Prehistoric rock art near Villar del Humo in Spain suggests that Psilocybe hispanica was used in religious rituals 6,000 years ago. The hallucinogenic species of the Psilocybe genus have a history of use among the native peoples of Mesoamerica for religious communion, divination, and healing, from pre-Columbian times to the present day.

Mushroom stones and motifs have been found in Guatemala A statuette dating from ca. 200 CE depicting a mushroom strongly resembling Psilocybe mexicana was found in the western Mexican state of Colima in a shaft and chamber tomb. A Psilocybe species known to the Aztecs as teōnanācatl (literally “divine mushroom”: an agglutinative form of teōtl (god, sacred) and nanācatl (mushroom) in the Nahuatl language) was reportedly served at the coronation of the Aztec ruler Moctezuma II in 1502.

Aztecs and Mazatecs referred to psilocybin mushrooms as genius mushrooms, divinatory mushrooms, and wondrous mushrooms when translated into English. Bernardino de Sahagún reported the ritualistic use of teonanácatl by the Aztecs when he traveled to Central America after the expedition of Hernán Cortés.

After the Spanish conquest, Catholic missionaries campaigned against the cultural tradition of the Aztecs, dismissing the Aztecs as idolaters, and the use of hallucinogenic plants and mushrooms, together with other pre-Christian traditions, was quickly suppressed. The Spanish believed the mushroom allowed the Aztecs and others to communicate with demons. Despite this history, the use of teonanácatl has persisted in some remote areas.