Background In the early twentieth century, ayahuasca gained popularity in northern Brazil, causing political tension due to moral hostility. However, over the course of the century, despite the proscription of DMT and the intensification of the ‘War on Drugs’, three phases of cumulative political gains eventually led to the full regulation of ayahuasca, in 2010. How was this achieved? Methods This paper provides a comprehensive reassessment of the existing literature on ayahuasca in Brazil, utilizing social movement theory. Emphasis is placed on framing methods, or how movements strategically present their aims to particular audiences, in order to effect political change. Results First, ayahuasca churches constructed a religious frame that emphasized their Christian pedigree. Second, when harassment intensified, ayahuasca was reframed as a charitable endeavour. Finally, in the transition to democracy, the religions added a scientific frame, collaborating with the state to review scientific evidence and establish policy parameters for regulation. Conclusion Framing ayahuasca as Christian and focusing on charity and science were neither straightforward nor unproblematic, but did allow ayahuasca groups to successfully avoid persecution, establish relationships with powerful actors, and eventually achieve full regulation. This case study provides unique insights into the role of social movements in successful drug policy reform, especially how movements can strategically adapt to and influence prevailing moral codes, resulting in concrete political victories.