Gamma-hydroxybutyrate can have legitimate uses as a treatment for narcolepsy or in cleaning agents, but it is mostly commonly used recreationally as a euphoric and sedative. It is usually ingested as a precursor drug, such as gamma-butyrolactone (GBL) or 1,4-butanediol (which the body rapidly converts to GHB).

Effects post ingestion are rapid in onset and given its steep dose-response curve, it is easy for accidental toxicity to occur. The hallmark of toxicity is sedation which if often profound, however due to the short duration of action can normally be managed supportively.

Dependence can develop in patients who use daily and withdrawal, typified by a marked delirium, can develop within hours of the last dose and be difficult to control.

Gamma hydroxybutyrate (GHB) is an inhibitory neurotransmitter which predominantly acts through specific GHB receptors. GHB is also produced in small quantities in the central nervous system. In toxic amounts it may also have weak agonist effects on the GABAB receptor (similar to baclofen). Stimulation of GHB receptors leads to a range of effects on other neurotransmitters – in particular it has complex effects on dopaminergic neurones. The end result of high concentrations of GHB is a general anaesthetic effect, but it is presumed lesser degrees of intoxication are euphoric through dopaminergic mechanisms. GHB is also formed from two precursors, gamma butyrolactone (GBL) and 1,4 butanediol (1,4BD). Conversion from GBL involves the enzymes alcohol and aldehyde dehydrogenase. Thus, high concentrations of alcohol inhibit this conversion. GBL may also act on GABAB receptors.

Given it is used recreationally and is not a manufactured product, the ingested dose is rarely known.

Tolerance develops with repeat use making prediction of toxicity based on ingested dose unreliable.

GHB, GBL and 1,4BD are all absorbed orally, with peak concentrations and effect occurring within 1 to 2 hours.

The onset of action is rapid and may be as early as 15 minutes after ingestion. GBL and 1,4BD are very rapidly converted to GHB and the onset of effect and time course is generally similar.

GBL is more lipid soluble and may act more quickly and for slightly longer than GHB by virtue of its more rapid absorption and different tissue distribution.

GHB, GBL and 1,4BD are not significantly bound to proteins and have a volume of distribution roughly equal to body water (0.6L/kg).

GHB is rapidly metabolised via the Krebs cycle to water and carbon dioxide.

A small amount is excreted unchanged in the urine where it may be detected for up to 4 to 6 hours.

The elimination half-life of GHB is less than half an hour. This is consistent with the observation that most patients recover consciousness rapidly within 2 hours of presentation to hospital.

The onset of effects post ingestion are rapid (15-60 minutes) but the duration of toxicity is normally short. Most patients will recover within 2-4 hours.

Longer duration of toxicity (still normally <10hrs) can be seen in those that take very large doses with intent to self-harm and in those that have been using stimulants for several days who have used GHB to ‘come-down’.

CNS effect predominate and include:

• CNS depression/coma
• Dose-dependant respiratory depression
• Myoclonus
• Hypotonia/hyporeflexia
• Seizures (uncommon)

When the sedative effects resolve, patients can wake up in an agitated, disoriented state and require sedation. On waking from this sedation, the patient is normally back to a normal state.

Other affects include:

• Mild bradycardia
• Mild hypotension
• Hypothermia
• Miosis
• Metabolic acidosis (seen only following large ingestions)

There are no specific investigations for GHB poisoning, but as with any patient with reduced level of consciousness it would be appropriate to check bloods glucose levels and if there were concerns for respiratory depression a bloods gas.

The main life threat in significant GHB intoxication is CNS depression and the associated risk to airway maintenance and breathing.

Observe all patients with depressed level of consciousness in a critical care area until sedation has improved. Patients are best managed in the left lateral position. Airway adjuncts are only suggested if the airway is compromised as they may stimulate vomiting and offer no benefit if there is no airway compromise.

If patency of the airway or adequate ventilation is not able to be maintained by supportive measures, then the patient should be intubated and ventilated until toxicity resolves.

Bradycardia is usually mild and does not require specify management. Hypotension, if it occurs will normally respond to intravenous fluids.

Myoclonic jerks are common and often mistaken for seizure activity. In the uncommon situation where seizures do occur, they are normally short and self-limiting. If they persist, they should respond to intravenous benzodiazepines.

There is no role for decontamination given the rapid onset of action and favourable outcomes with supportive care.

There is no role for enhanced elimination

There is no antidote for GHB.

Physostigmine has previously been suggested as an antidote based on reported responses in a small number of patients, however there is no well supported mechanism for its proposed effect and other cases have not shown similar positive effects (but have shown harms).

Given the potential risk-benefit of physostigmine in these cases, its use in not suggested.

All patients with CNS depression require close observation in a critical care area. Given the short duration of action, admission to an intensive care unit, can normally be avoided.

Discharge patients if they remain asymptomatic at 1 hour post ingestion.

In patients who have developed toxicity, observe until toxicity has resolved, and they are back to baseline (normally 2-6hr).

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