Ergot Alkaloids brings English readers Albert Hofmann‘s seminal 1960s encyclopedia detailing his historic investigation into magical plants and their psychotropic potential. Starting with the botany and cultivation of the ergot fungus, Hofmann chronicles the elaboration of ergot through history, from poisoning epidemics to early medical uses, leading to the pharmaceutical analysis and psychiatric application of compounds like LSD. With over 30 chemical structures depicted, the text explores ceremonial plants still used by indigenous peoples before ushering in modern scientific classification of hallucinogens, psychotomimetics, psychedelics and more. Hofmann combines observant accounts of traditional healing rituals with the next generation of research, providing a masterful intersection of indigenous knowledge and Western science on this psychoactive fungus and its alkaloid derivatives.
Summary Review of Ergot Alkaloids
Author: Joseph Lichter, Ph.D., is a renowned Chemistry Professor and Director of the Pre-Health Advising Office at Florida International University, with a background in protein chemistry, antiviral medicines, and chemical education.
20th-century psychedelia’s watershed moment is undoubtedly Albert Hofmann’s discovery of LSD.
When the Swiss chemist first synthesized Lysergic Acid Diethylamide in 1938, it was one of many amide-like derivatives of lysergic acid to be studied for pharmacological purposes. Lysergic acid had been identified as an alkaline hydrolysis product from ergotamine, an alkaloid derived from the purple/brown fungus known as ergot that grows on the rye plant.
Other lysergic acid derivatives Albert Hofmann made included methylamide, ethylamide, and dimethyl amide, to name a few. He hoped the diethylamide derivative of lysergic acid would have pharmacological properties similar to the diethylamide derivative of nicotinic acid, a respiratory stimulant at the time marketed as Coramine. Once synthesized, these derivatives were tested at Sandoz, and Hofmann explained in his memoir LSD: My Problem Child that for the LSD-25, there appeared to be a “strong effect on the uterus” of animals tested but ultimately “aroused no special interest in the pharmacologists.” LSD was shelved.
But what happens next makes this entirely fortuitous story all that more interesting.
Hofmann tells in his memoir that for five years afterwards, he continued to work on ergot derivatives but eventually felt a “peculiar presentiment” towards Lysergic Acid Diethylamide, and so on April 18, 1943, he synthesized a few centigrams [one-hundredths of a gram] of LSD again. During the final purification steps of the synthesis, he explained he FELT “unusual sensations” that were “dreamlike” and that he “perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with the intense, kaleidoscopic play of colours” which lasted for a couple of hours. Having this unexpected and unusual experience, he surmised that the compound he was synthesizing at the time of this occurrence, LSD, must have been the cause. He thought it would be prudent to self-administer the compound to test it at what he considered a small dose of 0.250mg. This turned out to be a significantly high dose, which led to his psychotomimetic [mimicking psychosis – which is how psychedelics were framed at that time] experience and a subsequent difficult and weird bicycle ride home, commemorated today by the psychonaut holiday Bicycle Day on April 20th.
And that is how LSD was discovered.
The truly curious part of this all is that Swiss culture is defined by its precision. Precise watchmaking. Precise chocolatiering. Engineering. Swiss culture is punctuated by timeliness, meticulousness, and well-kept standards of operation. How in the world then did a Swiss chemist, likely wearing required gloves and laboratory attire, ingest or be imbued with enough LSD to have this experience is baffling. Especially given the low permeability of the skin towards LSD as compared to oral ingestion or intravenous administration. Famed LSD researcher Dr. David Nichols has written elsewhere that it seems unlikely there was substantial contact with the drug itself, and instead, a separate, mystical experience may have providentially occurred.
As fantastical and as well-travelled as this tale of the discovery of LSD is, what is NOT appreciated enough in psychedelic lore is the incredible amount of ergot-related research that Dr. Hofmann had done years prior and after. It almost seems as though the excitement for this one diethylamide derivative is so great, that many miss out on the entire story of ergot, what it is, the molecules that exist naturally in the fungus and the chemistry in making derivatives from the natural ergolines.
Enter Albert Hofmann’s 1964 classic book Die Mutterkornalkaloide (“Mutterkorn” in German means “Mother Grain” and refers to the use of the ergot fungus as an oxytocic [hastening childbirth] for childbearing mothers in the Middle Ages). This book, originally written in German, provides extensively the chemistry for the extraction, identification and derivatization of ergot alkaloids. The focus is NOT on the diethylamide derivatively solely, but rather the full spectrum of ergoline compounds that exist and the other medicines that had been derived from this fungus. For those who may have read Sasha Shulgin’s PiHKaLor TiHKaL, there are some great similarities between Die Mutterkornalkaloide and the syntheses portion of those books.
On the 80th anniversary of the discovery of LSD, the English translation of Die Mutterkornalkaloide officially titled Ergot Alkaloids: History, Chemistry, and Therapeutic Uses has finally been made available thanks to co-publishers Transform Press and Synergistic Press.
Over the last few days, I have had the great pleasure of reviewing this book carefully, and I want to share some general thoughts below.
Chemists Shall Delight
Hofmann’s Ergot Alkaloids is organized in the following manner: the botany of the ergot fungus, the isolation and structural determination of molecules found in ergot (specifically the nitrogen-containing ones, referred to as “alkaloids”), the synthetic routes to making the biomolecules from organic synthetic routes, the properties of these molecules, the ways that molecules were structurally identified, the making of the derivatives (like the diethylamide derivative, LSD), and lastly there is a section on the pharmacology and therapeutic uses for both the alkaloids that exist in ergot and the derivatives.
For those with an excellent knowledge of organic chemistry, you will be able to follow from start to finish with no problems. It is a joy to see the extent of Hofmann’s literature review on the subject and the organization of how molecules were extracted, structures were elucidated, and derivatives were synthesized, characterized, and therapeutically studied.
It is also quite fascinating reading this text and realizing how different the chemical analyses are from then to now. In the mid-20th century, the structural identification of molecules was more heavily based on tools such as optical activity, melting point, infrared spectroscopy and fluorescence spectroscopy. Some of the tools used regularly by organic chemists today, like 1H NMR, 13C NMR and mass spectroscopy, are notably absent from this book because they did not exist to the level they do today or at all.
I’m not going to sugarcoat this: Each section is presented using the jargon of a chemistry journal. So be prepared. This means those who are not chemists may need to have a screen open where they may ask questions about what such words as stereoisomers, racemization, hydrazide, steric arrangement, and others mean.
Now, an additional reason as to why this book seems so timely is if you look at research today, ergot alkaloid chemistry is still playing a great role:
- In 2022, Garret Wong and colleagues at the National University of Singapore have figured out a way to use yeast to biosynthesize lysergic acid
- Just this year, Joel Smith and colleagues at FSU, published a new synthetic route for lysergic acid which would take 6 steps (which is an improvement from the 7 step route shown on page 78 of Ergot Alkaloids, initially published by the American chemist and 1965 Nobel prize winner for chemistry, Robert Burns Woodward). Dr. Smith has recently been awarded $1.8 from the US National Institute of Health to use towards synthesizing lysergic acid derivatives.
- Also this year, Polish researchers Ewelina Kowalczyk and Krzysztof Kwiatek have published their recently developed methods for detecting ergot alkaloids in livestock feed, showing how ergoline identification can be a valuable tool to help reduce economic loss from animal poisoning on farms.
Ergoline chemistry, which Hofmann published 60 years ago, is still such an area of great interest with room for more improvement. Scientists looking for some directional offshoots (or main directions), pick this up and consider reading with an eye for where more work can be done.
Psychedelic Historians Should Read This
To fully understand the depth of Dr. Hofmann’s interest in ergot and what may have been part of the “peculiar presentiment” described by him in his tale, it is important to see just how deep the research on Ergot goes.
Ergot Alkaloids provides this much-needed historical account both in the early chapter titled “On the History of Ergot and Its Active Substances” and in later chapters as it identifies the medicines that have been derived since. In the history chapter, we learn about the absence of ergot in antiquity due to the lack of rye cultivation in that era. We learn of the first recognition of ergot in history through epidemic mass poisonings, showing itself in the form of gangrene and convulsive ergotism. Then, a great deal is given to recognizing the first medicinal uses, mentioned in an herbal book dating back to 1582. The book provides the structure and pharmacological properties of such ergot-derived medicines as Gynergen, Neo-Gynergen, Cafergot, Bellergal, and Hydergine.
Lay Persons Should Own and Make the Effort
Though it will be a difficult read for someone with little to no chemistry background, it may be of interest to try and understand this fungus and the many molecules that come from it. (Besides, getting out of your comfort zone to try and learn something might help with neuroplasticity, which would be a very psychedelic thing to do for yourself.)
The Praise in the Introduction, Foreword, and Afterword Should Be Enough to Convince You to Get This
Whether you want to take my word for it or not, before you even have a chance to dig into the manuscript itself, you will see so much praise from such prominent figures in the psychedelic landscape as Dr. David Nichols (formerly Purdue, now UNC), Dr. Franz Vollenweider (University of Zurich), Dr. Charles Grob (UCLA), Dr. Albert Garcia-Romeu (Johns Hopkins) and others. The foreword is written by the psychedelic leader of the Beckley Foundation, Ms. Amanda Fielding. The translator, Jitka Nykodemova, provides insight into the translation. Research director of the Alexander Shulgin Institute, Paul F. Daley, provides a chemist’s note. And then lastly William Leonard Pickard, someone with quite a chemistry background and now a research affiliate with the Program on Psychedelics Law and Regulation at Harvard University, writes the afterword.
All of these leaders in the psychedelic space provide a great sense of admiration for the importance of this work.
Publisher Summary
“The masterpiece we have all been waiting for in this classic text from the 60s, Ergot Alkaloids comes to life in the English translation of Albert Hofmann’s historic encyclopedia of Ergot Alkaloids and their derivatives. This title is a detailed account of chemical compounds and pharmacological investigation into the potential of magical plants. Starting with the botany and cultivation of the ergot mushroom, Hofmann takes us through the historical elaboration of the fungus including the poisoning epidemic of ergot and its early medical uses all the way to the use of psilocybin as a “magical drug”. With a detailed timeline, we explore the growth of the pharmaceutical-chemical investigation from 1816 to 1961 with a total synthesis of ergotamine including tables of chemical structures and the role of lysergic acid, d-lysergic acid and diethylamide in experimental psychiatry gaining increasing importance in psychotherapy as a medical aid. Hofmann brings an observational account of these plants and their ceremonial and healing purposes still used by indigenous peoples such as the “Peyotl” cactus, “Teonanactl” the sacred mushroom of the Aztecs and “Ololiuqui” the seeds of bindweed plants. With representations of over 30 chemical structures and pharmaceutical analysis, Hofmann introduces the next generation of scientific knowledge into the world of hallucinogenic plants and special subgroups of psychotropic drugs which he calls phantastica, hallucinogens, psychotomimetic, psychedelica, psychodysleptics and more.”