Marijuana, absinthe and the central nervous system.
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Cannabis↗
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Absinthe: behind the emerald mask.
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Alcoholic Beverages↗
[Effect of chelidonium, curcuma, absinth and Carduus marianus on the bile and pancreatic secretion in liver diseases].
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Bile↗
[Partial atrophy of the optic nerve due to chronic use of absinth].
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Humans↗
A reappraisal of the possible seizures of Vincent van Gogh.
The tragic life of Vincent van Gogh is summarized, emphasizing his early departure from formal education, failure as a successful salesman in the art world, attempt at religious studies, difficulty with female and family relationships, return to the art world, and tendencies toward extremes of poor nutrition or near self-starvation and excessive drinking and smoking. In Paris he joined the Impressionists, but drank very heavily both absinthe and cognac. Southward he went to Arles and was joined by Paul Gauguin, with whom he had major personality problems, causing van Gogh to cut off part of his left ear. He experienced paranoid ideation and confinement in mental institutions in Arles, and then returned to Paris and onto Auvers-sur-Oise, where he committed suicide at age 37. Possible physical diagnoses include glaucoma, Meniere's disease, acute intermittent porphyria, and chronic lead poisoning, but these diagnoses seem unlikely. Possible psychiatric diagnoses include borderline personality disorder, anxiety-depressive disorder with episodes of depression and hypomania, and also paranoid schizophrenia. Van Gogh did not have spontaneous seizures and, therefore, did not have epilepsy. Before he began to drink heavily, when he was near starvation, he had "fainting fits," and after drinking, especially absinthe, a convulsant drug, he continued to have similar attacks. His episodes of unconsciousness can be well explained by chronic malnutrition and alcohol abuse, only possibly exacerbated by drinking large quantities of absinthe. Although van Gogh is an excellent example of the Geschwind syndrome, at times associated with temporal lobe epilepsy, this fact does not establish such an epilepsy. Thus, the syndrome is an orphan without the parent condition.
Adult↗
Thujone exhibits low affinity for cannabinoid receptors but fails to evoke cannabimimetic responses.
Absinthe, an abused drug in the early 1900s, has been speculated to activate the receptors responsible for marijuana intoxication (the CB1 cannabinoid receptor) (Nature 253:365-356; 1975). To test this hypothesis, we investigated oil of wormwood (Artemisia absinthium) the active plant product found in absinthe, and thujone, the active compound found in oil of wormwood. Radioligand receptor binding assays employing membrane preparations from rat brains containing CB1 cannabinoid receptors, and human tonsils containing CB2 receptors, demonstrated that thujone displaced [3H]CP55940, a cannabinoid agonist, only at concentrations above 10 microM. HPLC analysis of oil of wormwood revealed that only the fractions having mobility close to thujone displaced [3H]CP55940 from the CB1 cannabinoid receptor. [35S]GTPgammaS binding assays revealed that thujone failed to stimulate G-proteins even at 0.1 mM. Thujone failed to inhibit forskolin-stimulated adenylate cyclase activity in N18TG2 membranes at 1 mM. Rats administered thujone exhibited different behavioral characteristics compared with rats administered a potent cannabinoid agonist, levonantradol. Therefore, the hypothesis that activation of cannabinoid receptors is responsible for the intoxicating effects of thujone is not supported by the present data.
Adenylyl Cyclase Inhibitors↗
[Alcohol-related disorders: etiopathology and therapeutic considerations].
The scientific understanding of the neurobiological priniciples of alcoholism has made significant progress in recent years. Especially the effects of ethanol on the neurotransmitter-systems are well studied. Dopaminergic and GABAergic facilitation contribute to the stimulating effects of low doses of alcohol while many of its adverse effects are mediated by glutamatergic inhibition at higher doses. A reduced serotonine-metabolism was shown to be a risk factor for the development of an alcohol dependence. The historic success of absinthe is discussed in this context. Absinthe is a mixture of ethanol and thujone, a substance that leads to a GABAergic inhibition as well as a reduced serotonergic responsiveness. Many studies substantiate the role of cannabinoid as well as striatal opiate-receptors in alcohol-related disorders. Neuroimaging studies could prove the important role of the reward system in this connection. Genetic factors were shown to be predisposing, however biological and environmental factors have a regulatory effect on the gene expression. Disturbances of the hpa-axis (hypothalamus-pituitary gland-adrenal cortex) were also shown to play a role in alcohol dependence. The understanding of these neurobiological principles of alcohol-related disorders should contribute to enhance and improve their therapeutic options.
Alcohol-Related Disorders↗
The wing of madness: the illness of Vincent van Gogh.
This paper briefly describes some aspects of Vincent van Gogh's life and attitudes. It discusses absinthe and several psychodynamic factors that may have contributed to his psychotic episodes at Arles, when he cut off his ear. It discusses Vincent's descriptions of his illness, especially at Saint Rémy de Provence and concludes that he probably suffered from partial complex seizures (temporal lobe epilepsy) with manic depressive mood swings aggravated by absinthe, brandy, nicotine and turpentine.
Depressive Disorder↗
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.
Alcoholic Beverages↗
Experimental liver fibrosis induced in rats receiving high doses of alcohol and alternating between regular and vitamin-depleted diets.
Liver fibrosis was induced in rats by simulating human alcoholic eating and drinking patterns. Alcohol addiction was established by gradually increasing the ethanol concentration in the drinking water; salts were added at the terminal stage. The hepatocytes of rats receiving alcohol concentrations exceeding 50% (v/v) (similar to vodka) exhibited alcoholic hyaline (Mallory bodies). Alcoholic liver fibrosis was induced by alternating between regular and autoclaved (vitamin-depleted) diets, simulating the irregular eating habits of human alcoholics. In the livers of rats receiving 70% (v/v) ethanol (comparable to absinthe) with 25% saline and fed the alternating diets, pericellular fibrosis was induced. No significant difference in calorie intake between control and alcohol rats was detected except when rats underwent drinking bouts (heavy drinking phase). This indicates that neither a high-fat diet nor a choline-depleted diet is necessary to induce the alcoholic fibrosis seen in human alcoholics.
Animals↗
The human taste receptor hTAS2R14 responds to a variety of different bitter compounds.
The recent advances in the functional expression of TAS2Rs in heterologous systems resulted in the identification of bitter tastants that specifically activate receptors of this family. All bitter taste receptors reported to date exhibit a pronounced selectivity for single substances or structurally related bitter compounds. In the present study we demonstrate the expression of the hTAS2R14 gene by RT-PCR analyses and in situ hybridisation in human circumvallate papillae. By functional expression in HEK-293T cells we show that hTAS2R14 displays a, so far, unique broad tuning towards a variety of structurally diverse bitter compounds, including the potent neurotoxins, (-)-alpha-thujone, the pharmacologically active component of absinthe, and picrotoxinin, a poisonous substance of fishberries. The observed activation of heterologously expressed hTAS2R14 by low concentrations of (-)-alpha-thujone and picrotoxinin suggests that the receptor is sufficiently sensitive to caution us against the ingestion of toxic amounts of these substances.
Bicyclic Monoterpenes↗
Reversed-phase liquid chromatographic characterization and analysis of air particulates humic (-like) substances in presence of pollens.
Newly developed method for characterisation and analysis of humic substances (HS) and humic-like substances (HULIS) in air dust particles was tested for potential interferences caused by abundant co-sampled pollens (common dandelion, common wormwood-absinth, apple tree). RP-HPLC using 10-step gradient of dimethylformamide (DMF) in a buffered aqueous mobile phase and a wide-pore (30 nm) octadecylsilica column has been applied to the analysis of HS and HULIS using tandem of spectrophotometric (DAD) and fluorimetric detection (FLD). Achieved results suggest that the devised method is reliable for characterisation, fractionation and analysis of terrestrial HS, air dust HS and air particulate HULIS in liquid extracts at a trace concentration levels. Fluorimetric detection (ex. 470 nm/em. 530 nm; LOD, 3.1 microg/ml) enables sensitive, highly selective and interference free determination of HS and HULIS regardless the presence of pollen constituents, whereas spectrophotometric detection is susceptible to interferences in UV region above 260 nm. However, even in this case, the interfering substances can be revealed by both different pattern and shape of their peaks, as well as by spectral features different from HS or HULIS. Analytical procedure based on air sampling, extraction and above-mentioned HPLC method enables characterisation and analysis of HS and/or HULIS at relative concentration levels down to 0.1% (m/m) in 10 mg mass scale of sampled air dust and particulate material.
Air Pollutants↗
Alpha-thujone reduces 5-HT3 receptor activity by an effect on the agonist-reduced desensitization.
The convulsant effects of alpha-thujone, the psychotropic component of absinthe, were attributed to inhibitory actions at the GABAA receptor. Here, we investigated for the first time the 5-HT3 receptor as a potential site of the psychotropic actions of alpha-thujone. This cation permeable ligand-gated ion channel shows considerable homology to the GABAA receptor. We previously demonstrated that in homomeric assemblies of cloned human 5-HT,A receptor subunits. the endogenous agonist 5-HT induced desensitization via channel blockade. When the 5-HT3 B receptor subunit was co-expressed, the resulting heteromeric assemblies desensitized independent from channel blockade. In the present study, patch-clamp experiments revealed an inhibitory action of alpha-thujone on both homomeric and heteromeric 5-HT3 receptors. This inhibitory action was mediated via channel blockade. However, it was not alpha-thujone itself which blocked the channel. The present experiments suggested that, in homomeric receptors, alpha-thujone enhanced the inherent channel-blocking potency of the natural ligand. 5-HT. In heteromeric receptors, alpha-thujonerecruited an additional channel-blocking component of the agonist. By means of kinetic modeling, we simulated possible mechanisms by which alpha-thuljone decreased the 5-HT-induced responses. It is suggested that alpha-thujone reduced 5-HT3 receptor activity by an effect on mechanisms involved in receptor desensitization, which depend on receptor subunit composition. It remains to be shown if this inhibitory action on serotonergic responses contributes to behavioral effects of alpha-thujone.
Bicyclic Monoterpenes↗
Xanthopsia and van Gogh's yellow palette.
A survey of van Gogh's work from 1886 to 1890 indicated that paintings with a yellow dominance were numerous, episodic, and multi-regional. His underlying illness, by his own admission, affected his life and work; furthermore, episodes of malnutrition, substance abuse, environmental exposure, and drug experimentation (all evident from correspondence) exacerbated his condition. Accordingly, we reviewed plausible agents that might have modified the artist's colour perception. Xanthopsia due to overdosage of digitalis or santonin is well documented elsewhere, but evidence of useage of either drug by van Gogh cannot be substantiated. It is unlikely that ageing of the human lens was an influence because of the artist's youth. Sunstroke is too restrictive to fit the multiplicity of regions and motifs. Hallucinations induced by absinthe, the popular liqueur of the period, may explain particular canvases but not the majority of 'high yellow' paintings. Van Gogh's proclivity for exaggerated colours and his embrance of yellow in particular are clear from his letters and, in contradistinction to chemical or physical insults modifying perception, artistic preference is the best working hypothesis to explain the yellow dominance in his palette.
Adult↗
The illness of Vincent van Gogh.
Vincent van Gogh (1853-1890) had an eccentric personality and unstable moods, suffered from recurrent psychotic episodes during the last 2 years of his extraordinary life, and committed suicide at the age of 37. Despite limited evidence, well over 150 physicians have ventured a perplexing variety of diagnoses of his illness. Henri Gastaut, in a study of the artist's life and medical history published in 1956, identified van Gogh's major illness during the last 2 years of his life as temporal lobe epilepsy precipitated by the use of absinthe in the presence of an early limbic lesion. In essence, Gastaut confirmed the diagnosis originally made by the French physicians who had treated van Gogh. However, van Gogh had earlier suffered two distinct episodes of reactive depression, and there are clearly bipolar aspects to his history. Both episodes of depression were followed by sustained periods of increasingly high energy and enthusiasm, first as an evangelist and then as an artist. The highlights of van Gogh's life and letters are reviewed and discussed in an effort toward better understanding of the complexity of his illness.
Bipolar Disorder↗
[Drugs and poisons in the life of Vincent van Gogh].
Van Gogh was during his last years exposed to several potentially toxic substances such as; bromides, lead, camphor and terpene oils in absinthe liquor. All of them produce signs of toxicity which are similar to the symptoms known from van Gogh's attacks of illness; hallucinations, confusion, delirium, convulsions and agitation. However, the many interpretations of van Gogh's illness and state of mind have in most cases not taken into account the possible influence of toxic chemicals.
Belgium↗