Classic psychedelics have long been used in religious and healing rituals. A recent wave of scientific research has examined the acute effects of psychedelics, including how experiences with them are often described as spiritual, religious, or mystical. However, research has paid insufficient attention to the role of psychedelic experiences in the context of religious/spiritual development. In two studies, we examine religious and spiritual changes related to psychedelic use. In Study 1, using data from multiple birth cohort studies—the 1958 National Child Development Study and the 1970 British Cohort Study (for both, N > 11,000)—we examined the relationship between lifetime psychedelic use and religious affiliation, including religious changes (i.e., de/conversion or switching) and beliefs. In Study 2, we examined prospective changes in self-identification as religious and spiritual over a 2-month period among people who reported psychedelic use in a representative sample from the United Kingdom and the United States (N = 9,732). In Study 1, religious affiliation in childhood and adulthood were associated with reduced likelihood of psychedelic use. Also, lifetime psychedelic use was associated with greater likelihood of stable nonaffiliation with religion and with religious disaffiliation. lysergic acid diethylamide use predicted switching between religions as well. In Study 2, psychedelic use was not related to changes in religiosity or spirituality. Notably, psychedelics’ associations with religious changes did generally not differ from other illicit substances. We discuss our findings by highlighting the context-dependence of psychedelics and their effects and relating them to secularization-related trends. (PsycInfo Database Record (c) 2025 APA, all rights reserved)