Considering the very great number of other groups of substances that, like the indoles, were under consideration as active principles of ololiuhqui, it was indeed extremely improbable that this assumption would prove true. It could, however, very easily be tested. The presence of indole compounds, of course, may simply and rapidly be determined by colorimetric reactions. Thus even traces of indole substances, with a certain reagent, give an intense blue-colored solution.
We had luck with our hypothesis. Extracts of ololiuhqui seeds with the appropriate reagent gave the blue coloration characteristic of indole compounds. With the help of this colorimetric test, we succeeded in a short time in isolating the indole substances from the seeds and in obtaining them in chemically pure form. Their identification led to an astonishing result. What we found appeared at first scarcely believable. Only after repetition and the most careful scrutiny of the operations was our suspicion concerning the peculiar findings eliminated: the active principles from the ancient Mexican magic drug ololiuhqui proved to be identical with substances that were already present in my laboratory. They were identical with alkaloids that had been obtained in the course of the decades-long investigations of ergot; partly isolated as such from ergot, partly obtained through chemical modification of ergot substances.
Lysergic acid amide, lysergic acid hydroxyethylamide, and alkaloids closely related to them chemically were established as the main active principles of ololiuhqui. (See formulae in the appendix.) Also present was the alkaloid ergobasine, whose synthesis had constituted the starting point of my investigations on ergot alkaloids. Lysergic acid amide and lysergic acid hydroxyethylamide, active principles of ololiuhqui, are chemically very closely related to lysergic acid diethylamide (LSD), which even for the non-chemist follows from the names.
Lysergic acid amide was described for the first time by the English chemists S. Smith and G. M. Timmis as a cleavage product of ergot alkaloids, and I had also produced this substance synthetically in the course of the investigations in which LSD originated.
Certainly, nobody at the time could have suspected that this compound synthesized in the flask would be discovered twenty years later as a naturally occurring active principle of an ancient Mexican magic drug.
After the discovery of the psychic effects of LSD, I had also tested lysergic acid amide in a self-experiment and established that it likewise evoked a dreamlike condition, but only with about a tenfold to twenty-fold greater dose than LSD. This effect was characterized by a sensation of mental emptiness and the unreality and meaninglessness of the outer world, by enhanced sensitivity of hearing, and by a not unpleasant physical lassitude, which ultimately led to sleep. This picture of the effects of LA-111, as lysergic acid amide was called as a research preparation, was confirmed in a systematic investigation by the psychiatrist Dr. H. Solms.
When I presented the findings of our investigations on ololiuhqui at the Natural Products Congress of the International Union for Pure and Applied Chemistry (IUPAC) in Sydney, Australia, in the fall of 1960, my colleagues received my talk with skepticism.
In the discussions following my lecture, some persons voiced the suspicion that the ololiuhqui extracts could well have been contaminated with traces of lysergic acid derivatives, with which so much work had been done in my laboratory.
There was another reason for the doubt in specialist circles concerning our findings.
The occurrence in higher plants (i.e., in the morning glory family) of ergot alkaloids that hitherto had been known only as constituents of lower fungi, contradicted the experience that certain substances are typical of and restricted to respective plant families. It is indeed a very rare exception to find a characteristic group of substances, in this case the ergot alkaloids, occurring in two divisions of the plant kingdom broadly separated in evolutionary history.
Our results were confirmed, however, when different laboratories in the United States, Germany, and Holland subsequently verified our investigations on the ololiuhqui seeds.
Nevertheless, the skepticism went so far that some persons even considered the possibility that the seeds could have been infected with alkaloid-producing fungi. That suspicion, however, was ruled out experimentally.
These studies on the active principles of ololiuhqui seeds, although they were published only in professional journals, had an unexpected sequel. We were apprised by two Dutch wholesale seed companies that their sale of seeds of Ipomoea violacea, the ornamental blue morning glory, had reached unusual proportions in recent times. They had heard that the great demand was connected with investigations of these seeds in our laboratory, about which they were eager to learn the details. It turned out that the new demand derived from hippie circles and other groups interested in hallucinogenic drugs.
They believed they had found in the ololiuhqui seeds a substitute for LSD, which was becoming less and less accessible.
The morning glory seed boom, however, lasted only a comparatively short time, evidently because of the undesirable experiences that those in the drug world had with this "new" ancient inebriant. The ololiuhqui seeds, which are taken crushed with water or another mild beverage, taste very bad and are difficult for the stomach to digest.
Moreover, the psychic effects of ololiuhqui, in fact, differ from those of LSD in that the euphoric and the hallucinogenic components are less pronounced, while a sensation of mental emptiness, often anxiety and depression, predominates. Furthermore, weariness and lassitude are hardly desirable effects as traits in an inebriant. These could all be reasons why the drug culture's interest in the morning glory seeds has diminished.
Only a few investigations have considered the question whether the active principles of ololiuhqui could find a useful application in medicine. In my opinion, it would be worthwhile to clarify above all whether the strong narcotic, sedative effect of certain ololiuhqui constituents, or of chemical modifications of these, is medicinally useful.
My studies in the field of hallucinogenic drugs reached a kind of logical conclusion with the investigations of ololiuhqui. They now formed a circle, one could almost say a magic circle: the starting point had been the synthesis of lysergic acid amides, among them the naturally occurring ergot alkaloid ergobasin. This led to the synthesis of lysergic acid diethylamide, LSD. The hallucinogenic properties of LSD were the reason why the hallucinogenic magic mushroom teonanácatl found its way into my laboratory. The work with teonanácatl, from which psilocybin and psilocin were isolated, proceeded to the investigation of another Mexican magic drug, ololiuhqui, in which hallucinogenic principles in the form of lysergic acid amides were again encountered, including ergobasin—with which the magic circle closed.
In Search of the Magic Plant "Ska María Pastora" in the Mazatec Country R. Gordon Wasson, with whom I had maintained friendly relations since the investigations of the Mexican magic mushrooms, invited my wife and me to take part in an expedition to Mexico in the fall of 1962. The purpose of the journey was to search for another Mexican magic plant. Wasson had learned on his travels in the mountains of southern Mexico that the expressed juice of the leaves of a plant, which were called hojas de la Pastora or hojas de María Pastora, in Mazatec ska Pastora or ska María Pastora (leaves of the shepherdess or leaves of Mary the shepherdess), were used among the Mazatec in medico-religious practices, like the teonanácatl mushrooms and the ololiuhqui seeds.