The Effects of Diseases, Drugs, and Chemicals on the Creativity and Productivity of Famous Sculptors, Classic Painters, Classic Music Composers, and Authors

Continued

VINCENT VAN GOGH (1853–1890)

The Chemistry of His Yellow Vision

The color yellow fascinated the Dutch postimpressionist painter, Vincent van Gogh, in the last years of his life. His house was entirely yellow. He wrote How Beautiful Yellow Is, and all of his paintings in these years were dominated by yellow. Van Gogh's preference for the color yellow may have been that he simply liked the color (Figure 6 ). However, 2 speculations exist that his yellow vision was caused by overmedication with digitalis or excessive ingestion of the liqueur absinthe. The drink contains the chemical thujone. Distilled from plants such as wormwood, thujone poisons the nervous system. The chemistry of the effect of digitalis and thujone resulting in yellow vision has been identified. It also should be noted, prior to the discussion of van Gogh's yellow vision, that many clinicians have reviewed the medical and psychiatric problems of the painter posthumously, diagnosing him with a range of disorders, including epilepsy, schizophrenia, digitalis and absinthe poisoning, manic-depressive psychosis, acute intermittent porphyria, and Ménière disease. Psychiatrist Kay R. Jamison, PhD, believes that van Gogh's symptoms, the natural course of his illness, and his family psychiatric history strongly indicate manic-depressive illness. It is also possible that he suffered from both epilepsy and manic-depressive illness.9 If lithium carbonate had been available in the 19th century, it might have helped Van Gogh.

The Effect of Digoxin on the Retina and the Nervous System, Resulting in Yellow Vision

In 1785, William Withering observed that objects appeared yellow or green when foxglove was given therapeutically in large and repeated doses.¹⁰ Since 1925, various physicians, including Jackson,¹¹ Sprague,¹² and White,¹³ quoting Cushny, professor of pharmacology at the University of Edinburgh, have noted that patients overmedicated with digitalis develop yellow vision. According to Cushny, “All colors may be shaded with yellow or rings of light may be present.”

It has been established that van Gogh suffered from epilepsy, for which he was treated with digitalis, as was often the case in the late 19th century.¹⁴ Barton and Castle¹⁵ stated that Parkinson recommended a trial use of digitalis in epileptics. Digitalis may have been used to relieve his epilepsy. Physicians are more likely to consider a diagnosis of digoxin toxicity if a history of xanthopsia (yellow vision) is elicited, this being the symptom best known to physicians.¹⁶

William Withering described many of the toxic effects of the cardiac glycosides in his classic treatise on foxglove in 1785: “The foxglove when given in very large and quickly repeated doses, occasions sickness, vomiting, purging, giddiness, confused vision, objects appearing green or yellow; … syncope, death.” Since 1925, numerous studies have described the visual symptoms and attempted to identify the site of visual toxicity in digitalis intoxication.

The site of toxicity responsible for the visual symptoms has been debated for decades. Langdon and Mulberger¹⁷ and Carroll¹⁸ thought that the visual symptoms originated in the visual cortex. Weiss¹⁹ believed that xanthopsia was due to brainstem dysfunction. Demonstration of cellular alterations in the cerebral cortex and spinal cord of cats after administration of toxic doses of digitalis support the central dysfunction theory.

For many years, most investigators thought that the most likely site of damage in digitalis intoxication was the optic nerve. More recent investigations, however, have identified significant retinal dysfunction in digitalis toxicity and have shed some doubt on the older hypotheses.²⁰ Support for a retinal site of toxicity has been provided by studies that have shown much higher accumulations of digoxin in the retina than in other tissues, including the optic nerve and brain.²¹ Digoxin toxicity might involve inhibition of sodium-potassium–activated adenosine triphosphatase, which has been identified in high concentration in the outer segments of the rods; inhibition of the enzyme could impair photoreceptor repolarization.²² Lissner and colleagues,²³ however, found the greatest uptake of digoxin in the inner retinal layers, particularly in the ganglion cell layer, with little uptake in photoreceptors.

Another possible explanation for van Gogh's xanthopsia was his excessive ingestion of absinthe.²⁴ Van Gogh's taste for absinthe (a liqueur) may have also influenced his style of painting. The drink's effect comes from the chemical thujone.²⁵ Distilled from plants such as wormwood, thujone poisons the nervous system. Van Gogh had a pica (or hunger) for unnatural “foods,” craving the entire class of fragrant but dangerous chemicals called terpenes, including thujone. As van Gogh recovered from cutting off his ear, he wrote to his brother: “I fight this insomnia with a very, very strong dose of camphor in my pillow and mattress, and if ever you can't sleep, I recommend this to you.” Camphor is a terpene known to cause convulsions in animals when inhaled. Van Gogh had at least 4 such fits in his last 18 months of life.

Van Gogh's friend and fellow artist Paul Signac described an evening in 1889 when he had to restrain the painter from drinking turpentine. The solvent contains a terpene distilled from the sap of pines and firs. Van Gogh tried more than once to eat his paints, which contained terpenes as well. Signac also wrote that van Gogh, returning after spending the whole day in the torrid heat, would take his seat on the terrace of a cafe, with the absinthe and brandies following each other in quick succession. Toulouse-Lautrec drank absinthe from a hollowed walking stick. Degas immortalized absinthe in his bleary-eyed painting, Absinthe Drinker. Van Gogh nursed a disturbed mind on the aquamarine liqueur, which may have encouraged him to amputate his ear.

Absinthe is about 75% alcohol and has about twice the alcoholic volume of vodka. It is made from the wormwood plant, which is reputed to have a hallucinogenic effect, and is flavored with a blend of anise, angelica root, and other aromatics.

The chemical mechanism of α-thujone (the active component of absinthe) in neurotoxicity has been elucidated with identification of its major metabolites and their role in the poisoning process.²⁶ α-Thujone has a sort of double-negative effect on the brain. It blocks a receptor known as γ-aminobutyric acid–A (GABA-A), which has also been linked to a form of epilepsy. Under normal conditions, GABA-A inhibits the firing of brain cells by regulating the flux of chloride ions. By essentially blocking the blocker, thujone allows the brain cells to fire at will. α-Thujone acts at the noncompetitive blocker site of the GABA-A receptor and is rapidly detoxified, thereby providing a reasonable explanation for some of the actions of absinthe other than those caused by ethanol and allowing more meaningful evaluation of risks involved in the continued use of absinthe and herbal medicines containing α-thujone. Thus, the secret of absinthe, which is considered a fuel for creative fire, has been unlocked.

There is an increasing concern about the use of thujone substances with the rise in popularity of herbal medicines. Wormwood oil, which contains thujone, is present in some herbal preparations used to treat stomach disorders and other ailments. (In fact, wormwood, a relative of daisies, got its name from its use in ancient times as a remedy for intestinal worms.) Individuals ingesting these preparations have complained of developing yellow vision.²⁷ Scientific studies of thujone are investigating the active ingredients in many herbal preparations. Absinthe is still manufactured in Spain and the Czech Republic. In modern absinthe, alcohol, which makes up three quarters of the liqueur, may be the most toxic component. It is still illegal to buy absinthe in the United States, although it can be obtained through the Internet or when traveling overseas.

Recently, an article entitled “Poison on Line: Acute Renal Failure Caused by Oil of Wormwood Purchased Through the Internet” was published in the New England Journal of Medicine.²⁸ In this article, a 31-year-old man was found at home in an agitated, incoherent, and disoriented state by his father. Paramedics noted tonic-clonic seizures with decorticate posturing. His mental status improved after treatment with haloperidol, and he reported finding a description of the liqueur absinthe at a site on the World Wide Web entitled “What is Absinthe?” The patient obtained one of the ingredients described on the Internet, essential oil of wormwood. The oil was purchased electronically from a commercial provider of essential oils used in aromatherapy, a form of alternative medicine. Several hours before becoming ill, he drank approximately 10 mL of the essential oil, assuming it was absinthe liqueur. This patient's seizure, probably caused by essential oil of wormwood, apparently led to rhabdomyolysis and subsequent acute renal failure.

This case demonstrates the ease of obtaining substances with toxic and pharmacologic potential electronically and across state lines. Chinese medicinal herbs, some of which can cause acute renal failure, are easily procured by means of the Internet. Although absinthe liqueur is illegal in the United States, its ingredients are readily available. Absinthe is also currently a popular drink in the bars of Prague, in the Czech Republic. The essential ingredient in this ancient potion was purchased in this case by means of up-to-the-minute computer technology.

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A modern clinical chemistry and genetics laboratory could possibly have determined the following in van Gogh's case: (1) serum digitalis concentration, (2) serum thujone concentration, (3) urine porphobilinogen, and (4) serum lithium levels. These tests could possibly have confirmed that van Gogh suffered from chronic digitalis intoxication or intoxication from thujone related to excessive drinking of the liqueur absinthe. Modern tests could analyze his urine for the presence of porphobilinogen, which is the diagnostic test for acute intermittent porphyria, another speculated van Gogh illness. If Van Gogh had used lithium carbonate for bipolar illness, serum lithium levels might also have been important to monitor.

Continue to Louis Hector Berlioz and Thomas de Quincey
references ~ commencement

Last updated: 12/05

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