Wormwood, and its chemicals and concoctions, has an interesting history, and it’s difficult to know where to start.  And whenever I’m in doubt, I start at the beginning, despite what my favorite author says (see rule 5).

Artemisia absinthium

The plant genus Artemisia houses over 300 species, and includes the common sagebrush, as well as the cool sounding mugwort and wormwood.  Wormwood, Artemisia absinthium, is native to Europe, Asia, and northern Africa, and is a pretty ornamental, perennial shrub.  It gets its name by being an anthelmintic – an agent that expels parasitic worms from the body.  I wonder who tested this first, but I guess if you’ve got parasitic worms, you’ll try anything.  The leaves of wormwood also don’t decompose well, and it was probably this property that lead people to try it as an antiseptic.  And way back in the day, before instafacebookgram you had nothing else to do besides watching leaves rot.

Wormwood has a high alkaloid (chemical compounds that contain nitrogen) content, and typical of such, is extremely bitter.  So bitter, that it was used back in the Middle Ages to spice up mead (wine honey), or perhaps tone down the sweetness.  Later, it found use as a replacement for hops in making beer.  Hops, as some might know, was used in beer to prevent it from spoiling during long sea voyages.  But it wasn’t until the mid to late 1800’s that wormwood made its mark in history in the form of absinthe.

“Green Muse” by Albert Maignan

The green, alcoholic spirit absinthe became extremely popular in France in the mid 1800’s.  It was produced from grain alcohol steeped in anise, fennel, and wormwood.  The anise gives absinthe its licorice-like flavor, chlorophyll its green color, and wormwood its bad rap.  Because it was expensive to produce, absinthe was in the realm of the aristocrats and wealthy, while the poor commoners were stuck with lowly wine.  My how times have changed.  When a widespread wine grape crop failure struck France, absinthe was there to fill the void.  Even when the crops recovered, wine sales did not.  Absinthe was referred to as the “green fairy”, because of its color and rumored hallucinogenic properties (or maybe it was the 70% alcohol).  It was these properties that made absinthe popular with the Bohemian artists of the day.  Artists such as playwright Oscar Wilde, poet Charles Baudelaire, and painters Edouard Manet and Vincent van Gogh.  It is rumored that van Gogh cut off his ear while under the influence of absinthe.  An estimated 21 million liters was consumed annually in France by 1900.  And then it dropped to near zero overnight.

So what happened?  Well, the temperance movement was not just restricted to the United States, and when a Swiss man killed his family after two shots of absinthe (we’ll conveniently forget about the several liters of wine and brandy), that was the nail in the proverbial coffin.  Some pseudo-science acted as the hammer.  Dr. Valentin Magnan believed that alcohol, particularly absinthe, was responsible for the decline of French culture.  He studied heavy users of absinthe, and found them to have a different sort of addiction than that of alcoholics.  He called it absinthism.  How very clever.  To test his hypotheses, he subjected dogs to wormwood oil, and watched as they had seizures and died.

(-)-alpha-Thujone

The major component of wormwood oil is the alkaloid thujone, and the error of Dr. Magnans experiments is that wormwood oil is about 40% thujone, while that found in absinthe was about 30 milligrams per liter, or about 0.003%.  Big difference.  One would die of alcohol poisoning many times over before succumbing to thujone toxicity, but that fact was largely ignored.  And that was that.  Absinthe, besides being portrayed in movies and books, didn’t raise it’s green head again until about a decade ago, when bans were lifted.  In the United States, absinte was again made legal in 2007, provided the thujone concentration is less than 10 mg/L.  Now absinthe is a popular, and expensive, niche spirit industry.

So is thujone really responsible for hallucinations?  Some scientists in 1975 thought they had cracked the case when they published their findings in Nature (1).  They compared thujone to THC, and concluded that thujone could be a ligand for the cannabinoid receptors.  It took about twenty years, but this was disproven when it was found that thujone has very low affinity for the cannabinoid receptors and fails to stimulate them (2).  So what does thujone do?  Thujone acts on the GABA receptors as an antagonist, and inhibits activation (3).  Notable agonists are gamma-aminobutyric acid (GABA), ethanol and benzodiazepines, such as Valium and Xanax, and activate the receptors.  So in simplistic terms, thujone behaves oppositely those drugs.  GABA receptors affect the flow of ions into and out of the cell, which is important in neurons “firing”.  Activation slows it down.  Deactivation makes it speeds it up and misfire.  Think of it like the cylinders of your car.  If the cylinders aren’t firing quickly enough, the car becomes sluggish and slows down, like when you become sedated with ethanol or a benzodiazepine.  When the cylinders are firing away, and one is out of sync, the engine and whole car starts shaking – you can’t miss it.  This is what thujone does, causes misfires resulting in seizures.

In a 1997 case report published in the New England Journal of Medicine (4), a man purchased wormwood oil, which he mistook as absinthe, after reading about it on-line.  He drank 10 mL of the wormwood oil (2 teaspoons), became agitated, delirious, and had multiple seizures.  Upon hospitalization he suffered from rhabdomyolysis (breakdown of muscle fibers and common in seizures), and eventually developed renal failure.  He was released from the hospital after 8 days.  After looking at his reported serum electrolytes, I’m surprised he survived.  Two thumbs up for George Washington University Medical Center.

So is thujone safe?  Yes and no.  Remember your Paracelsus: “the dose makes the poison.”  Thujone in low absinthe concentrations is fine.  Thujone in straight up wormwood oil is bad.

References:
1. Del Castillo, J., M. Anderson, and G. M. Rubottom. “Marijuana, Absinthe and the Central Nervous System.” Nature 253.5490 (1975): 365-66.

2. Meschler, J.P, Howlett, A.C. “Thujone exhibits low affinity for cannabinoid receptors but fails to evoke cannabimimetic response.” Pharmacol. Biochem. Behav. 62 (1999): 473-80.

3. Höld KM, Sirisoma NS, Ikeda T, Narahashi T, Casida JE. “Alpha-thujone (the active component of absinthe): gamma-aminobutyric acid type A receptor modulation and metabolic detoxification”. Proc. Natl. Acad. Sci. 97 (2000): 3826–31.

4. “Poison on Line — Acute Renal Failure Caused by Oil of Wormwood Purchased through the Internet.” New England Journal of Medicine 337.20 (1997): 1483.