Thujone

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Thujone
Beta-thujone
Ball-and-stick model of β-thujone
IUPAC name (1S-(1-,4-,5-alpha))4-methyl-1-
propan-2-yl-bicyclo[3.1.0]hexan-3-one
Identifiers
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)
Properties
Molecular formula C10H16O
Molar mass 152.23 g/mol
Density 0.92 g/cm³
Boiling point

201 °C
Solubility in other solvents insoluble (water)
soluble (ethanol)
Except where noted otherwise, data are given for
materials in their standard state
(at 25 °C, 100 kPa)
Infobox 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 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.

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, common 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[2]. Thujone is a GABAA receptor antagonist.[3] By inhibiting GABA receptor activation neurons may fire more easily which can cause muscle spasms and convulsions.[4]

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.[4]

The LD50 dose in humans is not known; however a study in the Journal of Studies on Alcohol and Drugs[5] 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.[6]

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.[7]

[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,[8] 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.[9] These results match earlier findings showing a vintage 1900s bottle contained 6 mg/L.[10] 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.[11] Through these tests it has become evident absinthe contains very little thujone.

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

Although it contains thujone, anyone binging on absinthe would die of alcohol poisoning long before the thujone would cause any major, i.e. life-threatening, effects.[12]

[edit] 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.[13]

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:[14]

  • 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.[15] 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.[16] 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.[17]

[edit] 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)[citation needed]; 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.

[edit] References

  1. ^ a b Conrad III, Barnaby; (1988). Absinthe History in a Bottle. Chronicle books. ISBN 0-8118-1650-8 p. 152
  2. ^ Thujone exhibits low affinity for cannabinoid receptors but fails to evoke cannabimimetic responses., Meschler JP, Howlett AC. Retrieved 5, July, 2007.
  3. ^ Absinthe and gamma-aminobutyric acid receptors Olsen, Richard (2000). Retrieved Apr. 12, 2008.
  4. ^ 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
  5. ^ 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.
  6. ^ 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.
  7. ^ 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.
  8. ^ Absinthism: a fictitious 19th century syndrome with present impact, Padosch et al. Retrieved Oct. 28, 2006.
  9. ^ Thujone—Cause of absinthism? Lachenmeier, Emmert et al. Retrieved Oct. 28, 2006.
  10. ^ Thujone Separating Myth from Reality Ian Hutton Retrieved Oct. 28, 2006.
  11. ^ Determination of a-/b-Thujone and Related Terpenes in Absinthe using Solid Phase Extraction and Gas Chromatography, Emmert et al. Retrieved Oct. 28, 2006.
  12. ^ Howstuffworks "Does absinthe really cause hallucinations?"
  13. ^ Conrad III, Barnaby; (1988). Absinthe History in a Bottle. Chronicle books. ISBN 0-8118-1650-8 Pg. 101-105
  14. ^ Opinion of the Scientific Committee on Food on Thujone Scientific Committee on Food (2003) Retrieved Oct 28, 2006.
  15. ^ Food Additives Permitted for Direct Addition to Food for Human Consumption. Food and Drug Administration (2003). Retrieved Oct 28, 2006.
  16. ^ Substances generally recognized as safe. Food and Drug Administration (2003). Retrieved Oct 28, 2006.
  17. ^ http://drinklucid.com/faq.cfm Retrieved Nov. 29, 2007.

[edit] External links