This article offers critical sociological and philosophical reflections on ayahuasca and other psychedelics as objects of research in medicine, health and human sciences. It situates 21st century scientific inquiry on ayahuasca in the broader context of how early modern European social trends and intellectual pursuits translated into new forms of empiricism and experimental philosophy, but later evolved into a form of dogmatism that convenienced the political suppression of academic inquiry into psychedelics. Applying ideas from the field of science and technology studies, we consider how ayahuasca’s myriad ontological representations in the 21st century — for example, plant teacher, traditional medicine, religious sacrament, material commodity, cognitive tool, illicit drug — influence our understanding of it as an object of inquiry. We then explore epistemological issues related to ayahuasca studies, including how the indigenous and mestizo concept of “plant teacher” or the more instrumental notion of psychedelics as “cognitive tools” may impact understanding of knowledge. This leads to questions about whether scientists engaged in ayahuasca research should be expected to have personal experiences with the brew, and how these may be perceived to help or hinder the objectivity of their pursuits. We conclude with some brief reflections on the politics of psychedelic research and impediments to academic knowledge production in the field of psychedelic studies. Keywords: Ayahuasca, cognitive tool, epistemology, ontology, psychedelic, science and technology studies, self- experimentation.