Thujone is a
ketoneIn organic chemistry, a ketone is a type of compound that features a carbonyl group bonded to two other carbon atoms, i.e., R3CCO-CR3 where R can be a variety of atoms and groups of atoms...
and a
monoterpeneTerpenes are a large and varied class of hydrocarbons, produced primarily by a wide variety of plants, particularly conifers, though also by some insects such as termites or swallowtail butterflies, which emit terpenes from their osmeterium....
that exists in two
stereoisomericStereoisomers are isomeric molecules that have the same molecular formula and sequence of bonded atoms , but which differ only in the three-dimensional orientations of their atoms in space.-Difference from structural isomerism:...
forms: (+)-3-thujone or α-thujone and (−)-3-thujone or β-thujone. It has a
mentholMenthol 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 for being a chemical in
absintheAbsinthe is historically described as a distilled, highly alcoholic beverage. It is an anise-flavored spirit derived from herbs, including the flowers and leaves of the herb Artemisia absinthium, commonly referred to as "grande wormwood". Absinthe traditionally has a natural green color but can...
, 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 and exhibits slight psychoactive response .
Thujone is a
ketoneIn organic chemistry, a ketone is a type of compound that features a carbonyl group bonded to two other carbon atoms, i.e., R3CCO-CR3 where R can be a variety of atoms and groups of atoms...
and a
monoterpeneTerpenes are a large and varied class of hydrocarbons, produced primarily by a wide variety of plants, particularly conifers, though also by some insects such as termites or swallowtail butterflies, which emit terpenes from their osmeterium....
that exists in two
stereoisomericStereoisomers are isomeric molecules that have the same molecular formula and sequence of bonded atoms , but which differ only in the three-dimensional orientations of their atoms in space.-Difference from structural isomerism:...
forms: (+)-3-thujone or α-thujone and (−)-3-thujone or β-thujone. It has a
mentholMenthol 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 for being a chemical in
absintheAbsinthe is historically described as a distilled, highly alcoholic beverage. It is an anise-flavored spirit derived from herbs, including the flowers and leaves of the herb Artemisia absinthium, commonly referred to as "grande wormwood". Absinthe traditionally has a natural green color but can...
, 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 and exhibits slight psychoactive response . In many countries the amount of thujone allowed in food or drink products is regulated.
Sources
Thujone is found in a number of plants, such as
arborvitaeThuja 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 CypressNootka Cypress , formerly Cupressus nootkatensis, Xanthocyparis nootkatensis or Chamaecyparis nootkatensis, is a cypress with a chequered taxonomic and nomenclatural history....
, some
juniperJunipers 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,
common sageSalvia officinalis is a small perennial evergreen subshrub, with woody stems, grayish leaves, and blue to purplish flowers. It is a member of the mint family, Lamiaceae...
,
tansyTansy is a perennial, herbaceous flowering plant of the aster family that is native to temperate Europe and Asia. It has been introduced to other parts of the world and, in some areas, has become invasive...
and
wormwoodArtemisia 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 absinthiumArtemisia 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
menthaMentha is a genus of about 25 species of flowering plants in the family Lamiaceae . Species within Mentha have a subcosmopolitan distribution across Europe, Africa, Asia, Australia, and North America. Several mint hybrids commonly occur.Mints are aromatic, almost exclusively perennial, rarely...
(mint).
Pharmacology
For many years thujone was thought to act on the cannabinoid receptors similar to
THCTetrahydrocannabinol , also known as delta-9-tetrahydrocannabinol , Δ
1-THC , or dronabinol, is the main psychoactive substance found in the Cannabis plant....
based on studies that only looked at the molecules' shapes. This is known to be false today and studies show thujone does not activate these receptors. Thujone is a
GABAAγ-Aminobutyric acid is the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays an important role in regulating neuronal excitability throughout the nervous system. In humans, GABA is also directly responsible for the regulation of muscle tone...
receptor antagonist. By inhibiting GABA receptor activation neurons may fire more easily which can cause muscle spasms and convulsions.
A toxicology study of alpha-thujone, the more active of the two isomers, in mice found the median lethal dose, or
LD50In toxicology, the median lethal dose, LD50 , LC50 or LCt50 of a toxic substance or radiation is the dose required to kill half the members of a tested population...
, is around 45 mg/kg, with 0% mortality rate at 30 mg/kg and 100% at 60 mg/kg. Those exposed to the higher dose had convulsions that led to death in 1 minute. From 30 to 45 mg/kg the mice would experience muscle spasms in the legs which progressed to general convulsions until death or recovery. Pretreatment of
diazepamDiazepam , first marketed as Valium by Hoffmann-La Roche, is a benzodiazepine derivative drug. It possesses anxiolytic, anticonvulsant, hypnotic, sedative, skeletal muscle relaxant, and amnestic properties. It is commonly used for treating anxiety, insomnia, seizures, muscle spasms, restless legs...
,
phenobarbitalPhenobarbital or phenobarbitone is a barbiturate, first marketed as Luminal by Friedr. Bayer et comp. It is the most widely used anticonvulsant worldwide...
or 1 g/kg of
ethanolEthanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug, best known as the type of alcohol found in alcoholic beverages and in modern thermometers. Ethanol is one of the oldest recreational drugs...
protected against a lethal 100 mg/kg dose. These findings are in line with other GABA antagonists. This study also found alpha-thujone was quickly metabolized in the mouse's liver.
Researchers at Rutgers University tested attention performance with low, and high doses of thujone in alcohol. The researchers administered 0.28 mg/kg thujone 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
Arbor vitaeArbor vitae may refer to:In anatomy:* Arbor vitae , white matter of the cerebellum* arbor vitæ uteri, a part of the canal of the cervixIn other uses:* Arborvitae, Thuja, a genus of coniferous trees in the cypress family...
(
Thuja occidentalis) are used in herbal medicine, mainly for their immune-system stimulating effects, however side effects from the
essential oilAn essential oil is a concentrated, hydrophobic liquid containing volatile aroma compounds from plants. Essential oils are also known as volatile or ethereal oils, or simply as the "oil of" the plant from which they were extracted, such as oil of clove. An oil is "essential" in the sense that it...
of this plant include anxiety and sleeplessness, confirming the central nervous system effects of thujone.
Thujone in absinthe
Thujone is most famous for being a chemical in the drink
absintheAbsinthe is historically described as a distilled, highly alcoholic beverage. It is an anise-flavored spirit derived from herbs, including the flowers and leaves of the herb Artemisia absinthium, commonly referred to as "grande wormwood". Absinthe traditionally has a natural green color but can...
and some modern producers list their supposed thujone levels on the bottle. At one time it was estimated absinthe contained up to 260–350 mg/L thujone, but this has been shown false through testing. A 2005 study recreated three 1899 high-wormwood recipes and tested them with gas chromatography-mass spectrometry (GC-MS). The highest contained 4.3 mg/L thujone. A 1930s Pernod Tarragona was also tested and contained 1.8 mg/L thujone. These results match earlier findings showing a vintage 1900s bottle contained 6 mg/L. GC-MS testing is important in this capacity, because gas chromatography alone may record an inaccurately high reading of thujone because of other chemicals present that interfere and add to the apparent measured amount. Through these tests it has become evident that authentic absinthe contains very little thujone. Anyone bingeing on absinthe would die of alcohol poisoning long before the thujone could cause any life-threatening effects.
History
Thujone was an unknown chemical until absinthe became popular in the mid 1800s. Dr.
Valentin MagnanValentin Magnan was a French psychiatrist who was a native of Perpignan.He studied medicine in Lyon and Paris, where he was a student of Jules Baillarger and Jean-Pierre Falret...
, who studied
alcoholismAlcoholism is a term with multiple and sometimes conflicting definitions. In common and historic usage, alcoholism is any condition that results in the continued consumption of alcoholic beverages, despite health problems and negative social consequences...
, tested pure wormwood oil on animals and discovered it caused an epileptic reaction different from plain 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 noting that those who drank absinthe had epileptic attacks and hallucinations. In light of modern evidence, these conclusions are questionable and probably based on a poor understanding of other chemicals and diseases and were 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 Nature magazine published an article comparing the molecular shape of thujone to
THCThe acronym THC has several possible meanings:* Tetrahydrocannabinol, the main active chemical compound in Cannabis* Toronto Hemp Company, the world's largest Hemp and Cannabis Culture store, located in Toronto, Canada....
, and hypothesized it would act the same way on the brain, sparking the myth that thujone is a cannabinoid.
More recently, following the European Council Directive No. 88/388
http://ec.europa.eu/food/fs/sfp/addit_flavor/flav09_en.pdf allowing certain levels of thujone in foodstuffs in the EU, the studies described above were conducted and found only minute levels of thujone in
absintheAbsinthe is historically described as a distilled, highly alcoholic beverage. It is an anise-flavored spirit derived from herbs, including the flowers and leaves of the herb Artemisia absinthium, commonly referred to as "grande wormwood". Absinthe traditionally has a natural green color but can...
.
European Union
Maximum thujone levels in the EU are:
- 0.5 mg/kg in food not prepared with 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 mint family, Lamiaceae...
and non alcoholic beverages.
- 5 mg/kg in alcoholic beverages with 25% or less ABV
Alcohol by volume is a standard measure of how much alcohol is contained in an alcoholic beverage...
.
- 10 mg/kg in alcoholic beverages with more than 25% ABV.
- 25 mg/kg in food prepared with 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 mint family, Lamiaceae...
.
- 35 mg/kg in alcohol labeled as bitters
A bitters is an alcoholic beverage that contains herbal essences, has a bitter or bittersweet flavor, and is typically flavored with citrus...
.
United States
Foods or beverages that contain
ArtemisiaArtemisia 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 CedarWhite 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,
tansyTansy is a perennial, herbaceous flowering plant of the aster family that is native to temperate Europe and Asia. It has been introduced to other parts of the world and, in some areas, has become invasive...
or
YarrowAchillea millefolium or yarrow is a flowering plant in the family Asteraceae, native to the Northern Hemisphere...
must be thujone-free. Other herbs that contain thujone have no restrictions. For example,
sageSalvia officinalis is a small perennial evergreen subshrub, with woody stems, grayish leaves, and blue to purplish flowers. It is a member of the mint family, Lamiaceae...
and
sage oilSage oil is the essential oil made from the culinary herb sage, Salvia officinalis. In addition to its valuable flavoring characteristics, it has been suggested that 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...
(which can be up to 50% thujone) are on the
Food and Drug AdministrationThe Food and Drug Administration is a Government agency of the United States Department of Health and Human Services and is responsible for regulating and supervising the safety of foods, tobacco products, dietary supplements, Medication drugs, vaccines, Biopharmaceutical, blood transfusion,...
's list of substances
generally recognized as safeGenerally 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.GRAS exemptions are granted...
. 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 is a country occupying most of northern North America, extending 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 ColumbiaBritish Columbia is the westernmost of Canada's provinces and is famed for its natural beauty, as reflected in its Latin motto, Splendor sine occasu . In 1871, it became the sixth province of Canada.The capital of British Columbia is Victoria, the 15th largest metropolitan region in Canada...
has no limits on thujone content;
AlbertaAlberta is one of Canada's prairie provinces. It became a province on September 1, 1905.Alberta is located in western Canada, bounded by the provinces of British Columbia to the west and Saskatchewan to the east, the Northwest Territories to the north, and the U.S. state of Montana to the south....
,
OntarioOntario is a province located in east-central Canada, the largest by population and second largest, after Quebec, in total area. Ontario is bordered by the Canadian provinces of Manitoba to the west and Quebec to the east, and 5 U.S...
and
Nova ScotiaNova Scotia is a Canadian province located on Canada's southeastern coast. It is the most populous province in Atlantic Canada. Its capital, Halifax, is a major economic centre of the region. Nova Scotia is the second-smallest province in Canada with an area of...
allow 10 mg/kg thujone;
QuébecQuebec is a province in east-central Canada. It is the only Canadian province with a predominantly French-speaking identity and the only one whose sole official language is French at the provincial level....
allows 15 mg per kg (according to the SAQ);
ManitobaManitoba is a prairie province in Canada and has an area of . Manitoba is bordered by the provinces of Ontario to the east and Saskatchewan to the west, the territory of Nunavut to the north, and the U.S. states of North Dakota and Minnesota to the south...
allows 6–8 mg thujone per litre; and all other provinces do not allow the sale of absinthe containing thujone (although, in
SaskatchewanSaskatchewan is a prairie province in Canada, which has an area of and a population of 1,023,810 , mostly living in the southern half of the province. Of these, 233,923 live in the province's largest city, Saskatoon, while 194,971 live in the provincial capital, Regina...
, one can purchase any liquor available in the world upon the purchase of a minimum 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.
- Chemical Composition of Vintage Preban Absinthe with Special Reference to Thujone, Fenchone, Pinocamphone, Methanol, Copper, and Antimony Concentrations Dirk W. Lachenmeier, David Nathan-Maister, Theodore A. Breaux, Eva-Maria Sohnius, Kerstin Schoeberl, and Thomas Kuballa. Journal of Agricultural and Food Chemistry (2008).