Ayahuasca is a psychoactive brew from Amazonas, popularized in the last decades in part through transnational religious networks, but also due to interest in exploring spirituality through altered states of consciousness among academic schools and scientific researchers. In this article, the author analyzes the relation between science and religion proposing that the “demarcation problem” between the two arises from the relations among consciousness, intentionality, and spirituality. The analysis starts at the beginning of modern science, continues through the nineteenth century, and then examines the appearance of new schools in psychology and anthropology in the countercultural milieu of the 1960s. The author analyzes the case of ayahuasca against this historical background, first, in the general context of ayahuasca studies in the academic field. Second, he briefly describes three cases from Spain. Finally, he discusses the permeability of science to “spiritual ontologies” from an interdisciplinary perspective, using insights from social and cognitive sciences.