Editing Thujone (section)

==Pharmacology==
[[File:Thujone by Danny S. - 001.jpg|thumb|right|Research-grade thujone]]
Based on a hypothesis that considered only molecular shape, it was speculated that thujone may act similarly to [[Tetrahydrocannabinol|THC]] on the [[cannabinoid]] receptors;<ref name="thc">[[Barnaby Conrad III|Conrad, Barnaby, III]]; (1988). ''Absinthe: History in a Bottle.'' [[Chronicle Books]]. {{ISBN|0-8118-1650-8}} p. 152</ref> however, thujone failed to evoke a cannabimimetic response in a 1999 investigative study.<ref>{{cite journal |vauthors=Meschler JP, Howlett AC | title = Thujone exhibits low affinity for cannabinoid receptors but fails to evoke cannabimimetic responses | journal = Pharmacol. Biochem. Behav. | volume = 62 | issue = 3 | pages = 473–480 | date = March 1999 | pmid = 10080239 | doi = 10.1016/S0091-3057(98)00195-6 | s2cid = 30865036 }}</ref>  Thujone is a [[gamma-aminobutyric acid|GABA<sub>A</sub>]] receptor antagonist<ref>{{cite journal | author = Olsen RW | title = Absinthe and gamma-aminobutyric acid receptors | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 97 | issue = 9 | pages = 4417–4418 | date = April 2000 | pmid = 10781032 | pmc = 34311 | doi = 10.1073/pnas.97.9.4417 | bibcode = 2000PNAS...97.4417O | doi-access = free }}</ref> and more specifically, a [[GABAA receptor|GABA<sub>A</sub> receptor competitive antagonist]]. By inhibiting GABA receptor activation, neurons may fire more easily, which can cause muscle spasms and convulsions.<ref name="gaba">{{cite journal |vauthors=Höld KM, Sirisoma NS, Ikeda T, Narahashi T, Casida JE | title = Alpha-thujone (the active component of absinthe): gamma-aminobutyric acid type A receptor modulation and metabolic detoxification | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 97 | issue = 8 | pages = 3826–31 | date = April 2000 | pmid = 10725394 | pmc = 18101 | doi = 10.1073/pnas.070042397 | bibcode = 2000PNAS...97.3826H | doi-access = free }}</ref>  This interaction with the [[GABAA receptor|GABA<sub>A</sub> receptor]] is specific to alpha-thujone.<ref name="ReferenceA">{{Cite journal|last1=Höld|first1=Karin M.|last2=Sirisoma|first2=Nilantha S.|last3=Ikeda|first3=Tomoko|last4=Narahashi|first4=Toshio|last5=Casida|first5=John E.|date=2000-04-11|title=α-Thujone (the active component of absinthe): γ-Aminobutyric acid type A receptor modulation and metabolic detoxification|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=97|issue=8|pages=3826–3831|doi=10.1073/pnas.070042397|issn=0027-8424|pmid=10725394|pmc=18101|bibcode=2000PNAS...97.3826H|doi-access=free}}</ref> Thujone is also a [[5-HT3 antagonist|5-HT<sub>3</sub> antagonist]].<ref name="5-HT3">{{cite journal|date=Feb 2004|title=Alpha-thujone reduces 5-HT3 receptor activity by an effect on the agonist-reduced desensitization|journal=Neuropharmacology|volume=46|issue=2|pages=192–201|doi=10.1016/j.neuropharm.2003.09.022|pmid=15002407|vauthors=Deiml T, Haseneder R, Zieglgänsberger W, Rammes G, Eisensamer B, Rupprecht R, Hapfelmeier G|s2cid=54346490}}</ref><ref>[http://sydney.edu.au/medicine/pharmacology/adrien-albert/images/pdfs/RefsPDFs/376.pdf Modulation of Ionotropic GABA Receptors by Natural Products of Plant Origin]</ref>

The [[median lethal dose]], or LD<sub>50</sub>, of α-thujone, the more active of the two isomers, in mice, is around 45&nbsp;mg/kg, with  0% mortality rate at 30&nbsp;mg/kg and 100% at 60&nbsp;mg/kg.  Mice exposed to the higher dose have [[convulsions]] that lead to death within 1 minute.  From 30 to 45&nbsp;mg/kg, the mice experience muscle spasms in the legs, which progress to general convulsions until death or recovery. These effects are in line with other GABA antagonists.  Also, α-thujone is metabolized quickly in the liver in mice.<ref name="gaba" /> Pretreatment with GABA positive allosteric modulators like [[diazepam]], [[phenobarbital]], or 1&nbsp;g/kg of [[ethanol]] protects against a lethal dose of 100&nbsp;mg/kg.{{Citation needed|date=July 2018}}

Attention performance has been tested with low and high doses of thujone in alcohol.  The high dose had a short-term negative effect on attention performance. The lower dose showed no noticeable effect.<ref name="pmid15536765"/>

Thujone is reported{{By whom|date=January 2018}} to be toxic to brain, kidney, and liver cells and could cause convulsions if used in too high a dose. Other thujone-containing plants such as the tree [[Thuja|arborvitae]] (''Thuja occidentalis'') are used in herbal medicine, mainly for their alleged immune-system stimulating effects.{{Citation needed|reason=What does it even mean in a medical sense that thujone would "stimulate the immune system"?|date=January 2018}} Side effects from the [[essential oil]] of this plant include anxiety, sleeplessness, and convulsions, which confirms the central nervous system effects of thujone.<ref name=":0" /><ref>{{cite journal |vauthors=Naser B, Bodinet C, Tegtmeier M, Lindequist U | date = Mar 2005 | title = Thuja occidentalis (Arbor vitae): A Review of its Pharmaceutical, Pharmacological and Clinical Properties | journal = Evidence-Based Complementary and Alternative Medicine | volume = 2 | issue = 1| pages = 69–78 | doi=10.1093/ecam/neh065| pmid = 15841280 | pmc = 1062158 }}</ref>