Thujone

Chembox new
Name = Thujone
ImageFile = Beta-thujone.svg
ImageName = Beta-thujone
ImageFile1 = Beta-thujone-3D-balls.png ImageName1 = Ball-and-stick model of β-thujone
IUPACName = (1S-(1-,4-,5-alpha))4-methyl-1-
propan-2-yl-bicyclo [3.1.0] hexan-3-one
Section1 = Chembox Identifiers
CASOther = [546-80-5] (α-thujone)
[471-15-8] (β-thujone)
SMILES =C [C@@H] ( [C@@H] (C2) [C@] 2
( [C@@H] (C)C)C1)C1=O ("β"-thujone)
Section2 = Chembox Properties
Formula = C₁₀H₁₆O
MolarMass = 152.23 g/mol
Density = 0.92 g/cm³
Solvent = other solvents
SolubleOther = insoluble (water)
soluble (ethanol)
MeltingPt =
BoilingPt = 201 °C

Thujone is a ketone and a monoterpene that exists in two stereoisomeric forms: (+)-3-thujone or α-thujone and (−)-3-thujone or β-thujone. It has a menthol odor. Even though it is best known for being a chemical in 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 the GABA receptors in the brain and exhibits slight, if any, psychoactive response. In many countries the amount of thujone allowed in food or drink products is regulated.

ources

Thujone is found in a number of plants, such as arborvitae (genus "Thuja", hence the derivation of the name), Nootka Cypress, some junipers, mugwort, common sage, tansy and wormwood, most notably grand wormwood (Artemisia absinthium), usually as a mix of isomers in a 1:2 ratio.

Pharmacology

For many years thujone was thought to act on the cannabinoid receptors similar to THC based on studies that only looked at the molecules' shapes.Conrad III, Barnaby; (1988). "Absinthe History in a Bottle." Chronicle books. ISBN 0-8118-1650-8 p. 152] This is known to be false today and studies show thujone does not activate these receptors. [ [http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=10080239&dopt=Abstract Thujone exhibits low affinity for cannabinoid receptors but fails to evoke cannabimimetic responses.] , Meschler JP, Howlett AC. Retrieved 5, July, 2007.] Thujone is a GABA_A receptor antagonist. [ [http://www.pnas.org/cgi/content/full/97/9/4417 Absinthe and gamma-aminobutyric acid receptors Olsen, Richard (2000). Retrieved Apr. 12, 2008.] ] By inhibiting GABA receptor activation neurons may fire more easily which can cause muscle spasms and convulsions. [http://www.pnas.org/cgi/content/full/97/8/3826 Thujone Gamma-Aminobutyric acid type A receptor modulation and metabolic detoxification.] Hold K., Sirisoma N., Ikeda T., Narahashi T. and Casida J. (2000). Retrieved Oct.28, 2006]

A toxicology study of alpha-thujone, the more active of the two isomers, in mice found 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. 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 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. This study also found alpha-thujone was quickly metabolized in the mouse's liver.

The LD₅₀ dose in humans is not known; however a study in the Journal of Studies on Alcohol and Drugs [ [http://www.jsad.com/jsad/article/Absinthe_Attention_Performance_and_Mood_under_the_Influence_of_Thujone/1040.html Absinthe: Attention Performance and Mood under the Influence of Thujone.] A. Dettling, H. Grass, A. Schuff, G. Skopp, P. Strohbeck-Kuehner, H.-Th. Haffner. Retrieved Mar. 26, 2008.] 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. [ [http://www.thujone.info/thujone-absinthe-5.html Absinthe: Attention Performance and Mood under the Influence of Thujone.] DETTLING, A., GRASS, H., SCHUFF, A., SKOPP, G., STROHBECK-KUEHNER, P. AND HAFFNER, H.-TH. (2004) Retrieved Oct. 28, 2006.]

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 vitae" ("Thuja occidentalis") are used in herbal medicine, mainly for their immune-system stimulating effects, however side effects from the essential oil of this plant include anxiety and sleeplessness, confirming the central nervous system effects of thujone. [Naser B, Bodinet C, Tegtmeier M, Lindequist U. Thuja occidentalis (Arbor vitae): A Review of its Pharmaceutical, Pharmacological and Clinical Properties. "Evidence Based Complementary and Alternative Medicine". 2005 Mar;2(1):69–78.]

Thujone in absinthe

Thujone is most famous for being a chemical in the drink absinthe 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, [ [http://www.substanceabusepolicy.com/content/1/1/14 Absinthism: a fictitious 19th century syndrome with present impact] , Padosch et al. Retrieved Oct. 28, 2006.] 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. [ [http://www.thujone.info/thujone-absinthe-3.html Thujone—Cause of absinthism?] Lachenmeier, Emmert et al. Retrieved Oct. 28, 2006.] These results match earlier findings showing a vintage 1900s bottle contained 6 mg/L. [ [http://www.feeverte.net/thujone.html Thujone Separating Myth from Reality] Ian Hutton Retrieved Oct. 28, 2006.] 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. [ [http://www.emmert-analytik.de/DLR_100_9_S352-356.pdf Determination of a-/b-Thujone and Related Terpenes in Absinthe using Solid Phase Extraction and Gas Chromatography] , Emmert et al. Retrieved Oct. 28, 2006.] Through these tests it has become evident that authentic absinthe contains very little thujone. Anyone binging on absinthe would die of alcohol poisoning long before the thujone would cause any life-threatening effects. [ [http://home.howstuffworks.com/absinthe.htm Howstuffworks "Does absinthe really cause hallucinations?" ] ]

History

Thujone was an unknown chemical until absinthe became popular in the mid 1800s. Dr. Valentin Magnan, who studied alcoholism, 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. [Conrad III, Barnaby; (1988). Absinthe History in a Bottle. Chronicle books. ISBN 0-8118-1650-8 Pg. 101-105]

After absinthe was banned, research dropped off until the 1970s when Nature magazine published an article comparing the molecular shape of thujone to THC, 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 absinthe.

Regulations

European Union

Maximum thujone levels in the EU are: [ [http://ec.europa.eu/food/fs/sc/scf/out162_en.pdf Opinion of the Scientific Committee on Food on Thujone] Scientific Committee on Food (2003) Retrieved Oct 28, 2006.]
*0.5 mg/kg in food not prepared with sage and non alcoholic beverages.
*5 mg/kg in alcoholic beverages with 25% or less ABV.
*10 mg/kg in alcoholic beverages with more than 25% ABV.
*25 mg/kg in food prepared with sage.
*35 mg/kg in alcohol labeled as bitters.

United States

Foods or beverages that contain Artemisia species, White Cedar, oak moss, tansy or Yarrow must be thujone-free. [ [http://www.cfsan.fda.gov/~lrd/FCF172.html Food Additives Permitted for Direct Addition to Food for Human Consumption.] Food and Drug Administration (2003). Retrieved Oct 28, 2006.] Other herbs that contain thujone have no restrictions. For example, sage and sage oil (which can be 50%+ thujone) are on the Food and Drug Administration's list of substances generally recognized as safe. [ [http://www.cfsan.fda.gov/~lrd/fcf182.html Substances generally recognized as safe.] Food and Drug Administration (2003). Retrieved Oct 28, 2006.] Recently, the laws against absinthe have been relaxed in the U.S. as there is now a thujone-containing absinthe that can be legally imported. [http://drinklucid.com/faq.cfm Retrieved Nov. 29, 2007.]

Canada

In Canada, 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 (according to the SAQ)Fact|date=April 2007; 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 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.

References

* http://drinklucid.com/faq.cfm Retrieved Nov. 29, 2007

External links

Absinthe absolved http://cerncourier.com/cws/article/cern/34928
* [http://www.thujone.info Thujone.Info] — Databank of peer reviewed articles on thujone, absinthe, absinthism, and independent thujone ratings of some commercial brands.
* [http://www.wormwoodsociety.org/index.php?option=com_content&task=view&id=1&Itemid=85 The Shaky History of Thujone] - Wormwood Society article on thujone and its history.
* [http://dx.doi.org/10.1021/jf703568f 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).