Gamma-hydroxybutyrate and Gamma-butyrolactone Abuse
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Synonyms: street names - 'liquid ecstasy', 'scoop', 'easy lay', 'fantasy', 'Georgia home boy', 'G', 'grievous bodily harm', 'GBH', 'Great hormones at bedtime', 'poor man's heroin', '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. Its neurodepressant effect may be mediated by a specific GHB receptor, binding to GABA receptors, modulation of GABA levels, or interactions with other neurotransmitters.Its effects are similar to benzodiazepines, baclofen and alcohol.
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)).GHB is most commonly available in liquid form and is taken orally. It is also available in powder, putty, capsule and gel forms. Depending on the type of salt used, the liquid may be tasteless or slightly salty (the saltiness can be easily masked with fruit juice).
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 and sleep disorders - in particular, narcolepsy.[1, 3]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' but were also made Class C drugs in 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.
Across America, Europe and Australia, reports of the misuse of GHB have grown over the last two decades. There has been little systematic UK-based research into the use of GHB but a study in one emergency department showed a significant increase in GHB-associated presentations from 158 in 2006 to 270 in 2010.The prevalence of self-reported use by 'clubbers' is increasing and users account for a significant proportion of those requiring medical assistance for drug toxicity in a club environment. It is not a drug associated with naive drug users; mean age of first use was reported in one study as 26.8 years.
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.
The subjective effects of GHB are reported as:
- Feelings of relaxation
- Increased sociability
- Loss of inhibition
- Sense of well-being
- 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 puts 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:
- Blurred vision
- Hot/cold flushes
- Memory lapses
- Excess sweating.
- Bradycardia and hypotension.
- Respiratory depression, apnoea and Cheyne-Stokes breathing.
- Decreased levels of consciousness, and coma.
- Myoclonic jerks.
The differential is wide and includes:
- Alcohol poisoning.
- Overdose of another substance (eg, antidepressants, barbiturates, benzodiazepines, narcotics, neuroleptics).
- Subdural haematoma.
- Subarachnoid haemorrhage.
- Delirium tremors.
Remember that 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.
The initial assessment of a patient with altered mental status and suspected club-drug ingestion includes:[15, 16, 17]
- Check vital signs regularly.
- Ensure a good airway and check arterial blood gases.
- Obtain vascular access and send blood samples (FBC, U&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 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.
- A method to detect GHB in human hair has been developed.
- 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).
- The indiscriminate administration of the traditional coma 'cocktail' (dextrose, thiamine and naloxone) has been questioned. Some authorities recommend this only in cases of proven hypoglycaemia, thiamine deficiency and opiate co-ingestion respectively.
- 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.
- With GHB overdose, management is primarily supportive as there are no antidotes currently available. Physostigmine was once used but is now thought to be ineffective and possibly unsafe.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.
- Where patients are unaware of their ingestion of GHB and a possibility of 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 GHB, prognosis is normally good. Spontaneous recovery of consciousness is usual, within 2-6 hours.
- 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.
- Long-term use of GBH may have neurotoxic effects similar to ketamine, especially in young people. Further research is required to assess its effects on memory and cognitive function.
Beyond legal and law enforcement issues, much can be done to counsel and educate at an individual level, including:
- Clarifying the legal status of GHB, GBL and 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.
Further reading and references
Gamma Hydroxy Butyrate (GHB) Addiction Factsheet; Project GHB
Drugs A-Z; Frank
Ramchand R, Fisher MP, Griffin BA, et al; Drug use among gay and bisexual men at weekend dance parties: the role of intentions and perceptions of peers' behaviors. AIDS Behav. 2013 May17(4):1540-9. doi: 10.1007/s10461-012-0382-z.
Kapoor P, Deshmukh R, Kukreja I; GHB acid: A rage or reprive. J Adv Pharm Technol Res. 2013 Oct4(4):173-8. doi: 10.4103/2231-4040.121410.
Bertol E, Mari F, Vaiano F, et al; Determination of GHB in human hair by HPLC-MS/MS: Development and validation of a method and application to a study group and three possible single exposure cases. Drug Test Anal. 2014 Jun 19. doi: 10.1002/dta.1679.
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 172:CD006266.
Gunja N, Doyle E, Carpenter K, et al; gamma-Hydroxybutyrate poisoning from toy beads. Med J Aust. 2008 Jan 7188(1):54-55. Epub 2007 Nov 19.
Wood DM, Greene SL, Dargan PI; Five-year trends in self-reported recreational drugs associated with presentation to a UK emergency department with suspected drug-related toxicity. Eur J Emerg Med. 2013 Aug20(4):263-7. doi: 10.1097/MEJ.0b013e3283573115.
Wood DM, Nicolaou M, Dargan PI; Epidemiology of recreational drug toxicity in a nightclub environment. Subst Use Misuse. 200944(11):1495-502.
Barker JC, Harris SL, Dyer JE; Experiences of gamma hydroxybutyrate (GHB) ingestion: a focus group study. J Psychoactive Drugs. 2007 Jun39(2):115-29.
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 Feb24(2):89-91.
Estellon V, Mouras H; Sexual addiction: insights from psychoanalysis and functional neuroimaging. Socioaffect Neurosci Psychol. 2012 Jan 202:11814. doi: 10.3402/snp.v2i0.11814. eCollection 2012.
Nasrallah FA, Maher AD, Hanrahan JR, et al; gamma-Hydroxybutyrate and the GABAergic footprint: a metabolomic approach to unpicking the actions of GHB. J Neurochem. 2010 Oct115(1):58-67. doi: 10.1111/j.1471-4159.2010.06901.x.
Carter LP, Pardi D, Gorsline J, et al; Illicit gamma-hydroxybutyrate (GHB) and pharmaceutical sodium oxybate (Xyrem): differences in characteristics and misuse. Drug Alcohol Depend. 2009 Sep 1104(1-2):1-10. doi: 10.1016/j.drugalcdep.2009.04.012. Epub 2009 Jun 2.
Knudsen K; GHB and its analogues, Clinical Toxicology (2011) 49, 197–269.
CNS Depressants; EB Medicine, 2014
O'Connell T, Kaye L, Plosay JJ 3rd; Gamma-hydroxybutyrate (GHB): a newer drug of abuse. Am Fam Physician. 2000 Dec 162(11):2478-83.
Chakraborty K, Neogi R, Basu D; Club drugs: review of the 'rave' with a note of concern for the Indian scenario. Indian J Med Res. 2011 Jun133:594-604.
Linares LA, Golomb BA, Jaojoco JA, et al; The modern spectrum of rhabdomyolysis: drug toxicity revealed by creatine kinase screening. Curr Drug Saf. 2009 Sep4(3):181-7. Epub 2009 Sep 1.
Bledsoe BE; No more coma cocktails. Using science to dispel myths & improve patient care. JEMS. 2002 Nov27(11):54-60.
Stomberg MW, Knudsen K, Stomberg H, et al; Symptoms and signs in interpreting gamma-hydroxybutyrate (GHB) intoxication - an explorative study. Scand J Trauma Resusc Emerg Med. 2014 Apr 2322:27. doi: 10.1186/1757-7241-22-27.
Zvosec DL, Smith SW, Litonjua R, et al; Physostigmine for gamma-hydroxybutyrate coma: inefficacy, adverse events, and review. Clin Toxicol (Phila). 200745(3):261-5.
Kim SY, Anderson IB, Dyer JE, et al; High-risk behaviors and hospitalizations among gamma hydroxybutyrate (GHB) users. Am J Drug Alcohol Abuse. 200733(3):429-38.
Butler B, Welch J; Drug-facilitated sexual assault. CMAJ. 2009 Mar 3180(5):493-4. doi: 10.1503/cmaj.090006.
Kaminer Y et al; Clinical Manual of Adolescent Substance Abuse Treatment, 2010.
Wojtowicz JM, Yarema MC, Wax PM; Withdrawal from gamma-hydroxybutyrate, 1,4-butanediol and gamma-butyrolactone: a case report and systematic review. CJEM. 2008 Jan10(1):69-74.
van Amsterdam JG, Brunt TM, McMaster MT, et al; Possible long-term effects of gamma-hydroxybutyric acid (GHB) due to neurotoxicity and overdose. Neurosci Biobehav Rev. 2012 Apr36(4):1217-27. doi: 10.1016/j.neubiorev.2012.02.002. Epub 2012 Feb 10.