129
8
apply for beverages and food products from plants such as mint, thyme or rosemary,
which also contains thujone in their oils. It is therefore also a common component of
herbal medicine.
As with many other secondary metabolites, the function of thujone in plants is not
well understood. A role in protection against insect herbivores and pathogens can be
suggested from its human use as moth repellent, antimicrobial compound and for
embalming. Upon feeding by herbivores such as antelopes, sagebrush elicits volatiles
into the surrounding air and experimental exposure to these volatiles created an
increased resistance of exposed plants to herbivore attacks (Karban et al. 2006). GC-MS
analysis showed that these volatiles are highly variable between individuals but are generally dominated by either camphene or thujone (Karban et al. 2014). It was suggested
that these volatiles might be used to communicate the attack to other individuals in
order to reduce herbivory but it remains unclear whether such a communication between
plants indeed exist.
A noncompetitive GABA antagonist of different chemical nature is cicutoxin, a polyacetylene found in the highly toxic water hemlock (Cicuta) and hemlock water dropwort
(Oenanthe) (Schep et al. 2009). Poisoning is often accidental since roots of plants from the
genus Cicuta, all of which contain cicutoxin, are often mistaken for roots of edible plants
such as parsnip, wild carrot or wild ginseng. Such accidents can be severe, because the root
is the most toxic part of the plant, especially in early spring. Toxicity depends on various
factors, such as seasonal variation, temperature, geographical location or soil conditions,
and the high toxicity of roots could indicate a role in preventing underground attacks by
nematodes.
In a similar manner, toxic star anise species can be the cause of accidental poisoning
when the plant is mistaken for the non-toxic Chinese star anise (Illicium verum) that is
used to prepare spicy tea. Causative agent in this case is the sesquiterpene anisatin, another
noncompetitive GABA antagonist that can cause tonic-clonic seizures (Kakemoto et al.
1999).
Picrotoxin, another GABA A receptor active sesquiterpene, is found primarily in the
fruit of the climbing plant Anamirta cocculus, which also contains quaternary alkaloids
such as berberine. The crushed seeds of the Anamirta plant are an effective pediculicide
(anti-lice) and have a traditional use as a pesticide. In the nineteenth century, hard
multum, a preparation made from A. cocculus, was even suggested by some brewers as
an addition to malt liquors to strengthen their intoxicating properties.
Box 8.3 La fée verte
Absinthe is an anise-flavoured spirit made from extracts of Artemisia absinthium (for thujone
content) and Artemisia pontica (for colouring) together with other herbs such as green anise
and sweet fennel. In Europe, absinthe was forbidden from 1915 onwards because it was
labelled as a dangerously addictive drug, but its psychoactive properties (apart from that of the
alcohol) seem to have been exaggerated. Indeed, the symptoms of the so-called absinthism are
probably cause by chronic alcoholism since the high percentage of alcohol in absinthe would
cause effects long before thujone or other psychoactive compound present in the spirit could
become a factor
8.3 · GABA A Receptors: Thujone, Cicutoxin and Anisatin
8
apply for beverages and food products from plants such as mint, thyme or rosemary,
which also contains thujone in their oils. It is therefore also a common component of
herbal medicine.
As with many other secondary metabolites, the function of thujone in plants is not
well understood. A role in protection against insect herbivores and pathogens can be
suggested from its human use as moth repellent, antimicrobial compound and for
embalming. Upon feeding by herbivores such as antelopes, sagebrush elicits volatiles
into the surrounding air and experimental exposure to these volatiles created an
increased resistance of exposed plants to herbivore attacks (Karban et al. 2006). GC-MS
analysis showed that these volatiles are highly variable between individuals but are generally dominated by either camphene or thujone (Karban et al. 2014). It was suggested
that these volatiles might be used to communicate the attack to other individuals in
order to reduce herbivory but it remains unclear whether such a communication between
plants indeed exist.
A noncompetitive GABA antagonist of different chemical nature is cicutoxin, a polyacetylene found in the highly toxic water hemlock (Cicuta) and hemlock water dropwort
(Oenanthe) (Schep et al. 2009). Poisoning is often accidental since roots of plants from the
genus Cicuta, all of which contain cicutoxin, are often mistaken for roots of edible plants
such as parsnip, wild carrot or wild ginseng. Such accidents can be severe, because the root
is the most toxic part of the plant, especially in early spring. Toxicity depends on various
factors, such as seasonal variation, temperature, geographical location or soil conditions,
and the high toxicity of roots could indicate a role in preventing underground attacks by
nematodes.
In a similar manner, toxic star anise species can be the cause of accidental poisoning
when the plant is mistaken for the non-toxic Chinese star anise (Illicium verum) that is
used to prepare spicy tea. Causative agent in this case is the sesquiterpene anisatin, another
noncompetitive GABA antagonist that can cause tonic-clonic seizures (Kakemoto et al.
1999).
Picrotoxin, another GABA A receptor active sesquiterpene, is found primarily in the
fruit of the climbing plant Anamirta cocculus, which also contains quaternary alkaloids
such as berberine. The crushed seeds of the Anamirta plant are an effective pediculicide
(anti-lice) and have a traditional use as a pesticide. In the nineteenth century, hard
multum, a preparation made from A. cocculus, was even suggested by some brewers as
an addition to malt liquors to strengthen their intoxicating properties.
Box 8.3 La fée verte
Absinthe is an anise-flavoured spirit made from extracts of Artemisia absinthium (for thujone
content) and Artemisia pontica (for colouring) together with other herbs such as green anise
and sweet fennel. In Europe, absinthe was forbidden from 1915 onwards because it was
labelled as a dangerously addictive drug, but its psychoactive properties (apart from that of the
alcohol) seem to have been exaggerated. Indeed, the symptoms of the so-called absinthism are
probably cause by chronic alcoholism since the high percentage of alcohol in absinthe would
cause effects long before thujone or other psychoactive compound present in the spirit could
become a factor
8.3 · GABA A Receptors: Thujone, Cicutoxin and Anisatin