Gamma Hydroxy Butyrate (GHB) and Gamma Butyrolactone (GBL) Abuse

Street Names: Liquid Ecstasy, Scoop, Easy Lay, Fantasy, Georgia Home Boy, G, Grievous Bodily Harm or GBH, Liquid X, and 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 GABA_A and GABA_B receptors with actions similar to benzodiazepines, baclofen and alcohol, possibly by potentiation of the dopaminergic system.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 or 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 withdrawal² and sleep disorders, in particular, narcolepsy. In the 1980s, it grew popular amongst the bodybuilding fraternity who believed it to promote fat loss and muscle building (there is no supporting evidence for this belief). 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.

In the UK, GHB is a Class C drug under the Misuse of Drugs Act (1971). However, its precursors gamma-butyrolactone (GBL) and 1,4-butanediol (1,4BD) are legally and freely available via the internet and other sources, are metabolised to GHB in vivo and pose similar risks.³ GBL is a solvent found in substances such as cleaning products, nail polish, and superglue removers. There have been recent cases of children in Australia developing GHB poisoning following ingestion of toy beads containing 1,4BD.⁴

Across America, Europe and Australia, reports of the misuse of GHB have grown over the last two decades. Emergency admissions associated with its use have risen steeply - although a study in California suggests that, there at least, they are now falling again.⁵ Its emergence world-wide has been associated with particular groups, although it has spread beyond these:

• The dance-party/rave subculture
• Gay club and sex party subculture
• Bodybuilding and gym subculture

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 One survey from 2001 suggested that 13% of 'clubbers' had used GHB in the last 3 months and a further 3% were lapsed users.⁷ Interestingly 67% of users report using the drug within their homes and only 26% within nightclub environments, although this differed according to sexuality;⁸ amongst gay and bisexual men, use is primarily within a club and party environment.⁹
It is not a drug associated with naive drug users; mean age of first use was 22 years⁷ and it is often used as an adjunct drug in polydrug users with or following ecstasy, cocaine, 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.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 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.
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-Stoke breathing
• Confusion
• Agitation
• Vomiting
• Decreased levels of consciousness and coma
• Tremors
• Myoclonic jerks
• Seizures

The differential is wide and includes:

• Alcohol poisoning
• Overdose of other substance (e.g. 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.

• Urine and blood assays for GHB can be sent to reference labs but take time and are usually only important in forensic cases. Note 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
• Chest X-ray may be needed to exclude aspiration.
• ECG is usual.

Where the cause of decreased level of consciousness is unclear, a full investigational work up is required, including:

• Bloods (FBC, C&Es, LFTs, tox screen, arterial blood gases, osmolality, blood culture)
• Urine (pregnancy test, tox screen, urine culture)
• CSF (for microscopy and culture)
• Imaging (CT or MRI)

• 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
• 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 uncontrolled manner.
• Always check the oropharynx for burns.
• Whilst fatalities occur with isolated GHB use, co-ingestion of other drugs (e.g.ketamine or ethanol) create a more complex clinical picture and greater risk.¹⁴
• 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 e.g. 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.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, confusion, hallucinations and tachycardia and develop within 1-6 hours of 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 GHB's legal status.
• 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.