General · EdgepediaSeptember 17, 20267 min read

Γ-Hydroxybutyric acid

Γ-Hydroxybutyric acid (GHB, also called γ-hydroxybutyrate or 4-hydroxybutanoic acid) is an endogenous short-chain fatty acid (C₄H₈O₃) present in the mammalian central nervous system and an analog of GABA, the brain's major inhibitory neurotransmitter.¹ It occupies an unusual position among drugs: as its sodium salt, sodium oxybate, it is an approved prescription medicine for narcolepsy, while GHB itself is a Schedule I controlled substance used illicitly for its euphoric and sedative effects and known as a drug used in sexual assault.²^•³

Key fact	Detail
Chemical identity	Endogenous short-chain fatty acid, C₄H₈O₃, present in the CNS; analog of GABA¹
Main receptors	Binds GHB receptors and GABA_B receptors; pharmacological and toxicological effects are attributed mainly to GABA_B agonism¹
Pharmacokinetics	Rapidly absorbed from the gut; reported half-life of 20 to 60 minutes, with most of a dose eliminated within 4 to 8 hours⁴
Approved use	Sodium oxybate (Xyrem), the sodium salt of GHB, approved in the US in 2002 for cataplexy in narcolepsy and in 2005 for excessive daytime sleepiness⁵
US legal status	GHB is a Schedule I controlled substance (since March 2000); FDA-approved GHB products are Schedule III²
Overdose	Sedation, respiratory depression, coma, and death; no antidote exists and treatment is supportive care¹
Withdrawal	After chronic use, withdrawal can persist up to 21 days and can be life-threatening; benzodiazepines are the usual treatment⁴

Pharmacology

GHB occurs naturally in the brain and is both a precursor for and a breakdown product of GABA.⁶ It binds to dedicated GHB receptors and to GABA_B receptors, and studies attribute its behavioral, pharmacological, and toxicological effects mainly to agonism at GABA_B receptors.¹ GHB also affects the release of other neurotransmitters, including GABA, glutamate, and dopamine.¹

Its disposition in the body is complex. GHB is a substrate for monocarboxylate transporters, both sodium-dependent (SMCT1 and SMCT2) and proton-dependent (MCT1 through MCT4), which are significant determinants of intestinal absorption, renal reabsorption, and uptake into the brain and other tissues.¹ It is metabolized primarily in the liver and eliminated rapidly, with a reported half-life of 20 to 60 minutes.⁴ This short half-life shapes both its medical use, which requires divided nightly doses, and its abuse pattern of repeated redosing.

Therapeutic use in narcolepsy

GHB has been recognized as an effective treatment for narcolepsy since 1979, but formal approval came later: the US Food and Drug Administration approved its sodium salt, sodium oxybate (brand name Xyrem), for cataplexy in narcolepsy in 2002 and for excessive daytime sleepiness in adults with narcolepsy in 2005.⁵ Sodium oxybate is a central nervous system depressant indicated for the treatment of cataplexy or excessive daytime sleepiness in patients with narcolepsy.³

Dosing. The recommended adult regimen starts at 4.5 g per night, divided into two equal doses, one at bedtime and one taken 2.5 to 4 hours later, titrated in weekly increments of 1.5 g per night to an effective range of 6 to 9 g per night.³ Patients take each dose while in bed and remain there, because the drug can cause abrupt sleep within minutes; the two doses must never be taken together.³ Trials conducted under controlled conditions found that sodium oxybate enhanced sleep at night: higher doses produced greater slow wave sleep and longer total sleep time, while awakenings during the night decreased.⁷

Safety controls. Because of the risks of CNS depression and abuse, sodium oxybate is available only through a restricted distribution program, the Sodium Oxybate REMS Program, under which prescribers and the dispensing pharmacy must be certified and patients must be enrolled.³ The drug carries a boxed warning for CNS depression and abuse and misuse, and it is contraindicated in combination with alcohol or sedative hypnotics.³ Post-marketing surveillance reviewed during its development indicated an acceptable safety profile and minimal risk of developing physical dependence among approved patients.⁸

Alcohol withdrawal and dependence

GHB and its sodium salt have been studied for treating alcohol withdrawal syndrome and preventing relapse, on the rationale that GHB mimics some effects of alcohol and can rapidly reduce withdrawal symptoms.⁹ The evidence is mixed. A Cochrane review concluded that there is insufficient randomized evidence to be confident that GHB differs from placebo, or to determine reliably whether it is more or less effective than other drugs, for treating alcohol withdrawal or preventing relapses, though small trials suggested possible benefit over placebo and over naltrexone and disulfiram in maintaining abstinence at three months.¹⁰ A 2022 network meta-analysis of 149 trials found GHB improved endpoint Clinical Institute Withdrawal Assessment for Alcohol-Revised scores over placebo (d = −1.80; 95% CI, −3.35 to −0.26), while benzodiazepines showed the more consistent efficacy and safety across outcomes.¹¹ British Association for Psychopharmacology guidelines state there is insufficient evidence to recommend GHB for alcohol withdrawal, and note that sodium oxybate has mixed evidence for maintaining abstinence; it is licensed in Italy and Austria, and the European Medicines Agency has been reviewing its risk-to-benefit profile.¹²

Illicit use and toxicology

GHB misuse became popular among teens and young adults at dance clubs and raves in the 1990s and gained notoriety as a "date rape" drug.² Its euphoria, loss of inhibition, amnesia, and drowsiness also drive recreational use, including in the "chemsex" context.¹ Common street names include G, Liquid Ecstasy, Liquid X, Goop, Georgia Home Boy, Grievous Bodily Harm, and Easy Lay.² Illicit GHB is typically sold as a clear, colorless, slightly salty liquid in doses of roughly 1 to 5 grams, though concentrations in homemade solutions vary so much that users often do not know the dose they are taking.² Effects begin within 15 to 30 minutes and last 3 to 6 hours.²

Overdose. GHB has a narrow therapeutic index: modest dose increases can precipitate profound respiratory depression, coma, and bradycardia, particularly combined with alcohol or other central depressants.¹³ Overdose symptoms include nausea, sedation, dizziness, seizure, respiratory depression, hypothermia, coma, and death.¹ There is no antidote; physostigmine, naloxone, and activated charcoal have been tried with little to no effect, and treatment is limited to supportive care, principally airway protection and mechanical ventilation when respiratory depression is severe.¹^•⁴ Alcohol co-ingestion occurs in the majority of recreational cases and makes comas more life threatening, with more pronounced respiratory depression, hypotension, and bradycardia.¹^•⁶

Withdrawal. Abstinence after chronic use can produce a withdrawal syndrome that in severe cases persists for days to up to 21 days and can be life threatening. Features include auditory and visual hallucinations, tremors, tachycardia, hypertension, sweating, anxiety, agitation, paranoia, insomnia, confusion, and aggression. Benzodiazepines are the treatment of choice, with barbiturates, baclofen, or propofol as second-line options.⁴

Analogs. γ-Butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are structurally related compounds that are converted within the body to GHB and produce the same effects.⁶^•² Efforts to ban GHB have driven increased use of these analogs and prodrugs, which are sold legally as industrial solvents and illicitly as supplements; routine toxicological screens do not detect them.⁸^•²

Legal status

Over-the-counter sales of GHB were banned in 2000 following reports of respiratory depression and deaths from abuse, and GHB was placed on Schedule I of the US Controlled Substances Act in March 2000, a category with high abuse potential and no accepted medical use.¹^•² FDA-approved GHB products, such as Xyrem, are nonetheless listed as Schedule III substances, one of several drugs appearing in multiple schedules.² Medical demand for the approved products has grown: the DEA finalized the 2025 aggregate production quota for GHB at 49,675,266 grams, about 20,258,266 grams (almost 70 percent) above the 2024 quota, citing pending generic applications and expanded prescribing conditions.¹⁴

References

Topic: Encyclopedia › Life and health › Human health and medicine › Medicines and therapeutics › Psychiatric and neurological medications › Sedatives, hypnotics, and anxiolytics

Initially written Sep 17, 2026 · Reviewed: Sep 30, 2026; Oct 21, 2026 · Edited: Sep 30, 2026; Oct 21, 2026 · Last review: Oct 21, 2026

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