Native to certain areas of North and Central America, Psilocybe Mexicana has been used by indigenous cultures for over 2,000 years. Psilocybe Mexicana was the mushroom that originally launched the study and interest in psilocybin throughout the world.

First collected by Valentina Pavlovna Wasson and her husband Roger Gordon Wasson, during their exploration of Mexico (from 1953 to 1955), psilocybe mexicana gained notoriety and exposure to the rest of the world through their contact with a Mazatec curandera (a Mexican woman who practiced healing techniques inherited from the Mayans) by the name of Maria Sabina. She is the one credited with introducing psilocybin to the rest of the world.