Med 1998 Jun; 31 (6): 716-22.
[36] Viswanathan S, Chen C, Kolecki P. Revivarant (gamma-butyrolactone) poisoning. [Letter] Am J Emerg Med 2000 May; 18 (3): 358-9.
[37] Dyer JE. gamma-Hydroxybutyrate: a health-food product producing coma and seizurelike activity. Am J Emerg Med 1991 Jul; 9 (4): 321-4.
[38] Rambourg-Schepens MO, Buffet M, Durak C, Mathieu-Nolf M. Gamma butyrolactone poisoning and its similarities to gamma hydroxybutyric acid: two case reports. Vet Hum Toxicol 1997 Aug; 39 (4): 234-5.
[39] Gunja N, Doyle E, Carpenter K, Chan OT, Gilmore S, Browne G, Graudins A. Gamma-hydroxybutyrate poisoning from toy beads. Med J Aust 2008 Jan 7; 188 (1): 54-5.
[40] Knudsen K, Greter J, Verdicchio M. High mortality rates among GHB abusers in Western Sweden. Clin Toxicol (Phila) 2008 Mar; 46 (3): 187-92.
[41] Miró O, Nogué S, Espinosa G, To-Figueras J, Sánchez M. Trends in illicit drug emergencies: the emerging role of gamma-hydroxybutyrate. J Toxicol Clin Toxicol 2002; 40 (2): 129-35.
[42] Liechti ME, Kunz I, Greminger P, Speich R, Kupferschmidt H. Clinical features of gamma-hydroxybutyrate and gamma-butyrolactone toxicity and concomitant drug and alcohol use. Drug Alcohol Depend 2006 Feb 28; 81 (3): 323-6.
[43] Harraway T, Stephenson L. Gamma hydroxybutyrate intoxication: The Gold Coast experience. Emerg Med (Fremantle) 1999; 11 (1): 45-8.
[44] Dietze PM, Cvetkovski S, Barratt MJ, Clemens S. Patterns and incidence of gamma-hydroxybutyrate (GHB)-related ambulance attendances in Melbourne, Victoria. Med J Aust 2008 Jun 16; 188 (12): 709-11.
[45] Couper FJ, Thatcher JE, Logan BK. Suspected GHB overdoses in the emergency department. J Anal Toxicol 2004 Sep; 28 (6): 481-4.
[46] Anderson IB, Kim SY, Dyer JE, Burkhardt CB, Iknoian JC, Walsh MJ, Blanc PD. Trends in gamma-hydroxybutyrate (GHB) and related drug intoxication: 1999 to 2003. Ann Emerg Med 2006 Feb; 47 (2): 177-83.
[47] Bosman IJ, Lusthof KJ. Forensic cases involving the use of GHB in The Netherlands. Forensic Sci Int 2003 Apr 23; 133 (1-2): 17-21.
[48] Stephens BG, Baselt RC. Driving under the influence of GHB? J Anal Toxicol 1994 Oct; 18 (6): 357-8.
[49] Mégarbane B, Fompeydie D, Garnier R, Baud FJ. Treatment of a 1,4-butanediol poisoning with fomepizole. J Toxicol Clin Toxicol 2002; 40 (1): 77-80.
[50] Runnacles JL, Stroobant J. [gamma ]-Hydroxybutyrate poisoning: Poisoning from toy beads. [Letter] BMJ 2008 Jan 19; 336 (7636): 110.
[51] Adverse events associated with ingestion of gamma-butyrolactone--Minnesota, New Mexico, and Texas, 1998-1999. MMWR Morb Mortal Wkly Rep 1999 Feb 26; 48 (7): 137-40.
[52] Ortmann LA, Jaeger MW, James LP, Schexnayder SM. Coma in a 20-month-old child from an ingestion of a toy containing 1,4-butanediol, a precursor of gamma-hydroxybutyrate. Pediatr Emerg Care 2009 Nov; 25 (11): 758-60.
[53] Hefele B, Naumann N, Trollmann R, Dittrich K, Rascher W. Fast-in, fast-out. Lancet 2009 Apr 18; 373 (9672): 1398.
[54] Tancredi DN, Shannon MW. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 30-2003. A 21-year-old man with sudden alteration of mental status. N Engl J Med 2003 Sep 25; 349 (13): 1267-75.
[55] Liechti ME, Kupferschmidt H. Gamma-hydroxybutyrate (GHB) and gamma-butyrolactone (GBL): analysis of overdose cases reported to the Swiss Toxicological Information Centre. Swiss Med Wkly 2004 Sep 4; 134 (35-36): 534-7.
[56] Al-Samarraie MS, Karinen R, Mørland J, Stokke Opdal M. Blood GHB concentrations and results of medical examinations in 25 car drivers in Norway. Eur J Clin Pharmacol 2010 Oct; 66 (10): 987-98.
[57] Ingels M, Rangan C, Bellezzo J, Clark RF. Coma and respiratory depression following the ingestion of GHB and its precursors: three cases. J Emerg Med 2000 Jul; 19 (1): 47-50.
[58] Zvosec DL, Smith SW. Agitation is common in gamma-hydroxybutyrate toxicity. Am J Emerg Med 2005 May; 23 (3): 316-20.
[59] Louagie HK, Verstraete AG, De Soete CJ, Baetens DG, Calle PA. A sudden awakening from a near coma after combined intake of gamma-hydroxybutyric acid (GHB) and ethanol. J Toxicol Clin Toxicol 1997; 35 (6): 591-4.
[60] Galicia M, Nogue S, Miró O. Liquid ecstasy intoxication: clinical features of 505 consecutive emergency department patients. Emerg Med J 2011 Jun; 28 (6): 462-6.
[61] Krul J, Girbes AR. Gamma-hydroxybutyrate: experience of 9 years of gamma-hydroxybutyrate (GHB)-related incidents during rave parties in The Netherlands. Clin Toxicol (Phila) 2011 Apr; 49 (4): 311-5.
[62] Couper FJ, Logan BK. Determination of gamma-hydroxybutyrate (GHB) in biological specimens by gas chromatography--mass spectrometry. J Anal Toxicol 2000 Jan-Feb; 24 (1): 1-7.
[63] Chin MY, Kreutzer RA, Dyer JE. Acute poisoning from gamma-hydroxybutyrate in California. West J Med 1992 Apr; 156 (4): 380-4.
[64] Luby S, Jones J, Zalewski A. GHB use in South Carolina. [Letter] Am J Public Health 1992 Jan; 82 (1): 128.
[65] Price PA, Schachter M, Smith SJ, Baxter RC, Parkes JD. gamma-Hydroxybutyrate in narcolepsy. [Letter] Ann Neurol 1981 Feb; 9 (2): 198.
[66] Ryan JM, Stell I. Gamma hydroxybutyrate--a coma inducing recreational drug. J Accid Emerg Med 1997 Jul; 14 (4): 259-61.
[67] Ragg M. Gamma hydroxy butyrate overdose. Emerg Med (Fremantle). 1997; 9 (1): 29-31.
[68] Lenz D, Rothschild MA, Kröner L. Intoxications due to ingestion of gamma-butyrolactone: organ distribution of gamma-hydroxybutyric acid and gamma-butyrolactone. Ther Drug Monit 2008 Dec; 30 (6): 755-61.
[69] Suner S, Szlatenyi CS, Wang RY. Pediatric gamma hydroxybutyrate intoxication. Acad Emerg Med 1997 Nov; 4 (11): 1041-5.
[70] Eckstein M, Henderson SO, DelaCruz P, Newton E. Gamma hydroxybutyrate (GHB): report of a mass intoxication and review of the literature. Prehosp Emerg Care 1999 Oct-Dec; 3 (4): 357-61.
[71] Van Sassenbroeck DK, De Neve N, De Paepe P, Belpaire FM, Verstraete AG, Calle PA, Buylaert WA. Abrupt awakening phenomenon associated with gamma-hydroxybutyrate use: a case series. Clin Toxicol (Phila) 2007 Jun-Aug; 45 (5): 533-8.
[72] Munir VL, Hutton JE, Harney JP, Buykx P, Weiland TJ, Dent AW. Gamma-hydroxybutyrate: a 30 month emergency department review. Emerg Med Australas 2008 Dec; 20 (6): 521-30.
[73] Wood DM, Warren-Gash C, Ashraf T, Greene SL, Shather Z, Trivedy C, Clarke S, Ramsey J, Holt DW, Dargan PI. Medical and legal confusion surrounding gamma-hydroxybutyrate (GHB) and its precursors gamma-butyrolactone (GBL) and 1,4-butanediol (1,4BD). QJM 2008 Jan; 101 (1): 23-9.
[74] Yambo CM, McFee RB, Caraccio TR, McGuigan M. The inkjet cleaner "Hurricane"--another GhB recipe. Vet Hum Toxicol 2004 Dec; 46 (6): 329-30.
[75] Cisek J. Seziure associated with butanediol ingestion. Int J Med Toxicol 2001; 4 (1): 12.
[76] Theron L, Jansen K, Skinner A. New Zealand's first fatality linked to use of 1,4-butanediol (1,4-B, Fantasy): no evidence of coingestion or comorbidity. N Z Med J 2003 Oct 24; 116 (1184): U650.
[77] Osterhoudt KC, Henretig FM. Comatose teenagers at a party: what a tangled 'Web' we weave. Pediatr Case Rev 2003 Jul; 3 (3): 171-3.
[78] Higgins TF Jr, Borron SW. Coma and respiratory arrest after exposure to butyrolactone. J Emerg Med 1996 Jul-Aug; 14 (4): 435-7.
[79] Elliott SP. Nonfatal instances of intoxication with gamma-hydroxybutyrate in the United Kingdom. Ther Drug Monit 2004 Aug; 26 (4): 432-40.
[80] Lora-Tamayo C, Tena T, Rodríguez A, Sancho JR, Molina E. Intoxication due to 1,4-butanediol. Forensic Sci Int 2003 May 5; 133 (3): 256-9.
[81] Savage T, Khan A, Loftus BG. Acetone-free nail polish remover pads: toxicity in a 9-month old. [Letter] Arch Dis Child 2007 Apr; 92 (4): 371.
[82] Tunstall ME. Gamma-OH in anesthesia for caesarean section. Proc R Soc Med 1968 Aug; 61 (8): 827-30.
[83] Hunter AS, Long WJ, Ryrie CG. An evaluation of gamma-hydroxybutyric acid in paediatric practice. Br J Anaesth 1971 Jun; 43 (6): 620-8.
[84] Piastra M, Tempera A, Caresta E, Chiaretti A, Genovese O, Zorzi G, Pulitanò S, Pietrini D, Polidori G. Lung injury from "liquid ecstasy": a role for coagulation activation? Pediatr Emerg Care 2006 May; 22 (5): 358-60.
[85] Winickoff JP, Houck CS, Rothman EL, Bauchner H. Verve and Jolt: deadly new Internet drugs. Pediatrics 2000 Oct; 106 (4): 829-30.
[86] Blumenfeld M, Harmel MH, Suntay RG. Sodium gamma-hydroxybutyric acid: A new anesthetic adjuvant. Anesth Analg 1962; 41 (6): 721-6.
[87] Jones C. Suspicious death related to gamma-hydroxybutyrate (GHB) toxicity. J Clin Forensic Med 2001 Jun; 8 (2): 74-6.
[88] Piastra M, Barbaro R, Chiaretti A, Tempera A, Pulitanò S, Polidori G. Pulmonary oedema caused by "liquid ecstasy" ingestion. Arch Dis Child 2002 Apr; 86 (4): 302-3.
[89] Shannon M, Quang LS. Gamma-hydroxybutyrate, gamma-butyrolactone, and 1,4-butanediol: a case report and review of the literature. Pediatr Emerg Care 2000 Dec; 16 (6): 435-40.
[90] Brown TC. Gammahydroxybutyrate in paediatric anaesthesia. Aust N Z J Surg 1970 Aug; 40 (1): 94-9.
[91] Robert R, Eugène M, Frat JP, Rouffineau J. Diagnosis of unsuspected gamma hydroxy-butyrate poisoning by proton NMR. [Letter] J Toxicol Clin Toxicol 2001; 39 (6): 653-4.
[92] Vickers MD. Gammahydroxybutyric acid. Int Anesthesiol Clin 1969 Spring; 7 (1): 75-89.
[93] Price G. In-patient detoxification after GHB dependence. [Letter] Br J Psychiatry 2000 Aug; 177 (): 181.
[94] Mycyk MB, Wilemon C, Aks SE. Two cases of withdrawal from 1,4-Butanediol use. [Letter] Ann Emerg Med 2001 Sep; 38 (3): 345-6.
[95] Chin RL. A case of severe withdrawal from gamma-hydroxybutyrate. [Letter] Ann Emerg Med 2001 May; 37 (5): 551-2.
[96] Miglani JS, Kim KY, Chahil R. Gamma-hydroxy butyrate withdrawal delirium: a case report. [Letter] Gen Hosp Psychiatry 2000 May-Jun; 22 (3): 213-5.
[97] Hutto B, Fairchild A, Bright R. gamma-Hydroxybutyrate withdrawal and chloral hydrate. [Letter] Am J Psychiatry 2000 Oct; 157 (10): 1706.
[98] Gonzalez A, Nutt DJ. Gamma hydroxy butyrate abuse and dependency. J Psychopharmacol 2005 Mar; 19 (2): 195-204.
[99] Hernandez M, McDaniel CH, Costanza CD, Hernandez OJ. GHB-induced delirium: a case report and review of the literature of gamma hydroxybutyric acid. Am J Drug Alcohol Abuse 1998 Feb; 24 (1): 179-83.
[100] Bowles TM, Sommi RW, Amiri M. Successful management of prolonged gamma-hydroxybutyrate and alcohol withdrawal. Pharmacotherapy 2001 Feb; 21 (2): 254-7.
[101] Catalano MC, Glass JM, Catalano G, Burrows SL, Lynn WA, Weitzner BS. Gamma butyrolactone (GBL) withdrawal syndromes. Psychosomatics 2001 Jan-Feb; 42 (1): 83-8.
[102] Mahr G, Bishop CL, Orringer DJ. Prolonged withdrawal from extreme gamma-hydroxybutyrate (GHB) abuse. [Letter] Psychosomatics 2001 Sep-Oct; 42 (5): 439-40.
[103] McDaniel CH, Miotto KA. Gamma hydroxybutyrate (GHB) and gamma butyrolactone (GBL) withdrawal: five case studies. J Psychoactive Drugs 2001 Apr-Jun; 33 (2): 143-9.
[104] Schneir AB, Ly BT, Clark RF. A case of withdrawal from the GHB precursors gamma-butyrolactone and 1,4-butanediol. J Emerg Med 2001 Jul; 21 (1): 31-3.
[105] Perez E, Chu J, Bania T. Seven days of gamma-hydroxybutyrate (GHB) use produces severe withdrawal. [Letter] Ann Emerg Med 2006 Aug; 48 (2): 219-20.
[106] Zepf FD, Holtmann M, Duketis E, Maier J, Radeloff D, Wagner A, Poustka F, Wöckel L. A 16-year-old boy with severe gamma-butyrolactone (GBL) withdrawal delirium. [Letter] Pharmacopsychiatry 2009 Sep; 42 (5): 202-3.
[107] Bennett WR, Wilson LG, Roy-Byrne PP. Gamma-hydroxybutyric acid (GHB) withdrawal: a case report. J Psychoactive Drugs 2007 Sep; 39 (3): 293-6.
[108] Rosenberg MH, Deerfield LJ, Baruch EM. Two cases of severe gamma-hydroxybutyrate withdrawal delirium on a psychiatric unit: recommendations for management. Am J Drug Alcohol Abuse 2003 May; 29 (2): 487-96.
[109] Friedman J, Westlake R, Furman M. "Grievous bodily harm:" gamma hydroxybutyrate abuse leading to a Wernicke-Korsakoff syndrome. Neurology 1996 Feb; 46 (2): 469-71.
[110] Bell J, Collins R. Gamma-butyrolactone (GBL) dependence and withdrawal. Addiction 2011 Feb; 106 (2): 442-7.
[111] Miotto K, Darakjian J, Basch J, Murray S, Zogg J, Rawson R. Gamma-hydroxybutyric acid: patterns of use, effects and withdrawal. Am J Addict 2001 Summer; 10 (3): 232-41.
[112] Chew G, Fernando A 3rd. Epileptic seizure in GHB withdrawal. [Letter] Australas Psychiatry 2004 Dec; 12 (4): 410-1.
[113] Herold AH, Sneed KB. Treatment of a young adult taking gamma-butyrolactone (GBL) in a primary care clinic. J Am Board Fam Pract 2002 Mar-Apr; 15 (2): 161-3.
[114] LeTourneau JL, Hagg DS, Smith SM. Baclofen and gamma-hydroxybutyrate withdrawal. Neurocrit Care 2008; 8 (3): 430-3.
[115] Mullins ME, Fitzmaurice SC. Lack of efficacy of benzodiazepines in treating gamma-hydroxybutyrate withdrawal. [Letter] J Emerg Med 2001 May; 20 (4): 418-20.
[116] McCabe ER, Layne EC, Sayler DF, Slusher N, Bessman SP. ynergy of ethanol and a natural soporific--gamma hydroxybutyrate. Science 1971 Jan 29; 171 (3969): 404-6.
[117] Knudsen K, Jonsson U, Abrahamsson J. Twenty-three deaths with gamma-hydroxybutyrate overdose in western Sweden between 2000 and 2007. Acta Anaesthesiol Scand 2010 Sep; 54 (8): 987-92.
[118] Lewis RJ, editor. Sax’s dangerous properties of industrial materials. 9th ed. New York: Van Nostrand Reinhold; 1996. p. 1859.
[119] Tunstall ME. Placental transfer of 4-hydroxybutyrate. Anaesthesia 1968 Oct; 23 (4): 704-5.
[120] Xyrem Prescribing Information. United States of America: Jazz Pharmaceuticals, Inc.; 2015. [cited 2016 July 10]. URL:https://www.jazzpharma.com/
[121] Cavender FL, Sowinski EJ. Glycols. In: Clayton GD, Clayton FE, editors. Patty’s Industrial hygiene and toxicology, Volume II, Patr F. 4th Ed. New York: John Wiley & Sons, Inc.; 1994. p4645-719.
[122] Busardò FP, Bertol E, Mannocchi G, Tittarelli R, Pantano F, Vaiano F, Baglio G, Kyriakou C, Marinelli E. Determination of GHB levels in breast milk and correlation with blood concentrations. Forensic Sci Int 2016 Aug; 265 (): 172-181.
[123] Doherty JD, Stout RW, Roth RH. Metabolism of (1-14C)gamma-hydroxybutyric acid by rat brain after intraventricular injection. Biochem Pharmacol 1975 Feb 15; 24 (4): 469-74.
[124] Tunnicliff G. Sites of action of gamma-hydroxybutyrate (GHB)--a neuroactive drug with abuse potential. J Toxicol Clin Toxicol 1997; 35 (6): 581-90.
[125] Borgen LA, Okerholm R, Morrison D, Lai A. The influence of gender and food on the pharmacokinetics of sodium oxybate oral solution in healthy subjects. J Clin Pharmacol 2003 Jan; 43 (1): 59-65.
[126] Vree TB, Damsma J, van den Bogert AG, van den Kleijn E. Pharmocokinetics of 4-hydroxybutyric acid in man, rhesus monkey and dog . In: Frey R, ed. Neue Untersuchungen mit Gamma- Hydroxybuttersä ure. Berlin: Springer-Verlag; 1978: 21–39.
[127] Lettieri J, Fung HL. Absorption and first-pass metabolism of 14C-gamma-hydroxybutyric acid. Res Commun Chem Pathol Pharmacol 1976 Mar; 13 (3): 425-37.
[129] Metcalf DR, Emde RN, Stripe JT. An EEG-behavioral study of sodium hydroxybutyrate in humans. Electroencephalogr Clin Neurophysiol 1966 May; 20 (5): 506-12.
[130] Abanades S, Farré M, Segura M, Pichini S, Barral D, Pacifici R, Pellegrini M, Fonseca F, Langohr K, De La Torre R. Gamma-hydroxybutyrate (GHB) in humans: pharmacodynamics and pharmacokinetics. Ann N Y Acad Sci 2006 Aug; 1074 (): 559-76.
[131] Scharf MB, Lai AA, Branigan B, Stover R, Berkowitz DB. Pharmacokinetics of gammahydroxybutyrate (GHB) in narcoleptic patients. Sleep 1998 Aug 1; 21 (5): 507-14.
[132] Borgen LA, Okerholm RA, Lai A, Scharf MB. The pharmacokinetics of sodium oxybate oral solution following acute and chronic administration to narcoleptic patients. J Clin Pharmacol 2004 Mar; 44 (3): 253-7.
[133] Ferrara SD, Zotti S, Tedeschi L, Frison G, Castagna F, Gallimberti L, Gessa GL, Palatini P. Pharmacokinetics of gamma-hydroxybutyric acid in alcohol dependent patients after single and repeated oral doses. Br J Clin Pharmacol 1992 Sep; 34 (3): 231-5.
[134] Hoes MJ, Vree TB, Guelen PJ. Gamma-hydroxybutyric acid as hypnotic. Clinical and pharmacokinetic evaluation of gamma-hydroxybutyric acid as hypnotic in man. Encephale 1980; 6 (1): 93-9.
[135] Lettieri JT, Fung HL. Dose-dependent pharmacokinetics and hypnotic effects of sodium gamma-hydroxybutyrate in the rat. J Pharmacol Exp Ther 1979 Jan; 208 (1): 7-11.
[136] Snead OC 3rd. The gamma-hydroxybutyrate model of absence seizures: correlation of regional brain levels of gamma-hydroxybutyric acid and gamma-butyrolactone with spike wave discharges. Neuropharmacology 1991 Feb; 30 (2): 161-7.
[137] Snead OC 3rd, Yu RK, Huttenlocher PR. Gamma hydroxybutyrate. Correlation of serum and cerebrospinal fluid levels with electroencephalographic and behavioral effects. Neurology 1976 Jan; 26 (1): 51-6.
[138] Snead OC 3rd. Gamma hydroxybutyrate in the monkey. I. Electroencephalographic, behavioral, and pharmacokinetic studies. Neurology 1978 Jul; 28 (7): 636-42.
[139] O'Neill M, editor. The Merck index. 14th ed. Whitehouse Station (NJ): Merck & Co; 2006. p. 834.

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