Taken from Erowid:
Another candidate is the monoterpene, thujone, which is considered a psychoactive convulsant. The sources of thujone in absinthe are the herbs wormwood (Artemisia absinthium) and Roman wormwood (Artemisia pontica). There is good evidence that both thujone and wormwood have psychoactive properties. Some have suggested that this effect is due to thujone binding at the cannabinoid receptor, at which the active components in marijuana act (delCastillo et al 1974). This seems unlikely. Furthermore, it is not even clear that thujone is present in sufficient quantities to play a role in absinthe intoxication. However, it is possible that thujone accumulates in the body and plays a role in the psychoactivity and toxicity of chronic absinthe use.
Thujone is named after the plant from which it was first extracted, thuja (Thuja occidentalis). Since thujone was also extracted from other plants before its structure was identified, it is also known as absinthol, tanacetone, and salviol. According to IUPAC (International Union of Pure and Applied Chemists) nomenclature, it is officially called 3 thujamone or 3 sabinone (Albert-Puleo 1978). There are two stereoisomers of thujone: (-)-3-isothujone (or - or l-thujone) and (+)-3-thujone (or - or d-thujone). Thujone is the major component of wormwood oil and accounts for up to 90% of the oil's weight (Simonsen 1949).
There have been several reports that wormwood has psychoactive effects. In his excellent book, Pharmacotheon, J. Ott writes that he tried smoking dried wormwood leaves and found it had a definite psychoactive effect (Ott 1993). Pendell (1994) repeated this experiment with similar effects. Furthermore, various other species of the Artemisia genus have been smoked and used as intoxicants in other cultures. Artemisia nilagirica is reportedly smoked in West Bengal for its psychoactive effects (Pal and Jain 1989). Similarly, Artemisia caruthii is inhaled by the Zuni as an analgesic (Ott 1993). However, these experiments yield little insight into the active component(s) of wormwood and whether these components play a role in absinthe's effects. For example, despite being smoked for its psychoactive effects, an assay of Artemisia nilagirica oil found it contained less than one percent total thujones (Uniyal, Singh, Shah, and Naqvi 1985).
There are also indications that thujone itself is psychoactive. Rice and Wilson (1976) have found that (-)-3-isothujone, the dominant isomer in wormwood oil, has an antinociceptive (pain killing) effect, comparable to codeine, when injected subcutaneously in rats. Because the effect is stereospecific and not elicited by similar compounds, the researchers suggest that (-)-3-isothujone acts at a specific pharmacological site.
Thujone's mechanism of action is unknown. Structural similarities between thujone (in its delta-3,4 enol form) and tetrahydrocannabinol (THC, the active component in marijuana) have led some to hypothesize that both substances have the same site of action in the brain (del Castillo et al 1975). However, Meschler et al. (1997) recently presented evidence that that neither thujone, wormwood, nor HPLC fractions from oil of wormwood bind to the cannabinoid receptor at physiologically relevant concentrations. This finding confirms earlier but less direct evidence that thujone does not act at the cannabinoid receptor (Greenberg, Mellors, and McGowan 1978, Browne and Weissman, 1981, Rice and Wilson, 1976). It would seem that thujone acts through some other, yet unidentified, mechanism.
Although thujone is apparently psychoactive, there isn't much direct evidence to confirm its importance in absinthe intoxication. Absinthe is approximately 75% alcohol. Therefore, alcohol's effects should limit the amount of thujone one can ingest. Quite simply, you can only drink a moderate amount of thujone before you become very drunk from the alcohol. Thujone would have to be active at a very low dose or be present in high quantities in order to have any appreciable effect.
Arguing against thujone's importance, B. Max, in the "This and That" column in Trends in the Pharmacological Sciences, made the following dose calculations:
How much thujone was present in absinthe? Steam distillation of wormwood yields 0.27-0.40% of a bitter, dark-green oil (Guenther 1952) In a typical recipe for absinthe, 2.5 kg of wormwood were used in preparing 100 liters of absinthe (Arnold 1989). Typically, 1.5 oz was consumed (diluted with water) per tipple (Vogt & Montagne 1982). This is equivalent to 4.4 mg wormwood oil per drink, or 2-4 mg thujone. This is far below the level at which acute pharmacological effects are observed. Even chronic administration of 10 mg/kg oral thujone to rats does not alter spontaneous activity or conditioned behavior (Pinto-Scognamiglio 1968). The literature on the pharmacology of thujone is, to put it bluntly, second rate, and conclusions as to its effects have been extrapolated far beyond the experimental base (Max 1990).
Although I agree with his feelings about the literature on thujone's activity, Max may underestimate the possible effects of chronic thujone intake. The reference which he uses to support his claim (Pinto-Scognamiglio 1968) actually did find some indications of an effect from chronic thujone intake. Rats treated with 10 mg/kg/day oral thujone increased their spontaneous activity from 4pm to 8pm (the early part of the nocturnal rats' active period). In addition, a subgroup of 6 slow-learning rats significantly improved (in comparison to controls) their acquisition of a shock avoidance task after 7 days of 10 mg/kg/day oral thujone. However, this effect was not replicable in a larger group of 34 rats. Because these 34 rats were naive to the task and therefore of unknown learning ability, we cannot rule out the possibility that thujone may somehow alter the learning abilities of slow-learning rats but not fast-learners.
The appearance of thujone's effects after chronic administration of an otherwise ineffective dose is consistent with the toxicological data on thujone. In rats, at least, thujone accumulates with regular use. In Margaria's (1963) unpublished rat research (cited in Pinto-Scognamiglio 1967), rats fed 10 mg/kg/day orally accumulated about 5% of the daily dose. On the 38th day of the research, convulsions were evident in the rats. Similarly, in the human data, quoted in the toxicology section below, humans taking thujone-containing essential oils experienced convulsions after taking approximately the same dose of oil for several days without incident (Millet et al 1980).
Thus, there are indications that a large enough dose of thujone will be psychoactive and that thujone can accumulate in one's body. However, this does not prove that accumulated thujone was partially responsible for absinthe's psychoactivity. When chronically exposed to a drug, receptors in the brain often become less sensitive to a drug's effects. The brain of a chronic absinthe user might become tolerant to the slow accumulation of thujone, thus blocking any possible psychoactivity. On the other hand, in some cases, repeated doses of drugs can cause hypersensitivity. It is also possible that this occurred with absinthe drinkers. This is just speculation. The toxic effects of repeated thujone ingestion are more definite.
In summary, thujone seems psychoactive although probably not by acting at the cannabinoid receptor. Small ineffective doses may accumulate in the body to the point of having psychoactive and toxic effects. If this is the case, it validates absinthe's reputation for producing an unusual intoxication. Still, this reputation mostly dates to the beginning of the century or earlier, a time when medicine and science were very different from today. Lacking more recent research on thujone and absinthe, it seems reasonable to take reports of absinthe's uniqueness with skepticism. Thujone may play a role in absinthe, but the evidence is not conclusive. Finally, it should be noted that by focusing on one component of wormwood oil, we ignore the many other poorly characterized compounds in wormwood and absinthe's other herbal ingredients which may play some role in absinthe's intoxicating and toxic effects.
I'm going to buy into the build-up theory. Because nothing happened to me. I do know it's bad for the liver.
Speaking of Thujone-free products, what ever happened to Safrole? Did they do away with it because it was harmful or because it was a precurser to MDMA? For those who don't know, Safrole comes from sassafras and they used to flavor rootbeer with it. If you've ever had sassafras tea then that's what makes it smell sooo good.
I need to go collect some sassafras rootbark this spring. The tea is SOOOOOOOOOOOOOOO good!
And also speaking of the lethal level, I think I just read that the LD-50 level was 500 mg's of pure thujone for a mouse/rat (Or it could have said bunny, I just skimmed the article)
A half a gram of anything is a lot! The amount to kill a human must be really astronomical, beyond human capabilities unless they ate handfulls of the pure extract. Once again, the LD-50 level and the level that builds over time aren't the same, however.
All I know is it tastes HORRIBLE! The smoke wasn't too bad, though. I'd say I got closer to being intoxicated from smoking it than I did drinking it, although in my opinion nothing really happened on either. What a waste of money
Another little disclaimer, don't drink absinthe or break any laws.
