Gamma-Butyrolactone
Encyclopedia
gamma-Butyrolactone is a hygroscopic colorless oily liquid with a weak characteristic odor
and is soluble in water. GBL is a common solvent
and reagent
in chemistry
and is used as an aroma compound
, as a stain remover, as a superglue remover, as a paint stripper
, and as a solvent
in some wet aluminium electrolytic capacitors. In humans it acts as a prodrug
for GHB
, and it is used as a recreational intoxicant.
analysis.
(GHB) by removal of water or by distillation from such a mixture. It may also be obtained via oxidation of tetrahydrofuran
(THF). One such process, which affords GBL in yields of up to 80%, utilises bromine
generated in situ
from an aqueous solution of sodium bromate
and potassium hydrogen sulfate
. Another process can proceed by using commercially-available calcium hypochlorite
in the presence of activating acetic acid
and an appropriate solvent such as acetonitrile. γ-aminobutryic acid (GABA) can also be converted into GBL via a quite simple Sandmeyer reaction: with the addition of sodium nitrite (to an aqueous solution of GABA) and then acidified with an appropriate acid like hydrochloric acid. The acidification allows the sodium nitrite to act as nitrous acid, in layman's terms, and through an intermediary reaction (converting GABA, an amine, to its diazatonium salt, which is then hydrolyzed leaving behind a hydroxyl group where the amino group was), form γ-butyrolactone. The resulting GBL is simply combined with a stoichiometrically correct amount of sodium hydroxide resulting in sodium γ-hydroxybutyrate.
. It is hydrolyzed
under basic conditions, for example in a sodium hydroxide solution
into sodium gamma-hydroxybutyrate, the sodium
salt of gamma-hydroxybutyric acid
. Under acidic conditions it forms an equilibrium
mixture of both compounds. These compounds then may go on to form a polymer
.
of GHB.
The hypnotic effect of GHB is enhanced by combination with alcohol. A 2003 rat study showed that GBL in combination with ethanol showed a potentiated hypnotic effect, as the sleep-timing measure was longer than both of the individual components combined.
; 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 lactonase enzyme can vary between individuals, meaning that first-time users can show unpredictable results, even from small doses. In many this manifests as slow onset of effects, followed by headaches, semi-consciousness which is distinct from GBL sleep in normal users. If the user decides to try again at a later date, they appear to be able to enjoy the effects normally. Because of these pharmacokinetic differences, GBL tends to be more potent and faster-acting than GHB, but has a shorter duration; whereas the related compound 1,4-butanediol
(1,4-B) tends to be slightly less potent, slower to take effect but longer-acting than GHB.
of GHB
, GBL was sold as a nutritional supplement after the scheduling of GHB, under the names Revivarant and Renewtrient in the U.S. at least until the end of 1999.
GBL (as well as GHB), when taken internally in therapeutic doses without the presence of other drugs (especially alcohol, as mixing the two can be fatal), has been shown to elevate growth hormone levels in humans to at least 5 times the baseline.
of GHB
. To bypass GHB restriction laws, home synthesis kits were introduced to transform GBL and/or 1,4-B into GHB. GBL can also be used as a recreational drug by itself.
GBL overdose can cause irrational behaviour, severe sickness, coma
and death
.
Metabolism takes place in stomach and blood plasma. The duration and onset of GBL is shorter and has a faster onset than GHB. Otherwise, effects are similar to GHB, although weight for weight it is significantly more powerful due to being absorbed faster and its higher bioavailability, meaning dosage must be lowered accordingly. If taken undiluted by mouth, GBL can cause esophageal and gastro-intestinal irritation. It is possible for oral ingestion of GBL to cause nausea and other similar problems, possibly more so than with GHB.
Frequent use of alcohol (which induces similar effects) can directly translate to physical and usually psychological addiction, where the heavy user can suffer painful and even life-threatening withdrawals.
There are some reports of GHB/GBL users adopting a '24/7' dosing regime. This is where the user has become tolerant to the effects of the drug, increasing the dosage and frequency of dosage simply to avoid withdrawal symptoms.
For those users who do report withdrawal symptoms upon quitting the use of GHB/GBL, symptoms seem to depend on the dosage and the length of time the drug was used for. Light to moderate users often experience insomnia and sleep-related problems, whereas heavy, prolonged use can cause severe withdrawal symptoms similar to Benzodiazepine withdrawal syndrome
(BWS).
United Kingdom: GBL was classified as a Class C drug from 23 December 2009, with a prison term of up to two years for possession and 14 years for dealing, by the end of 2009.
Sweden: GBL is not classified as a drug but as a health-endangering substance. Although recently passed legislation to enter into force on 1 April 2011 will make it possible to handle narcotics for industrial purposes will enable GBL and 1,4-Butanediol to be classified as controlled substances.
Australia: GBL is a border controlled substance and is illegal to import into Australia without a permit. The importation of a commercial quantity of a border controlled drug (over 1kg of GBL) is punishable by up to life imprisonment and/or an $825000 fine.
United States: GBL is regulated as a List 1 controlled chemical. As a GHB analog, it is treated as a controlled substance under Schedule I of the "Controlled Substances Act" if intended for human consumption.
Poland: In Poland
, GBL is not classified as a drug and can be purchased in chemistry shops as a solvent.
Germany: GBL is not listed in the narcotics law, but its distribution is controlled. Possession is not illegal, but may be punished according to the Medicines Act, when intended to be sold for human consumption or synthesis of GHB. In recent years, an increase of GBL consumption has been observed due to the prohibition of GHB.
Israel: GBL was classified as a proscribed substance from 2007, .
Odor
An odor or odour is caused by one or more volatilized chemical compounds, generally at a very low concentration, that humans or other animals perceive by the sense of olfaction. Odors are also commonly called scents, which can refer to both pleasant and unpleasant odors...
and is soluble in water. GBL is a common solvent
Solvent
A solvent is a liquid, solid, or gas that dissolves another solid, liquid, or gaseous solute, resulting in a solution that is soluble in a certain volume of solvent at a specified temperature...
and reagent
Reagent
A reagent is a "substance or compound that is added to a system in order to bring about a chemical reaction, or added to see if a reaction occurs." Although the terms reactant and reagent are often used interchangeably, a reactant is less specifically a "substance that is consumed in the course of...
in chemistry
Chemistry
Chemistry is the science of matter, especially its chemical reactions, but also its composition, structure and properties. Chemistry is concerned with atoms and their interactions with other atoms, and particularly with the properties of chemical bonds....
and is used as an aroma compound
Aroma compound
An aroma compound, also known as odorant, aroma, fragrance or flavor, is a chemical compound that has a smell or odor...
, as a stain remover, as a superglue remover, as a paint stripper
Paint stripper
Paint stripper, or paint remover, is the generic name given to solvent mixtures designed to remove paint and other finishes and also to clean the underlying surface. The principal active ingredient is usually dichloromethane...
, and as a solvent
Solvent
A solvent is a liquid, solid, or gas that dissolves another solid, liquid, or gaseous solute, resulting in a solution that is soluble in a certain volume of solvent at a specified temperature...
in some wet aluminium electrolytic capacitors. In humans it acts as a prodrug
Prodrug
A prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...
for GHB
Gamma-Hydroxybutyric acid
γ-Hydroxybutyric acid , also known as 4-hydroxybutanoic acid and sodium oxybate when used for medicinal purposes, is a naturally occurring substance found in the central nervous system, wine, beef, small citrus fruits, and almost all animals in small amounts. It is also categorized as an illegal...
, and it is used as a recreational intoxicant.
Occurrence
GBL has been found in extracts from samples of unadulterated wines. This finding indicates that GBL is a naturally occurring component in some wines and may be present in similar products. The concentration detected was approximately 5 μg/mL and was easily observed using a simple extraction technique followed by GC/MSGas chromatography-mass spectrometry
Gas chromatography–mass spectrometry is a method that combines the features of gas-liquid chromatography and mass spectrometry to identify different substances within a test sample. Applications of GC-MS include drug detection, fire investigation, environmental analysis, explosives investigation,...
analysis.
Preparation
GBL can be synthesized from gamma-hydroxybutyric acidGamma-Hydroxybutyric acid
γ-Hydroxybutyric acid , also known as 4-hydroxybutanoic acid and sodium oxybate when used for medicinal purposes, is a naturally occurring substance found in the central nervous system, wine, beef, small citrus fruits, and almost all animals in small amounts. It is also categorized as an illegal...
(GHB) by removal of water or by distillation from such a mixture. It may also be obtained via oxidation of tetrahydrofuran
Tetrahydrofuran
Tetrahydrofuran is a colorless, water-miscible organic liquid with low viscosity at standard temperature and pressure. This heterocyclic compound has the chemical formula 4O. As one of the most polar ethers with a wide liquid range, it is a useful solvent. Its main use, however, is as a precursor...
(THF). One such process, which affords GBL in yields of up to 80%, utilises bromine
Bromine
Bromine ") is a chemical element with the symbol Br, an atomic number of 35, and an atomic mass of 79.904. It is in the halogen element group. The element was isolated independently by two chemists, Carl Jacob Löwig and Antoine Jerome Balard, in 1825–1826...
generated in situ
In situ
In situ is a Latin phrase which translated literally as 'In position'. It is used in many different contexts.-Aerospace:In the aerospace industry, equipment on board aircraft must be tested in situ, or in place, to confirm everything functions properly as a system. Individually, each piece may...
from an aqueous solution of sodium bromate
Sodium bromate
Sodium bromate, the inorganic compound with the chemical formula of NaBrO3, is the sodium salt of bromic acid. It is a strong oxidant, mainly used in continuous or batch dyeing processes involving sulfur or vat dyes and as a hair-permagent, chemical agent, or gold solvent in gold mines when used...
and potassium hydrogen sulfate
Potassium hydrogen sulfate
Potassium bisulfate is the potassium salt of bisulfate anion, with the molecular formula . This compound is commonly used in the conversion of tartrates to bitartrates in wine. Potassium bisulfate is also used as a disintegrating agent in analytical chemistry....
. Another process can proceed by using commercially-available calcium hypochlorite
Calcium hypochlorite
Calcium hypochlorite is a chemical compound with formula 2. It is widely used for water treatment and as a bleaching agent...
in the presence of activating acetic acid
Acetic acid
Acetic acid is an organic compound with the chemical formula CH3CO2H . It is a colourless liquid that when undiluted is also called glacial acetic acid. Acetic acid is the main component of vinegar , and has a distinctive sour taste and pungent smell...
and an appropriate solvent such as acetonitrile. γ-aminobutryic acid (GABA) can also be converted into GBL via a quite simple Sandmeyer reaction: with the addition of sodium nitrite (to an aqueous solution of GABA) and then acidified with an appropriate acid like hydrochloric acid. The acidification allows the sodium nitrite to act as nitrous acid, in layman's terms, and through an intermediary reaction (converting GABA, an amine, to its diazatonium salt, which is then hydrolyzed leaving behind a hydroxyl group where the amino group was), form γ-butyrolactone. The resulting GBL is simply combined with a stoichiometrically correct amount of sodium hydroxide resulting in sodium γ-hydroxybutyrate.
Chemistry
GBL is a lactoneLactone
In chemistry, a lactone is a cyclic ester which can be seen as the condensation product of an alcohol group -OH and a carboxylic acid group -COOH in the same molecule...
. It is hydrolyzed
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...
under basic conditions, for example in a sodium hydroxide solution
Solution
In chemistry, a solution is a homogeneous mixture composed of only one phase. In such a mixture, a solute is dissolved in another substance, known as a solvent. The solvent does the dissolving.- Types of solutions :...
into sodium gamma-hydroxybutyrate, the sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
salt of gamma-hydroxybutyric acid
Gamma-Hydroxybutyric acid
γ-Hydroxybutyric acid , also known as 4-hydroxybutanoic acid and sodium oxybate when used for medicinal purposes, is a naturally occurring substance found in the central nervous system, wine, beef, small citrus fruits, and almost all animals in small amounts. It is also categorized as an illegal...
. Under acidic conditions it forms an equilibrium
Chemical equilibrium
In a chemical reaction, chemical equilibrium is the state in which the concentrations of the reactants and products have not yet changed with time. It occurs only in reversible reactions, and not in irreversible reactions. Usually, this state results when the forward reaction proceeds at the same...
mixture of both compounds. These compounds then may go on to form a polymer
Polymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...
.
Pharmacology
GBL is not active in its own right; its mechanism of action stems from its identity as a prodrugProdrug
A prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...
of GHB.
The hypnotic effect of GHB is enhanced by combination with alcohol. A 2003 rat study showed that GBL in combination with ethanol showed a potentiated hypnotic effect, as the sleep-timing measure was longer than both of the individual components combined.
Pharmacokinetics
GBL is rapidly converted into GHB by lactonase enzymes found in the blood. GBL is more lipophilic (fat soluble) than GHB, and so is absorbed faster and has higher bioavailabilityBioavailability
In pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...
; 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 lactonase enzyme can vary between individuals, meaning that first-time users can show unpredictable results, even from small doses. In many this manifests as slow onset of effects, followed by headaches, semi-consciousness which is distinct from GBL sleep in normal users. If the user decides to try again at a later date, they appear to be able to enjoy the effects normally. Because of these pharmacokinetic differences, GBL tends to be more potent and faster-acting than GHB, but has a shorter duration; whereas the related compound 1,4-butanediol
1,4-Butanediol
1,4-Butanediol is the organic compound with the formula HOCH2CH2CH2CH2OH. This colorless viscous liquid is derived from butane by placement of alcohol groups at each end of the chain. It is one of four stable isomers of butanediol.-Synthesis:...
(1,4-B) tends to be slightly less potent, slower to take effect but longer-acting than GHB.
Use as a nutritional supplement
Due to its property of being a prodrugProdrug
A prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...
of GHB
Gamma-Hydroxybutyric acid
γ-Hydroxybutyric acid , also known as 4-hydroxybutanoic acid and sodium oxybate when used for medicinal purposes, is a naturally occurring substance found in the central nervous system, wine, beef, small citrus fruits, and almost all animals in small amounts. It is also categorized as an illegal...
, GBL was sold as a nutritional supplement after the scheduling of GHB, under the names Revivarant and Renewtrient in the U.S. at least until the end of 1999.
GBL (as well as GHB), when taken internally in therapeutic doses without the presence of other drugs (especially alcohol, as mixing the two can be fatal), has been shown to elevate growth hormone levels in humans to at least 5 times the baseline.
Recreational use
GBL is a prodrugProdrug
A prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...
of GHB
Gamma-Hydroxybutyric acid
γ-Hydroxybutyric acid , also known as 4-hydroxybutanoic acid and sodium oxybate when used for medicinal purposes, is a naturally occurring substance found in the central nervous system, wine, beef, small citrus fruits, and almost all animals in small amounts. It is also categorized as an illegal...
. To bypass GHB restriction laws, home synthesis kits were introduced to transform GBL and/or 1,4-B into GHB. GBL can also be used as a recreational drug by itself.
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
and death
Death
Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....
.
Metabolism takes place in stomach and blood plasma. The duration and onset of GBL is shorter and has a faster onset than GHB. Otherwise, effects are similar to GHB, although weight for weight it is significantly more powerful due to being absorbed faster and its higher bioavailability, meaning dosage must be lowered accordingly. If taken undiluted by mouth, GBL can cause esophageal and gastro-intestinal irritation. It is possible for oral ingestion of GBL to cause nausea and other similar problems, possibly more so than with GHB.
Excessive use
GHB (gamma hydroxybutyrate) and GBL (gamma butyrolactone) are substances which are often used as recreational drugs. GHB has two effects, at low doses it has a euphoric effect (which is why it is sometimes referred to as liquid ecstasy). At higher doses it acts like a sedative and can make the user unconscious very quickly.Addictiveness
Frequent use of GHB/GBL, even when taken long-term and in moderate doses, does not appear to cause significant physical dependency in the greater majority of its users. In many people, quitting or temporarily abstaining from use of the drugs is achieved with minimal or no difficulty. However, when consumed in excessive amounts with a high frequency of dosing, physical and psychological dependence can develop.Frequent use of alcohol (which induces similar effects) can directly translate to physical and usually psychological addiction, where the heavy user can suffer painful and even life-threatening withdrawals.
There are some reports of GHB/GBL users adopting a '24/7' dosing regime. This is where the user has become tolerant to the effects of the drug, increasing the dosage and frequency of dosage simply to avoid withdrawal symptoms.
For those users who do report withdrawal symptoms upon quitting the use of GHB/GBL, symptoms seem to depend on the dosage and the length of time the drug was used for. Light to moderate users often experience insomnia and sleep-related problems, whereas heavy, prolonged use can cause severe withdrawal symptoms similar to Benzodiazepine withdrawal syndrome
Benzodiazepine withdrawal syndrome
Benzodiazepine withdrawal syndrome—often abbreviated to benzo withdrawal—is the cluster of symptoms which appear when a person who has taken benzodiazepines long term and has developed benzodiazepine dependence stops taking benzodiazepine drug or during dosage reductions...
(BWS).
Dose
A milliliter of pure GBL metabolizes to roughly 1.4 g of GHB, so doses are measured in the single milliliter range, either taken all at once or sipped over the course of a night. GBL has a distinctive taste and odour, described as being bitter and comparable to stale water or burnt plastic. This differs significantly from GHB, which is described as having a decidedly "salty" taste.Legal status of GBL
Canada: GBL is a Controlled Substance under Schedule VI of the "Controlled Drugs and Substances Act" in Canada. Schedule VI of the "Controlled Drugs and Substances Act" requires vendors to collect information regarding purchases of GBL. The Act also prohibits the import and export of GBL into or out of Canada classifying it as either an indictable offense punishable with up to 10 years in prison or an offense punishable on summary conviction liable to imprisonment for up to eighteen months. It is not illegal for an individual to possess GBL in Canada.United Kingdom: GBL was classified as a Class C drug from 23 December 2009, with a prison term of up to two years for possession and 14 years for dealing, by the end of 2009.
Sweden: GBL is not classified as a drug but as a health-endangering substance. Although recently passed legislation to enter into force on 1 April 2011 will make it possible to handle narcotics for industrial purposes will enable GBL and 1,4-Butanediol to be classified as controlled substances.
Australia: GBL is a border controlled substance and is illegal to import into Australia without a permit. The importation of a commercial quantity of a border controlled drug (over 1kg of GBL) is punishable by up to life imprisonment and/or an $825000 fine.
United States: GBL is regulated as a List 1 controlled chemical. As a GHB analog, it is treated as a controlled substance under Schedule I of the "Controlled Substances Act" if intended for human consumption.
Poland: In Poland
Poland
Poland , officially the Republic of Poland , is a country in Central Europe bordered by Germany to the west; the Czech Republic and Slovakia to the south; Ukraine, Belarus and Lithuania to the east; and the Baltic Sea and Kaliningrad Oblast, a Russian exclave, to the north...
, GBL is not classified as a drug and can be purchased in chemistry shops as a solvent.
Germany: GBL is not listed in the narcotics law, but its distribution is controlled. Possession is not illegal, but may be punished according to the Medicines Act, when intended to be sold for human consumption or synthesis of GHB. In recent years, an increase of GBL consumption has been observed due to the prohibition of GHB.
Israel: GBL was classified as a proscribed substance from 2007, .
See also
- gamma-Hydroxybutyrate (GHB)
- 1,4-Butanediol1,4-Butanediol1,4-Butanediol is the organic compound with the formula HOCH2CH2CH2CH2OH. This colorless viscous liquid is derived from butane by placement of alcohol groups at each end of the chain. It is one of four stable isomers of butanediol.-Synthesis:...
(1,4-B)
External links
- Erowid on GBL
- BBC News story: The paint stripper drug that kills, October 7, 2005.
- “All About GHB," a NIDA Neuroscience Consortium and OSPC “Cutting Edge” colloquium (27 June 2000 at the Doubletree hotel, Rockville, MD) Organized by Drs. Jerry Frankenheim and Minda Lynch in response to the rapid ascent of GHB and its precursors, GBL and 1,4-butanediol, as public health concerns.