This presentation looks at the wide range of uses and effects of psilocybin in modern history. Popularized initially in the 1950s in a secret CIA mind control project by R. Gordon Wasson, psilocybin then developed into a tool of the avant garde to further spiritual and artistic expression, including use by President John Kennedy, who seems to have been motivated by his experience to transform the American military state. Timothy Leary further shifted the course of psilocybin uses when he urged political rebellion, informed by the expansion of consciousness. But by the mid 60s because of scarcity of material, and repressive laws forbidding research, psilocybin all but vanished from popular culture, being replaced by LSD, until Terence and Dennis McKenna began to popularize it again with their best selling Psilocybin: The Magic Mushroom Grower’s Guide (1976) a book which taught easy home cultivation. In recent years government approved, university sponsored research is showing promising clinical, psychiatric uses in several areas, a development which is also attracting corporate commodification of what some consider a sacred drug. In our conversation about this history we will examine the various set and settings that have been deployed with a critical and appreciative eye, with the hope to maximize the spiritually transformative, creative effects and to diminish the more profane.