Wikipedia

γ-Hydroxybutyric acid

(Redirected from4-Hydroxybutyric acid)
"GHB" redirects here. For other uses, seeGHB (disambiguation).

γ-Hydroxybutyric acid,also known asgamma-hydroxybutyric acid,GHB,or4-hydroxybutanoic acid,is a naturally occurringneurotransmitterand adepressant drug.It is a precursor toGABA,glutamate,andglycinein certain brain areas. It acts on theGHB receptorand is a weakagonistat theGABABreceptor. GHB has been used in the medical setting as ageneral anestheticand as treatment forcataplexy,narcolepsy,andalcoholism.[10][11]The substance is also used illicitly for various reasons, including as aperformance-enhancing drug,date rape drug,and as arecreational drug.[12]

γ-Hydroxybutyric acid
Clinical data
Other names
  • γ-hydroxybutyric acid
  • γ-hydroxybutyrate
  • GHB
  • fishies[1]
  • G[2]
Addiction
liability		High[3]
Routes of
administration		By mouth,intravenous
Drug classGABA analogue,GHB receptor agonists—GABA receptor agonist;Psycholeptic; Depressant;
Hypnotic
Sedative
ATC code
Legal status
Legal status
Pharmacokineticdata
Bioavailability25% (oral)
Metabolism95–98%, mainlyliver,also in blood and tissues[9]
Onset of actionWithin 5–15 minutes[8]
Eliminationhalf-life30–60 minutes
Excretion1–5%,kidney[9]
Identifiers
  • 4-hydroxybutanoic acid
CAS Number
PubChemCID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard(EPA)
ECHA InfoCard100.218.519Edit this at Wikidata
Chemical and physical data
FormulaC4H8O3
Molar mass104.105g·mol−1
3D model (JSmol)
  • O=C(O)CCCO
  • InChI=1S/C4H8O3/c5-3-1-2-4(6)7/h5H,1-3H2,(H,6,7)checkY
  • Key:SJZRECIVHVDYJC-UHFFFAOYSA-NcheckY
(verify)

It is commonly used in the form of a salt, such as sodium γ-hydroxybutyrate (NaGHB,sodium oxybate,or Xyrem) or potassium γ-hydroxybutyrate (KGHB, potassium oxybate). GHB is also produced as a result of fermentation, and is found in small quantities in some beers and wines, beef, and small citrus fruits.[13]

Succinic semialdehyde dehydrogenase deficiencyis a disease that causes GHB to accumulate in the blood.

Medical use

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Main article:Sodium oxybate

GHB is used for medical purposes in the treatment ofnarcolepsy[14]and, more rarely,alcohol dependence,[15][16]although there remains uncertainty about its efficacy relative to other pharmacotherapies for alcohol dependence.[17]The authors of a 2010 Cochrane review[18]concluded that "GHB appears better than NTX anddisulfiramin maintaining abstinence and preventing craving in the medium term (3 to 12 months) ". It is sometimes usedoff-labelfor the treatment offibromyalgia.[19][20]GHB is the active ingredient of theprescription medicationsodium oxybate(Xyrem). Sodium oxybate is approved by theU.S. Food and Drug Administrationfor the treatment of cataplexy associated with narcolepsy[21]andexcessive daytime sleepiness(EDS) associated with narcolepsy.[22]

GHB has been shown to reliably increaseslow-wave sleep[23][24][25]and decrease the tendency for REM sleep in modified multiple sleep latency tests.[26][23]

The FDA-approved labeling for sodium oxybate[27]suggests no evidence GHB hasteratogenic,carcinogenicor hepatotoxic properties. Its favorable safety profile relative to ethanol may explain why GHB continues to be investigated as a candidate foralcoholsubstitution.[28]

Recreational use

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GHB is a central nervous systemdepressantused as anintoxicant.[29]It has many street names. Its effects have been described as comparable withethanol(alcohol) andMDMAuse, such aseuphoria,disinhibition, enhanced libido andempathogenicstates. A review comparing ethanol to GHB concluded that the dangers of the two drugs were similar.[30]At higher doses, GHB may inducenausea,dizziness,drowsiness,agitation,visual disturbances, depressedbreathing,amnesia,unconsciousness,and death. One potential cause of death from GHB consumption is polydrug toxicity. Co-administration with other CNS depressants such as alcohol orbenzodiazepinescan result in an additive effect (potentiation), as they all bind togamma-aminobutyric acid(or "GABA" ) receptor sites. The effects of GHB can last from 1.5 to 4 hours, or longer if large doses have been consumed.[31]Consuming GHB with alcohol can cause respiratory arrest and vomiting in combination with unarousable sleep, which can lead to death.[32][33]

Recreational doses of 1–2 g generally provide a feeling of euphoria, and larger doses create deleterious effects such as reduced motor function and drowsiness.[9]The sodium salt of GHB has a salty taste.[31]Other salt forms such as calcium GHB and magnesium GHB have also been reported,[34]but the sodium salt is by far the most common.

Someprodrugs,such asγ-butyrolactone(GBL), convert to GHB in the stomach and bloodstream. Other prodrugs exist, such as1,4-butanediol(1,4-B).[35]GBL and 1,4-B are normally found as pure liquids, but they can be mixed with other more harmful solvents when intended for industrial use (e.g. aspaint stripperor varnish thinner).[citation needed]

GHB can be manufactured with little knowledge of chemistry, as it involves the mixing of its two precursors, GBL and analkali hydroxidesuch assodium hydroxide,to form the GHB salt. Due to the ease of manufacture and the availability of its precursors, it is not usually produced in illicit laboratories like other synthetic drugs, but in private homes by low-level producers.[36]

GHB is colourless and odourless.[37]

Party use

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GHB has been used as aclub drug,apparently starting in the 1990s, as small doses of GHB can act as a euphoriant and are believed to be aphrodisiac.[38][39]Slang terms for GHB includeliquid ecstasy,lollipops,liquid Xorliquid Edue to its tendency to produce euphoria and sociability and its use in the dance party scene.[40]

Sports and athletics

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Some athletes have used GHB or its analogs because of being marketed as anabolic agents, although there is no evidence that it builds muscle or improves performance.[31]

Usage as a date-rape drug

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FDA warning against products containing GHB and its prodrugs

GHB became known to the general public as adate-rape drugby the late 1990s.[12][41][9]GHB is colourless and odorless and has been described as "very easy to add to drinks".[37]When consumed, the victim will quickly feel groggy and sleepy and may become unconscious. Upon recovery they may have an impaired ability to recall events that have occurred during the period of intoxication. In these situations evidence and the identification of the perpetrator of the rape is often difficult.[42][43]

It is also 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 only recall the rape some time after its occurrence; however, a 2006 study suggested that there was "no evidence to suggest widespread date rape drug use" in the UK, and that less than 2% of cases involved GHB, while 17% involvedcocaine,[44][45]and a survey in the Netherlands published in 2010 found that the proportion of drug-related rapes where GHB was used appeared to be greatly overestimated by the media.[42][46][47]More recently, a study in Western Australia reviewed the pre-hospital context given in medical records around emergency department presentations with analytical confirmation of GHB exposure. This study found that most cases reported daily dosing and subsequentaccidental overdoserather than their presentation being associated with date-rape.[48]

There have been several high-profile cases of GHB as a date-rape drug that received national attention in the United States. In early 1999, a 15-year-old girl,Samantha ReidofRockwood, Michigan,died from GHB poisoning. Reid's death inspired the legislation titled the "Hillory J. Farias and Samantha Reid Date-Rape Drug Prohibition Act of 2000". This is the law that made GHB a Schedule 1 controlled substance.[49]In the United Kingdom, British serial killerStephen Portadministered GHB to his victims by adding it to drinks given to them, raping them, and murdering four of them in his flat inBarking,East London.[50]

GHB can be detected in hair.[51]Hair testing can be a useful tool in court cases or for the victim's own information.[52]Most over-the-counter urine test kits test only for date-rape drugs that arebenzodiazepines,which GHB is not. To detect GHB in urine, the sample must be taken within four hours of GHB ingestion, and cannot be tested at home.[53]

Adverse effects

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Table from the 2010DrugSciencestudy ranking various drugs (legal and illegal) based on statements by drug-harm experts. GHB was found to be the ninth overall most dangerous drug.[54]

Combination with alcohol

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In humans, GHB has been shown to reduce the elimination rate (thus increasing the eliminationtime) of alcohol. This may explain the respiratory arrest that has been reported after ingestion of both drugs.[55]A review of the details of 194 deaths attributed to or related to GHB over a ten-year period found that most were from respiratory depression caused by interaction with alcohol or other drugs.[56]

Deaths

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One publication has investigated 226 deaths attributed to GHB.[57]Of the 226 deaths included, 213 had a cardiorespiratory arrest and 13 had fatal accidents. Seventy-one of these deaths (34%) had no co-intoxicants. Postmortem blood GHB was 18–4400 mg/L (median=347) in deaths negative for co-intoxicants.

One report has suggested that sodium oxybate overdose might be fatal, based on deaths of three patients who had been prescribed the drug.[58]However, for two of the three cases, post-mortem GHB concentrations were 141 and 110 mg/L, which is within the expected range of concentrations for GHB after death, and the third case was a patient with a history of intentional drug overdose.[59]The toxicity of GHB has been an issue in criminal trials, as in the death ofFelicia Tang,where the defense argued that death was due to GHB, not murder.

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.[60]Levels higher than this are found in GHB deaths. Levels lower than this may be due to GHB or to postmortem endogenous elevations.

Neurotoxicity

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In multiple studies, GHB has been found to impairspatial memory,working memory,learningandmemoryin rats with chronic ad­min­is­tra­tion.[61][62][63]These effects are associated with decreasedNMDA receptorexpression in thecerebral cortexand possibly other areas as well.[61]In addition, the neu­ro­tox­icity appears to be caused byoxidative stress.[64][65]

Addiction

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Addiction occurs when repeated drug use disrupts the normal balance of brain circuits that control rewards, memory and cognition, ultimately leading to compulsive drug taking.[66][67]

Rats forced to consume massive doses of GHB will intermittently prefer GHB solution to water.[68][69]

Withdrawal

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GHB has also been associated with awithdrawal syndromeofinsomnia,anxiety, andtremorthat usually resolves within three to twenty-one days.[29][70][71]The withdrawal syndrome can be severe producing acute delirium and may require hospitalization in an intensive care unit for management.[29]Management of GHB dependence involves considering the person's age, comorbidity and the pharmacological pathways of GHB.[72]The mainstay of treatment for severe withdrawal is supportive care andbenzodiazepinesfor control of acutedelirium,but larger doses are often required compared to acute delirium of other causes (e.g. > 100 mg/d ofdiazepam).Baclofenhas been suggested as an alternative or adjunct to benzodiazepines based on anecdotal evidence and some animal data.[73]However, there is less experience with the use of baclofen for GHB withdrawal, and additional research in humans is needed. Baclofen was first suggested as an adjunct because benzodiazepines do not affect GABABreceptors and therefore have nocross-tolerancewith GHB while baclofen, which works via GABABreceptors, is cross-tolerant with GHB and may be more effective in alleviating withdrawal effects of GHB.[74]

GHB withdrawal is not widely discussed in textbooks and some psychiatrists, general practitioners, and even hospital emergency physicians may not be familiar with this withdrawal syndrome.[75]

Overdose

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Overdose of GHB can sometimes be difficult to treat because of its multiple effects on the body.[11][76][77]GHB tends to cause rapid unconsciousness at doses above 3500 mg, with single doses over 7000 mg often causing life-threateningrespiratory depression,and higher doses still inducingbradycardiaandcardiac arrest.Other side-effects includeconvulsions(especially when combined withstimulants), and nausea/vomiting (especially when combined with alcohol).[29]

The greatest life threat due to GHB overdose (with or without other substances) is respiratory arrest.[29][78]Other relatively common causes of death due to GHB ingestion includeaspirationof vomitus, positional asphyxia, and trauma sustained while intoxicated (e.g., motor vehicle accidents while driving under the influence of GHB).[79]The risk of aspiration pneumonia and positional asphyxia risk can be reduced by laying the patient down in therecovery position.People are most likely to vomit as they become unconscious, and as they wake up. It is important to keep the victim awake and moving; the victim must not be left alone due to the risk of death through vomiting. Frequently the victim will be in a good mood but this does not mean the victim is not in danger. GHB overdose is a medical emergency and immediate assessment in an emergency department is needed.

Convulsions from GHB can be treated with thebenzodiazepinesdiazepamorlorazepam.[29]Even though these benzodiazepines are also CNS depressants, they primarily modulate GABAAreceptors whereas GHB is primarily a GABABreceptor agonist, and so do not worsen CNS depression as much as might be expected.[80]

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 amedical emergencyand should be cared for by appropriately trained personnel.

A newer synthetic drug,SCH-50911,which acts as a selective GABABantagonist, quickly reverses GHB overdose in mice.[81]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.[9]

Detection of use

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GHB may be quantitated in blood or plasma to confirm a diagnosis of poisoning in hospitalized patients,[29]to provide evidence in an impaired driving, or to assist in a medicolegal death investigation. Blood or plasma GHB concentrations are usually in a range of 50–250 mg/L in persons receiving the drug therapeutically (during general anesthesia), 30–100 mg/L in those arrested for impaired driving, 50–500 mg/L in acutely intoxicated patients and 100–1000 mg/L in victims of fatal overdosage. Urine is often the preferred specimen for routine drug abuse monitoring purposes. Bothγ-butyrolactone(GBL) and1,4-butanediolare converted to GHB in the body.[82][83][84]

In January 2016, it was announced scientists had developed a way to detect GHB, among other things, in saliva.[85]

Endogenous production

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Cells produce GHB by reduction ofsuccinic semialdehydeviasuccinic semialdehyde reductase(SSR). This enzyme appears to be induced by cAMP levels,[86]meaning substances that elevate cAMP, such asforskolinandvinpocetine,may increase GHB synthesis and release. Conversely, endogeneous GHB production in those takingvalproic acidwill be inhibited via inhibition of the conversion from succinic acid semialdehyde to GHB.[87]People with the disorder known as succinic semialdehyde dehydrogenase deficiency, also known asγ-hydroxybutyric aciduria,have elevated levels of GHB in theirurine,blood plasma andcerebrospinal fluid.[88]

The precise function of GHB in the body is not clear. It is known, however, that the brain expresses a large number of receptors that are activated by GHB.[89]These receptors are excitatory, however, and therefore not responsible for the sedative effects of GHB; they have been shown to elevate the principal excitatory neurotransmitter,glutamate.[90]Thebenzamideantipsychotics—amisulpride,nemonapride,etc.—have been shown to bind to these GHB-activated receptors in vivo.[91]Other antipsychotics were tested and were not found to have an affinity for this receptor.

GHB is a precursor toGABA,glutamate, andglycinein certain brain areas.[92]

In spite of its demonstrated neurotoxicity, (seerelevant section,above), GHB has neuroprotective properties, and has been found to protect cells fromhypoxia.[93]

Natural fermentation by-product

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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. The amount found in wine is pharmacologically insignificant and not sufficient to produce psychoactive effects.[94]

Pharmacology

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GHB has at least two distinct binding sites in the central nervous system.[95]GHB acts as anagonistat theinhibitoryGHB receptor[96][97]and as a weak agonist at theinhibitoryGABABreceptor.[97]GHB is a naturally occurring substance that acts in a similar fashion to someneurotransmittersin the mammalian brain.[98]GHB is probably synthesized from GABA in GABAergicneurons,and released when the neurons fire.[97]

GHB has been found to activateoxytocinergicneuronsin thesupraoptic nucleus.[99]

If taken orally, GABA itself does not effectively cross theblood–brain barrier.[100]

GHB induces the accumulation of either a derivative oftryptophanor tryptophan itself in the extracellular space, possibly by increasing tryptophan transport across the blood–brain barrier.[101]The blood content of certain neutral amino-acids, including tryptophan, is also increased by peripheral GHB administration. GHB-induced stimulation of tissueserotoninturnover may be due to an increase in tryptophan transport to the brain and in its uptake by serotonergic cells.[101][102]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.[103]

However, at therapeutic doses, GHB reaches much higher concentrations in the brain and activates GABABreceptors, which are primarily responsible for its sedative effects.[104]GHB's sedative effects are blocked by GABABantagonists.[105]

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 principal excitatory neurotransmitter.[90][106]Drugs that selectively activate the GHB receptor causeabsence seizuresin high doses, as do GHB and GABABagonists.[107]

Activation of both the GHB receptor and GABABis responsible for the addictive profile of GHB. GHB's effect on dopamine release is biphasic.[108][106]Low concentrations stimulate dopamine release via the GHB receptor.[109][110]Higher concentrations inhibit dopamine release via GABABreceptors as do other GABABagonists such asbaclofenandphenibut.[111]After an 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 asnaloxoneandnaltrexone.Dynorphinmay play a role in the inhibition of dopamine release viakappa opioid receptors.[112]

This explains the paradoxical mix of sedative and stimulatory properties of GHB,[113]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 GABABreceptor activation and activates predominantly the GHB receptor, leading to wakefulness.

Recently, analogs of GHB, such as4-hydroxy-4-methylpentanoic acid(UMB68) have been synthesised and tested on animals, in order to gain a better understanding of GHB's mode of action.[114]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 a prodrug formγ-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-butanediol diacetate (BDDA/DABD), methyl-4-acetoxybutanoate (MAB), andethyl-4-acetoxybutanoate(EAB),[9]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 compoundγ-hydroxybutyraldehyde(GHBAL) is also a prodrug for GHB; however, as with allaliphaticaldehydes 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

Only a minor portion (1–5%) of the administered GHB dose is excreted unchanged in the urine. Studies have shown that the maximum concentration of GHB in urine appears within 1 hour and rapidly declines thereafter.[9]The vast majority (95–98%) undergoes extensive metabolism in the liver. GHB is broken down through a series of enzymatic pathways. The primary route involves conversion to succinic semialdehyde (SSA) by either GHB dehydrogenase (ADH) or GHB transhydrogenase. SSA is further oxidized by succinic semialdehyde dehydrogenase (SSADH) tosuccinic acid,which enters theKrebs cycleand is ultimately converted into carbon dioxide and water.[9][115][116][117]

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 forrecreationalor 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.

History

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Alexander Zaytsevworked on this chemical family and published work on it in 1874.[118][119]The first extended research into GHB and its use in humans was conducted in the early 1960s byHenri Laboritto use in studying the neurotransmitter GABA.[120]: 11–12 [121]It was studied in a range of uses including obstetric surgery and during childbirth and as an anxiolytic; there were anecdotal reports of it having antidepressant and aphrodisiac effects as well.[120]: 27 It was also studied as an intravenousanestheticagent and was marketed for that purpose starting in 1964 in Europe but it was not widely adopted as it caused seizures; as of 2006 that use was still authorized in France and Italy but not widely used.[120]: 27–28 It was also studied to treat alcohol addiction; while the evidence for this use is weak;[120]: 28–29 however, sodium oxybate is marketed for this use in Italy.[122]

GHB and sodium oxybate were also studied for use innarcolepsyfrom the 1960s onwards.[120]: 28 

In May 1990 GHB was introduced as adietary supplementand was marketed to body builders, for help with weight control and as a sleep aid, and as a "replacement" forl-tryptophan,which was removed from the market in November 1989 when batches contaminated with trace impurities[123]were found to causeeosinophilia–myalgia syndrome,although eosinophilia–myalgia syndrome is also tied to tryptophan overload.[124]In 2001 tryptophan supplement sales were allowed to resume, and in 2005 the FDA ban on tryptophan supplement importation was lifted.[125]By November 1989 57 cases of illness caused by the GHB supplements had been reported to theCenters for Disease Control and Prevention,with people having taken up to three teaspoons of GHB; there were no deaths but nine people needed care in anintensive care unit.[126][127]The FDA issued a warning in November 1990 that sale of GHB was illegal.[126]GHB continued to be manufactured and sold illegally and it and analogs were adopted as aclub drugand came to be used as adate rape drug,and the DEA made seizures and the FDA reissued warnings several times throughout the 1990s.[128][129][130]

At the same time, research on the use of GHB in the form of sodium oxybate had formalized, as a company called Orphan Medical had filed an investigational new drug application and was running clinical trials with the intention of gaining regulatory approval for use to treat narcolepsy.[120]: 18–25, 28 [131]: 10 

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 ismetabolizedinto GHB, had been substituted for the non-toxic plasticiser1,5-pentanediolin 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.[132]


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GHB sold in Italy for therapeutic use

In the United States, GHB was placed onSchedule Iof the Controlled Substances Act in March 2000. However, used in sodium oxybate under an IND or NDA from the US FDA, it is considered a Schedule III substance but with Schedule I trafficking penalties, one of several drugs that are listed in multiple schedules.[7][133]

On 20 March 2001, the UNCommission on Narcotic Drugsplaced GHB in Schedule IV of the 1971Convention on Psychotropic Substances.[134]

In the UK GHB was made a class C drug in June 2003. In October 2013 theACMDrecommended upgrading it from schedule IV to schedule II in line with UN recommendations. Their report concluded that the minimal use of Xyrem in the UK meant that prescribers would be minimally inconvenienced by the rescheduling.[135]This advice was followed and GHB was moved to schedule 2 on 7 January 2015.[136][137]In April 2022 GHB was changed from class C to class B.[138]

In Hong Kong, GHB is regulated under Schedule 1 of Hong Kong's Chapter 134Dangerous 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$10,000. The penalty for trafficking or manufacturing the substance is a HK$150,000 fine and life imprisonment. Possession of the substance for consumption without license from the Department of Health is illegal with a HK$100,000 fine or five years of jail time.

In Canada, GHB has been a Schedule I controlled substance since 6 November 2012 (the same schedule that contains heroin and cocaine). Prior to that date, it was a Schedule III controlled substance (the same schedule that contains amphetamines and LSD).[139]

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 (γ-hydroxyvaleric acid, GHV) and its prodrug form γ-valerolactone (GVL), but these are also covered under the law by virtue of their being "substantially similar" to GHB or GBL, so importation, sale, possession and use of these compounds is also considered to be illegal.

In Chile, GHB is a controlled drug under the lawLey de substancias psicotrópicas y estupefacientes(psychotropic substances and narcotics).

In Norway[140]and in Switzerland,[141]GHB is considered a narcotic and is only available by prescription under the trade name Xyrem (Union Chimique Belge S.A.).

Sodium oxybate is also used therapeutically in Italy under the brand name Alcover for treatment ofalcohol withdrawaland dependence.[142]

See also

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References

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  2. ^"GHB/GBL" G "".Archivedfrom the original on 24 May 2024.Retrieved24 May2024.
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  4. ^"Therapeutic Goods (Poisons Standard—June 2024) Instrument 2024".30 May 2024.
  5. ^Anvisa(31 March 2023)."RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial"[Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese).Diário Oficial da União(published 4 April 2023).Archivedfrom the original on 3 August 2023.Retrieved16 August2023.
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  7. ^ab"2000 – Addition of Gamma-Hydroxybutyric Acid to Schedule I".US Department of Justice via the Federal Register. 13 March 2000. Archived fromthe originalon 1 May 2021.Retrieved16 April2018.
  8. ^Riviello RJ (2010).Manual of forensic emergency medicine: a guide for clinicians.Sudbury, MA: Jones and Bartlett Publishers. p. 42.ISBN978-0763744625.
  9. ^abcdefghBusardò FP, Jones AW (January 2015)."GHB pharmacology and toxicology: acute intoxication, concentrations in blood and urine in forensic cases and treatment of the withdrawal syndrome".Current Neuropharmacology.13(1): 47–70.doi:10.2174/1570159X13666141210215423.PMC4462042.PMID26074743.
  10. ^"Sodium Oxybate: MedlinePlus Drug Information".Nlm.nih.gov. 28 July 2010.Archivedfrom the original on 11 April 2010.Retrieved1 August2010.
  11. ^abBenzer TI, Cameron S (8 January 2007). VanDeVoort JT, Benitez JG (eds.)."Toxicity, Gamma-Hydroxybutyrate".eMedicine.Archivedfrom the original on 28 November 2021.Retrieved16 January2007.
  12. ^abUS Drug Enforcement Administration."GHB, GBL and 1,4BD as Date Rape Drugs".Archived fromthe originalon 10 May 2012.Retrieved10 May2012.
  13. ^Weil A,Winifred R (1993)."Depressants".From Chocolate to Morphine(2nd ed.). Boston/New York: Houghton Mifflin Company. p.77.ISBN978-0-395-66079-9.
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