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Gamma-Hydroxybutyric acid chemical structure
Gamma-Hydroxybutyric acid

4-Hydroxybutanoic acid
IUPAC name
CAS number
ATC code

N01AX11 .

Chemical formula {{{chemical_formula}}}
Molecular weight 104.10 g/mol (GHB)
126.09 g/mol (sodium salt)
142.19 g/mol (potassium salt)
Bioavailability 25% (oral)
Metabolism 95%, mainly Hepatic, also in blood and tissues
Elimination half-life 30–60 minutes
Excretion 5%, renal
Pregnancy category B
Legal status Class B (NZ), Schedule I and III (US)
Routes of administration Usually oral; intravenous

γ-Hydroxybutyric acid (GHB), also known as 4-hydroxybutanoic acid and sodium oxybate[1], is a naturally-occurring substance found in the central nervous system, wine, beef, small citrus fruits, and almost all animals in small amounts.[2] It is also a neuroprotective therapeutic nutrient [citation needed] that is categorized as an illegal drug in many countries.[3] It is currently regulated in the US. GHB as the sodium salt, known as sodium oxybate, is sold by Jazz Pharmaceuticals under the name Xyrem[4] to treat cataplexy and excessive daytime sleepiness in patients with narcolepsy.

GHB has been used in a medical setting as a general anesthetic, to treat conditions such as insomnia, clinical depression, narcolepsy, and alcoholism, and to improve athletic performance.[5] It is also used as an intoxicant (illegally in many jurisdictions) or as a date rape drug.[6] GHB is naturally produced in the human body's cells and is structurally related to the ketone body beta-hydroxybutyrate. As a supplement/drug, it is used most commonly in the form of a salt.[7] GHB is also produced as a result of fermentation, and so is found in small quantities in some beers and wines. Succinic semialdehyde dehydrogenase deficiency is a disease that causes GHB to accumulate in the blood.


Synthesis of the chemical GHB was first reported in 1874 by Alexander Zaytsev,[8] but the first major research into its use in humans was conducted in the early 1960s by Dr. Henri Laborit to use in studying the neurotransmitter GABA.[9] It quickly found a wide range of uses due to its minimal side-effects and short duration of action, the only difficulties being the narrow therapeutic dosage range (despite an unusually high LD50) and the dangers presented by its combination with alcohol and other central nervous system depressants.

GHB was widely used in France, Italy, and other European countries for several decades as a sleeping agent and an anesthetic in childbirth, but problems with its abuse potential and development of newer drugs have led to a decrease in legitimate medical use of GHB in recent times. The only common medical applications for GHB today are in the treatment of narcolepsy and more rarely alcoholism. In the typical scenario, GHB has been synthesized from γ-butyrolactone (GBL) by adding sodium hydroxide (lye) in ethanol or water. As of late, GBL has become controlled and more circuitous routes have to be taken, such as those starting with tetrahydrofuran (THF).

A popular children's toy, Bindeez (also known as Aqua Dots, in the United States), produced by Melbourne company Moose, was banned in Australia in early November 2007 when it was discovered that 1,4-butanediol (1,4-B), which is metabolized into GHB, had been substituted for the non-toxic plasticiser 1,5-pentanediol in the bead manufacturing process. Three young children were hospitalized as a result of ingesting a large number of the beads, and the toy was recalled.[10]


GHB has at least two distinct binding sites[11] in the central nervous system. GHB is an agonist at the newly-characterized GHB receptor, which is excitatory,[12][13] and it is a weak agonist at the GABAB receptor, which is inhibitory.[13] GHB is a naturally-occurring substance that acts in a similar fashion to some neurotransmitters in the mammalian brain.[14] GHB is probably synthesized from GABA in GABAergic neurons, and released when the neurons fire.[13]

GHB induces the accumulation of either a derivative of [3H]-tryptophan or [3H]-tryptophan itself in the extracellular space, possibly by increasing tryptophan transport across the blood-brain barrier. The blood content of certain neutral amino-acids, including tryptophan, is also increased by peripheral GHB administration. GHB-induced stimulation of tissue serotonin turnover may be due to an increase in tryptophan transport to the brain and in its uptake by serotonergic cells. As the serotonergic system may be involved in the regulation of sleep, mood, and anxiety, the stimulation of this system by high doses of GHB may be involved in certain neuropharmacological events induced by GHB administration.

If taken orally, GABA itself very poorly crosses the blood-brain-barrier, nor do high concentrations very effectively reach the GABA receptors once inside the brain. Since GABA is naturally synthesized in the brain, a higher-than-normal concentration would be quickly metabolized.[15]

However, at pharmacological doses, GHB reaches much higher concentrations in the brain and activates GABAB receptors, which are primarily responsible for its sedative effects.[16] GHB's sedative effects are blocked by GABAB antagonists.

The role of the GHB receptor in the behavioural effects induced by GHB is more complex. GHB receptors are densely expressed in many areas of the brain, including the cortex and hippocampus, and these are the receptors that GHB displays the highest affinity for. There has been somewhat limited research into the GHB receptor; however, there is evidence that activation of the GHB receptor in some brain areas results in the release of glutamate, the principle excitatory neurotransmitter.[17] Drugs that selectively activate the GHB receptor cause absence seizures in high doses, as do GHB and GABA(B) agonists.[18]

Activation of both the GHB receptor and GABA(B) is responsible for the addictive profile of GHB. GHB's effect on dopamine release is biphasic,[19] low concentrations stimulate dopamine release via the GHB receptor.[20] Higher concentrations inhibit dopamine release via GABA(B) receptors as do other GABA(B) agonists such as baclofen and phenibut.[21] After the initial phase of inhibition, dopamine release is then increased via the GHB receptor. Both the inhibition and increase of dopamine release by GHB are inhibited by opioid antagonists such as naloxone and naltrexone. Dynorphin may play a role in the inhibition of dopamine release via kappa opioid receptors.[22]

This explains the paradoxical mix of sedative and stimulatory properties of GHB, as well as the so-called "rebound" effect, experienced by individuals using GHB as a sleeping agent, wherein they awake suddenly after several hours of GHB-induced deep sleep. That is to say that, over time, the concentration of GHB in the system decreases below the threshold for significant GABAB receptor activation and activates predominantly the GHB receptor, leading to wakefulness.

Recently, analogs of GHB, such as 4-hydroxy-4-methylpentanoic acid have been synthesised and tested on animals, in order to gain a better understanding of GHB's mode of action.[23] Analogues of GHB such as 3-methyl-GHB, 4-methyl-GHB and 4-phenyl-GHB have been shown to produce similar effects to GHB in some animal studies, but these compounds are even less well researched than GHB itself. Of these analogues, only 4-methyl-GHB (γ-hydroxyvaleric acid, GHV) and its prodrug form gamma-valerolactone (GVL) have been reported as drugs of abuse in humans, and on the available evidence seem to be less potent but more toxic than GHB, with a particular tendency to cause nausea and vomiting.

Other prodrug ester forms of GHB have also rarely been encountered by law enforcement, including 1,4-diacetoxybutane, methyl-4-acetoxybutanoate, and ethyl-4-acetoxybutanoate, but these are, in general, covered by analogue laws in jurisdictions where GHB is illegal, and little is known about them beyond their delayed onset and longer duration of action. The intermediate compound 4-hydroxybutaldehyde is also a prodrug for GHB; however, as with all aldehydes this compound is caustic and is strong-smelling and foul-tasting; actual use of this compound as an intoxicant is likely to be unpleasant and result in severe nausea and vomiting.

Metabolic pathway of GHB.

Also note that both of the metabolic breakdown pathways shown for GHB can run in either direction, depending on the concentrations of the substances involved, so the body can make its own GHB either from GABA or from succinic semialdehyde. Under normal physiological conditions, the concentration of GHB in the body is rather low, and the pathways would run in the reverse direction to what is shown here to produce endogenous GHB. However, when GHB is consumed for recreational or health promotion purposes, its concentration in the body is much higher than normal, which changes the enzyme kinetics so that these pathways operate to metabolise GHB rather than producing it.

Medical uses

GHB has been used as a general anesthetic in the 1960s,[5] as a hypnotic in the treatment of insomnia, to treat depression, and to improve athletic performance. In Italy, under the trade name Alcover (ATC code N07BB), GHB is used in the treatment of alcoholism (50 to 100 milligrams per kilogram per day, in 3 or more divided doses), both for acute alcohol withdrawal and medium- to long-term detoxification.[24] In the United States, the Food and Drug Administration permits the use of GHB under the trade name Xyrem to reduce the number of cataplexy attacks and excessive daytime sleepiness in patients with narcolepsy.[25]

When GHB is used in its sodium or potassium salt form, a significant quantity of excess sodium or potassium may be consumed, which should be taken into consideration by people with heart conditions, hypertension or compromised renal function. The bioavailability of sodium GHB is considerably reduced when it is consumed with food, and so it is advised to wait at least two hours after eating before consuming the dose. Because of its strong sedative effects, patients should not drive or operate heavy machinery for at least six hours after taking sodium GHB.

Adverse effects from Xyrem in clinical trials included: headache, nausea, dizziness, nasopharyngitis, somnolence, vomiting, urinary incontinence, confusion, dyspnea, hypoesthesia, paresthesia, tremor, vertigo, and blurred vision. Out of the 717 patients and 182 healthy volunteers who took part in the trials (899 total), two of them died from drug overdoses, although only one of these involved GHB.[26]

In January 2008, Jazz Pharmaceuticals completed enrollment in the second Phase III trial for a modified version of sodium oxybate for use by people with Fibromyalgia, whose sufferers endure much pain and difficulty with sleep.[27][28]

The company completed one of the Phase III clinical trials in September 2008.[29] It expects to submit a New Drug Application to the US Federal Drug Administration (FDA) before the end of 2009 for JZP-6, for use in treating Fibromyalgia.

Non-medical use

gamma-hydroxybutyrate powder

GHB is a CNS depressant used as an intoxicant. It has many street names, including "Georgie Home Boy", "Liquid Ecstasy", "Liquid X", and "Liquid G", as well as "Fantasy" and the reordered initialism GBH. At recreational doses, GHB can cause a state of euphoria, increased enjoyment of movement and music, increased libido, increased sociability and intoxication. At higher doses, GHB may induce nausea, dizziness, drowsiness, agitation, visual disturbances, depressed breathing, amnesia, unconsciousness, and death. The effects of GHB can last from 1.5 to 3 hours, or even longer if large doses have been consumed or if it is mixed with alcohol. [citation needed]

In general, the doses used recreationally are between 500 mg and 3000 mg. When used as a recreational drug, GHB may be found as the sodium or potassium salt, which is a white crystalline powder, or as GHB salt dissolved in water to form a clear solution. The sodium salt of GHB has a thin, very salty, chemical taste.[citation needed]. Other salt forms such as calcium GHB and magnesium GHB have also been reported, but the sodium salt is by far the most common.

Some chemicals convert to GHB in the stomach and blood. GBL, or gamma-butyrolactone, is one such prodrug. Other prodrugs include 1,4-butanediol. There may be additional toxicity concerns with these precursors. 1,4-B and GBL are normally found as pure liquids, although they may be mixed with other more harmful solvents when intended for industrial use, e.g., as paint stripper or varnish thinner.

GHB can be produced in clandestine labs, and it is claimed that most of the GHB used in the U.S. is illegally manufactured within its borders. While available as a prescription for sleep disorders in some other countries, GHB was banned (in the U.S.) by the FDA in 1990. However, on 17 July 2002, GHB was approved for treatment of cataplexy, often associated with narcolepsy. GHB is "colourless and odorless".[30]


Club scene or "rave"

Since the 1970s club scene, club-goers have used a range of drugs to enhance their experience on the dance floor such as amyl nitrite "poppers" and cocaine. In the 1990s, newer "club drugs" became popular, such as ketamine and "designer" phenethylamines designed to circumvent contemporary drug laws, "ecstasy" (chemically MDMA, 3,4-methylenedioxy methamphetamine, or 3,4-methylenedioxy methyl alpha-methyl phenethylamine) and 2C-I (chemically 2,5-dimethoxy-4-iodophenethylamine) being prominent examples. When the laws "catch up" to certain drugs, clandestine chemists manufacture another drug, designed to affect the user in the same way as the now-banned drug. Since most of these drugs are congeners of the banned drugs, the Federal Analogue Act was introduced to ban these substances proactively, based on the proclivity of a said chemical to mimic either the structure or the effects of the banned drug.

Like these other "club drugs," GHB is taken because users feel that it enhances the experience of being in a club or at a party; small doses of GHB are thought to act as a stimulant and aphrodisiac. GHB is sometimes referred to as liquid ecstasy, liquid X, or liquid E due to its tendency to produce euphoria and sociability and its use in the dance party scene. When GHB was banned, several "designer drugs" were made to replicate its effects - GBL and 1,4-butanediol, all of which metabolized into GHB in vivo and are now banned.[31]Cite error: Invalid <ref> tag; refs with no name must have content Despite this nickname, GHB is not related to "Ecstasy," either chemically or in affect upon the user.

Date rape

The drug has been identified as a date rape drug,[6] much the same way as alcohol and potent benzodiazepines, often known colloquially as "Rohypnol," the trade name of a certain potent benzodiazepine, flunitrazepam. (It should be noted that several other vastly more common benzodiazepines are as potent or more potent than Rohypnol - Xanax, Ativan, Klonopin, Halcion [the most potent of all benzodiazepines], and Estazolam.) It has a salty taste, but as it is colourless and odorless,[30] it has been described as "very easy to add to drinks"[30] that mask the flavor. GHB has been used in cases of drug-related sexual assault, usually when the victim is vulnerable due to intoxication with a sedative, generally alcohol.[32] However it is difficult to establish how often GHB is used to facilitate rape as it is difficult to detect in a urine sample after a day, and many victims may not recall the rape until some time after this.[33][34] However cases of GHB being used as a date rape drug is quite rare, see the date rape drug article for more information.

GHB, produced as a sodium salt (sodium oxybate, Jazz Pharmaceuticals' Xyrem), may provide a noticeable salty character to the drink, although individual sensitivity to the taste of salt varies.[35] GHB can also be produced as different salts, some of which may not have a taste as distinctive as the sodium salt (e.g., magnesium oxybate), or much less commonly in the unstable free-acid form.[36]


File:Dangerous dietary supplements.gif

FDA warning against products containing GHB and its prodrugs.

Some athletes and bodybuilders also use GHB, as GHB has been shown to elevate human growth hormone in vivo.[37] The growth hormone elevating effects of GHB are mediated through muscarinic acetylcholine receptors and can be prevented by prior administration of pirenzepine, a muscarinic acetylcholine receptor blocking agent.[38]

As certain succinate salts have been shown to elevate growth hormone in vitro,[39] and because GHB is metabolized into succinate some people have suggested this may play a role in the growth hormone elevations from GHB. There is however currently no evidence to show that succinate plays any role in the growth hormone elevations from GHB.

Endogenous production by the body

Cells produce GHB by reduction of succinic semialdehyde via the enzyme succinic semialdehyde dehydrogenase. This enzyme appears to be induced by cAMP levels,[40] meaning substances that elevate cAMP, such as forskolin and vinpocetine, may increase GHB synthesis and release. People with the disorder known as succinic semialdehyde dehydrogenase deficiency, also known as gamma-hydroxybutyric aciduria, have elevated levels of GHB in their urine, blood plasma and cerebrospinal fluid.[41]

The precise function of GHB in the body is not clear. It is known, however, that the brain expresses a large amount of receptors that are activated by GHB.[42] These receptors are excitatory and not responsible for the sedative effects of GHB - they have been shown to elevate the principle excitatory neurotransmitter—glutamate.[17] The benzamide antipsychotics—amisulpride, sulpiride—have been shown to bind to this receptor in vivo.[43] Other antipsychotics were tested and were not found to have an affinity for this receptor.

It is a precursor to GABA, glutamate, and glycine in certain brain areas.[44]

GHB has neuroprotective properties and has been found to protect cells from hypoxia.[45]

Natural fermentation by-product

GHB is also produced as a result of fermentation and so is found in small quantities in some beers and wines, in particular fruit wines. However, the amount of GHB found in wine is insignificant and not sufficient to produce any effects.[46]


Dose response curve

As with pure alcohol, the dose-response curve of GHB is very steep, and "proper" dosing of illegal GHB can be difficult since it often comes as a salt dissolved in water, and the actual amount of GHB and/or other additives per "capful" can vary. Legal GHB comes in standardized doses and is free from contaminants, so it is much safer (cf. legal alcohol vs. bathtub gin). Also, like pure alcohol, small doses of GHB are considered safe, but high doses can cause unconsciousness, convulsions, vomiting, suppression of the gag reflex, respiratory depression, and death. These effects vary between persons and are dose-dependent. Synergy of its sedative effects are seen when combined with other CNS depressants such as alcohol, benzodiazepines (e.g., diazepam), barbiturates, and others.

Combination with alcohol

Alcohol worsens both CNS depression and vomiting, so combining alcohol with GHB or its precursors can be particularly dangerous. Another factor to be considered is that people who drink alcohol regularly tend to induce expression of their dehydrogenase enzymes, and thus have higher levels of these enzymes than people that do not drink alcohol regularly; this means that regular alcohol drinkers will both convert 1,4-B into GHB more rapidly and also break down GHB into succinate faster than people that do not drink alcohol. This multitude of different factors can make the interactions between 1,4-B, GHB and alcohol very complicated and highly variable between different individuals.

Death while using GHB is most likely when it is combined with alcohol or other depressant drugs; however, an overdose of GHB alone may be lethal. A review of the details of 194 deaths attributed to or related to GHB over a ten-year period[47] found that most were from respiratory depression caused by interaction with alcohol or other drugs; several were from choking on vomit and asphyxiating; remaining causes of death included motor vehicle and other accidents. The review included 70 cases in which high levels of GHB were found post-mortem without concomitant ingestion of other drugs or alcohol.

If alcohol has also been consumed this can saturate the dehydrogenase enzymes and so delays the conversion of 1,4-B into GHB, meaning that 1,4-B takes much longer to take effect and people may re-dose thinking it has not done anything, leading to an accidental overdose later on once it finally takes effect. 1,4-B itself can also contribute to the enzyme saturation, so, when alcohol and 1,4-B are consumed together, it produces a complex and somewhat unpredictable interaction between the varying levels of alcohol, 1,4-B and GHB present in the body. Alcohol also makes the GHB last longer in the body by competing for dehydrogenase enzymes, and hence delaying the conversion of GHB into succinate.

Other combinations

Another complication is the difference in pharmacokinetics between GHB and its two prodrugs, 1,4-B and GBL. 1,4-B is converted into GHB in the body by two enzymes alcohol dehydrogenase and aldehyde dehydrogenase, which gives it a delayed onset of effects and a longer duration of action. GHB is then further metabolised, again by alcohol dehydrogenase and aldehyde dehydrogenase, into the inactive succinate.

The other precursor GBL is rapidly converted into GHB by lactamase enzymes found in the blood. GBL is more lipophilic (fat soluble) than GHB, and so is absorbed faster and has higher bioavailability; the paradox is that this can mean that GBL has a faster onset of effects than GHB itself, even though it is a prodrug. The levels of lactamase enzyme can vary between individuals, and GBL is not active in its own right, so people who have never tried GBL before may have delayed or fewer effects than expected; however, once someone has taken GBL a few times, the production of lactamase enzymes is increased and he/she will feel the effects like a regular user.

Because of these pharmacokinetic differences, 1,4-B tends to be slightly less potent, slower to take effect but longer-acting than GHB, whereas GBL tends to be more potent and faster-acting than GHB, and has around the same duration.

Death and other harmful effects

GHB use is conclusively associated with death, as documented by many reports, including one in which 3 deaths were associated with Xyrem use (pharmaceutical GHB, or "Sodium Oxybate"),[48]. Because rodents are particularly resistant to death from GHB, many have assumed that GHB is equally safe in humans. The fact that clinical effects of GHB occur at approximately 1/10th the dose in humans as in rodents is evidence that GHB is much more toxic in humans than in rodents. One large series documents 226 deaths attributed to GHB; this will be published in the American Journal of Emergency Medicine this year.[49] A preliminary report of this case series, with 194 deaths, was presented at the American Academy of Forensic Science. [50] In this series, death records were reviewed for toxicology, autopsy findings, and history. Of 226 deaths included, 213 suffered cardiorespiratory arrest and 13 suffered fatal accidents. Seventy-one deaths (34%) had no co-intoxicants. Postmortem blood GHB was 18-4400mg/L (median=347) in deaths negative for co-intoxicants.

GHB is produced in the body in very small amounts, and blood levels may climb after death to levels in the range of 30-50 mg/L. [51] Levels higher than this are found in GHB deaths. Levels lower than this may be due to GHB or to postmortem endogenous elevations. Only careful attention to historical details, and analysis of other body fluids (e.g., vitreous) can determine for with any certainly whether measurable levels below 30-50 mg/L are exogenous or endogenous.

There have been no systematic studies into the effects of GHB if taken chronically in humans, and hence whether prolonged use of GHB causes any bodily harm remains unknown. A UK parliamentary committee commissioned report found the use of GHB to be less dangerous than tobacco and alcohol in social harms, physical harm and addiction.[52]

Treatment of overdose

Overdose of GHB can be difficult to treat because of its multiple effects on the body.[5][53][54] GHB tends to cause rapid unconsciousness at doses above 3500 mg, with single doses over 7000 mg often causing life-threatening respiratory depression, and higher doses still inducing bradycardia and cardiac arrest. Other side-effects include convulsions (especially when combined with stimulants), and nausea/vomiting (especially when combined with alcohol).

The greatest life threat due to GHB overdose (with or without other substances) is respiratory arrest.[55] Other relatively common causes of death due to GHB ingestion include aspiration of vomitus, positional asphyxia, and trauma sustained while intoxicated (e.g., motor vehicle accidents while driving under the influence of GHB).[55] The risk of aspiration pneumonia and positional asphyxia risk can be reduced by laying the patient down in the recovery position. People are most likely to vomit as they become unconscious, and as they wake up. GHB overdose is a medical emergency and assessment in an emergency department is needed.


Convulsions from GHB can be treated with diazepam or lorazepam, even though these are also CNS depressants they are GABAA agonists, whereas GHB is primarily a GABAB agonist, so the benzodiazepines do not worsen CNS depression as much as might be expected.

Most stimulants are not effective at counteracting the unconsciousness from GHB.[citation needed]

Because of the faster and more complete absorption of GBL relative to GHB, its dose-response curve is steeper, and overdoses of GBL tend to be more dangerous and problematic than overdoses involving only GHB or 1,4-B. Any GHB/GBL overdose is a medical emergency and should be cared for by appropriately trained personnel.

A newer synthetic drug SCH-50911, which acts as a selective GABAB antagonist, quickly reverses GHB overdose in mice.[56] However this treatment has yet to be tried in humans, and it is unlikely that it will be researched for this purpose in humans due to the illegal nature of clinical trials of GHB, and the lack of medical indemnity coverage inherent in using an untested treatment for a life-threatening overdose.


GHB can be physically addictive and may result in psychological addiction. Physical dependence develops when GHB is taken on a regular basis (i.e., every 2–4 hours for multiple consecutive days or weeks). Withdrawal effects may include insomnia, restlessness, anxiety, tremors, sweating, loss of appetite, edginess, tachycardia, chest pain and tightness, muscle and bone aches, sensitivity to external stimuli (sound, light, touch), dysphoria, and mental dullness. These side-effects will subside after 2 – 21 days, depending on frequency of usage and the size of the doses used. In particularly severe cases, withdrawal from GHB may cause symptoms similar to acute withdrawal from alcohol or barbiturates (delirium tremens) and can cause convulsions and hallucinations.

Although there have been reported fatalities due to GHB withdrawal, reports are inconclusive and further research is needed. Unlike alcohol, there is no firm data that chronic use of GHB causes permanent damage to the body. In rats, no organ or brain damage was observed after chronic administration of GBL (a precursor to GHB).[57]


Withdrawal from GHB can be a life-threatening condition. Treatment with benzodiazepines can be used, although extremely high doses may be required (e.g. > 100 mg/d of diazepam). With the exception of baclofen, other treatments are often ineffective. Evidence shows that baclofen is the most effective drug for GHB withdrawal. GHB and baclofen are agonists for the GABAb receptor.[58]

Legal status

In the United States, it was placed on Schedule I of the Controlled Substances Act in March 2000. However, when sold as Xyrem, it is considered Schedule III, one of several drugs that are listed in multiple schedules.[3][59] On 20 March 2001, the Commission on Narcotic Drugs placed GHB in Schedule IV of the 1971 Convention on Psychotropic Substances.[60] In the UK it was made a class C drug in June 2003.

In Hong Kong, GHB is regulated under Schedule 1 of Hong Kong's Chapter 134 Dangerous Drugs Ordinance. It can only be used legally by health professionals and for university research purposes. The substance can be given by pharmacists under a prescription. Anyone who supplies the substance without prescription can be fined HK$10000. The penalty for trafficking or manufacturing the substance is a HK$5,000,000 fine and life imprisonment. Possession of the substance for consumption without license from the Department of Health is illegal with a HK$1,000,000 fine and/or 7 years of jail time.

In New Zealand and Australia, GHB, 1,4-B and GBL are all Class B illegal drugs, along with any possible esters, ethers and aldehydes. GABA itself is also listed as an illegal drug in these jurisdictions, which seems unusual given its failure to cross the blood-brain barrier, but there was a perception among legislators that all known analogues should be covered as far as this was possible. Attempts to circumvent the illegal status of GHB have led to the sale of derivatives such as 4-methyl-GHB (gamma-hydroxyvaleric acid, GHV) and its prodrug form gamma-valerolactone (GVL), but these are also covered under the law by virtue of their being "substantially similar" to GHB or GBL and; so importation, sale, possession and use of these compounds is also considered to be illegal.

In Norway, GHB is considered a narcotic[61] and is only available by prescription under the trade name Xyrem (Union Chimique Belge S.A.).

See also

  • 1,4-Butanediol (1,4-BD)
  • gamma-Butyrolactone (GBL)
  • gamma-Hydroxyvaleric acid (GHV)
  • gamma-Valerolactone (GVL)


  1. Sodium Oxybate: MedlinePlus Drug Information
  2. Weil, Andrew; Winifred Rosen (1993). "Depressants" From Chocolate to Morphine, 2nd, Boston/New York: Houghton Mifflin Company.
  3. 3.0 3.1 Erowid GHB Vault : Legal Status.
  4. Jazz Pharmaceuticals Inc (JAZZ.O) Full Description | Stocks |
  5. 5.0 5.1 5.2 Theodore I Benzer. Toxicity, Gamma-Hydroxybutyrate. eMedicine.
  6. 6.0 6.1 GHB, GBL and 1,4BD as Date Rape Drugs.
  7. e.g., sodium gamma-hydroxybutyrate (Na.GHB, sodium oxybate) or potassium gamma-hydroxybutyrate (K.GHB).
  8. Alexander Saytzeff (1874). Über die Reduction des Succinylchlorids. Liebigs Annalen der Chemie 171: 258–290.
  9. H. Laborit, J.M. Jouany, J. Gerald, F. Fabiani (1960). Generalities concernant l’etude experimentale de l’emploi clinique du gamma hydroxybutyrate de Na. Aggressologie 1.
  10. includeonly>Michael Perry, James Pomfret, Roger Crabb. "Australia bans China-made toy on toxic drug risk", Reuter, 7 November 2007.
  11. Wu Y, Ali S, Ahmadian G, et al. (December 2004). Gamma-hydroxybutyric acid (GHB) and gamma-aminobutyric acidB receptor (GABABR) binding sites are distinctive from one another: molecular evidence. Neuropharmacology 47 (8): 1146–56.
  12. Cash, C (1999). γ-hydroxybutyrate receptor function studied by the modulation of nitric oxide synthase activity in rat frontal cortex punches. Biochemical Pharmacology 58.
  13. 13.0 13.1 13.2 Maitre M, Humbert JP, Kemmel V, Aunis D, Andriamampandry C (March 2005). [A mechanism for gamma-hydroxybutyrate (GHB) as a drug and a substance of abuse]. Med Sci (Paris) 21 (3): 284–9.
  14. Waszkielewicz A, Bojarski J (2004). Gamma-hydrobutyric acid (GHB) and its chemical modifications: a review of the GHBergic system. Pol J Pharmacol 56 (1): 43–9.
  15. OTC GABA and the Blood-Brain Barrier.
  16. Dimitrijevic N, Dzitoyeva S, Satta R, Imbesi M, Yildiz S, Manev H (September 2005). Drosophila GABA(B) receptors are involved in behavioral effects of gamma-hydroxybutyric acid (GHB). Eur. J. Pharmacol. 519 (3): 246–52.
  17. 17.0 17.1 Castelli MP, Ferraro L, Mocci I, et al. (November 2003). Selective gamma-hydroxybutyric acid receptor ligands increase extracellular glutamate in the hippocampus, but fail to activate G protein and to produce the sedative/hypnotic effect of gamma-hydroxybutyric acid. J. Neurochem. 87 (3): 722–32.
  18. Banerjee PK, Snead OC (June 1995). Presynaptic gamma-hydroxybutyric acid (GHB) and gamma-aminobutyric acidB (GABAB) receptor-mediated release of GABA and glutamate (GLU) in rat thalamic ventrobasal nucleus (VB): a possible mechanism for the generation of absence-like seizures induced by GHB. J. Pharmacol. Exp. Ther. 273 (3): 1534–43.
  19. Hechler V, Gobaille S, Bourguignon JJ, Maitre M (March 1991). Extracellular events induced by gamma-hydroxybutyrate in striatum: a microdialysis study. J. Neurochem. 56 (3): 938–44.
  20. Maitre M, Hechler V, Vayer P, et al. (November 1990). A specific gamma-hydroxybutyrate receptor ligand possesses both antagonistic and anticonvulsant properties. J. Pharmacol. Exp. Ther. 255 (2): 657–63.
  21. Smolders I, De Klippel N, Sarre S, Ebinger G, Michotte Y (September 1995). Tonic GABA-ergic modulation of striatal dopamine release studied by in vivo microdialysis in the freely moving rat. Eur. J. Pharmacol. 284 (1-2): 83–91.
  22. Mamelak M (1989). Gammahydroxybutyrate: an endogenous regulator of energy metabolism. Neurosci Biobehav Rev 13 (4): 187–98.
  23. Wu, H. (2003). A Tertiary Alcohol Analog of gamma-Hydroxybutyric Acid as a Specific gamma -Hydroxybutyric Acid Receptor Ligand. Journal of Pharmacology and Experimental Therapeutics 305.
  24. An author/scientist Gian Luigi Gessa has been researching alcoholism and the effects of various drugs to persons afflicted with said disease for the past ten years. His studies in 1998 note that GHB, as a pharmaceutical aid, can be much less toxic and much more effective than the leading pharmaceutical compound (disulfiram).
  25. In clinical trials Xyrem significantly reduced cataplexy attacks at a dose of 6000–9000 mg per night. This is around three times the dose used recreationally, but almost all narcolepsy patients in the clinical trials were already stabilized on CNS stimulants such as modafinil; in patients not prescribed modafinil, this dosage could be dangerous and should be reduced appropriately. Also, the prescribing information for Xyrem states that patients should take the dose immediately before going to bed, and then a second dose 3–4 hours later. The maximum dose taken at one time should not exceed 4500 mg. Patients with hepatic insufficiency (compromised liver function) have slower clearance of GHB and require reduced doses, typically half the normal dose. Xyrem oral solution is standardised to 500 mg Na.GHB/1 mL water, buffered to pH 7.5 with malic acid.
  26. Xyrem drug data sheet.
  30. 30.0 30.1 30.2 Jones, C. (2001). Suspicious death related to gamma-hydroxybutyrate (GHB) toxicity (2001). Journal of Clinical Forensic Medicine 8.
  31. Mary Klein, Frances Kramer, "Rave drugs: Pharmacological considerations", AANA Journal, Vol. 72 (2004), 61–67.
  32. ElSohly MA, Salamone SJ (1999). Prevalence of drugs used in cases of alleged sexual assault. J Anal Toxicol 23 (3): 141–6.
  33. S.O.S. - Date Rape Drugs.
  34. "Labs making date-rape drug raided", The Independent World, 10 July 2008.
  35. Pangborn RM, Pecore SD (March 1982). Taste perception of sodium chloride in relation to dietary intake of salt. Am. J. Clin. Nutr. 35 (3): 510–20.
  36. Witkowski, Mark R.; Ciolino, Laura A.; De Francesco, James V. (2006). GHB Free Acid: II. Isolation and Spectroscopic Characterization for Forensic Analysis. Journal of Forensic Sciences 51.
  37. Riccardo Volpi, Paolo Chiodera, Paolo Caffarra, Augusto Scaglioni, Antonella Saccani and Vittorio Coiro (1997). Different control mechanisms of growth hormone (GH) secretion between γ-amino- and γ-hydroxy-butyric acid: neuroendocrine evidence in parkinson's disease. Psychoneuroendocrinology 22 (7): 531–538.
  38. Volpi, R (2000). Muscarinic cholinergic mediation of the GH response to gamma-hydroxybutyric acid: neuroendocrine evidence in normal and parkinsonian subjects. Psychoneuroendocrinology 25.
  39. Badamchian, M (1995). Alpha-Tocopherol Succinate, But Not Alpha-Tocopherol Or Other Vitamin E Analogs Stimulates Prolactin And Growth Hormone Release From Rat Anterior Pituitary Cells in vitro. The Journal of Nutritional Biochemistry 6.
  40. Kemmel V, Taleb O, Perard A, et al. (October 1998). Neurochemical and electrophysiological evidence for the existence of a functional gamma-hydroxybutyrate system in NCB-20 neurons. Neuroscience 86 (3): 989–1000.
  42. C. Andriamampandry, O. Taleb, S. Viry, C. Muller, J. P. Humbert, S. Gobaille, D. Aunis and M. Maitre (2003). Cloning and characterization of a rat brain receptor that binds the endogenous neuromodulator γ-hydroxybutyrate. The FASEB Journal.
  43. Maitre M, Ratomponirina C, Gobaille S, Hodé Y, Hechler V (April 1994). Displacement of [3H] gamma-hydroxybutyrate binding by benzamide neuroleptics and prochlorperazine but not by other antipsychotics. Eur. J. Pharmacol. 256 (2): 211–4.
  44. Gobaille S, Hechler V, Andriamampandry C, Kemmel V, Maitre M (July 1999). gamma-Hydroxybutyrate modulates synthesis and extracellular concentration of gamma-aminobutyric acid in discrete rat brain regions in vivo. J. Pharmacol. Exp. Ther. 290 (1): 303–9.
  45. Ottani A, Saltini S, Bartiromo M, et al. (October 2003). Effect of gamma-hydroxybutyrate in two rat models of focal cerebral damage. Brain Res. 986 (1–2): 181–90.
  46. Elliott S, Burgess V. "The presence of gamma-hydroxybutyric acid (GHB) and gamma-butyrolactone (GBL) in alcoholic and non-alcoholic beverages". Forensic Science International. 2005 July 16;151(2–3):289–92.
  47. Zvosec et al. American Academy of Forensic Science in Seattle, 2006
  48. (Zvosec DL, Smith SW, Hall BJ. Three deaths associated with use of Xyrem�. Sleep Med 2009;10:490–3.)
  49. Zvosec DL, Smith SW, Porrata T, Strobl AQ, Dyer JE. Case series of 226 gamma-hydroxybutyrate-associated deaths: lethal toxicity and trauma. Am J Emerg Med In Press.
  50. Zvosec DL et al. Gamma Hydroxybutyrate (GHB)-Related Deaths: Review of 194 Cases. Proceedings of the American Academy of Forensic Sciences, February 2006; Volume XII, page 359. URL link:
  51. Zvosec DL. Smith SW. Response to Editorial: “Xyrem safety: The debate continues”. Sleep Medicine 2010; 11:105-109.
  52. Science and Technology Committee Report (p. 176), 2006)
  53. Allen, L., Alsalim, W. (1 April 2006). Gammahydroxybutyrate overdose and physostigmine. Emergency Medicine Journal 23 (4).
  54. Michael, H., Harrison, M. (1 January 2005). Endotracheal intubation in γ-hydroxybutyric acid intoxication and overdose. Emergency Medicine Journal 22 (1).
  55. 55.0 55.1 Zvosec, DL, Smith, SW, Porrata, T, et al. Preventable deaths from Gamma hydroxybutyrate ingestion (Abstract). Ann Emerg Med 2006; 48:S75
  56. Carai, M.A.M., Colombo, G.; Gessa, G.L. (2005). Resuscitative Effect of a γ-Aminobutyric Acid B Receptor Antagonist on γ-Hydroxybutyric Acid Mortality in Mice. Annals of Emergency Medicine 45 (6): 614–619.
  57. National Toxicology Program (March 1992), Toxicology and Carcinogenesis Studies of g-Butyrolactone (CAS No. 96-48-0) in F344/N Rats and B6C3F1 Mice (Gavage Studies), Department of Health and Human Services, NIH, 
  58. Letourneau JL,, Hagg DS, Smith SM (12 February 2008). Baclofen and Gamma-Hydroxybutyrate Withdrawal. Neurocrit Care 8.
  61. FOR 30 June 1978 nr 08: Forskrift om narkotika m.v. (Narkotikalisten).

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