In recent years, the historical record of psychedelic therapy in Europe and the Americas has undergone considerable revision. In this article, we contribute to this re-interpretation by sharing documentation relating to psychedelic therapy carried out in Italy during the period 1927–1966. Our library research has uncovered one hundred publications, documenting at least 60 clinical studies in which psychedelics were administered. There is evidence of some primacy regarding this psychedelic research: Italy has the world record, for the twentieth century, for having carried out the largest number of clinical studies on patients with psilocybin and with lysergic acid amide (LSA); humans first received the high dose of 500 mcg of lysergic acid diethylamide (LSD) in Italy; and LSD plus LSA, and LSD plus psilocybin, were administered simultaneously for the first time. The most successful Italian clinical studies appear to have been those in which psilocybin was used in the treatment of depressive states, with the observed optimal dose being that of 3 mg administered intravenously every second or third day, alternated with placebo injections. Another therapeutic target that seems to have provided interesting results concerns the use of LSD and psilocybin for what was then called “neurosis.” Italian psychiatrists have also made useful contributions to theoretical aspects concerning psychedelic therapies, for example in the conflicting debate on the “psychotomimetic paradigm” and in the distinction between the “primary” and “secondary” effects of these substances.