3. Gamma-hydroxybutyrate and Gamma-butyrolactone Abuse

Gamma-hydroxybutyrate and Gamma-butyrolactone Abuse

This PatientPlus article is written for healthcare professionals so the language may be more technical than the condition leaflets. You may find the abbreviations list helpful.

Synonyms: street names - 'liquid ecstasy', 'scoop', 'easy lay', 'fantasy', 'Georgia home boy', 'G', 'grievous bodily harm', 'GBH', 'liquid X', 'goop'

Gamma-hydroxybutyrate (GHB) is a naturally occurring fatty acid found throughout the human body. It has a structure similar to the neurotransmitter gamma-aminobutyric acid (GABA). It readily crosses the blood-brain barrier with rapid onset of anxiolytic, sedative and euphoric effects. It appears to act on both GABAA and GABAB receptors with actions similar to benzodiazepines, baclofen and alcohol.[1]

Its notoriety stems from its relatively recent use as a recreational drug and as a so-called 'date-rape' drug (used in drug-facilitated sexual assault (DFSA)). It is usually ingested as an odourless, clear liquid or in powdered form. It tastes mildly salty but this is easily masked by flavoured drinks.

It was first manufactured in the 1960s and used medically as an anaesthetic agent. It now has very limited medical indications, usually in a research context, to treat alcohol or opioid withdrawal[2][3] and sleep disorders, in particular, narcolepsy. In the 1980s, it grew popular amongst bodybuilders who believed it promoted fat loss and muscle building. During this period it could be bought as an over-the-counter (OTC) food supplement in America. In 1990 the Food and Drug Administration banned its OTC sales as mounting evidence of its misuse grew.

GHB has been classified as a Class C drug under the Misuse of Drugs Act (1971) in the UK since 2003. However, its precursors, gamma-butyrolactone (GBL) and 1,4-butanediol (1,4BD), which are metabolised to GHB in vivo and pose similar risks, were freely available via the internet and other sources as 'legal highs' until very recently.[4] GBL and 1,4BD (when intended for human consumption) were added to the list of Class C drugs in December 2009. GBL is a solvent found in substances such as cleaning products, nail polish, and superglue removers. There have been cases of children in Australia developing GHB poisoning following ingestion of toy beads containing 1,4BD.[5]

Across America, Europe and Australia, reports of the misuse of gamma-hydroxybutyrate (GHB) have grown over the last two decades. There has been little systematic UK-based research into the use of GHB but the prevalence of self-reported use by 'clubbers' is increasing[6] and users account for a significant proportion of those requiring medical assistance for drug toxicity in a club environment.[7] It is not a drug associated with naive drug users; mean age of first use was 22 years[8] and it is often used as an adjunct drug in polydrug users with or following ecstasy, cocaine, lysergic acid diethylamide (LSD), cannabis and alcohol. Its sedative effects mean that it is used as a 'comedown' drug following the use of stimulants.

GHB's use as a 'date rape' drug appears still to be relatively rare in the UK. In a London-based study, only 2% of those concerned that they had consumed a deliberately spiked drink had been unknowingly exposed to sedative drugs, of which only 1 out of 8 cases involved GHB.[9]

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The subjective effects of gamma-hydroxybutyrate (GHB) are reported as:

  • Euphoria
  • Feelings of relaxation
  • Increased sociability
  • Loss of inhibition
  • Sense of wellbeing
  • Heightened sexual interest
  • Restful sleep

GHB has a steep dose-response curve, making a very small increment in dose likely to result in toxicity. This combined with its unpredictable potency put users at risk of side-effects and overdose. There are also wide individual differences in response to the drug so some may experience adverse side-effects even at low dose.

Central nervous system (CNS) depression is the hallmark of GHB ingestion. Deaths have occurred where individuals have been 'left to sleep it off'. Individuals tend to come to medical attention as a result of adverse effects or overdose. Diagnosis is usually based on history (typically third party or collateral information from paramedics, etc.) and on clinical examination. Symptoms include:

  • Dizziness
  • Blurred vision
  • Hot/cold flushes
  • Memory lapses

Signs include:

  • Excess sweating.
  • Miosis.
  • Bradycardia and hypotension.
  • Respiratory depression, apnoea and Cheyne-Stokes breathing.
  • Confusion.
  • Agitation.
  • Vomiting.
  • Decreased levels of consciousness and coma.
  • Tremors.
  • Myoclonic jerks.
  • Seizures.

The differential is wide and includes:

Remember that gamma-hydroxybutyrate (GHB) is frequently used in combination with other recreational drugs, so a mixed picture is likely. Serious complications, eg respiratory arrest or coma, are more likely where GHB has been taken with other sedatives or alcohol.

Initial assessment

The initial assessment of a patient with altered mental status and suspected club-drug ingestion includes:[11]

  • Check vital signs regularly.
  • Ensure a good airway and check arterial blood gases.
  • Obtain vascular access and send blood samples (FBC, C&Es, LFTs, creatine kinase, osmolality, myoglobin, lactic acid) urgently. Check BM.
  • Send blood and urine specimens for drug toxicology. Extra specimens should be obtained and stored as not all drugs are detected by routine screens and may be needed to be sent away to reference laboratories. Assays for gamma-hydroxybutyrate (GHB) fall into this category: confirmation by this route is very delayed and usually only important in forensic cases. There is a very limited window (approximately 12 hours) for detection of GHB in biological specimens, although efforts are being made to extend this.[12]
  • Urine should also be tested for urinary sodium, osmolality and creatine kinase. Pregnancy testing may also be appropriate.
  • Do an ECG and CXR to exclude aspiration.
  • Assess for potential infection (blood and urine cultures; consider a lumbar puncture).
  • Give glucose, thiamine and naloxone.
  • Check head CT or MRI scan for space-occupying lesion or raised intracranial pressure.
  • Use activated charcoal if there has been recent drug ingestion.
  • Consider the possibility of physical dependence and withdrawal.

Further management

  • With GHB overdose, management is primarily supportive as there are no antidotes currently available. Physostigmine has been used but there is no good quality supportive evidence for this practice.[13] Gastric lavage is rarely useful due to rapid absorption of GHB.
  • The course of uncomplicated GHB ingestion may be short-lived with rapid recovery from sedation but, where airway and/or respiratory drive are compromised, intubation and intensive care are required. Ingestion of precursor forms (particularly 1,4BD) may have a more prolonged clinical course. The recovery to a normal level of consciousness may be very abrupt, leading to patients self-extubating in an agitated and uncontrolled manner so post-intubation sedation with a short-acting benzodiazepine may be useful.
  • Always check the oropharynx for burns.
  • Whilst fatalities occur with isolated GHB use, co-ingestion of other drugs (eg ketamine or ethanol) creates a more complex clinical picture and greater risk.[14]
  • Where patients are unaware of their ingestion of GHB and a possibility of drug-facilitated sexual assault (DFSA) exists, requirements include:
    • Full forensic and medical examination.
    • STI screen and prophylaxis.
    • Pregnancy counselling +/-emergency contraception.
    • Psychological and support counselling.
  • Increased sexual risk-taking.
  • Interactions with other drugs (recreational and prescribed, eg protease inhibitors).
  • Alkaline burns due to contamination during manufacture.
  • Gastric aspiration.
  • Coma, respiratory depression and death.
  • With isolated use of gamma-hydroxybutyrate (GHB), prognosis is normally good. Spontaneous recovery of consciousness is usual, within 2-6 hours.[15]
  • With repeated use, evidence exists for the development of tolerance and physical dependence. Symptoms of withdrawal are similar to alcohol withdrawal and include insomnia, anxiety, tremor, confusion, hallucinations and tachycardia and develop within 1-6 hours of the last dose. Delirium is common amongst the most dependent users and can be life-threatening. High-dose benzodiazepines are used for pharmacological detoxification but some cases are refractory.[16]
  • Long-term emotional, neuropsychological and behavioural consequences are unknown.

Beyond legal and law enforcement issues, much can be done to counsel and educate at an individual level including:

  • Clarifying the legal status of gamma-hydroxybutyrate (GHB), gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD).
  • Emphasising the risk of overdose (influenced by interactions with other drugs and alcohol, the steep dose-response curve, large individual differences and unknown potency of street drugs).
  • Pointing out the risk of dependence and withdrawal syndromes.
  • Discussing the lack of evidence supporting its use as an anabolic supplement in bodybuilding.
  • Teaching first aid and the importance of not assuming someone is 'sleeping it off' when instead they are deeply unconscious.
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Further reading & references

  1. Rodgers J, Ashton CH, Gilvarry E, et al; Liquid ecstasy: a new kid on the dance floor. Br J Psychiatry. 2004 Feb;184:104-6.
  2. Leone MA, Vigna-Taglianti F, Avanzi G, et al; Gamma-hydroxybutyrate (GHB) for treatment of alcohol withdrawal and prevention of Cochrane Database Syst Rev. 2010 Feb 17;2:CD006266.
  3. Gallimberti L, Spella MR, Soncini CA, et al; Gamma-hydroxybutyric acid in the treatment of alcohol and heroin dependence. Alcohol. 2000 Apr;20(3):257-62.
  4. Wood DM, Warren-Gash C, Ashraf T, et al; 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.
  5. Gunja N, Doyle E, Carpenter K, et al; gamma-Hydroxybutyrate poisoning from toy beads. Med J Aust. 2008 Jan 7;188(1):54-55. Epub 2007 Nov 19.
  6. McCambridge J, Winstock A, Hunt N, et al; 5-Year trends in use of hallucinogens and other adjunct drugs among UK dance drug users. Eur Addict Res. 2007;13(1):57-64.
  7. Wood DM, Nicolaou M, Dargan PI; Epidemiology of recreational drug toxicity in a nightclub environment. Subst Use Misuse. 2009;44(11):1495-502.
  8. Winstock AR, Griffiths P, Stewart D; Drugs and the dance music scene: a survey of current drug use patterns among a sample of dance music enthusiasts in the UK. Drug Alcohol Depend. 2001 Sep 1;64(1):9-17.
  9. Hughes H, Peters R, Davies G, et al; A study of patients presenting to an emergency department having had a "spiked drink". Emerg Med J. 2007 Feb;24(2):89-91.
  10. Benzer TI; Gamma-Hydroxybutyrate Toxicity, eMedicine, Feb 2009
  11. Ricaurte GA, McCann UD; Recognition and management of complications of new recreational drug use. Lancet. 2005 Jun 18-24;365(9477):2137-45.
  12. Larson SJ, Putnam EA, Schwanke CM, et al; Potential surrogate markers for gamma-hydroxybutyrate administration may extend the detection window from 12 to 48 hours. J Anal Toxicol. 2007 Jan-Feb;31(1):15-22.
  13. Allen L, Alsalim W; Best evidence topic report. Gammahydroxybutyrate overdose and physostigmine. Emerg Med J. 2006 Apr;23(4):300-1.
  14. Kim SY, Anderson IB, Dyer JE, et al; High-risk behaviors and hospitalizations among gamma hydroxybutyrate (GHB) users. Am J Drug Alcohol Abuse. 2007;33(3):429-38.
  15. O'Connell T, Kaye L, Plosay JJ 3rd; O'Connell T, Kaye L, Plosay JJ 3rd; Gamma-hydroxybutyrate (GHB): a newer drug of abuse. Am Fam Physician. 2000 Dec 1;62(11):2478-83.
  16. McDonough M, Kennedy N, Glasper A, et al; Clinical features and management of gamma-hydroxybutyrate (GHB) withdrawal: a review. Drug Alcohol Depend. 2004 Jul 15;75(1):3-9.
Original Author: Dr Chloe Borton Current Version:
Last Checked: 20/04/2011 Document ID: 8635  Version: 4 © EMIS

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