Thujone is a terpenoid ketone which exists in two stereo-isomeric forms:
R1 = CH3; R2 = H: (+)-3-thujone
R1 = H; R2 = CH3: (-)-3-thujone
(+)-3-thujone is also known as alpha-thujone and (-)-3-isothujone is also known as ß-thujone. The two isomers occur widely in essential oils,
most notably in Artemisia spp., Salvia spp., Juniperus, Tanacetum (tansy), Thuja spp. and Cedris spp. in varying proportions.
Description: Colorless or almost colorless liquid with a menthol-like odor
Boiling Point: 201°C
Flash Point: 148°F, CC
Density: 0.9109 at 25°C/4°C
Solubility: Insoluble in water; soluble in ethanol, diethyl ether and chloroform
Vapor Pressure: ~0.2 mm Hg @ 20°C
Studies on the pharmacological and toxicological properties of the thujones are complicated by the fact that many experiments involved the
use of ill-defined mixtures of the two isomers. Since the isomers differ markedly in toxicity and convulsant activity, quantitative data on mixtures
of unspecified composition have to be interpreted with caution. The EU restrictions on thujone content in liquors refer to alpha and ß-thujone
Thujone (isomer not specified) was a weak inhibitor of acyl-CoA:lysophosphatidylcholine acyltransferase activity in mouse brain
synaptosomes compared to psychoactive cannabinoids (Greenberg et al, 1978).
Thujone was without effect on respiratory activity of the cerebral cortex of rats pretreated with single oral doses of 10-100 mg/kg or repeated
daily doses of 10 mg/kg for up to 15 days (Pinto-Scognamiglio, 1968).
Toxicolgical studies on oil of tansy (Tanacetum vulgare)
The principal constituents of tansy oil are alpha- and ß-thujone, camphor and borneol, the average content of thujones is approximately 50%.
The acute oral LD50 (median lethal dose) in rats was reported as 1.15 g/kg and the acute dermal LD50 in rabbits as >5 g/kg. When tested on
dogs with intestinal helminths, tansy oil was toxic at oral doses of 300 mg/kg.
Oil of tansy causes convulsions and signs of poisoning (stated to be due to thujone) include vomiting, gastroenteritis, flushing, cramps,
loss of consciousness, rapid breathing, cardiac arrhythmia, enteric bleeding and hepatitis. Death occurs from circulatory or respiratory
arrest and degenerative organ changes, and human fatalities have been reported.
Undiluted tansy oil was not a skin irritant in hairless mice or swine, was slightly irritating to rabbit skin in a 24-hour patch test but was
non-irritant in a 48-hour patch test in human subjects. No sensitization reactions were seen in a maximization test on 25 volunteers and no
phototoxic effects were observed in mice and swine (Opdyke, 1976).
Toxicological studies on oil of wormwood (Artemisia absinthium)
Artemisia oil contains mainly thujone (Guenther, 1952). The acute oral LD50 in rats was reported as 960 mg/kg; the acute dermal LD50 in
rabbits exceeded 5 g/kg. Undiluted oil was not a skin irritant to hairless mice, was mildly irritating to rabbit in a 24-hour patch test and
produced no irritation in a 48-hour patch test on human subjects. No sensitization reactions were observed in a maximization test on 25
volunteers and no phototoxic effects were reported in hairless mice and swine (Opdyke, 1975).
Studies on th pharmacological activity of thujone
The convulsant properties of thujone, and of thujone-containing plant extracts, have been recognized for a long time (see review by
Pinto-Scognamiglio, 1967). The doses required to produce convulsions are tabulated below:
|Accurate, authoritative information about THUJONE, the
controversial active ingredient in ABSINTHE
The distinctive herb in absinthe is grand wormwood (Artemesia absinthium),
and the chemical name for the principle active ingredient in wormwood is
thujone. Thujone is a terpene and is related to menthol, which is known for its
healing and restorative qualities. In its chemically pure form, it is a colourless
liquid with a menthol-like aroma. Oil of Artemesia absinthium (or wormwood oil
as it's usually called) is approximately 40-60% thujone.
Thujone – pronounced "thoo-jone" with a soft 'J' – is a naturally occurring
substance, also found in the bark of the thuja, or white cedar, tree, and in other
herbs besides wormwood - including tansy and the comon sage used in
cooking. Aside from absinthe, other popular liquors, including vermouth,
Chartreuse, and Benedictine, also contain small amounts of thujone. In fact,
vermouth, which was originally made using the flower heads from the wormwood
plant, takes its name from the German "wermut" ("wormwood").
Extremely high doses of thujone are dangerous, and have been shown to
cause convulsions in laboratory animals, but the concentration of thujone
actually found in absinthe is many thousands of times lower than this.
Thujone's mechanism of action on the brain is not fully understood although
certain structural similarities between thujone and tetrahydrocannabinol (the
active component in marijuana) led to some speculation in the 1970's that both
substances have the same site of action in the brain. Doubt was cast on this
hypothesis almost immediately, and more recent scientific research has
completely discredited this idea.
Some researchers have now hypothesised that the reputed "secondary
effects" of absinthe have nothing directly to do with thujone at all - if they in
fact exist at all, they may be caused by the interaction of some of the other
constituent herbs ( fenchone in fennel, pinocamphonethe in hyssop, and the
anethole in anise, have all been shown to cause epileptiform convulsions in
laboratory animals when administered in very large doses).
The effect of well-made absinthe varies from person to person, but is typically
no more marked than the mild “buzz” one gets from drinking tequila. Generally,
it can best be described as a kind of heightened clarity of mind and vision,
warmed by the effect of the alcohol. This seems to wear off after 20 or 30
minutes. Some users report unusually vivid dreams. Since absinthe is 55%
-72% alcohol, the alcohol's effects will in any event limit the amount of thujone
you can ingest. Most modern “legal” absinthes, in keeping with EU regulations,
contains less than 10mg of thujone per litre, and recent research has shown
that pre-ban Pernod Fils, contrary to speculation by several authors,
including Strang and Arnold in a widely quoted 1999 British Medical
Journal article, also had relatively low thujone levels.
Increasingly it seems clear in fact that well-made absinthes following authentic
traditional recipes seldom have thujone levels much in excess of 35mg/l, the EU
standard for thujone in bitters (a category that can, in practice, include
absinthe), and many quite naturally fall under the 10mg/l level. It seems that
irrespective of the quantity of wormwood used, relatively little thujone makes it
through the distilling process into the final distillate. So the entire historical
demonization of absinthe based on its allegedly high thujone content now
appears to have been based on a wholly false premise.
The high thujone levels claimed by many Czech and German made "absinths"
are invariably false (in fact, some of these products, when analysed by gas
chromatograph and mass spectrometer, show no detectable thujone at all).
As a rule of thumb, any absinthe claiming exceptionally high thujone levels
should be avoided, as it's almost certainly a poor quality oil-mix, supported by
bogus marketing hype.
The aim of this site is to provide a comprehensive reference on all aspects of
thujone, including abstracts (and wherever possible full-text versions) of
all significant peer-reviewed scientific papers on the subject. For
historical interest a selection of Belle Epoque era scientific articles are included
Lastly, the site includes information on the process of thujone detection and
analysis, together with independent data on the actual thujone level of many
contemporary absinthes, often strikingly at variance with the levels claimed
by the manufacturers.
7 key scholarly papers on thujone and its role in absinthe.
For the far more extensive complete range of available papers see the section on Scientific Research.
For a briefer one page guide dealing with the most commonly asked questions by newcomers to the world of absinthe, with
special emphasis on thujone, absinthe's legal status in the US and elsewhere, and so-called 'secondary effects',
see our Fee Verte Absinthe FAQ.
The toxicity and pharmacological effects of thujone
A brief overview of the scientific data on the effects of thujone on laboratory animals.
Adapted and expanded from the World Health Organisations's Food Additives report (#16).
For another good general overvew, see the Opinion of the EU Scientific Committee on Food on Thujone
The thujone-induced convulsions are epileptiform in character and are preceded by general vaso-dilation, fall in blood pressure, slowing
of cardiac rhythm and augmentation of respiratory amplitude (Pinto-Scognamiglio, 1967).
(-)-3-isothujone and (+)-3-thujone were examined for antinociceptive activity using the hot-plate and Nilsen tests. In the hot-plate test,
(-)-3-isothujone was found to be codeine-like (ED50 =6.5 mg/kg) and equipotent with (-)delta-tetrahydrocannabinol while the racemic mixture
was essentially half as potent as isothujone; (+)-3-thujone was inactive in both tests. Less antinociceptive activity was observed in the Nilsen
test (ED50 = 14.1 mg/kg) than in the hot-plate assay (Rice & Wilson, 1976).
(+)-3-thujone was examined for psychotropic activity in mice using a series of coordination and behavioural tests, and for analgesic and
hypnotic properties. At low, sub-convulsive doses, thujone produced a slight augmentation of motility at a dose of 3 mg/kg i.p. and a
depression of activity and exploratory behaviour at 24 mg/kg i.p. Thujone did not reinforce the convulsant activity of pentetrazol or electric
shocks and had no effect on barbiturate sleeping time. On the other hand, barbiturates (10 mg/kg) or trans-anethole (200-300 mg/kg i.p.)
protected mice against the convulsant action of thujone (150 mg/kg i.p.) (Le Bourhis & Soenen,1973).
Pinto-Scognamiglio (1968) studied the effects of repeated oral doses of thujone (10 mg/kg daily for 25 days) on spontaneous activity
and ability to learn conditioned behaviour of rats. Thujone did not qualitatively modify either spontaneous activity or conditioned behaviour but
produced an improvement in coordination. Previous work had indicated that thujone given to rats at doses of 50 mg/kg s.c. produced a
marked increase in activity equivalent to that seen after a dose of 2 mg amphetamine/kg bw (cited from Pinto-Scognamiglio, 1967).
It was suggested (Castillo et al, 1975) that thujone and tetrahydrocannabinol exert psychomimetic effects by interacting with a common
receptor but this hypothesis is not supported by the work of Greenberg et al. (1978).
Short-term studies on rats
Four groups of 10 male and 10 female rats received thujone in doses of 0, 5, 10 or 20 mg/kg by gavage on six days per week for 14 weeks.
The isomeric composition of the material was not specified. Convulsions were observed after dosing in many instances in nine female and
six male animals in the top dose group; only one female animal from the 10 mg/kg dose group had one convulsion on the thirty-eighth day.
The ED50 for both sexes lay between 10 and 20 mg/kg daily for three months. Three female and one male rat of the top dose group died in
At termination, no significant differences were observed between groups with respect to weight gain, haematology (Hb, RBC, WBC), or
weights of heart, liver, spleen, kidney and adrenals. No treatment-dependent gross pathological or histopathological lesions were observed.
The no-effect level was 5 mg/kg/day for females and 10 mg/kg/day for males (Margaria, 1963).
A commercial mixture of alpha- and ß-thujone was administered by gavage to groups of 20 male and 20 female weanling rats at doses of 0,
12.5, 15.0 and 50.0 mg/kg/day for 13 weeks. The dose was given in five increments daily as a suspension in aqueous agar. Five rats (four
male and one female) died during acclimatization and three others (one male from each of the low and middle dose groups; one female
control) died during treatment from a viral infection.
No dose-related deaths occurred in the rats receiving 12.5 or 25.0 mg/kg bw but 37% of the males and 60% of the females in the 50.0 mg/kg
dose group died under test. Post-treatment convulsions were frequently observed and the number of animals affected was as follows:
The convulsive ED50 was estimated as 35.5 mg/kg/day for males and 26.3 mg/kg/day for females. No correlation was seen between the
number of convulsions in an animal and death; in the extreme, one survivor had 10 convulsions and one animal died without convulsions.
No effects were observed on body weight gain, or haematology, and histopathological examination at termination did not reveal any dose-
The no-effect level for males was 12.5 mg/kg/day; a no-effect level cannot be established for female rats since one rat in the lowest dose
group displayed convulsions on two occasions.
No data from metabolic, reproductive or long-term studies were available. Much of the information reported related to unspecified isomers or
mixtures thereof. It appears that ß-thujone is significantly more toxic than the alpha-isomer and that female animals are more sensitive to the
toxic effects than males. It is not possible to establish an ADI for man on the information available.
Castillo, J. del, Anderson, M. & Rubottom, G. M. (1975) Marijuana, absinthe and the central nervous system, Nature (Lond.), 253, 365-366
Greenberg, J. H., Mellors, A. & McGowan, J. C. (1978) Molar volume relationships and the specific inhibition of a synaptosomal enzyme by
psychoactive cannabinoids, J. Med. Chem., 21, 1208
Guenther, E. (1962) The essential oils, Vol. V, p. 487, Van Nostrand: Princeton, New Jersey
Ionescu, C. N. et al. (1958) Extragerea principiilor activi din Tanacetum vulgare, Communie Acad. Rep.pop.rom 8, 279 (cited by Opdyke, 1976)
Keith, H. M. & Stavaky, G. W. (1935) Experimental convulsions induced by administration of thujone. A pharmacologic study of the influence of
the autonomic nervous system on these convulsions, Arch. Neurol. Psych., 34, 1022-1040
Le Bourhis, B. & Soenen, A.-M. (1973) Recherches sur l'action psychotrope de quelques substances aromatiques utilisées en alimentation,
Fd. Cosmet. Toxicol., 11, 1-9
Margaria, R. (1963) Acute and sub-acute toxicity study on thujone. Unpublished report of Istito di Fisiologia, Università di Milano
Opdyke, D. L. J. (1975) Monographs on fragrance raw materials - artemisia oil (wormwood), Fd. Cosmet. Toxicol., 13 (suppl.), 721-722
Opdyke, D. L. J. (1976) Monograph on fragrance raw materials - tansy oil, Fd. Cosmet. Toxicol., 14 (suppl.), 869-871
Opper, L. (1939) Pathologic picture of thujone and monobrominated camphor convulsions: comparison with pathologic picture of human
epilepsy, Arch. Neurol. Psych., 41, 460
Pinto-Scognamiglio, W. (1967) Connaissances actuelles sur l'activité pharmacodynamique de la thujone, aromatisant naturel d'un emploi
entendu, Boll. chim. farm., 106, 292-300
Pinto-Scognamiglio, W. (1968) Effeti del tujone sull'attività spontanea e sul comportamento condizionato del ratto, Boll.chim. farm.107,
Rice, K. C. & Wilson, R. S. (1976) (-)-3-isothujone, a small non-nitrogenous molecule with antinociceptive activity in mice, J. Med. Chem.19,
Sampson, W. L. & Fernandez, L. (1939) Experimental convulsions in the rat, J. Pharm. exptl. Therap., 65, 275
Wenzel, D. G. & Ross, C. R. (1957) Central stimulating properties of some terpenones, J. Amer. pharm. Ass., 46, 77
Chemical Composition of Vintage Preban Absinthe with Special Reference to Thujone, Fenchone, Pinocamphone, Methanol, Copper, and
By Dirk W. Lachenmeier, David Nathan-Maister, Theodore A. Breaux, Eva-Maria Sohnius, Kerstin Schoeberl, and Thomas Kuballa
Published in Journal of Agricultural and Food Chemistry, April 2008
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