Thujonen

http://www.ema.europa.eu/docs/en_GB/document_library/Public_statement/2011/02/WC500102294.pdf

References 
Abass K, Reponen P, Mattila S, Pelkonen O. (2010) Metabolism of α-thujone in human liver preparations in vitro. Xenobiotica in press 
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Council of Europe (1999) Document RD 4.2/14-44. Revised Detailed Datasheet on Thujone Dettling A, Grass H, Schuff A, Skopp G, Strohbeck-Kuehner P, Haffner HT. (2004) Absinthe: attention performance and mood under the influence of thujone. J Stud Alcohol 65: 573-581 
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Höld KM, Sirisoma NS, Ikeda T, Narahashi T, Casida JE. (2000) α-Thujone (the active component of absinthe): γ-Aminobutyric acid type A receptor modulation and metabolic detoxification. PNAS 97(8): 3826-3831 

Thujone, a major component of the notoriously famous absinthe drink, is neurotoxic, although the current view rather downgrades its risk to humans. In animal studies, thujone inhibits the gamma-aminobutyric acid A (GABAA) receptor causing excitation and convulsions in a dose-dependent manner, although there are uncertainties about the doses required in humans. Toxicity of thujone has been extensively studied. Neurotoxicity is the principal toxic outcome in acute and chronic studies. There is some equivocal evidence of carcinogenicity in rats. Metabolism of thujone has been elucidated both in vitro and in vivo in several species and in vitro in human liver preparations. CYP2A6 is the principal metabolic enzyme, followed by CYP3A4 and, to a lesser extent, CYP2B6. CYP-associated metabolism may give rise to some potential pharmacogenetic and metabolic interaction consequences. Although the data base for determining exposure limits is of variable usefulness, the best estimates for allowable daily intakes via herbal preparations and diet are of the order of 3–7 mg/day. There are still important gaps in the knowledge required to assess thujone toxicity, the most important ones being human dose-concentration-effect relationships including the elucidation of bioavailability, and the actual toxicological consequences of potential pharmacogenetic variations and environmental factors.

Highlights
► Thujone (e.g. in absinthe) has a long-term reputation as a neurotoxicant. ► α-Thujone is rapidly acting modulator of the GABAA-receptor. ► Thujone occurs widely in essential oils of medicinal and botanical plants. ► Analytical techniques are available to detect α- and β-thujone in various matrices. ► Regulatory status needs re-assessment based on focussed investigations.
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