Vincent van Gogh and the Thujone Connection

During his last two years Vincent van Gogh experienced fits with hallucinations that have been attributed to a congenital psychosis. But the artist admitted to episodes of heavy drinking that were amply confirmed by colleagues and there is good evidence to indicate that addiction to absinthe exacerbated his illness. Absinthe was distilled from an alcoholic steep of herbs. Wormwood (Artemisia absinthium) was the most significant constituent because it contributed thujone. This terpene can cause excitation, convulsions that mimic epilepsy. and even permanent brain damage. Statements in van Gogh's letters and from his friends indicate that he had an affinity for substances with a chemical connection to thujone; the documented examples are camphor and pinene. Perhaps he developed an abnormal craving for terpenes, a sort of pica, that would explain his attempts to eat paints and so on, which were previously regarded as unrelated absurdities. 

THE BENCHMARK position of his Postimpressionism paintings ensures Vincent van Gogh a prominent place in art history. But he has attracted, and continues to intrigue, a wider audience to the extent that polls invariably find van Gogh near the top of recognized artists, irrespective of the aesthetic background of the survey. Posthumous praise of his canvases roused attention but surely it has been interest in extraordinary aspects of the person that has made his a household name. His short life span (1853-1890), range of trials and tribulations, intensity and productivity of his last two years, and his suicide add opts a package that elicits a haunting curiosity and gnawing sympathy even in the most casual observer. 


A checkered career as art dealer's associate, schoolteacher, divinity student, and preacher-cum-pastoral volunteer preceded van Gogh's declared commitment in 1880 to become a full-time artist.1 The next six years were spent in various towns and cities of Belgium and Holland, mostly occupied with self-study but interspersed with brief periods of professional instruction and occasional interludes of companionship with other practicing artists. In February 1886, van Gogh came to Paris and stayed for two years with his brother Theo, who had supported him, both practically and emotionally, and would continue to do so for all ten of his artistically productive years.

Theo managed a branch gallery of Goupil & Co, where he was a successful art dealer but also conducted something of a running battle with the ownership over his support of artists outside the main-stream.2 Theo introduced van Gogh to Camille Pissarro and other impressionists, as well as younger painters such as Paul Signac and Henri Toulouse-Lautrec. Toward the end of the winter of 1888, van Gogh forsook Paris for the southern city of Arles. where he was later joined by Paul Gauguin. This 15-month period culminated in the incident of self-mutilation of the left ear that led to his hospitalization and was followed by a year of self-commitment in the asylum at nearby Saint Remy. He came north again in 1890 and stayed a few days in Paris with Theo, then went to Auvers-sur-Oise (about an hour away by train) to be under the observation of Dr Paul Gachet from May 23 until his death on July 29. Pissarro had recommended Dr Gachet because of his enthusiasm for the visual arts as well as his experience in attending melancholic patients. It can be mentioned in passing that Dr J. Baillarger,one of Gachet's professors in Paris,4 was the first to delineate manic-depressive psychosis in 1854. Gachet prescribed work therapy (in the best tradition of another mentor, Dr J. P. Falret), but the deep-seated problems that beset van Gogh were not reversed. There is no indication that any physician of the day could have intervened successfully. 


Much has been written about the nature of van Gogh's illness. There is general agreement that he had a psychosis but no consensus has been reached on a specific diagnosis. However, there is evidence to indicate that other factors exacerbated his congenital problems, and they shall be the focus herein. I am convinced that during his last decade van Gogh developed an affinity for chemicals of the terpene class and that they contributed to his early demise. Moreover, in the most bizarre of juxtapositions, they followed him even beyond interment.

Hemphill5 reached the conclusion that van Gogh was a manic-depressive who developed confusional episodes and fits due to his addiction to absinthe. The toxic agent in absinthe was thujone. This terpene occurs in a variety of plants but was named for its presence in thuja oil, the essential oil that can be distilled from Thuja occidentalis (white cedar) and other coniferous trees of the arborvitae group. The evidence for thujone involvement in van Gogh's pathogenesis is compelling and I believe that a connection with two related compounds can now be offered. Anton Kerssemakers, an amateur artist who associated with van Gogh in 1884, commented on van Gogh's penchant for carrying brandy on painting excursions and also made a point about his simple (and perhaps inadequate) daily food intake.6 But it is clear that van Gogh started drinking heavily after his arrival in Paris in 1886; there are numerous anecdotes along these lines from relatives and friends. Toulouse-Lautrec, who supposedly introduced him to the popularity of absinthe in the Parisian cafes, later did a pastel portrait of van Gogh partaking of a glass. Van Gogh's nephew7 and others have acknowledged the possible contribution of the artist's drinking habits to his failing health but they have confused the literature by missing or underestimating his proclivity for absinthe (and its damaging components in addition to alcohol). Absinthe drinking became a major social problem in 19th and early 20th century France. Common observation suggested that frank mental deterioration often attended excessive imbibing of absinthe. 


In the first century a wine fortified with extract of wormwood (Artemisia absinthium) was described as "absinthites" by Pliny the Elder.8 The interesting taste imparted to beverages by wormwood extract seems to have been frequently rediscovered during the next 1700 years. A stronger drink, with 70% to 80% alcohol by volume, was devised by a general practitioner,9 a Frenchman residing in Switzerland. He sold the recipe to M. Pernod in 1797. According to Fournier,10 absinthe was an emerald-green liquor distilled from wormwood, anise, fennel, melissa, hyssop, and other aromatic plants that had been steeped in alcohol. The deleterious compound in absinthe proved to be thujone; the major source was wormwood although other herbs contributed. Poets and painters depicted absinthe and absinthe drinkers,11 and van Gogh himself painted a still life with absinthe. The bronze and silver absinthe glasses by Pablo Picasso in 1914 came hard on legislative attempts to ban absinthe from France and have been interpreted by Adams12 as an artist's celebration of the individual's freedom of choice in matters alcoholic. It was not until 1922 that absinthe was effectively banned from France, although other countries had enacted similar legislation much earlier.13

Regular consumption of absinthe caused stomach irritation and eventually general upset of the nervous system. In a letter14 written from Arles in April 1888 (to Emile Bernard), van Gogh complained of a major stomach disorder. Shortly after, in a letter to his brother Theo.15 he admitted to drinking and smoking too much during the preceding period and to "certainly going the right way for a stroke when I left Paris." Later he was to say that his digestion was greatly improved and that he felt "as well as other men now"16 and also, "far from losing my physical strength, I am regaining it, and my stomach especially is stronger."17 The early letters from Arles are full of sanctimonious warnings to Theo about the dangers of smoking, drinking, and sex. Notwithstanding best intentions for moderation it is clear that van Gogh resumed all three fairly heavily. The brief visit by Gauguin did more harm than good for van Gogh's sobriety. Signac later commented that, 'Though he [van Gogh) ate hardly anything, what he drank was always too much . . . after spending all day in the sun [painting] . . the absinthes and brandies would follow each other in quick succession."18 

Intravenous injection of 0.05 mL of absinthe oil (as a 5% alcohol solution) into a rabbit produces marked excitation of the autonomic nervous system followed by unconsciousness and convulsions that mimic epilepsy.19 When pure thujone is injected into the circulation it produces convulsions that are clonic and then tonic.20 Permanent damage to the central nervous system occurs with repeated exposures to thujone.19  

In the last 18 months of his life, when van Gogh experienced at least four fits with hallucinations21 resembling those described by absinthe drinkers,22 he was exposing himself to increasing amounts of thujone. Even when he was given leave from the hospital at Arles or the asylum at Saint Remy there are good indications that he drank absinthe (thanks in part to the unwitting assistance of well-wishing friends) and that he relapsed accordingly. In a letter23 from Saint Remy to Theo, van Gogh writes about visiting old friends and neighbors in Arles and then in the next letter24 of another attack. Although van Gogh was not convinced that the visit (more absinthe?) and the subsequent attack were related, he broached the question.25 


Chemical structures of selected terpenes. See text for details. In the late 19th century, chemists defined the constituents of many essential oils. These included the terpenes, and thujone falls into the subclass of ketones. The German organic chemists Wallach, Tiemann, and Semmler were particularly active in elucidating the chemical structures of these compounds at the turn of the century. By 1900, Professor Semmler of Greifswald had proposed the correct structure of thujone, as shown in the Figure26; initially he called it tanacetone because his starting material was tansy oil (Tanacetum vulgare)  but it had already become clear that Wallach's thujone from thuja oil was identical. Thujone occurs in other essential oils including those from wormwood, sage, and related species.

Sollmann19 documents several compounds that either raise or lower the response to thujone if given in concert; of these we should mention bromides, which ameliorate the convulsions, and, on the other hand, nicotine, which lowers the convulsant threshold. Bromides were frequently employed in the treatment of mental disorders during the second half of the 19th century and were given to van Gogh at Arles and Saint Remy.27 Van Gogh exposed himself to nicotine and thujone, he was never without his pipe, and frequently judged himself as smoking too much, but we can only speculate on an interaction of medical import. Van Gogh's fits and confusion21 were controlled by bromide27 and withholding alcoholic beverages, which would be indicated for absinthe addiction according to Hemphill5 but not likely tube effective in temporal lobe epilepsy, one of the alternate diagnoses with some adherents.25 From the earliest records in Arles to recent retrospective analyses some degree of indulgence in alcohol (specifically absinthe) has usually been invoked as playing a role in the development of van Gogh's illness; characterization has ranged from exacerbating factor,29 through one working hypothesis among many,30 to major cause.5 Consumption of absinthe was high in Paris and four times the national average in Arles during van Gogh's time.31 An article in the American Journal of Pharmacy32 reveals how prevalent absinthe addiction was in France as early as 1868. Although that report predates a complete chemical and pharmacologic description of the wormwood component in absinthe it is clear that the deleterious effects of overindulgence were known, even if not heeded by the general population. That absinthe drinking was so commonplace may explain why van Gogh's habit (and we may never know the exact degree) was not more noteworthy to associates or attending physicians. 


A case can now be made for two other chemicals and their intriguing connection with thujone. While recovering in the Arles Hospital from his self-inflicted wound, van Gogh made a valiant effort to write an optimistic letter to his brother.33 He mentioned that the wound was healing, he was eating better, and he was making up the great loss of blood. But he went on to complain of insomnia that he was "fighting" himself without consultation with Dr Rey. Van Gogh described his cure as follows: "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." The chemical structure of camphor is shown in the Figure. Camphor is another ketone-terpene, with with the same empirical structure (C10H15O) as thujone and, most interestingly, similar pharmacodynamics. (A contemporary report34 on the composition of commercial "camphor oil" indicates the presence of pinene and other terpenes as well as camphor.) In fact, the margin between convulsant and fatal doses is even smaller for camphor than for thujone but, otherwise, the effects on mammals are similar.19

About this time, just before commitment to Saint Remy, van Gogh was visited by Signac, who was interviewed about it many years later by Gustave Coequiot.35 From all accounts Signac was a good friend, took van Gogh out for relaxation, visited his old quarters in Arles, admired his paintings, and reminisced about better times. Toward the end of the evening he had to restrain van Gogh, who "wanted to drink about a quart of essence of turpentine from the bottle." The attempt has usually been regarded as demented but there is a chemical connection. Turpentine is extruded from the sapwood of firs, pines, and other conifers. The essential oil is separated from the rosin by steam distillation as an oily, colorless liquid with a penetrating odor and a characteristic taste. It contains a large proportion of pi nene (Figure) and other terpenes; it is used chiefly as a solvent and drying agent in paints and varnishes. I believe that van Gogh had developed an affinity for terpenes, the documented examples being thujone, camphor, and pinene. Perhaps it. is not too strong to even suggest that he had a pica; that is, a craving for unnatural articles of food, a depraved appetite such as is seen in hysteria and pregnancy. The pica theory would help to resolve some of the strangest of van Gogh's acts during the last two years-his attempts to eat his paints and so on-that were previously regarded as absurdities and unrelated.  


Van Gogh's brief period in Auvers-sur-Oise was intense. Dr Gachet's firm but supportive therapy was acknowledged in a letter to the artist's mother. 36 "He tells me that in my case work is the best thing to keep my balance"; and another to friends in Arles,37 "The doctor here says that I ought to throw myself into my work with all my strength, and so distract my mind." Some of his best known works were created during this period. He was a frequent guest at the doctor's house for meals, discussion, and an introduction to etching. Van Gogh painted the doctor's portrait (twice), see JAMA THE COVER, Feb 20, 1981, as well as his daughter (at the piano and in the garden). Van Gogh was enamored of cypress trees and incorporated his flamelike interpretations of their form into many of his southern pictures. The species did not grow that far north but van Gogh found the ornamental shrubs in Gachet's terraced garden to be adequate "imitation" cypresses, according to the doctor's son, Paul Louis Gachet.  The boy, who was 17 years old at the time, was later to write extensively on his family's interaction with the artist and to provide an endowment for the perpetual upkeep of the van Gogh graves in Auvers-sur-Oise.

Van Gogh shot himself on the afternoon of July 27, 1890, died in the early morning of July 29, and was buried in the local cemetery. The grave was decorated by an ornamental tree provided by Dr Gachet. The initial arrangement was a nonrenewable 15-year concession on the grave plot. This necessitated exhumation and reburial in 1905. Gachet obtained a larger plot so that the casket of Theo could later be transferred from Holland and lie side by side with his brother's. Paul L. Gachet took care of arrangements for the reburial of van Gogh, on behalf of his father. When the casket was about to be disinterred it was found that the roots of the ornamental tree now completely entwined it; it was "as though they held him in a strong embrace."(U. F. Vandenbroucke, written communication, Nov 7, 0987) (Details of the tree and the casket were given to a Parisian print dealer by P. L. Gachet and thence to Madame Vandenbroucke. ) Yet the younger Gachet extricated the coffin carefully and brought the live tree back to their house. The transfer of Theo's casket from Utrecht to Auvers-sur-Oise was accomplished in 1919; Dr Gachet had been dead five years and his son again took care to the details in Auvers-sur-Oise. At the request of Theo's widow the two graves were now decorated only with ivy; the cuttings originating from the Cachet garden.

That ornamental tree is still growing in the garden of Dr Gachet. The present owners, Colonel and Madame Vandenbroucke. have proudly preserved the distinguished three-story home and the beautifully landscaped grounds. They graciously received me and pointed out that special tree. There it stands-a Thuja tree -a classic source of thujone, the slow poison that probably shortened van Gogh's life, and it grew over his grave for 15 years! 


Journal of the American Medical Association
Nov 25. 1988—Vol 260. No 20
From the Department of Biochemistry University of Kansas Medical Center, Kansas City
Reprint requests to the Department or Biochemistry  
University of Kansas Medical Center. Kansas City, KS 661031(Dr. Arnold) 



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