The Phytochemistry of Some Mammillaria There is limited research on the phytochemistry of Mammillaria spp. but it is generally considered that they contain alkaloids, flavonoids and terpenoids. The flowers are rich in betalain pigments. Some simple alkaloids, N-methyltyramine and hordenine have been isolated from M. microcarpa and M. grahamii . Tyramine and 3,4-dimethoxyphenethylamine have also been isolated from M. microcarpa M. tetrancista has also demonstrated the simple alkaloidal profile of N-methyltyramine and hordenine. M. heyderi has been found to contain normacromerine, others describing 3,4-dimethoxyphenethylamine. The phytochemistry and/or alkaloid profile from M. craigii remains unstudied [1, 2]. Some specific Mammillaria have found ethnobotanical use, namely M. heyderi, M. craigii, M. grahamii, M. longimamma , (Solisia) pectinifera , (Mamillopsis) senilis , sonorensis ; and other species. Sometimes these fall under the characterisation of "Lost Peyotes". Some reports of M. craigii mention psychostimulant effects, others mentioning sedative effects and vision-inducing effects, others empathogenic effects [3]. There has been mention that the so called "ethnobotanical complex of Peyote" including Mammillaria spp. often contain simple, often methoxylated PEAs and/or tetrahydroisoquinolines but are devoid of mescaline, the more commonly known alkaloid in psychoactive Cactaceae [4]. Some mention of M. heyderi and M. craigii are that they are used "by runners for indurance", "clarifies vision", produces "sleep and dreams" along with analgesic effects. M. grahamii has been said to "produce brillant colours and dizziness" Mammillaria craigii: This "peyotl" cactus is known to the Tarahumara as "wichuri" or "peyote de San Pedro." It is split open, occasionally roasted, and the inner tissue is used. Mammillaria grahamii: Used in special ceremonies by shamans. Fruits are also said to produce effects. 1 Mammillaria grahamii v. oliviae: This peyote cactus is often called "hikuri." Mammillaria heyderii: "Mammillaria heyderi is a little discussed species, which is reported to be used by the Tarahumaras. We first encountered this species in the Tarahumara-English dictionary compiled by the Swedish explorer Ivar Thord-Gray. Discussing sorcery and black magic among the Tarahumaras, Thord-Gray reports, that 'only the shaman is umeru-ame (powerful) enough to locate wizards and witches. To do this he will make medicine from ball-cactus wichu-ri-ki, which is greatly feared for its magical powers. This medicine will clear his vision. It matters not how well the suku-ru-ame (wizard, witch) is hidden, the shaman can see him clearly' ...Not only is this cactus useful for locating wizards and supplying food, but it is also used as a medicine to cure or relieve headaches. 'After the spines are removed, the plant is cut up into two or more pieces, roasted for a few minutes, and then part of the stuff is pushed into the ear.' ...(This) is corroborated by Bennett & Zingg, who describe the same manner of roasting the cactus before 'the soft center in pushed into the ear in the case of ear-ache or deafness.' Thord-Gray also reports that wichu-ri-ki is an important medicine that will prolong life, 'make the foot light and increase the speed of a runner in a race.' The Tarahumara name for the cacti listed by Bennett & Zingg is witculiki. Witculiki and wichu-ri-ki are possibly related to wichuwa-ka, which means 'crazy, demented, mad, insane, etc." (Bruhn and Bruhn, 1973) Known in Spanish as "biznaga de chilillos," with the edible red fruits called "chilitos." This species, and other latex-containing Mammillarias are often sold in the drug stalls of Mexico and are used as popular folk remedies. M. applanata, M. hemisphaerica and M. Meiacantha are generally believed to be M. heyderi. Narcotic and Hallucinogenic Cacti of the New World By Michael S. Smith The simple PEAs have a fairly well-characterised pharmacological profile, tyramine being a catecholamine releasing agent and TAAR1 agonist but limitations of CNS permeability and rapid metabolism by monoamine oxidase mean the effect, if any, is mainly limited to peripheral sympathomimetic effects, hordenine being able to competitively inhibit MAO-B and also exerting adrenergic effects. The more substituted/phenolic ether derivatives often exert more complex pharmacology including actions at adrenergic receptors, 5-HT receptors etc [5]. The pharmacology of the tetrahydroisoquinolines is less studied, some such as pellotine having 5-HT1D, 5-HT6, and 5-HT7 receptor affinity in the nanomolar range with resulting sedative-hypnotic effects [6]. 2 As the phytochemistry of M. craigii seems unstudied, a small sample was subjected to colourimetric reagent analysis via Marquis reagent after maceration in 95% EtOH and concentration to a small dry sample. 3,4,5-trimethoxy substitutions tend to produce a strong orange colour, and aromatically unsubstituted PEAs a reddish orange-brown. 3,4- dimethoxy substitutions tend to result in olive colouration [7]. A strong brownish-orange result was strongly obtained. While not definitive in any way, there is preliminary indication of a relatively strong presence of an alkaloid. Marquis reagent on M. craigii References [1] Howet, Roberta C., Jerry L. McLaughlin, and Duwayne Statz. "N-Methyltyramine and hordenine from Mammillaria microcarpa." Phytochemistry 16, no. 1 (1977): 151. http://doi.org/10.1016/0031-9422(77)83046-X [2] Cavéquia, Bruna Moreira. Alcaloides da família Cactaceae. BS thesis. Universidade Tecnológica Federal do Paraná, 2020. 3 http://repositorio.utfpr.edu.br/jspui/bitstream/1/24744/1/alcaloidesfamiliacactaceae.pdf [3] "Lost Peyotes" and other Psychoactive or Medicinal Cacti https://www.shaman- australis.com/forum/index.php?/topic/17797-lost-peyotes-and-other-psychoactive-or- medicinal-cacti/ [4] Díaz JL. Ethnopharmacology and taxonomy of Mexican psychodysleptic plants. J Psychedelic Drugs. 1979 Jan-Jun;11(1-2):71-101. https://doi.org/10.1080/02791072.1979.10472094 [5] Ray TS. Psychedelics and the human receptorome. PLoS One. 2010 Feb 2;5(2):e9019. Erratum in: PLoS One. 2010;5(3). https://doi.org/10.1371/journal.pone.0009019 [6] Christian B. M. Poulie, Camilla B. Chan, Aleksandra Parka, Magnus Lettorp, Josephine Vos, Amanda Raaschou, Eline Pottie, Mikkel S. Bundgaard, Louis M. E. Sørensen, Claudia R. Cecchi, Emil Märcher-Rørsted, Anders Bach, Matthias M. Herth, Ann Decker, Anders A. Jensen, Betina Elfving, Andreas C. Kretschmann, Christophe P. Stove, Kristi A. Kohlmeier, Claus Cornett, Christian Janfelt, Birgitte R. Kornum, and Jesper L. Kristensen. In Vitro and In Vivo Evaluation of Pellotine: A Hypnotic Lophophora Alkaloid ACS Pharmacology & Translational Science 2023 6 (10), 1492-1507 https://doi.org/10.1021/acsptsci.3c00142 [7] https://www.ojp.gov/pdffiles1/nij/183258.pdf 4