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The fourfold discovery of Mescaline (1896–1919)

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Abstract

This is an historical account of the pharmacological, chemical, and anthropological research concerning the molecular makeup of the peyote cactus (Lophophora williamsii) that laid the ground for Ernst Spaeth’s structural elucidation of mescaline as 3,4,5-trimethoxyphenethylamine.

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Notes

  1. For more information on Lewin’s historical role with regard to toxicology, see [3].

  2. Probably by Parke-Davis’ superintendent H. A. Wetzel; for more on this ‘back story’, including the role of the Texas-based physician John Raleigh Briggs (1851–1907), whose horror trip caught the attention of George S. Davis, general manager of the respective company, see [4].

  3. Meanwhile, in the United States, Parke-Davis contacted Sereno Watson from the Botanic Garden at Harvard University in Cambridge, Massachusetts. He also recognized the cactus as belonging to the genus Anhalonium, and also thought it might be a new species [7].

  4. Actually, it was Frank Augustus Thompson, a chemist at Parke-Davis, who was first to discover the alkaloidal content of this plant. But, since he documented his findings only in a laboratory report (dated 5 July 1887, cf. [10], they were neither available to the public, nor to the scientific community. Hence this does, according to the intersubjective nature of science, not count.

  5. This, and the quotations from Heffter to follow, are personal translations.

  6. This is, of course, a rather doubtful suggestion. To use indigenous knowledge for bioprospecting plants, while at the same time questioning its reliability is an epistemic strategy with a long tradition. A ‘pinnacle’ in this regard is William E. Safford’s (1859–1926) estimation that the vainly sought for teonanacatl or “magic mushroom”, as documented in a number of ancient Aztec texts and anthropological accounts, was actually no mushroom at all, but that very peyote cactus! He explains this theory with the morphological similarity of the button-like form of dried slices of peyote with that of mushroom caps, together with the insinuation that “it is very probable that they [the Aztecs] had not the slightest notion of the difference between a flowering plant and a fungus” [13]. As disconcerting as this hypothesis seems today, it was quite influential and only began to be questioned—notably, and independently, by the two exiled Austrians Blas Pablo Reko (1877–1953) and Robert J. Weltlaner (1883–1968)—a decade later [14].

  7. This was later corrected by Heffter himself to C13H19NO3 [15].

  8. Pellotine has markedly sedating effects, which is the reason why it immediately caught the attention of psychiatry and was already tested in 1896 in Vienna [16] and in Berlin [17]. The results were promising, but the first synthetically produced sedatives, especially the blockbuster-drug Veronal, pushed the less cost-effective cactus-alkaloid aside.

  9. As Heffter noted meticulously, he did not have more than “four fresh plants, with a total weight of 399 g” at hand [12].

  10. With Lumholtz, Heffter even exchanged letters and acquired material for his research (peyote from the Huicholes, used for his series of self-experiments in 1898, cf. [15]).

  11. Merck was, at least since 1895, when the first official report regarding “Anhalonium” was published, well aware of the developments in this nascent cactus field. The first entry on Mescalinum sulfuricum appears in 1913 [21, 22].

  12. These formulas are still valid; for more details, and a complete account of additional, pharmacologically active as well as non-active alkaloids of peyote, cf. [30].

  13. The resulting confusion reverberates until today, with people thinking of schnapps when hearing mescaline. Similar to “Indian”, the misnomer “mescaline” may be read as a verbal monument for the white man’s ignorance in anthropological affairs.

  14. A step that Lewin, for whatever reason, was not willing to take. Instead, he sent samples to psychiatrists, among them Alfred Guttmann (1873–1951) in Berlin, who was the first German psychiatrist to experiment on himself with anhalonine. Guttmann also had chopped up pieces of cactus at hand, and states that he took these, and anhalonine, with breaks over a period of 1–4 weeks. But he does not specify which one of these led to the exhilarating experiences he goes on to describe in much detail. It can, however, be inferred, that it was the cactus itself that brought about all sorts of “hallucinations” [32]. While Guttmann administered the cactus (and anhalonine) only on himself and his colleague Dr. K., it was another psychiatrist, namely Johannes Bresler (1866–1942), who gave it to patients already in 1905. Most of his unsuspecting subjects realized that they were ‘under the influence' and they had visions with a religious pull. Bresler suggested that peyote might be used as a means to “push back on usually occurring and persistently distressing hallucinations with more pleasant mescal-hallucinations” [33] (personal translation).

  15. Much has been said about the so-called “Anhalonium controversy” and the difficult relationship between Heffter and Lewin (cf. [9, 25]. Regarding the question of the identity of the cactus, and its proper place in the taxonomic order, these supposed animosities were, however, put aside and there was a disciplinary closing of ranks, in which Heffter and Lewin stood united against the ‘scholastic’ botanists.

  16. Cf. [34, 35] and Perrine [25], who attributes Briggs, Lumholtz, and Mooney as “first psychonauts”; the term, originally coined by the German author Ernst Juenger (1895–1998), seems, however, better to fit to Ellis and Mitchell, since they made use of the cactus in their own way, as contrasted to the anthropologists, and did attain a state of mind that was more than sheer panic, as in the case of Briggs.

  17. Remarkably, Heffter does not note anything about the emotive side of the experience but feeling nauseous.

  18. To paraphrase Bruno Latour (*1947) celebrating the very first synthesized compound, lactic acid: “Once discovered by Pasteur in 1857, lactic acid yeast has always already been there, from Neolithic times in the gourds of homo sapiens to the present in the whey that is souring in all the dairies on earth” [37].

  19. This is to be read in direct opposition to Mitchell and Ellis. Says the latter: “I fully agree with Dr. Weir Mitchell, that there is every likelihood, that mescal (read “peyote”) will become popular” [35]. Not yet aware of the existence of mescaline, it is also the cactus as such that Ellis believes to be “the most democratic of the plants which lead men to an artificial paradise” [38].

  20. Cf. footnote 8 above.

  21. Year of birth and death in both cases unknown. Knauer presented his initial findings at the “Versammlung der deutschen Irrenärzte” (meeting of the Bavarian alienists), held at Pentecost 1911 in Munich [39]. The only other available source for these trials is “A preliminary note on the psychic action of mescaline, with special reference to the mechanism of visual hallucinations” (1913), co-written by Maloney [40].

  22. “The hospital environment with its white walls, institutional sounds and smells, and constant associations with illness and medical authority has on occasion contributed a psychotic note to the drug experiment”, says Shulgin in view of the history of mescaline [41].

  23. For an overview of the human trials with mescaline, see [42, 43].

  24. The oldest existing peyote buttons, whose alkaloidal content was proven by thin-layer chromatography and gas chromatography–mass spectrometry, have, by radiocarbon dating, been shown to have a mean age of 5700 years [44]. At the beginning of the twentieth century, while peyote was being broken down into its parts in Europe, in the US, where cacti are, of course, endemic, the Native American Church was established. It is a noteworthy coincidence that the first initiatives for the foundation of this religion can be traced back to the year 1896, the same year mescaline was isolated, and that it was consolidated in the same year (1918) Spaeth actually accomplished his synthesis (which was only published a year later). (cf. [45]).

  25. Still today, the official umbrella term to be used in “normal science” [46] is “hallucinogens”. Insofar as this expression evokes associations with madness it is not only implicitly pathologizing, but also metaphysically naive, since the absence of something that somehow obviously is there, is simply taken for granted.

  26. For more cf. [49].

  27. Spaeth even corresponded with the latter, although not concerning mescaline, but anhalonine, which he dealt with in the same paper [50].

  28. Spaeth’s original notation was α-[3,4,5-trimethoxyphenyl]-β-aminoäthan] [50].

  29. For peyote being “the prototype of New World hallucinogens”, cf. [9] and for defining mescaline as “central standard”, cf. [51] as quoted at the beginning of this paper.

  30. Lewin, who was probably the first researcher to single out this class of drugs, named it “Phantastica” [52]. Before they were officially labeled as “hallucinogens”, mescaline and LSD had been tested as “psychotics” or “psychotomimetics”. The British psychiatrist Humphry Osmond (1917–2004) coined the term “psychedelics” in correspondence with Aldous Huxley (1896–1963), whom he inspired to write The Doors of Perception (1954) and other ‘pharmacognostic’ treatises by administering mescaline. Later, ethnobotanist Jonathan Ott (*1949) et al. came up with another neologism, namely “entheogens”, which may best be translated as “becoming divine within” [53].

  31. Among the first who did a psychoanalytically informed differential diagnosis of LSD and mescaline was Walter Frederking, the psychologist who also dosed Ernst Juenger with mescaline [54, 55].

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    Ivo Gurschler

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Gurschler, I. The fourfold discovery of Mescaline (1896–1919). Monatsh Chem 150, 941–947 (2019). https://doi.org/10.1007/s00706-019-02444-0

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