Gamma-hydroxybutyrate and gamma-butyrolactone abuse

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'

What is gamma-hydroxybutyrate?

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.¹ Its effects are similar to benzodiazepines, baclofen and alcohol.

What is gamma-hydroxybutyrate abuse?

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)).² 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).¹

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 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 has largely replaced GHB as a recreational drug because it is cheaper and widely available;³ it 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.⁴

How common is gamma-hydroxybutyrate abuse? (Epidemiology)

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 2010.⁵ A Norwegian observational study found a sharp rise in cases between 2008-2012, which then plateaued by 2015.⁶

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.⁷ 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.⁶ Its sedative effects mean that it is used as a 'comedown' drug following the use of stimulants.⁸

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

Gamma-hydroxybutyrate symptoms (presentation)¹⁰

The subjective effects of GHB are reported as:

• Euphoria.

• 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.¹¹

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: ¹²

• Dizziness.

• Blurred vision.

• Hot/cold flushes.

• Memory lapses.

Signs include:¹³

• 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.

Differential diagnosis

The differential is wide and includes:¹⁴

• Alcohol poisoning.

• Overdose of another substance (eg, antidepressants, barbiturates, benzodiazepines, narcotics, neuroleptics).

• Stroke.

• Encephalitis.

• Subdural haematoma.

• Subarachnoid haemorrhage.

• Hypoglycaemia.

• 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.

Gamma-hydroxybutyrate abuse treatment

Initial assessment

The initial assessment of a patient with altered mental status and suspected club-drug ingestion includes:³

• 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.¹

• A method to detect GHB in human hair has been developed but no methods for rapid testing are currently available.²

• 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.¹⁵

• 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 management¹³

• 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.¹⁶ 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.¹⁷

• Where patients are unaware of their ingestion of GHB and a possibility of sexual assault exists, requirements include:¹⁸
  

  • Full forensic and medical examination.

  • STI screen and prophylaxis.

  • Pregnancy counselling +/-emergency contraception.

  • Psychological and support counselling.

Complications

• 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.¹⁹

Prognosis

• With isolated use of GHB, prognosis is normally good. Spontaneous recovery (usually abrupt) of consciousness is usual, within 2-4 hours.¹⁴

• 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 and baclofen may be used for pharmacological detoxification but some cases are refractory.²⁰

• 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.²¹

Prevention

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.