The fourfold discovery of Mescaline (1896–1919)
Chemical Monthly, 2019, 150, 941–947
© Springer-Verlag GmbH Austria, part of Springer Nature 2019
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.
Keywords : History of science · Psychedelic studies · Organic chemistry · Alkaloids · Mescaline · Drugs
The exploration of the constituents of the peyote cactus and its effects upon the human psyche was an interdisciplinary undertaking that defied national borders. The material way to the heart of the matter, however, was mainly paved in Europe—first in Berlin by the independent toxicologist Louis Lewin (1850–1929), next at the Institute of Pharmacology at the University of Leipzig by Arthur Heffter
(1859–1925), and finally by Ernst Spaeth (1886–1946) at the Institute for Chemistry in Vienna. Especially after the isolation of mescaline by Heffter, and even more so after Spaeth’s synthesis, mescaline itself began to be considered as having no therapeutic potential whatsoever. How did this excessively restricted view on a substance that was determined to be the main psychoactive ingredient of a traditional plant medicine and later was defined as “central standard against which all other [psychedelic] compounds are viewed”  come about? To find an answer to this question, one has to go back to the end of the nineteenth century and reconstruct how mescaline came into being in the first place.
How it all began
Let us start with the usual beginning of an often-told story: at the age of 38, Louis Lewin, by then a scholar with an international reputation, went on a trip across North America .1 His last stop was at the pharmaceutical corporation Parke, Davis & Co, where he was asked for his learned opinion on some dried specimens of an allegedly unknown plant.2 He was only told that this plant was from Mexico, “used as a narcotic, food, or relish” and traded as “Muscale Buttons” . Back in Berlin, the plant was classified as belonging to the family of cactaceae and registered as a new species by Paul Christoph Hennings (1841–1902), then custodian at the Botanical Gardens .3 As the first demonstration of the toxicity of a cactus, the text “Ueber Anhalonium Lewinii”  will become the common cornerstone of the scientific investigations to come. Lewin managed to extract a syrupy, resinous substance and called it “Anhalonin”. He went on to administer “this substance, which”, according to Bruhn/Holmstedt, “was in fact a crude mixture of alkaloids” to some animals (frogs, rabbits) to ascertain the lethal dose . The graphic descriptions of the dying animals were documented with morbid fascination, since it was “the first time”, as Lewin solemnly concludes his paper, “that any such violent symptoms have ever been accredited to a Cacteæ” .4 Lewin’s findings were published in the renowned Naunyn–Schmiedeberg Archive and a slightly edited translation of the same paper appeared in the Therapeutic Gazette in the same year. In the American publication, Lewin ends with the wish to soon be able to publish a more detailed account of ‘his’ plant and surmises that “it is far from improbable that this substance [i.e., anhalonine] may also be of therapeutic value” . Indeed, already in the following year, a resourceful medical doctor—S. F. Landry, from Logansport, Indiana—ascertained that “Anhalonium Lewinii” was a valuable adjuvant to digitalis, especially helpful for the treatment of pneumatic disorders. Along with this assertion, he disseminated the recipe for a homeopathic tincture that additionally contained belladonna, cannabis indica, and water .