Gamma hydroxybutyrate (GHB) is a sedative and euphoriant that causes intoxication similar to alcohol intoxication. It is usually used by ingestion. Toxicity includes dizziness, loss of coordination, ataxia, nausea, and vomiting. When combined with alcohol, GHB can cause decreased mental status or coma, respiratory depression, seizures, and, rarely, death. Diagnosis is by history and physical examination and sometimes urine testing. Management is by monitoring and sometimes mechanical ventilation.
Gamma hydroxybutyrate (GHB) is structurally similar to the neurotransmitter gamma-aminobutyric acid (GABA). Although the sale of GHB is banned in many countries, 2 immediate precursors, gamma butyrolactone (GBL) and 1,4-butadione, are usually readily available for retail purchase.
GHB is used and misused in various contexts. The drug has been used in drug-facilitated sexual assault. Body builders may use GHB because it releases growth hormone, although this increase is minimal. In therapeutic use, GHB is called sodium oxybate and is a treatment for narcolepsy.
Street names for gamma hydroxybutyrate include G, GHB, Goop, and Liquid Ecstasy.
Pathophysiology of GHB Use
GHB binds to the GABA-B receptor, similar to the medications phenibut and baclofen. In contrast, benzodiazepines and barbiturates bind to the GABA-A receptor. Nevertheless, the clinical effects are comparable.
The route of use of GHB is typically oral ingestion of the drug in liquid form. After it enters the systemic circulation, it can cross the blood-brain barrier.
Symptoms and Signs of GHB Toxicity
Short-term effects of use of GHB include feelings of relaxation, tranquility, fatigue, and disinhibition.
At higher doses, signs of toxicity may develop, including dizziness, loss of coordination, ataxia, nausea, and vomiting.
The presentation of overdose is a brief period of euphoria followed by a comatose state. Myoclonus is a unique but not diagnostic feature in some cases of GHB overdose. Myoclonus may be distinguished from convulsive activity because it is brief and does not involve the whole body.
Combining GHB with other sedatives, including ethanol, potentiates its sedative effects and may lead to apnea.
Diagnosis of GHB Toxicity
History and physical examination
For definitive diagnosis, urine GHB testing with gas chromatography-mass spectrometry
The definitive diagnosis of GHB toxicity requires demonstrating that a toxic amount of GHB was present in the patient when the patient had concordant symptoms. In practice this level of certainty is difficult to achieve and treatment should proceed based on a presumptive diagnosis while awaiting confirmatory testing. A suggestive clinical scenarios is a patient who reports ingestion of a liquid followed by euphoria and then somnolence.
There are no physical examination findings that reliably differentiate GHB toxicity from toxicity from other sedative-hypnotics. The clinician should proceed with the usual evaluation of a sedative-hypnotic toxidrome. A blood gas should be obtained and other blood tests include: serum glucose (use a rapid point-of-care test, if available); complete metabolic profile; concentrations of salicylate, acetaminophen, and ethanol; and concentrations of any current medications prescribed to the patient. A urinalysis and a urine toxicological screen should be performed.
For patients with hypoventilation, a single dose of naloxone is administered to exclude opioid toxicity. Flumazenil, which is useful for diagnosing acute benzodiazepine toxicity, has no role in diagnosing or reversing GHB toxicity. GHB and benzodiazepines bind to different receptors.
GHB is not detected on routine urine drug screening tests. It can be detected in urine for up to 12 hours by gas chromatography-mass spectrometry. The longer the interval between ingestion and collection of the sample, the more difficult it is to estimate the amount ingested. The clinician should be cautious of attributing a patient's somnolence to GHB based on a laboratory finding because habitual users develop tolerance.
There is no role in testing for GBL or 1,4-butanediol. Both are rapidly converted to GHB.
Treatment of GHB Use
Monitoring with pulse oximetry, capnography
Sometimes mechanical ventilation
A medical toxicologist should be consulted for ingestions involving a combination of GHB and another substance or for isolated GHB ingestions if a patient does not spontaneously recover after 8 hours of the monitoring, as described below.
Preventing absorption
There are no routine measures to prevent absorption of GHB.
There is no role for activated charcoal, gastric lavage, or whole bowel irrigation in treating GHB toxicity because GHB is most commonly ingested as a liquid.
Enhancing excretion
The pKa of GHB is approximately 4.7, which is a weak acid. There is no established role for alkalinizing the urine in treating GHB toxicity.
Mitigating toxicity
The profundity of the sedation of GHB toxicity may be disconcerting to the clinician unfamiliar with GHB use; however, most patients recover completely within 6 to 8 hours.
If hypoxia develops and persists despite supplemental oxygen or hypercarbia develops and persists despite stimulation (eg, placement of a nasal airway), the patient should be intubated. If no need for intubation is identified, the patient should be placed on continuous pulse oximetry and capnography, with an anticipated course of full recovery within 8 hours.
Chronic Use of GHB
Tolerance and Dependence
Tolerance to GHB develops rapidly with frequent use, with users needing to consume GHB every 3 hours to prevent withdrawal after only a few months of use (1). With chronic use the brain expresses fewer GABAB receptors and the remaining receptors desensitize to GHB meaning that users need to take larger doses over time to achieve the same desired effects. Increased tolerance can increase the risk of overdose because users may unknowingly consume dangerously high amounts trying to replicate the initial effects.
Long-Term Complications
Chronic GHB use can lead to memory problems and amnesia, difficulty concentrating, and impaired decision-making as well as mood swings, depression, and anxiety (2).
Withdrawal
Withdrawal symptoms occur if GHB is not taken for several hours after previous frequent use. Symptoms resemble those of alcohol withdrawal or benzodiazepine withdrawal (eg, tremors, tachycardia, seizures, and delirium) (3, 4). GHB withdrawal can be life-threatening (5).
The treatment of GHB withdrawal involves reintroducing GHB and tapering the dose gradually. Previous approaches involved using a benzodiazepine taper, but this leads to frequent relapse (6). In patients for whom this approach has failed, baclofen may be considered. There is no established dosing regimen. Case reports suggest 10 mg 3 times a day replaces 6 g GHB (7). Some patients self-treat their withdrawal symptoms with phenibut, an illicit GABA-B agonist. When treating GHB withdrawal, the clinician should inquire about phenibut use to determine adequate starting doses of baclofen or GHB. A medical toxicologist should be consulted for guidance on dosing.
Chronic use references
1. Dyer JE, Roth B, Hyma BA. Gamma-hydroxybutyrate withdrawal syndrome. Ann Emerg Med. 2001;37(2):147-153. doi:10.1067/mem.2001.112985
2. Raposo Pereira F, McMaster MTB, Schellekens A, et al. Effects of Recreational GHB Use and Multiple GHB-Induced Comas on Brain Structure and Impulsivity. Front Psychiatry. 2020;11:166. Published 2020 Apr 2. doi:10.3389/fpsyt.2020.00166
3. Wolf CJH, Beurmanjer H, Dijkstra BAG, et al. Characterization of the GHB Withdrawal Syndrome. J Clin Med. 2021;10(11):2333. Published 2021 May 26. doi:10.3390/jcm10112333
4. Neu P, Danker-Hopfe H, Fisher R, Ehlen F. GHB: a life-threatening drug complications and outcome of GHB detoxification treatment-an observational clinical study. Addict Sci Clin Pract. 2023;18(1):62. Published 2023 Oct 21. doi:10.1186/s13722-023-00414-w
5. 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;101(1):23-29. doi:10.1093/qjmed/hcm117
6. Beurmanjer H, Luykx JJ, De Wilde B, et al. Tapering with Pharmaceutical GHB or Benzodiazepines for Detoxification in GHB-Dependent Patients: A Matched-Subject Observational Study of Treatment-as-Usual in Belgium and The Netherlands. CNS Drugs. 2020;34(6):651-659. doi:10.1007/s40263-020-00730-8
7. LeTourneau JL, Hagg DS, Smith SM. Baclofen and gamma-hydroxybutyrate withdrawal. Neurocrit Care. 2008;8(3):430-433. doi:10.1007/s12028-008-9062-2
Key Points
Gamma hydroxybutyrate (GHB) is a sedative and euphoriant that causes intoxication similar to alcohol intoxication.
Toxicity includes dizziness, loss of coordination, ataxia, nausea, and vomiting. When combined with alcohol, GHB can cause respiratory depression, seizures, and, rarely, death. .
Diagnose with history and physical examination, excluding other drug use (eg, alcohol), and sometimes urine testing.
Treatment of mild toxicity with observation. Severe toxicity may require mechanical ventilation.
Withdrawal symptoms include tremors that resemble rigors and tachycardia, are similar to those of alcohol withdrawal and benzodiazepine withdrawal, and can be life-threatening.
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