Journal of Pharmaceutical DECEMBER 1970 Sciences VOLUME 59 NrJMBER 12 REVIEW ARTICLE Peyote Constituents: Chemistry, Biogenesis, and Biological Effects GOVIND J. KAPADIA and M. B. E. FAYEZ ogy of these products and their synthetic analogs along Keyphrases 0 Peyote constituents-chemistry 0 Biogenesis- with their possible medicinal applications (40). peyote alkaloids 0Biological effects-peyote constituents 0 Mes- caline-behavioral effects Addiction, habituation, tolerance- In the past decade or so, there has been no such com- mescaline Metabolism-mescaline 0 Structure-activity rela- prehensive coverage in one review. The need for one is tionships-mescaline derivatives accentuated by the fact that during the past 5 years alone, more than 31 new constituents of peyote were discovered (compared to six before 1900 and five during CONTENTS the 1930’~)~several synthetic methods were developed, and an important part of the pharmacological and clini- BACKGROUND.......................................... 1699 cal (as well as social) studies and practically all the bio- CHEMISTRY OF PEYOTE CONSTITUENTS. .................... 1701 ANALYTICALMETHODS. ................................. 1711 genetic studies of the major peyote constituents were BIOGENE~ISOF PEYOTE ALKALOIDS........................ 1712 conducted, with impressive revelations made. BIOLOGICALEFFECTS OF PEYOTe ALKALOIDS............... 1717 Names-Peyote, a member of the family Cactaceae, has received varied taxonomical treatments with time by different botanists. The first “scientific” name given BACKGROUND to it was Peyotl zacatensis by Hernandez in 1638. Peyote represents one of the earliest known hallucino- The designation Echinocactus williamsii was used by genic drugs, the use of which was exclusively limited to Lemaire in 1840, Anhalonium williamsii by Engelman, the New World. Today much more potent hallucino- Lophophora williamsii by Coulter in 1894, Anhalonium gens, of natural and synthetic origin, are known, yet lewinii by Lewin, and A. jourdanianwn by Rebut. Al- investigation into the chemistry and pharmacology of though the name Echinocactus williamsii appears in the peyote constituents and their synthetic analogs does not Kew Index (vol. 11, p. 813), it does not seem to be as seem to have relented. The literature contains several commonly used as A. lewinii or L. williamsii (7, 37). The early surveys covering various aspects of peyote and its latter name is the one more commonly used in the current constituents. These include articles and monographs chemical literature. The introduction of these names, dealing with cactus alkaloids ( 1-7) and natural hallucino- and there seems to be more, appears to be the result of gens (8-27) in general and more specialized ones dealing confusion between the different types of peyote which mainly with peyote and its active principle, mescaline actually belong to a single species (37, 39).* The confu- (28-40). Several of the earlier articles also cover, more or less adequately, such diverse aspects of peyote as * According to E. F. Anderson [Brittonia, 21. 299(1969)], the genus Lophophora, which has an extensive range within the Chihuahuan Desert history, cultic and modern uses, chemical composition, of Texas and. Mexico, consists of two spies, L. wjlliamsii and L. d@sa. synthesis of its constituents-as phenethylamines (41) The former is both wide rangme and highly variable morpholo@qally, whereas the latter consists of a angle, fairly small population restricted and tetrahydroisoquinolines (42)-and the pharmacol- to an area in the state of Queretaro. Vol. 59, No. 12, December 1970 01699 sion arises from the differences between the young pey- thirst, and they say it protects them from every kind of ote individual specimens, with eight straight ribs, and danger.” At that time, missionaries and administrators the mature ones, with about 12 sinuous ribs, and a third tried to suppress peyote consumption for various social, form with irregular ribs, in addition to slight morpho- political, and religious reasons, apparently without logical variations according to locality. much success. Peyote is a popular name given to the cactus under During the 17th and 18th centuries, peyote was used discussion; other less common names are peyotl, pel- in vast areas stretching northward up to the Arkansas lote, challote, and devil’s root. The name peyote derives River (44), and it was consumed by many Indian tribes from peyotl which appears to be of Aztec origin. The including the Apaches, Comanches, and Kiowas. Al- sun-dried slices of the plant constitute the “mescal but- though a true peyote cult did not seem to have existed at tons” of commerce. It is this material, which can be that time, the drug was taken mainly: (a)by individuals preserved for a very long time, that is usually consumed‘ as a medicine and to induce visions leading to prophetic in ritual ceremonies or for nonreligious purposes to pro- utterances, and (b)collectively to obtain the desired state duce euphoric effects. The name mescal buttons2 is of trance for ritual dances. incorrect, since the material is not related to the non- During the 19th century, the ritual use of peyote cactus succulent, the mescal proper, from which fer- (peyotism) extended among Indian tribes with their mented beverages are prepared. Another incorrect name migrations northward and southward and gradually is “mescal beans,” which is also given to the buttons but became more fully organized into isolated cult groups in fact is the Red Bean, Sophora secundifrora (Legumi- (4446). This led, toward the end of the century, to the nosae). establishment of the “Peyote Church.” With time, Habitat-The cactus (L. williumsii) grows wild on the peyote votaries increased in number, variety, and dis- Mexican plateau and in the southwestern United States tribution; the Church, founded in Oklahoma, gradually in dry places, on cliffs, or on rocky slopes. These regions joined in a strange synthesis of old Mexican, Christian, are very hot and the vegetation is subtropical. Peyote is and local religious rites (47). The advocates of this encountered sometimes singly but more often in clusters. Church remained predominantly Indians, although they It is barely visible, except when in flower, since it is were joined by some Negroes, and the cult remained mostly covered with earth and looks like a pebble. essentially an ethnographical curiosity rather than a Peyote, like most cacti, can be grown practically any- serious movement. The present believers worship God where under glass or in a room. The plant seems to be as the great spirit who, as a master of the universe, in- capable of standing adverse conditions of drought, fused some of his being into peyote; Christ is regarded heat, and cold. as the man who made the cactus available to them when Description-The peyote plant is a small (rarely they needed it. Usually the ceremony is conducted at exceeding 15-20 cm. in total length), fleshy, spineless Saturday night gatherings in a large Indian tepee. Par- cactus, simple or cespitose, proliferous, turbinate with ticipants then sit around a fire and spend the evening in a thick napiform root. The cylindrical stalk, which has ritual singing, prayer, and contemplation (39). horizontal wrinkles, is suberized and grayish-fawn in In the United States, peyote is not regarded as a color. At the top it becomes more chlorophyllose, narcotic drug, although its use is controlled by the federal globular, flattened, and sage-green in color and appears government except in bona jide religious ceremonies of divided into 5-13 thick ribs, only slightly salient, the Native American Church. rounded, and separated from each other by well-marked The history, economic importance, cultic use, and longitudinal grooves. In the center of the spherical psychic effects of peyote are described at length by portion (2-50 mm. in diameter) of the plant, there is a several authors (9-1 1,31-33,35,38,45,49-58). tuft of silky hairs from which the flowers (usually one Constituents of Peyote-The first chemical investiga- or two) emerge; the latter are usually pink but are some- tions of peyote were made by Lewin in 1888 (52). times white or yellow. The fruit is a flesh-colored, or While traveling in America, he collected peyote plants; sometimes grayish-yellow, berry which contains a few these were identified by Hennings as a new An- small black seeds. halonium species that was named A. lewinii. He was History-Peyote was used and revered-as a pan- able to isolate the first crystalline constituent, an alkaloid acea, an amulet, and a hallucinogen-in the mountain- which was called anhalonine and shown to be devoid ous regions of northern Mexico centuries before of any hallucinatory action. This initial finding, how- the settlers arrived; it was probably known to the ever, aroused considerable interest in the drug and the Chichimec tribe long before the Christian era (43). possible constituents that would account for the sensory Bernardino de Sahagun (43), a Franciscan missionary excitations produced in those who took it. Up to that and chronicler of the Spanish conquest of Mexico, time, the family Cactaceae was regarded as being free of wrote about peyote, which was eaten by local natives alkaloids ; as a result of Lewin’s findings, more attention because “it gives them strength and incites them to bat- was directed to the study of several other cacti. tle, alleviates fear, and they feel neither hunger nor In 1894, Heffter (59-64), working with fresh plants, isolated another alkaloid which received the name pello- 1 The drug is usually taken orally. The buttons, whole or chopped, ~ are brewed with tea or chewed while drinking tea, coffee, wine, or milk aIn the United States, about 1950, some ethnologists protested (to conceal an unpleasant taste). Less commonly, a liquid concoction is strongly the idea that the use of peyote should be prohibited on the injected intravenously. pretext that the Native American Church (practicing peyotism) is a 2 Other slang names include: tops, moon, full moon (a large button) legitimate religious organizationwith the same right to relisous freedom and bad seed.