Ayahuasca is an entheogenic brew from the Amazon originally used by indigenous peoples for spiritual, medicinal, and cultural purposes. Its medicinal and therapeutic properties include treatment for depression, drug addiction, and PTSD, following growing scientific research. Demand for ayahuasca has increased in the modern world, both within and outside of its original cultural and historical context, now including the West. This presents challenges for governments, policymakers, and other stakeholders regarding its legal status, regulation, and transnational governance. To contribute to understandings of these challenges, this paper aims to explore, from a sociological perspective, how collective strategic action can be a source of both social change and stability for the governance of ayahuasca. It does so by looking at two opposing collective strategic groups as a case study: The Ethnobotanical Stewardship Council (ESC), and a group of more than 60 academics and other experts who disagree with the ESC’s approach. Issues of participant safety, fair trade, and environmental sustainability are explored alongside the notion of indigenous representation. Results from interviews and discourse analysis of documents during the episode of contention in 2014, between the ESC and the opposition, suggest that to change the governance of ayahuasca, collective strategic action of the ESC was based on cooperation while the oppositions was based on coercion to restore the status quo and stabilise the field.