The primary purpose of this thesis is to stress that there is a relationship between the texts one reads and the psychedelic experiences one may have. Reading texts has an effect on set and setting with respect to psychedelic experiences. Further, texts read—by figures like Timothy Leary—in the afterglow of a psychedelic experience can influence later integration of said experiences into one’s worldview. This thesis tracks this through the influence of mind-altering substances in the works of both William James (1842-1910) and Timothy Leary (1920-1996) in order to display James’ influence on Leary. James’ impact of Leary intellectually is critical because recent scholarship and changes in cultural and societal perspectives have led to a Psychedelic Renaissance in many disciplines from the clinical-therapeutic to the religious-spiritual. The paper covers select and relevant historical information relating to periods of the Anesthetic Revolution and the Long Sixties. I show how James came to experiment with various mind-altering substances and the results of those experiments. For this reason, the thesis also interacts with Benjamin Paul Blood, a figure whose work guided James’ thought towards the use of mind-altering substances. These mind-altering substances include nitrous oxide, diethyl ether, alcohol, chloroform, and peyote. I apply Leary’s theory of set and setting to better understand James’ Hegelian insights while on nitrous oxide. The thesis explicitly shows how James’ mystical hallmarks of noetic quality and ineffability were influential in Leary’s early psychedelic research. Further, I argue for the thesis that James set a precedent for the use of mind-altering substances for religio-mystical insight that was later expanded upon and entrusted to the masses in the form of Leary’s psychedelic projects. Evidence suggests that these theorists used psychedelics for insights akin to an anagogic interpretation of various works from Hegel to the Tao Te Ching. The conclusion of this thesis briefly ties in contemporary examples and suggests these trends will continue today in the wake of the current Psychedelic Renaissance.