This presentation focuses on the uses, conceptions and policies of the plant Lophophora williamsii in México from a historical and anthropological perspective. We will move through the first prohibition of peyote in the Americas from 1620–in which the religious practices and rituals of the Indigenous population began to be considered as superstitions and associated with the demonic by the Inquisition–continuing with the mention of the first literary, traveler and anthropological writings that were interested in this psychoactive cactus. We will explore scientific studies produced in Mexico during the 19th and 20th centuries on peyote and its relationship with the history of peyote in other latitudes, in order to make visible the psychedelic studies of the historical knowledge that have been produced from the Global South. There will also be an analysis of the more recent anthropological representations on the ritual, legal, medicinal and religious practices of the Indigenous populations with this cactus. The presentation will conclude with a reflection about the current controversies surrounding including the legal status of peyote in Mexico, its prohibited status at the federal level and risk of extinction, which has led to resistance to the possibility of its regulation and conservation.