In the second half of the twentieth century, when psychopharmacology was not developed as we know it today and psychoanalysis was an influential school, various psychiatrists began to develop a ‘pharmacology of consciousness,’ and became interested in hallucinogens as new paths for accessing the unconscious. However, with the psychedelic model, the pharmacology of consciousness turned also into a ‘pharmacology of spirituality,’ focused on the use of spiritual experiences as catalyzers of psychological change. This article is a historical review of the origins and development of this spiritual aspect of psychedelic research, from its beginnings in the 1950s to the ‘Renaissance of psychedelic studies’ that we have witnessed in recent decades. The guiding principle is that spiritual experiences have played a key role in psychedelic studies, shaping scientific ideas, psychotherapeutic strategies, and the ideological positions of many of the researchers interested in the clinical applications of hallucinogens.