This chapter provides an ethnographically-grounded, qualitative analysis of the experiences of people recovering from substance dependence among Italian and Brazilian chapters of the Santo Daime church and among Brazilian spiritualist communities that make ceremonial use of ayahuasca. It suggests that substances such as ayahuasca are very peculiar pharmacological tools whose value needs to be made sense of within specific ecologies of use and care that are not yet easily comprehensible within the biomedical paradigm. The goal is to reveal how the pharmacology of ayahuasca, its rich semiotic worlds, and the thick relational fabric within which it is used, together, produce a uniquely potent and deeply caring, situated efficacy. The healing presented here emerges out of a loose assemblage of empirical, case-by-case assessments within structured networks of support. This gives the ritual space an iterative and reflexive dimension, thereby enabling a form of care that is attentive to the specificity of different situations and contexts. The chapter concludes with reflections on the conceptual challenges biomedical studies of ayahuasca face in making sense of the complex, dynamic, and amplified efficacy of psychedelic-assisted interventions within an epistemology that presumes a radical distinction between the "pharmaceutical" and the "social."Within such an epistemology, it becomes difficult to account for the specific, situated, and contextual efficacy that healers witness and patients experience. Supporting such a dynamic of care and making it legible within current evidentiary norms-that are standardized according to universal normspresents a considerable challenge.