Ayahuasca is a psychoactive brew that has origins in the indigenous traditions of the Amazon regions of South America. It is known as a healing medicine that is deeply embedded in shamanic practices and spiritual beliefs. In the last few decades the use of Ayahuasca has developed outside of the Amazon and has since become a transnational phenomenon, crossing boundaries between Western and non-Western healing contexts. This increasing popularity has attracted a multidisciplinary array of research interests, of which anthropology has significantly contributed. It has become evident for those engaged in Ayahuasca research that Western epistemology is limited by its longstanding constraints of objectivism, rationalism and scientific materialism. In this thesis, I provide an analysis of Ayahuasca to outline the spiritual centrality of its use and appropriation, especially in context of healing beliefs and practices. I apply the concept of neo-enchantment to outline how the globalization of Ayahuasca challenges the hegemony of rationalism and secularism in industrialized society. This is achieved through reference to recent Ayahuasca research and analysis that seek to overcome limitations of Western epistemology, through dialectically synthesizing scientific and indigenous paradigms of healing and knowledge. While focused on Ayahuasca research, the outcomes of this thesis relates to broader issues in the social sciences and beyond, and raises some important questions for future research.