Between approximately 1450 BCE and 392 CE, people from across the Mediterranean traveled from Athens to Eleusis(the current city of Elefsina, Greece) to participate in one of the most revered spiritual traditions of the classical world: the Eleusinian Mysteries 1,2.
For nearly two millennia, some of the most influential philosophers, politicians, and emperors of antiquity, such as Plato, Marcus Aurelius, Cicero, or Octavian, and thousands of other initiates joined the procession through “The Sacred Way” for the cult of Demeter and Persephone, undergoing days of pilgrimage, fasting, and ritual preparation before entering a darkened hall where they drank a sacred beverage of concealed ingredients, known as kykeon. And the rest, as they say, is history. Secret history, however. The rites at Eleusis were considered of the utmost sacredness and essential to the connectedness and survival of humanity, but initiates were forbidden from revealing the experience, under penalty of death1. Yet, the transformative nature of the mysteries endured thousands of years of secrecy, and reports of profound shifts in understanding life, death, and the nature of existence itself remained alive until the present day.
Understandably, scholars have wondered for decades whether the kykeon may have contained a psychoactive substance. In more recent years, the renaissance in psychedelic research has produced findings that can be interpreted as direct translations of the aforementioned historical accounts from ancient Greece. These include observations such as reduced anxiety about death after experiences with Psilocybin 3, as well as lasting changes in people’s metaphysical beliefs following psychedelic use 4,5. Given these parallels, it should come as no surprise that many researchers have revisited the idea that this sacred beverage may have been psychedelic. Now, a recent scientific study brings fresh evidence to this long-standing debate.
The Psychedelic Hypothesis of Kykeon
One of the most influential ideas about the Eleusinian Mysteries emerged when Gordon Wasson and Albert Hofmann proposed that the sacred drink might have contained compounds derived from Claviceps purpurea, a fungus that parasites barley, rye, and other grains, producing chemicals known as ergot alkaloids6. Ergot alkaloids are products derived from tryptophan metabolism and represent the largest group of fungal metabolites found in nature. These include ergotamine, ergonovine, lysergic acid amide (LSA or ergine), and iso-LSA7. Under certain conditions, as famously experienced by Albert Hofmann while working with ergot derivatives and inadvertently synthesizing lysergic acid diethylamide (LSD), some of these alkaloids can produce profound changes in perception, emotion, and sense of self 8.
There has always been a major problem with the psychedelic hypothesis of kykeon, however. Ergot not only contains potentially psychoactive molecules, but is in fact very dangerous. Accidental consumption of ergot-contaminated grain in medieval Europe caused devastating outbreaks, as entire communities fell under an illness known as “Saint Anthony’s Fire” (ergotism), characterized by severe pain, convulsions, hallucinations, and even blood flow so restricted that it led to gangrene and amputations, which ultimately took tens of thousands of lives9.
Thus, the central question lies beyond whether ergot could produce visionary experiences, but how ancient practitioners could harness its effects without poisoning themselves, using equipment and knowledge thousands of years prior to that of Albert Hofmann.
Recreating an ancient ritualistic preparation in a modern science laboratory
A study, published in Nature, approached this question experimentally. Instead of speculating about historical reports, a team of researchers at the National and Kapodistrian University of Athens (Greece), University of Granada (Spain), and Boston University (USA) asked a practical question: Could people in antiquity have prepared ergot in a way that preserved its psychoactive properties while reducing its toxicity?
To test this idea, they carefully considered traditional practices and recreated a simple preparation method under controlled laboratory conditions, using materials and techniques known to be available and performed in the ancient world. Deliberately ignoring advanced 21st-century chemistry, they treated powdered ergot with an alkaline solution made from water and wood ashes, commonly known as lye, a technique that has been used for thousands of years in Greece in activities such as soap making.
This somewhat primitive technique, which could have been readily employed by Eleusinian priestesses, was subsequently followed by some of the most advanced analytical chemistry tools available to today’s researchers. Using nuclear magnetic resonance (NMR), they obtained spectroscopic and spectrometric data of recrystallized LSA and iso-LSA, and then used UHPLC/Q-TOF-HRMS (Ultra-High-Performance Liquid Chromatography-Quadrupole Time-of-Flight High-Resolution Mass Spectrometry) to, with the highest resolution and sensitivity, separate, identify, and quantify similar components in a total of 48 “traditionally obtained” kykeon preparations.
Their analyses show that this very simple lye treatment broke down the most toxic components of the fungus, while leaving behind LSA and iso-LSA, related compounds that are less harmful and still capable of affecting consciousness. In other words, the study took Wasson’s and Hoffman’s idea from speculation into the realm of possibility, demonstrating the chemical plausibility that ancient people could have produced psychoactive preparations from ergot using simple techniques available at the time.
Why preparation matters more than the substance
One of the most interesting implications of this research is not solely about chemistry. It is about process. Understandably, in modern neuropsychopharmacology, discussions of broadly psychoactive substances often focus solely on the molecule itself. In traditional contexts, however, the method of preparation is just as important as the plant or fungus being used. Heating plants like cannabis 10, fermenting the sinicuichi 11,12, combining Banisteriopsis caapi and Psychotria viridis to yield ayahuasca 13, or altering the acidity of a mixture (as in the present case) can dramatically change the chemical profile of a substance, reduce its toxicity, enable or enhance its psychoactivity, or create entirely new compounds.
Paraphrasing Paracelsus: “All things are poison, and nothing is without poison; solely the method of preparation determines that a thing is not a poison”. Insights into dose and preparation are well known in traditional and indigenous practices around the world, where plant medicines require specific preparation steps developed through generations of experimentation and observation. While this study does not prove that the kykeon was psychedelic, nor that ergot was used in the Eleusinian Mysteries, nor, regrettably, does it expand our knowledge about the kind of experiences that the initiates may have undergone, it does demonstrate that the “ergotism objection” to the psychedelic hypothesis of kykeon may not be an insurmountable barrier.
A broader reminder to the psychedelic research field
Beyond the historical significance of the kykeon, perhaps the most important contribution of this study is not that it might get us closer to solving an ancient mystery, but that, in being part of a larger shift in how fundamental research is approaching the study of psychedelic substances, it contributes to the legitimacy of this way of asking questions. Rather than disregarding ancient traditions, this increasingly larger trend treats them as sources of testable hypotheses.
The authors of the paper themselves emphasize that, beyond chemical identity and the preparation methods that could have yielded the kykeon, its ritual context, symbolism, and collective participation likely shaped the experience’s effects as much as the substance itself. In their words:
“In an ancient ritual framework, marked by botanical synergism, fasting, and heightened expectancy, their psychedelic potential would have been amplified. At Eleusis, optimal ceremonial conditions gave these entheogens a meaningful role, showing that their effects must be understood within a religious context, rather than purely pharmacological terms.”
These cultural frameworks, when carefully considered and studied, can contain practical knowledge about chemistry, physiology, and human experiences. Whether it is through the use of cutting-edge proteomics, metabolomics, genetics, and synchrotron radiation-based Fourier Transformed Infrared microSpectroscopy (SR µ-FTIR) to characterize organic residues in a Ptolemaic Egyptian vase and thus increase our understanding of ancient belief systems, cultural practices, and how past societies connected to the natural world 14; or through metabolomic, biomolecular, and behavioral assays to show that full mushroom extract performs better than chemically synthesized psilocybin in stimulating neuroplasticity, synaptogenesis 15, and anxiety alleviation 16; traditional practices can be investigated with modern tools without dismissing the cultural knowledge that produced them.
As interest in psychedelic research continues to grow, and the pharmacopeia of substances under scrutiny broadens, this approach will become increasingly valuable. Traditional and indigenous knowledge systems hold insights that modern science has only begun to rediscover: rituals, guided physical, mental, and contextual preparation, and shared meaning shape the individual and collective salience and valence of these deeply transformative experiences, and studying those systems respectfully may help us answer some of the most complex questions in psychedelic science today.
REFERENCES
- 1 Keller, M. L. The ritual path of initiation into the Eleusinian mysteries. Rosicrucian Digest 2, 28-42 (2009).
- 2 Antonopoulos, R. K.et al. Investigating the psychedelic hypothesis of kykeon, the sacred elixir of the Eleusinian Mysteries. Scientific Reports (2026).
- 3 Griffiths, R. R.et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. Journal of psychopharmacology 30, 1181-1197 (2016).
- 4 Timmermann, C.et al. Psychedelics alter metaphysical beliefs. Scientific Reports 11, 22166 (2021).
- 5 Yaden, D., Nayak, S. M. & Griffiths, R. Belief change and agnostic frames in psychedelic research and clinical contexts. Philosophical Perspectives on Psychedelic Psychiatry, 166-184 (2024).
- 6 Hofmann, A., R. Wasson, G. & A. P. Ruck, C. The road to Eleusis: Unveiling the secret of the mysteries. (Harcourt Brace Jovanovich, 1978).
- 7 Schiff Jr, P. L. Ergot and its alkaloids. American journal of pharmaceutical education 70, 98 (2006).
- 8 Hofmann, A. LSD: My problem child. ( McGraw-Hill Book Company, 1979).
- 9 Van Dongen, P. W. & de Groot, A. N. History of ergot alkaloids from ergotism to ergometrine. European Journal of Obstetrics & Gynecology and Reproductive Biology 60, 109-116 (1995).
- 10 Eichler, M.et al. Heat exposure of Cannabis sativa extracts affects the pharmacokinetic and metabolic profile in healthy male subjects. Planta medica 78, 686-691 (2012).
- 11 Wasson, R. G. THE ROLE OF’FLOWERS’IN NAHUATL CULTURE: A SUGGESTED INTERPRETATION. Botanical Museum Leaflets, Harvard University 23, 305-324 (1973).
- 12 Schultes, R. E. The plant kingdom and hallucinogens (part III). Bulletin on Narcotics 22, 25-53 (1970).
- 13 Frecska, E., Bokor, P. & Winkelman, M. The therapeutic potentials of ayahuasca: possible effects against various diseases of civilization. Frontiers in pharmacology 7, 35 (2016).
- 14 Tanasi, D.et al. Multianalytical investigation reveals psychotropic substances in a ptolemaic Egyptian vase. Scientific Reports 14, 27891 (2024).
- 15 Shahar, O.et al. Effect of chemically synthesized psilocybin and psychedelic mushroom extract on molecular and metabolic profiles in mouse brain. Molecular Psychiatry 29, 2059-2073 (2024).
- 16 Brownstien, M.et al. Striking long-term beneficial effects of single dose psilocybin and psychedelic mushroom extract in the SAPAP3 rodent model of OCD-like excessive self-grooming. Molecular Psychiatry 30, 1172-1183 (2025).
AUTHOR
Sergio is a PhD student with a passion for understanding how psychedelics reshape the brain.
His academic journey began with a degree in Biotechnology from the Universidad Politécnica de Madrid. He then completed a traineeship in regenerative neuroscience at the GlowLab at the University of Zagreb. Following this, he pursued a Research Master’s in Cognitive and Clinical Neuroscience at Maastricht University in the Netherlands, where his fascination with the neurobiology of psychedelics developed.
Sergio was awarded the atai Fellowship for the Neuroscience of Psychedelics, which allowed him to join the Center for the Neuroscience of Psychedelics (CNP) at Massachusetts General Hospital, Harvard Medical School.
As a PhD student at the CNP, he specializes in fundamental research to investigate how natural and synthetic psychedelics, along with other neuroplasticity modulators, can drive structural and functional changes in the brain.
