After being outlawed in 1970, psychedelics have reemerged in the consciousness of Western society in the form of the so-called psychedelic renaissance. This has led to widespread interest in psychedelic compounds being used for recreation, treatment of mental illness and addiction, and even the so-called “enhancement” of individuals and society. This renewed interest in psychedelics has resulted in seemingly endless publications in both the popular and the academic press, including authors from fields as diverse as philosophy, theology, pharmacology, neuroscience, and clinical medicine. A common thread in this developing literature is the claim that psychedelic compounds mediate their reported benefits by inducing the so-called psychedelic mystical experience (PME). The nature of PME is hotly debated, with some claiming that it is entirely psychological and others proposing that it involves contact with extramental reality. This raises a number of important questions for Catholics, especially whether PME should be considered properly “mystical,” how PME compares with traditionally understood Catholic mysticism, and whether, and if so under what conditions, psychedelics could be licitly used by the Catholic faithful. This paper is an attempt to begin the process of reconciling empiric scientific data regarding psychedelics generally, and PME specifically, with Catholic philosophical and theological considerations, with the goal of both providing recommendations regarding the licitness of the use of psychedelic compounds and inviting conversation about this important and challenging topic. Summary Over the past 20 years, there has been a renewed interest in of psychedelics. Many articles have been published extoling the benefits of psychedelics, including for the treatment of mental illness and addiction, recreation, and “enhancement” of individuals and society. A common claim is that the benefits of psychedelics are a result of the psychedelic mystical experience (PME). This paper considers both the use of psychedelics and PME from the perspective of Catholic theology, provides recommendations about their use for the Catholic faithful, and invites further conversation about this important and challenging topic. Short Summary This paper considers challenges posed by psychedelics, considers licitness of use, and calls for further discussion.