In the 20th century, as a consequence of the description of the bicyclic monoterpene thujone as the main component of wormwood oil, the main focus of scientific studies was changed from the research of wormwood extract to isolated thujone. It must be stressed, however, that besides the β-thujone chemotype of the wormwood plant further chemotypes were described, which contain cis-chrysanthenylacetat, cis-chrysanthenol, cis-expoxyocimene, sabinylacetate or bornylacetate as principal component [57-63]. In the west alpine area above 1000 m the cis-epoxyocimen type is predominat, while the β-thujone type rather exists in the lower zones [60]. In wormwood oil from the Tuscany [64] or the Pyrenees [58] neither α- nor β-thujone could be detected. These significant differences in composition of wormwood may also be attributable for the previously described failure of some researchers to replicate the animal experiments of Magnan.

The acute and chronic toxicology of thujone were reviewed in the WHO Food Additives Series 16 [65] and more recently by the Scientific Committee on Food of the European Commission [67]. The principal data are summarized in Table 3. The toxicological evaluations led to the establishment of maximum limits for thujone (35 mg/l in bitters) by the Codex Alimentarius Commission of the FAO/WHO [67], which were adopted by many countries including the European Union [8] and Switzerland [68] but not the USA, where manufacture and importation of absinthe is still prohibited [69,70]. It was noted, however, that in the USA consumption and possession remained legal, so that travelers returning to the USA with a bottle or customers buying it from Europe on the internet are not guilty of any crime, though they could have their bottle confiscated [71].

 

Until today, only little valid data are available concerning the effect of α-/β-thujone, especially in regard to the influence on the central nervous system after absinthe consumption. In comparison to β-thujone, α-thujone is believed to be 2.3 fold more toxic [72]. A recent study of Dettling et al. showed that the administration of alcohol containing a high concentration of thujone (100 mg/l) had a negative effect on attention performance [73]. When the subjects were under the influence of alcohol or were administered both alcohol and low thujone concentrations (10 mg/l), these effects were not observed. Similarly, it was found that only high concentrations of thujone could temporarily counteract the anxiolytic effect of alcohol.

The interaction of α-thujone with γ-amino butyric acid (GABA) dependent chloride channels can explain its convulsant effects [72,74-76]. It was determined that α-thujone acts like many naturally occurring and synthetic convulsive agents (e.g. picrotoxin) by blocking GABA mediated inhibition. The effect on the brain is excitatory (analeptic). Anxiogenic and possibly alerting effects of GABA antagonists were also noted. However, Olsen commented that in absinthe one is balancing the effect of thujone with the intoxicating, disinhibitory, and depressant effects of ethanol [74].

Deiml et al. were not addressing the toxicity but instead were researching the 5-HT3 receptor as a potential site of psychotropic actions of α-thujone. In homomeric receptors, α-thujone enhanced the inherent channel-blocking potency of the natural ligand, 5-HT. In heteromeric receptors, α-thujone recruited an additional channel-blocking component of the agonist. The authors could, therefore, prove a reduction of the 5-HT3 receptor activity, but it stayed open if this inhibitory action on serotonergic responses contributes to behavioral effects of thujone [77].