The use of psychedelic substances within a context that emphasizes religious experiences and aims to provide spiritual insights is not a new phenomenon. However, the proscription of these substances in most modem societies leads to such use now typically occurring in an underground and idiosyncratic manner that often leaves individuals on their own with regard to the interpretation and integration of their experiences and insights. In contrast, the numerous examples in the ethnographic and the historical literature indicate that many cultures independently developed similar frameworks for using these substances for both individually and socially beneficial purposes and arrived at similar conclusions as to which of the substances available to them were the most appropriate for these purposes. This article focuses on a special type of socially sanctioned framework called a “sacrament” and contrasts this with other, more idiosyncratic forms of psychedelic use. It discusses how this framework helps to structure and channel the experiences induced by these substances, thereby increasing the likelihood of individually constructive and socially integrative experiences.