Psychedelics extracted by plants have been used in religious, spiritual and mystic practices for millennia. In 1957, Dr. Hofmann have identified and synthesized the prodrug psilocybin, a substance present in more than 200 species of psychedelic mushrooms. Although the limitations related to the scientific design of many studies, clinical observations performed during the 1950s and the 1960s have shown a potential therapeutic effect of psilocybin in patients affected by depressive symptoms, anxiety, and conversion disorder. Psilocybin was classed as a schedule I substance in 1970, but the fascination for psychedelics remained almost unchanged over time promoting a new scientific interest starting from the 1990s. Recent studies provided further evidences supporting the suggestive hypothesis of a therapeutic use of psilocybin for treating various psychiatric disorders including: pathological anxiety, mood depressive disorder and addiction.