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

Written by Paul L. Wolf MD

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 y-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.

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