Thujone

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Thujone
Beta-thujone Ball-and-stick model of β-thujone
Systematic name (1S-(1-,4-,5-alpha))4-methyl-1-
propan-2-yl-bicyclo[3.1.0]hexan-3-one
Chemical formula C10H16O
Molecular mass 152.23 g/mol
Density 0.92 g/cm³
Solubility insoluble (water)
soluble (ethanol)
Melting point xx.x °C
Boiling point 201 °C
CAS number [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)
Disclaimer and references

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 it is not responsible for absinthe's reported hallucinogenic effects. Thujone acts on the GABA receptors in the brain and does not cause hallucinations. In many countries the amount of thujone allowed in food or drink products is regulated.

Contents

[edit] Sources

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

[edit] 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.[1] This is known to be false today and studies show 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.[2]

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 inline with other GABA antagonists. This study also found alpha-thujone was quickly metabolized in the mouse's liver.[2]

The LD50 dose in humans is not known however a study in the "Journal of Studies of alcohol" 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.[3]

There is no evidence any size dose will cause hallucinations.

[edit] Thujone in absinthe

Thujone is most famous for being a chemical in the drink absinthe and many 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,[4] but this has been shown false through testing. A 2005 study recreated three 1899 high-wormwood recipes and tested them with a GC-MS, the highest contained 4.3 mg/L thujone. A 1930s Pernod Tarragona was also tested and contained 1.8 mg/L thujone. [5] These results match earlier findings showing a vintage 1900s bottle contained 6 mg/L.[6] GC-MS testing is important in this capacity, because gas chromatography alone may record an abnormally high reading of thujone because of other chemicals present.[7] Through these tests it has become evident absinthe contains very little thujone.

Despite these studies, many companies still play up the myth that absinthe contains a large amount of thujone and that it will produce some sort of hallucinatory effect on the drinker.

[edit] History

Thujone was an unknown chemical until absinthe hit the scene 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 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 alcohol and absinthe was "degenerating" the French race.[8]

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.[1]

More recently, following the European Council Directive No. 88/388 [1] 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.

[edit] Regulations

[edit] European Union

Maximum thujone levels in the EU are: [9]

  • 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.

[edit] United States

Foods or beverages that contain Artemisia species, White Cedar, oak moss, tansy or Yarrow must be thujone free.[10] 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. [11]

[edit] References

  1. ^ a b Conrad III, Barnaby; (1988). Absinthe History in a Bottle. Chronicle books. ISBN 0-8118-1650-8 p. 152
  2. ^ a b 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
  3. ^ 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.
  4. ^ Absinthism: a fictitious 19th century syndrome with present impact, Padosch et al. Retrieved Oct. 28, 2006.
  5. ^ Thujone—Cause of absinthism? Lachenmeier, Emmert et al. Retrieved Oct. 28, 2006.
  6. ^ Thujone Separating Myth from Reality Ian Hutton Retrieved Oct. 28, 2006.
  7. ^ Determination of a-/b-Thujone and Related Terpenes in Absinthe using Solid Phase Extraction and Gas Chromatography, Emmert et al. Retrieved Oct. 28, 2006.
  8. ^ Conrad III, Barnaby; (1988). Absinthe History in a Bottle. Chronicle books. ISBN 0-8118-1650-8 Pg. 101-105
  9. ^ Opinion of the Scientific Committee on Food on Thujone Scientific Committee on Food (2003) Retrieved Oct 28, 2006.
  10. ^ Food Additives Permitted for Direct Addition to Food for Human Consumption. Food and Drug Administration (2003). Retrieved Oct 28, 2006.
  11. ^ Substances generally recognized as safe. Food and Drug Administration (2003). Retrieved Oct 28, 2006.

[edit] External links

  • 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.