Thujone
Encyclopedia
Thujone is a ketone
and a monoterpene
that occurs naturally in two diastereomer
ic forms: (−)-α-thujone and (+)-β-thujone. It has a menthol
odor. Even though it is best known as a chemical compound
in the spirit absinthe
, recent tests show absinthe contains only small quantities of thujone, and may or may not be responsible for absinthe's reported psychedelic effects. Thujone acts on GABA and 5-HT3
receptors in the brain. In many countries the amount of thujone allowed in food or drink products is regulated.
In addition to (−)-α-thujone and (+)-β-thujone, there are their enantiomeric forms, (+)-α-thujone and (−)-β-thujone:
(genus Thuja, hence the derivation of the name), Nootka Cypress
, some juniper
s, mugwort, oregano
, common sage
, tansy
and wormwood
, most notably grand wormwood (Artemisia absinthium
), usually as a mix of isomers in a 1:2 ratio. It is also found in various species of mentha
(mint).
on the cannabinoid receptors. Today this is known to be false because studies have shown that thujone does not activate these receptors. Thujone is a GABAA
receptor antagonist. By inhibiting GABA receptor activation, neurons may fire more easily which can cause muscle spasms and convulsions. Thujone is also a 5-HT3 antagonist
.
A toxicology study in mice of alpha-thujone, the more active of the two isomers, found that the median lethal dose, or LD50, is around 45 mg/kg, with 0% mortality rate at 30 mg/kg and 100% at 60 mg/kg. Mice exposed to the higher dose had convulsions that led to death in 1 minute. From 30 to 45 mg/kg the mice experienced muscle spasms in the legs which progressed to general convulsions until death or recovery. Pretreatment with diazepam
, phenobarbital
or 1 g/kg of ethanol
protected against a lethal 100 mg/kg dose. These findings are in line with other GABA antagonists. The study also found that alpha-thujone was metabolized quickly in the liver.
Researchers at Rutgers University tested attention performance with low and high doses of thujone in alcohol. The researchers administered 0.28 mg/kg in alcohol, 0.028 mg/kg in alcohol and just alcohol to their subjects. The high dose had a short term negative effect on attention performance. The lower dose showed no noticeable effect.
Thujone is reported to be toxic to both brain and liver cells and could cause convulsions if used in too high a dose. Other thujone-containing plants such as the tree Arborvitae
(Thuja occidentalis) are used in herbal medicine, mainly for their immune-system stimulating effects. Side-effects from the essential oil
of this plant include anxiety and sleeplessness, which confirms the central nervous system effects of thujone.
. In the past it was thought that absinthe contained up to 260–350 mg/L thujone, but modern tests have shown this to be far too high. A 2008 study of 13 pre-ban (1895–1910) bottles using gas chromatography-mass spectrometry (GC-MS) found that the bottles had between 0.5 mg/L and 48.3 mg/L and averaged 25.4 mg/L A 2005 study recreated three 1899 high-wormwood recipes and tested with GC-MS, and found that the highest contained 4.3 mg/L thujone. GC-MS testing is important in this capacity, because gas chromatography alone may record an inaccurately high reading of thujone as other compounds may interfere with and add to the apparent measured amount.
Absinthe produced under the modern EU (European Union
) limits for thujone content may have a maximum of 35 mg/L, as well as any alcoholic beverage prepared with Artemisia
species. Other alcoholic beverages may contain 10 mg/L. Some modern producers list their thujone levels on the bottle, with some producers claiming over 100 mg/L thujone.
s. In light of modern evidence, these conclusions are questionable, as they are based on a poor understanding of other compounds and diseases, and clouded by Magnan's belief that alcohol and absinthe were "degenerating" the French race.
After absinthe was banned, research dropped off until the 1970s when the British scientific journal Nature
published an article comparing the molecular shape of thujone to tetrahydrocannabinol
(THC), the primary psychoactive substance found in cannabis
(marijuana), and hypothesized it would act the same way on the brain, sparking the myth that thujone was a cannabinoid.
More recently, following European Council Directive No. 88/388/EEC (1988) allowing certain levels of thujone in foodstuffs in the EU, the studies described above were conducted and found only minute levels of thujone in absinthe.
species, White Cedar
, oak moss, tansy
or Yarrow
must be thujone-free. Other herbs that contain thujone have no restrictions. For example, sage
and sage oil
(which can be up to 50% thujone) are on the Food and Drug Administration
's list of substances generally recognized as safe
. Absinthe offered for sale in the United States must be "thujone-free", which is interpreted as containing less than 10 mg/kg . There are now therefore a number of thujone-containing absinthes that can be legally imported.
, liquor laws are the domain of the provincial governments. British Columbia
has no limits on thujone content; Alberta
, Ontario
and Nova Scotia
allow 10 mg/kg thujone; Québec
allows 15 mg per kg ; Manitoba
allows 6–8 mg thujone per litre; and all other provinces do not allow the sale of absinthe containing thujone (although, in Saskatchewan
, one can purchase any liquor available in the world upon the purchase of a maximum of one case, usually twelve 750-mL bottles or 9L). The individual liquor boards must approve each product before it may be sold on shelves.
Ketone
In organic chemistry, a ketone is an organic compound with the structure RCR', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group bonded to two other carbon atoms. Many ketones are known and many are of great importance in industry and in biology...
and a monoterpene
Terpene
Terpenes are a large and diverse class of organic compounds, produced by a variety of plants, particularly conifers, though also by some insects such as termites or swallowtail butterflies, which emit terpenes from their osmeterium. They are often strong smelling and thus may have had a protective...
that occurs naturally in two diastereomer
Diastereomer
Diastereomers are stereoisomers that are not enantiomers.Diastereomerism occurs when two or more stereoisomers of a compound have different configurations at one or more of the equivalent stereocenters and are not mirror images of each other.When two diastereoisomers differ from each other at...
ic forms: (−)-α-thujone and (+)-β-thujone. It has a menthol
Menthol
Menthol is an organic compound made synthetically or obtained from peppermint or other mint oils. It is a waxy, crystalline substance, clear or white in color, which is solid at room temperature and melts slightly above. The main form of menthol occurring in nature is -menthol, which is assigned...
odor. Even though it is best known as a chemical compound
Chemical compound
A chemical compound is a pure chemical substance consisting of two or more different chemical elements that can be separated into simpler substances by chemical reactions. Chemical compounds have a unique and defined chemical structure; they consist of a fixed ratio of atoms that are held together...
in the spirit absinthe
Absinthe
Absinthe is historically described as a distilled, highly alcoholic beverage. It is an anise-flavoured spirit derived from herbs, including the flowers and leaves of the herb Artemisia absinthium, commonly referred to as "grande wormwood", together with green anise and sweet fennel...
, recent tests show absinthe contains only small quantities of thujone, and may or may not be responsible for absinthe's reported psychedelic effects. Thujone acts on GABA and 5-HT3
5-HT3 receptor
The 5-HT3 receptor is a member of the superfamily of ligand-gated ion channels, a superfamily that also includes the neuronal nicotinic acetylcholine receptors , and the inhibitory neurotransmitter receptors for GABA and glycine...
receptors in the brain. In many countries the amount of thujone allowed in food or drink products is regulated.
In addition to (−)-α-thujone and (+)-β-thujone, there are their enantiomeric forms, (+)-α-thujone and (−)-β-thujone:
Sources
Thujone is found in a number of plants, such as arborvitaeThuja
Thuja is a genus of coniferous trees in the Cupressaceae . There are five species in the genus, two native to North America and three native to eastern Asia...
(genus Thuja, hence the derivation of the name), Nootka Cypress
Callitropsis nootkatensis
Nootka Cypress , formerly Cupressus nootkatensis, Xanthocyparis nootkatensis or Chamaecyparis nootkatensis, is a cypress with a chequered taxonomic and nomenclatural history. This species goes by many common names including Nootka Cypress, Yellow Cypress, and Alaska Cypress...
, some juniper
Juniper
Junipers are coniferous plants in the genus Juniperus of the cypress family Cupressaceae. Depending on taxonomic viewpoint, there are between 50-67 species of juniper, widely distributed throughout the northern hemisphere, from the Arctic, south to tropical Africa in the Old World, and to the...
s, mugwort, oregano
Oregano
Oregano – scientifically named Origanum vulgare by Carolus Linnaeus – is a common species of Origanum, a genus of the mint family . It is native to warm-temperate western and southwestern Eurasia and the Mediterranean region.Oregano is a perennial herb, growing from 20–80 cm tall,...
, common sage
Common sage
Salvia officinalis is a small, perennial, evergreen subshrub, with woody stems, grayish leaves, and blue to purplish flowers. It is a member of the family Lamiaceae and is native to the Mediterranean region, though it has naturalized in many places throughout the world...
, tansy
Tansy
Tansy is a perennial, herbaceous flowering plant of the aster family, native to temperate Europe and Asia. It has been introduced to other parts of the world and in some areas has become invasive...
and wormwood
Artemisia (plant)
Artemisia is a large, diverse genus of plants with between 200 to 400 species belonging to the daisy family Asteraceae. It comprises hardy herbs and shrubs known for their volatile oils. They grow in temperate climates of the Northern Hemisphere and Southern Hemisphere, usually in dry or semi-dry...
, most notably grand wormwood (Artemisia absinthium
Artemisia absinthium
Artemisia absinthium is a species of wormwood, native to temperate regions of Eurasia and northern Africa....
), usually as a mix of isomers in a 1:2 ratio. It is also found in various species of mentha
Mentha
Mentha is a genus of flowering plants in the family Lamiaceae . The species are not clearly distinct and estimates of the number of species varies from 13 to 18. Hybridization between some of the species occurs naturally...
(mint).
Pharmacology
Based on studies that looked only at molecular shape, for many years thujone was thought to act similarly to THCTetrahydrocannabinol
Tetrahydrocannabinol , also known as delta-9-tetrahydrocannabinol , Δ1-THC , or dronabinol, is the main chemical psychoactive substance found in the cannabis plant. It was first isolated in 1964. In pure form, it is a glassy solid when cold, and becomes viscous and sticky if warmed...
on the cannabinoid receptors. Today this is known to be false because studies have shown that thujone does not activate these receptors. Thujone is a GABAA
Gamma-aminobutyric acid
γ-Aminobutyric acid is the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays a role in regulating neuronal excitability throughout the nervous system...
receptor antagonist. By inhibiting GABA receptor activation, neurons may fire more easily which can cause muscle spasms and convulsions. Thujone is also a 5-HT3 antagonist
5-HT3 antagonist
The 5-HT3 antagonists are a class of medications that act as receptor antagonists at the 5-HT3 receptor, a subtype of serotonin receptor found in terminals of the vagus nerve and in certain areas of the brain....
.
A toxicology study in mice of alpha-thujone, the more active of the two isomers, found that the median lethal dose, or LD50, is around 45 mg/kg, with 0% mortality rate at 30 mg/kg and 100% at 60 mg/kg. Mice exposed to the higher dose had convulsions that led to death in 1 minute. From 30 to 45 mg/kg the mice experienced muscle spasms in the legs which progressed to general convulsions until death or recovery. Pretreatment with diazepam
Diazepam
Diazepam , first marketed as Valium by Hoffmann-La Roche is a benzodiazepine drug. Diazepam is also marketed in Australia as Antenex. It is commonly used for treating anxiety, insomnia, seizures including status epilepticus, muscle spasms , restless legs syndrome, alcohol withdrawal,...
, phenobarbital
Phenobarbital
Phenobarbital or phenobarbitone is a barbiturate, first marketed as Luminal by Friedr. Bayer et comp. It is the most widely used anticonvulsant worldwide, and the oldest still commonly used. It also has sedative and hypnotic properties but, as with other barbiturates, has been superseded by the...
or 1 g/kg of ethanol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
protected against a lethal 100 mg/kg dose. These findings are in line with other GABA antagonists. The study also found that alpha-thujone was metabolized quickly in the liver.
Researchers at Rutgers University tested attention performance with low and high doses of thujone in alcohol. The researchers administered 0.28 mg/kg in alcohol, 0.028 mg/kg in alcohol and just alcohol to their subjects. The high dose had a short term negative effect on attention performance. The lower dose showed no noticeable effect.
Thujone is reported to be toxic to both brain and liver cells and could cause convulsions if used in too high a dose. Other thujone-containing plants such as the tree Arborvitae
Thuja
Thuja is a genus of coniferous trees in the Cupressaceae . There are five species in the genus, two native to North America and three native to eastern Asia...
(Thuja occidentalis) are used in herbal medicine, mainly for their immune-system stimulating effects. Side-effects from the essential oil
Essential oil
An essential oil is a concentrated hydrophobic liquid containing volatile aroma compounds from plants. Essential oils are also known as volatile oils, ethereal oils or aetherolea, or simply as the "oil of" the plant from which they were extracted, such as oil of clove...
of this plant include anxiety and sleeplessness, which confirms the central nervous system effects of thujone.
Thujone in absinthe
Thujone is most famous for being a compound in the spirit absintheAbsinthe
Absinthe is historically described as a distilled, highly alcoholic beverage. It is an anise-flavoured spirit derived from herbs, including the flowers and leaves of the herb Artemisia absinthium, commonly referred to as "grande wormwood", together with green anise and sweet fennel...
. In the past it was thought that absinthe contained up to 260–350 mg/L thujone, but modern tests have shown this to be far too high. A 2008 study of 13 pre-ban (1895–1910) bottles using gas chromatography-mass spectrometry (GC-MS) found that the bottles had between 0.5 mg/L and 48.3 mg/L and averaged 25.4 mg/L A 2005 study recreated three 1899 high-wormwood recipes and tested with GC-MS, and found that the highest contained 4.3 mg/L thujone. GC-MS testing is important in this capacity, because gas chromatography alone may record an inaccurately high reading of thujone as other compounds may interfere with and add to the apparent measured amount.
Absinthe produced under the modern EU (European Union
European Union
The European Union is an economic and political union of 27 independent member states which are located primarily in Europe. The EU traces its origins from the European Coal and Steel Community and the European Economic Community , formed by six countries in 1958...
) limits for thujone content may have a maximum of 35 mg/L, as well as any alcoholic beverage prepared with Artemisia
Artemisia (plant)
Artemisia is a large, diverse genus of plants with between 200 to 400 species belonging to the daisy family Asteraceae. It comprises hardy herbs and shrubs known for their volatile oils. They grow in temperate climates of the Northern Hemisphere and Southern Hemisphere, usually in dry or semi-dry...
species. Other alcoholic beverages may contain 10 mg/L. Some modern producers list their thujone levels on the bottle, with some producers claiming over 100 mg/L thujone.
History
The compound was discovered after absinthe became popular in the mid-19th century. Dr. Valentin Magnan, who studied alcoholism, tested pure wormwood oil on animals and discovered it caused seizures independent from the effects of alcohol. Based on this, it was assumed that absinthe, which contains a small amount of wormwood oil, was more dangerous than ordinary alcohol. Eventually thujone was isolated as the cause of these reactions. Magnan went on to study 250 abusers of alcohol and noted that those who drank absinthe had seizures and hallucinationHallucination
A hallucination, in the broadest sense of the word, is a perception in the absence of a stimulus. In a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid,...
s. In light of modern evidence, these conclusions are questionable, as they are based on a poor understanding of other compounds and diseases, and clouded by Magnan's belief that alcohol and absinthe were "degenerating" the French race.
After absinthe was banned, research dropped off until the 1970s when the British scientific journal Nature
Nature (journal)
Nature, first published on 4 November 1869, is ranked the world's most cited interdisciplinary scientific journal by the Science Edition of the 2010 Journal Citation Reports...
published an article comparing the molecular shape of thujone to tetrahydrocannabinol
Tetrahydrocannabinol
Tetrahydrocannabinol , also known as delta-9-tetrahydrocannabinol , Δ1-THC , or dronabinol, is the main chemical psychoactive substance found in the cannabis plant. It was first isolated in 1964. In pure form, it is a glassy solid when cold, and becomes viscous and sticky if warmed...
(THC), the primary psychoactive substance found in cannabis
Cannabis (drug)
Cannabis, also known as marijuana among many other names, refers to any number of preparations of the Cannabis plant intended for use as a psychoactive drug or for medicinal purposes. The English term marijuana comes from the Mexican Spanish word marihuana...
(marijuana), and hypothesized it would act the same way on the brain, sparking the myth that thujone was a cannabinoid.
More recently, following European Council Directive No. 88/388/EEC (1988) allowing certain levels of thujone in foodstuffs in the EU, the studies described above were conducted and found only minute levels of thujone in absinthe.
European Union
Maximum thujone levels in the EU are:- 0.5 mg/kg in food not prepared with sageCommon sageSalvia officinalis is a small, perennial, evergreen subshrub, with woody stems, grayish leaves, and blue to purplish flowers. It is a member of the family Lamiaceae and is native to the Mediterranean region, though it has naturalized in many places throughout the world...
and non alcoholic beverages prepared with ArtemisiaArtemisia (plant)Artemisia is a large, diverse genus of plants with between 200 to 400 species belonging to the daisy family Asteraceae. It comprises hardy herbs and shrubs known for their volatile oils. They grow in temperate climates of the Northern Hemisphere and Southern Hemisphere, usually in dry or semi-dry...
species. - 10 mg/kg in alcoholic beverages not prepared with Artemisia species.
- 25 mg/kg in food prepared with sageCommon sageSalvia officinalis is a small, perennial, evergreen subshrub, with woody stems, grayish leaves, and blue to purplish flowers. It is a member of the family Lamiaceae and is native to the Mediterranean region, though it has naturalized in many places throughout the world...
. - 35 mg/kg in alcoholic beverages prepared with Artemisia species.
United States
Foods or beverages that contain ArtemisiaArtemisia (plant)
Artemisia is a large, diverse genus of plants with between 200 to 400 species belonging to the daisy family Asteraceae. It comprises hardy herbs and shrubs known for their volatile oils. They grow in temperate climates of the Northern Hemisphere and Southern Hemisphere, usually in dry or semi-dry...
species, White Cedar
White Cedar
White Cedar may refer to several different trees:* Cupressaceae:** Chamaecyparis thyoides – Atlantic White Cypress** Cupressus lusitanica – Mexican White Cedar** Thuja occidentalis – Eastern Arborvitae* Meliaceae:...
, oak moss, tansy
Tansy
Tansy is a perennial, herbaceous flowering plant of the aster family, native to temperate Europe and Asia. It has been introduced to other parts of the world and in some areas has become invasive...
or Yarrow
Yarrow
Achillea millefolium or yarrow is a flowering plant in the family Asteraceae, native to the Northern Hemisphere. In New Mexico and southern Colorado, it is called plumajillo, or "little feather", for the shape of the leaves. In antiquity, yarrow was known as herbal militaris, for its use in...
must be thujone-free. Other herbs that contain thujone have no restrictions. For example, sage
Common sage
Salvia officinalis is a small, perennial, evergreen subshrub, with woody stems, grayish leaves, and blue to purplish flowers. It is a member of the family Lamiaceae and is native to the Mediterranean region, though it has naturalized in many places throughout the world...
and sage oil
Sage oil
Sage oil is the essential oil made from the culinary herb sage, Salvia officinalis. In addition to its valuable flavoring characteristics, sage oil can contain as much as 50% thujone by weight. The exact amount varies based on the time in the season and which part of the plant is tested...
(which can be up to 50% thujone) are on the Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
's list of substances generally recognized as safe
Generally recognized as safe
Generally recognized as safe is an American Food and Drug Administration designation that a chemical or substance added to food is considered safe by experts, and so is exempted from the usual Federal Food, Drug, and Cosmetic Act food additive tolerance requirements.-History:On January 1, 1958,...
. Absinthe offered for sale in the United States must be "thujone-free", which is interpreted as containing less than 10 mg/kg . There are now therefore a number of thujone-containing absinthes that can be legally imported.
Canada
In CanadaCanada
Canada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...
, liquor laws are the domain of the provincial governments. British Columbia
British Columbia
British Columbia is the westernmost of Canada's provinces and is known for its natural beauty, as reflected in its Latin motto, Splendor sine occasu . Its name was chosen by Queen Victoria in 1858...
has no limits on thujone content; Alberta
Alberta
Alberta is a province of Canada. It had an estimated population of 3.7 million in 2010 making it the most populous of Canada's three prairie provinces...
, Ontario
Ontario
Ontario is a province of Canada, located in east-central Canada. It is Canada's most populous province and second largest in total area. It is home to the nation's most populous city, Toronto, and the nation's capital, Ottawa....
and Nova Scotia
Nova Scotia
Nova Scotia is one of Canada's three Maritime provinces and is the most populous province in Atlantic Canada. The name of the province is Latin for "New Scotland," but "Nova Scotia" is the recognized, English-language name of the province. The provincial capital is Halifax. Nova Scotia is the...
allow 10 mg/kg thujone; Québec
Quebec
Quebec or is a province in east-central Canada. It is the only Canadian province with a predominantly French-speaking population and the only one whose sole official language is French at the provincial level....
allows 15 mg per kg ; Manitoba
Manitoba
Manitoba is a Canadian prairie province with an area of . The province has over 110,000 lakes and has a largely continental climate because of its flat topography. Agriculture, mostly concentrated in the fertile southern and western parts of the province, is vital to the province's economy; other...
allows 6–8 mg thujone per litre; and all other provinces do not allow the sale of absinthe containing thujone (although, in Saskatchewan
Saskatchewan
Saskatchewan is a prairie province in Canada, which has an area of . Saskatchewan is bordered on the west by Alberta, on the north by the Northwest Territories, on the east by Manitoba, and on the south by the U.S. states of Montana and North Dakota....
, one can purchase any liquor available in the world upon the purchase of a maximum of one case, usually twelve 750-mL bottles or 9L). The individual liquor boards must approve each product before it may be sold on shelves.
External links
- Absinthe absolved, Cern Courier, July 8, 2008
- Thujone.Info — Databank of peer reviewed articles on thujone, absinthe, absinthism, and independent thujone ratings of some commercial brands.
- The Shaky History of Thujone - Wormwood Society article on thujone and its history.