Hypotheses advanced in The Road to Eleusis concerning the possible composition and method of preparation of the kykeon are evaluated in light of published criticism. Objections to the Eleusis theory are countered, and based on a largely overlooked aspect of the chemical hydrolysis of ergot alkaloids, a new hypothesis is suggested that reinvigorates the Eleusis debate. In part 2 of this essay, organic chemist Daniel M. Perrine provides further considerations that build upon the new idea, and a technical discussion of the practicality and realisability of the “Ergine Hypothesis” paves the way for new chemical and psychopharmacological research. In part 3, co-author of The Road to Eleusis Carl A. P. Ruck re-examines the Eleusis mythologies and ritual practises from which appear a much expanded understanding of the entheo-pharmacology of the ancient world.