http://www.erowid.org/chemicals/absinthe/absinthe_images.shtml
Absinthe
active ingredient α-thujone
| introduction | structure and mode of action | signs and symptoms | interesting information | reference |
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L'absinthe painted by Degas In the late 1800s to the early 1900s
absinthe was a popular drink. Its origins go back to the early 1800s
when a French doctor, Pierre Ordinaire, distilled alcohol with wormwood,
anise, fennel, hyssop and other herbs to create a herbal remedy for
his patients. The remedy was considered a cure all and Ordinaire gave
it to many of his patients. Because of its extraordinary curing abilities
and its unique color absinthe adopted the name "la Fee Verte" which translates
to the green fairy. The popular remedy's secret recipe was left to two
Henriod sisters from Couvet on Ordinaire's deathbed. They in turn left
it to a visiting Frenchman, Major Dubied, whose son in law was named
Pernod. Pernod is known for mass producing and distributing absinthe,
thus greatly increasing the drinks popularity. The herbal infusion is
usually served in a absinthe glass and served with iced water (4:1 ratio)
that has been poured over a slotted spoon with a sugar cube on it. The
sugar reduces the bitter taste of the drink and the water disrupts the suspension
of the wormwood oil in the drink causing it to precipitate out of the drink
turning it slightly cloudy. Other than thujone the other component
of the drink is ethanol. The drink's bright green color can be attributed
to the chlorophyll present from the wormwood extraction.
As portrayed in the 2001 film Moulin Rouge, absinthe was popular with the Bohemian crowd at the time as well as much of the population of France. Famous artists such as Degas, Picasso, and VanGogh were found of the drink (L'absinthe by Degas shown right) as it supposedly cleared their thoughts and allowed them to better express their creativity. VanGogh's craziness is partially blamed on absinthism, this disease is characterized by addiction, problems with gastrointestinal tract, auditory and visual hallucinations, epilepsy, brain damage, and increased risk of psychiatric illness that may result in suicide. The drink found its way across the Atlantic to US, more specifically New Orleans, which later became the "Absinthe capitol of the world." In the early 1900s the drink was banned in Switzerland, France and the US because of the toxic effects of the drug. Recently new interest in the drink has recently spawned in Europe and is making its way to the US. Spain and the Czech Republic are major supplier of Absinthe with production recently starting in Britain after it was found that it was never officially outlawed there. The European Union has put limits on the manufacture or sale of absinthe that contains more than 10 parts per million of thujone. This is significantly less than the absinthe produced at the turn of the last century. Reports of thujone concentration of absinthe from the early 20th century vary from 60-260 part per million. Surprisingly enough many of the newer drinks marketed as absinthe contain no little or no thujone at all.
As portrayed in the 2001 film Moulin Rouge, absinthe was popular with the Bohemian crowd at the time as well as much of the population of France. Famous artists such as Degas, Picasso, and VanGogh were found of the drink (L'absinthe by Degas shown right) as it supposedly cleared their thoughts and allowed them to better express their creativity. VanGogh's craziness is partially blamed on absinthism, this disease is characterized by addiction, problems with gastrointestinal tract, auditory and visual hallucinations, epilepsy, brain damage, and increased risk of psychiatric illness that may result in suicide. The drink found its way across the Atlantic to US, more specifically New Orleans, which later became the "Absinthe capitol of the world." In the early 1900s the drink was banned in Switzerland, France and the US because of the toxic effects of the drug. Recently new interest in the drink has recently spawned in Europe and is making its way to the US. Spain and the Czech Republic are major supplier of Absinthe with production recently starting in Britain after it was found that it was never officially outlawed there. The European Union has put limits on the manufacture or sale of absinthe that contains more than 10 parts per million of thujone. This is significantly less than the absinthe produced at the turn of the last century. Reports of thujone concentration of absinthe from the early 20th century vary from 60-260 part per million. Surprisingly enough many of the newer drinks marketed as absinthe contain no little or no thujone at all.
Absinthe spoon used in the preparation of absinthe http://www.eabsinthe.com/acatalog/lafeespoon.jpg |
www.absinthebuyersguide.com/images/glass_spoon_saucer_sm.gif |
Structure, Composition, and Mode of Action
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3D structure of thujone
www.chem.ox.ac.uk/mom/absinthe/ absinthe.html |
http://www.erowid.org/chemicals/absinthe/absinthe_images.shtml
Absinthe is composed of four main compounds
absinthin (which gives absinthe its bitter taste), ethanol, and two isomers
of thujone (α-thujone 33% and b-thujone 67%). The active component
of Absinthe is α-thujone, a monoterpene which is considered a convulsant
and acts on the central nervous system. Thujone is a colorless molecule
that has the odor of methanol. It is found in essential oil extracted
from wormwood and other spices such as sage and cedar. In the mid-1970s
it was proposed that α-thujone had similar effects on the body as tetrahydocannabinole
(THC). This was because of the strong structural similarity between the two
molecules. Although the structural similarity does exist the drugs act very
differently. It has been shown that thujone readily fails to displace the
cannabinoid ligands from their receptor. Furthermore, thujone doesn't stimulate
a response in the G-proteins or adenyl cyclase activity in these receptors
meaning the compound has no cannabimimetic activity. This data disproved
what thujone was responsible for affecting in the body.
Recently, Hold et al at Berkeley found that α-thujone is a modulator of g-aminobtyric acid (GABA) type A receptors. This proves that α-thujone is a convulsant. In mice they determined an LD50 of α-thujone to be 45 mg/kg, with no mice dying at 30 mg/kg and all the mice dying at 60 mg/kg. The mice that were given large doses of the drugs died after undergoing violent convulsions that lead to the animals death. If mice were administered diazepam or phenobarbital 15 minutes before exposure to α-thujone, most of the mice were able to tolerate and recover from higher doses of α-thujone. More importantly they found when administered with ethanol (as in absinthe) before thujones the mice were also able to survive the higher doses of α-thujone. This data suggests that the two components of absinthe rely on each other and that the two components affect each others mode of action. Showing that absinthe has a two fold mode of action. The ethanol acts a depressant and sedates the user while the thujone mildly stimulates them.
They also found in mice microsomes that α-thujone is quickly broken down into several metabolites. All which have no or substantially reduced activity. They examined metabolites from the microsome of the P450 system in mice as well as those found in the brain of mice, and urine of thujone treated rabbits. They found when the metabolites were re-introduced into back into the body that the mice had no toxic effects as they did to α-thujone.
Recently, Hold et al at Berkeley found that α-thujone is a modulator of g-aminobtyric acid (GABA) type A receptors. This proves that α-thujone is a convulsant. In mice they determined an LD50 of α-thujone to be 45 mg/kg, with no mice dying at 30 mg/kg and all the mice dying at 60 mg/kg. The mice that were given large doses of the drugs died after undergoing violent convulsions that lead to the animals death. If mice were administered diazepam or phenobarbital 15 minutes before exposure to α-thujone, most of the mice were able to tolerate and recover from higher doses of α-thujone. More importantly they found when administered with ethanol (as in absinthe) before thujones the mice were also able to survive the higher doses of α-thujone. This data suggests that the two components of absinthe rely on each other and that the two components affect each others mode of action. Showing that absinthe has a two fold mode of action. The ethanol acts a depressant and sedates the user while the thujone mildly stimulates them.
They also found in mice microsomes that α-thujone is quickly broken down into several metabolites. All which have no or substantially reduced activity. They examined metabolites from the microsome of the P450 system in mice as well as those found in the brain of mice, and urine of thujone treated rabbits. They found when the metabolites were re-introduced into back into the body that the mice had no toxic effects as they did to α-thujone.
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Structures of α-thujone and its metabolites
as found in the microsomal p450 system, the brain of mice,and
urine of rabbits.
http://www.pnas.org/cgi/reprint/97/8/3826.pdf |
The green fairy as seen by the users of absinthe
in the movie Moulin Rouge
http://www.fakewings.net/feeverte/home.html |
Many critics state the major symptoms from Absinthe are
generated from the ethanol that makes up 75% of the drink. Reported symptoms
from absinthe include hallucinations, sleeplessness, tremors, paralysis,
and convulsions. The similarity in symptoms between alcoholism and the syndrome
absinthism suggest that they may have been caused by high concentration
of the alcohol and not so much by the prescence of thujone. Little
research has been done on absinthe recently because of its lack of popularity.
This could pose to be a problem because of the resurgence of the drug in
recent years and the lack of clarity with its mode of action and full effects
of the compounds of the drug are not clearly known. The reports the toxicity
of the drug revolve around reports from the late 19th early 20th centuries.
The current data suggests that the most potent chemical in absinthe is ethanol.
Symptoms from thujone include
More Interesting Stories about absinthe
But why did people think an absinthe high was so different than just alcohol?
Explanations of this most recently can be traced back to be traced back to the quality of the absinthe. Like many illegal club drugs of today, absinthe
was made by many people and you never knew quite what was in it. Many of
the harmful versions of cheap absinthe contained substances like cupric acetate
(provides a green color), antimony trichloride (turns cloudy when mixed with
water), and methanol as a base instead of ethanol. In addition, nutmeg, which
has phsycaldelliac effects, was also used in some recipes for absinthe.
How come a drug with side effects similar to alcohol was banned when we are not even sure how it works?
One story says that absinthe experienced its demise back in 1905. A farmer by the name of Jean Lanfrey drunk absinthe, brandy, and wine all day. That evening he got into an argument with his wife which eventually led to him shooting his wife and his unborn child as well as his two and four year old. He ultimately tried to commit suicide as well but failed. Neighbors and friend of the Lanfrey's testified that his rampage didn't fit his personality. The media at the time played up the fact that this was probably due to the Absinthe he had drunk earlier that day. Absinthe was blamed for the "bloodthirsty crime" and an anti absinthe campaign banned absinthe in Switzerland by 1908 and then eventually France, Germany, and the US banned it as well.(10)
More Interesting Stories about absinthe
But why did people think an absinthe high was so different than just alcohol?
Explanations of this most recently can be traced back to be traced back to the quality of the absinthe. Like many illegal club drugs of today, absinthe
http://www.frencheuropean.com/ images/images-tinplates/absinthe.jpg |
How come a drug with side effects similar to alcohol was banned when we are not even sure how it works?
One story says that absinthe experienced its demise back in 1905. A farmer by the name of Jean Lanfrey drunk absinthe, brandy, and wine all day. That evening he got into an argument with his wife which eventually led to him shooting his wife and his unborn child as well as his two and four year old. He ultimately tried to commit suicide as well but failed. Neighbors and friend of the Lanfrey's testified that his rampage didn't fit his personality. The media at the time played up the fact that this was probably due to the Absinthe he had drunk earlier that day. Absinthe was blamed for the "bloodthirsty crime" and an anti absinthe campaign banned absinthe in Switzerland by 1908 and then eventually France, Germany, and the US banned it as well.(10)
References
1) Hutton, Ian; Myth, reality, and absinthe; Current Drug Discovery, Sept. 2002 pg. 62-64
2) Wake G, Court J, et al. (2000) CNS acetylcholine receptor activity in European medicinal plants traditionally used to improve failing memory. Journal of Ethnopharmacology 69(2); 105-114
3) Del Castillo J, Anderson M, Rubottom GM (1975); Marijuana, absinthe and the central nervous system, Nature 253; pg 365-366
4) Meschler JP, Howlett AC (1999) Thujone exhibits low affinity for cannabinoid receptors but fails to evoke cannabimimetic responses. Pharmacology Biochemisty and Behavior 62(3) pg 473-480
5) Gambelunghe C., Melai P (2002) Absinthe: enjoying a new popularity among young people?; Forensic Science International; 130 pg 183-186
6) Hold et al.; α-Thujone( the active component of absinthe):γ-Aminobutyric acid type A receptor modulation and metabolic detoxification; PNAS 97(8), pg 3826-3831
7)Erowid Absinthe Vault. http://www.erowid.org/chemicals/absinthe/absinthe.shtml Last Accessed: Mar. 11, 2003
8) Absinthe and Thujone http://www.chem.ox.ac.uk/mom/absinthe/absinthe.html Last Accessed: Mar 11, 2003
9) Thujone, Thomas Prisinzano, http://www.phc.vcu.edu/feature/thuj/thujone.html Last Accessed: Mar 11, 2003
10) A short history of Absinthe http://www.absinth24.com/html/absinth-geschichte-main.html Last Accessed: Mar 10, 2003
www.alltel.net/~treecast/ catalog.htm |
1) Hutton, Ian; Myth, reality, and absinthe; Current Drug Discovery, Sept. 2002 pg. 62-64
2) Wake G, Court J, et al. (2000) CNS acetylcholine receptor activity in European medicinal plants traditionally used to improve failing memory. Journal of Ethnopharmacology 69(2); 105-114
3) Del Castillo J, Anderson M, Rubottom GM (1975); Marijuana, absinthe and the central nervous system, Nature 253; pg 365-366
4) Meschler JP, Howlett AC (1999) Thujone exhibits low affinity for cannabinoid receptors but fails to evoke cannabimimetic responses. Pharmacology Biochemisty and Behavior 62(3) pg 473-480
5) Gambelunghe C., Melai P (2002) Absinthe: enjoying a new popularity among young people?; Forensic Science International; 130 pg 183-186
6) Hold et al.; α-Thujone( the active component of absinthe):γ-Aminobutyric acid type A receptor modulation and metabolic detoxification; PNAS 97(8), pg 3826-3831
7)Erowid Absinthe Vault. http://www.erowid.org/chemicals/absinthe/absinthe.shtml Last Accessed: Mar. 11, 2003
8) Absinthe and Thujone http://www.chem.ox.ac.uk/mom/absinthe/absinthe.html Last Accessed: Mar 11, 2003
9) Thujone, Thomas Prisinzano, http://www.phc.vcu.edu/feature/thuj/thujone.html Last Accessed: Mar 11, 2003
10) A short history of Absinthe http://www.absinth24.com/html/absinth-geschichte-main.html Last Accessed: Mar 10, 2003
11) Absinthe buyers guide. http://www.absinthebuyersguide.com
Last Accessed: Mar 10, 2003
12) Absinthe shop - The green fairy. www.laboheme.uk.com/ absinthe.htm Last Accessed: Mar 9, 2003
13) Lanier, Doris; Absinthe: Cocaine of the 19th century; 1995, McFarland and Co.; Jefferson, NC pg 1-29
14) Wu, C ; Toxin in absinthe makes neurons run wild.(alpha-thujone); Science News 2000 ;
http://www.findarticles.com/cf_0/m1200/14_157/61617774/p1/article.jhtml Last Accessed: Mar 13 2003
12) Absinthe shop - The green fairy. www.laboheme.uk.com/ absinthe.htm Last Accessed: Mar 9, 2003
13) Lanier, Doris; Absinthe: Cocaine of the 19th century; 1995, McFarland and Co.; Jefferson, NC pg 1-29
14) Wu, C ; Toxin in absinthe makes neurons run wild.(alpha-thujone); Science News 2000 ;
http://www.findarticles.com/cf_0/m1200/14_157/61617774/p1/article.jhtml Last Accessed: Mar 13 2003
www.laboheme.uk.com/ absinthe.htm |