Science

Madness in a Bottle

Prior to the Anslinger era of Reefer Madness, there was another botanical substance that caused a global frenzy. Analogous to the Waldos daily appointment for cannabis consumption, there was another slice of time in the 19th century called “The Green Hour”. The green, however, had nothing to do with cannabis. Rather, it referred to the distilled spirits created from the plant Artemisia absinthium, better known as wormwood, and some other botanicals like anise, fennel, hyssop, and lemon balm. Absinthe was consumed in large quantities by the working class, bohemians, poets, and painters, in avant-garde cities like Paris and Prague. It’s estimated that nearly 24,000,000 liters of absinthe were consumed in France in 1913, which averages to about 60 liters per inhabitant. [1] At the beginning of the 20th century, absinthe consumption mushroomed, and worried governments sought to exercise a stranglehold on the escalating ingestion. So, they did what many government bodies have tried to do with other natural substances, and enacted prohibition. And with prohibition, of course, comes propaganda.

Bohemians were the epoch’s beatniks or hippies, and you’ve likely recognized that the Establishment tends to frown upon the activities of these types of nonconformists. So, it’s no surprise that the more conservative types got flustered. But the medical community also felt action must be taken, since they correlated heavy absinthe consumption with insanity. [2] A tally of those residing in French mental institutions in 1907, however, revealed that just 1/40th of the people in the asylums were indeed absinthe drinkers. [3] Interestingly, the cause of France springing to action and banning absinthe in 1915 during World War I has been postulated as coming from the fear of a weakened military from excessive absinthe intake. [4]

Fretting physicians termed the resultant symptoms of absinthe consumption “absinthism”, which included vertigo, brain damage, delirium, and suicide. [4] Oh, the madness. Clinical definitions of absinthism were suspect, though, and conjure visions of Renfield locked away in the sanitarium, having succumbed to the mind control of Count Dracula.

The essential oil extracted from wormwood provided the characteristic physiological effects from drinking absinthe, and the finger-pointing focused on the monoterpenoid thujone. Even when absinthe was reintroduced into modern culture, permissible levels of thujone were limited to no more than 35 mg/L. [5] Thujone toxicity involves the modulation of γ-aminobutyric acid type A receptor (GABAA). [6] These receptors are ubiquitous in any creature that has a nervous system. Thujone is a competitive antagonist of GABAA, which translates to the terpenoid’s binding to, but not activating the receptor, preventing GABA, a vital neurotransmitter, from distributing its chemical messages throughout the body.

Molecules that activate GABAA receptors can confer calming, hypnotic, anti-anxiety, anti-convulsant properties. Common examples include barbiturates, benzodiazepines, and alcohol. When the opposite occurs, as is the case with thujone, increased anxiety and convulsions can occur. Thujone is also a porphyrogenic molecule, meaning it produces increased levels of molecules called porphyrins, leading to porphyria, a range of diseases affecting the skin and/or nervous system. [7] Interestingly, porphyria cutanea tarda presents symptoms that sound vampiric and lycanthropic [8], including excessive reactions to light, burns from the sun, and hair growth, especially on the face. (Note: You may never look at the references at the end of our posts, but you should for #8. It was a glorious event to find that in the literature.) And in sanguinary fashion, drinking blood is thought to provide relief from porphyria.

But thujone got a bit of a bad rap. It’s concentration in different wormwood cultivars varies widely, comprising anywhere from zero up to 71% of the essential oil from different wormwood cultivars. [9] Thus, researchers have concluded that it can’t be the only molecular source inciting absinthism madness. [9] Some equated the physiological effects of thujone to that of tetrahydrocannabinol (THC) [10], but that notion has since been dispelled in the scientific literature. [11]

Like most terpenes you’ll read about, thujone has medicinal properties. The extract from Northern White Cedar leaves, containing approximately 65% thujone, was tested against a human skin cancer cell line. [12] The thujone-rich fraction of the essential oil demonstrated cytotoxic (toxicity to cells), anti-proliferative, and apoptotic (cell death-inducing) properties against the malignant cells, while no inhibitory effects were measured on normal, healthy cells. Thujone also exhibited anti-cancer properties in mice induced with lung metastasis, inhibiting tumor proliferation by 58-59%, depending on the route of administration, increasing the survival rate by 32-33%. [13] Lastly, thujone has demonstrated anti-mutagenic (a mutagen can alter genetic material) properties against ultraviolet (UV) radiation-induced DNA damage [14], and low concentrations of the monoterpenoid have facilitated DNA repair following induced DNA damage from UV radiation or 4-nitroquinoline-1-oxide [15].

It’s astonishing how so many botanicals can easily whip up a frightened and frenzied population faster than a few choice tweets. But a little bit of scientific research can go a long way when dispelling folly with fact. The tale of the anathema towards thujone orbits that of THC, and provides a natural depiction of the adage, “a little goes a long way, but a lot will kill you”.

References

[1] The conquest of absinthe – French national curse suppressed. The Times, Issue 40819, 1915, Apr 03:7.

 

[2] Lanier, D. Absinthe-the cocaine of the nineteenth century: a history of the hallucinogenic drug and its effect on artists and writers in Europe and the United States, Jefferson, North Carolina, USA, McFarland; 1995.

 

[3] Conrad B. Absinthe: History in a Bottle. San Francisco: Chronicle Books; 1988.

 

[4] Padosch, S. et al. “Absinthism: a fictitious 19th century syndrome with present impact”, Substance Abuse Treatment, Prevention, and Policy, 2006, 1:14. [journal impact factor = 2.155; cited by 63]

 

[5] Council Directive (EEC) No 88/388 on the approximation of the laws of the Member States relating to flavourings for use in foodstuffs and to source materials for their production. Off J Europ Comm 1988, L184:61-66.

 

[6] Höld, K. et al. “α-Thujone (the active component of absinthe): γ-Aminobutyric acid type A receptor modulation and metabolic detoxification”, PNAS, 2000, Volume 97(8): Pages 3826-3831. [journal impact factor = 9.504; cited by 317]

 

[7] Bonkovsky, H. et al. “Porphyrogenic properties of the terpenes camphor, pinene, and thujone: with a note on historic implications for absinthe and the illness of Vincent Van Gogh”, Biochemical Pharmacology, 1992, Volume 43(11): Pages 2359-2368. [journal impact factor = 5.009; cited by 95]

 

[8] Illis, L. “On Porphyria and the Etiology of Werwolves”, Proceedings of the Royal Society of Medicine, 1964, Volume 57: Pages 23-26. [journal impact factor = 2.118; cited by 68]

 

[9] Lachenmeier, D. and Nathan-Maister, D. “Systematic Misinformation about Thujone in Pre-Ban Absinthe”, Deutsche Lebensmittel-rundschau, 103 (2007): 255-262. [journal impact factor = 0.045; cited by 18]

 

[10] Del Castillo, J. et al. “Marijuana, absinthe and the central nervous system”, Nature, 1975, Volume 253: Pages 365-366. [journal impact factor = 41.577; cited by 82]

 

[11] Meschler J. and Howlett A. “Thujone exhibits low affinity for cannabinoid receptors but fails to evoke cannabimimetic responses”, Pharmacol Biochem Behav., 1999, Volume 62(3): Pages 473-80. [journal impact factor = 2.781; cited by 125]

 

[12] Biswas, R. et al. “Thujone-Rich Fraction of Thuja occidentalis Demonstrates Major Anti-Cancer Potentials: Evidences from In Vitro Studies on A375 Cells”, Evidence-Based Complementary and Alternative Medicine, Volume 2011, Article ID 568148, 16 pages [journal impact factor = 1.931; cited by 97]

 

[13] Siveen, K. and Kuttan, G. “Thujone inhibits lung metastasis induced by B16F-10 melanoma cells in C57BL/6 mice”, Can. J. Physiol. Pharmacol. 89: 691–703 (2011) [journal impact factor = 1.770; cited by 24

 

[14] Vuković-Gacić, B. et al. “Antimutagenic effect of essential oil of sage (Salvia officinalis L.) and its monoterpenes against UV-induced mutations in Escherichia coli and Saccharomyces cerevisiae”, Food Chem. Toxicol. 44, 1730–1738.

 

[15] Nikolić, B. et al. “Modulation of genotoxicity and DNA repair by plant monoterpenes camphor, eucalyptol and thujone in Escherichia coli and mammalian cells”, Food Chem. Toxicol, 2011, Volume 49: Pages 2035-2045.

 

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About the author

Jason S. Lupoi, Ph.D.

Jason S. Lupoi, Ph.D.

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