Although so-called “psychedelic” substances have recently experienced a revival of interest in their therapeutic properties, the underpinnings of their effectiveness remain poorly understood. Based on data collected during ethnographic fieldwork in a Peruvian Amazon clinic, this article proposes an anthropological approach to their therapeutic efficacy in the treatment of addiction. Using an analytical framework rooted in interactionism, narrative approaches, and cultural phenomenology, I argue that psychedelic rituals are best conceptualized as transformative techniques of the self leading the participants to reinterpret their identity, their biography, and their daily behaviors in the light of a new cultural model. I claim that the “dissociative” states induced by psychedelics, usually considered as side effects or adverse reactions, are in fact a driving force in therapy. Beyond neuropharmacological and psychodynamic models, my analysis points out the importance of relational, narrative, and “spiritual” processes as key therapeutic mechanisms of psychedelics. Keywords: psychedelics, self, addiction, therapy, Amazonia, ayahuasca, shamanism