Although so-called “hallucinogenic” or “psychedelic” substances such as ayahuasca have recently experienced a revival of interest in their therapeutic properties, particularly in the field of mental health, the reasons for their effectiveness remain poorly understood. Based on data collected during an ethnographic survey conducted in a clinic in the Peruvian Amazon, this article explores the reasons for ayahuasca’s effectiveness in the treatment of addiction. Using an anthropological approach in dialogue with systems theory, the author shows that the therapeutic effectiveness of ayahuasca is based on the development of relationships with non-human beings who are usually invisible, which conditions profound identity reconfigurations for the subject. The hallucinogenic rite, described in this sense as a “spiritual” practice by the users, thus appears as a “technique of the Ego” that leads the participants to reinterpret their biography and their daily behaviours in the light of a new cultural model. The transformation of identity and the theory of the Self conditioned by this dynamic of narrative reconfiguration as well as its behavioural and cognitive implications then appear as the main catalysts of the cure. The proposed anthropological approach invites us to rethink drug addiction and the therapeutic effectiveness of psychedelics beyond neuropharmacological and psychodynamic models in order to take better account of identity, narrative and social processes in the understanding of addictive behaviours as well as the “spiritual” dimension of these practices, the importance of which is underlined by users of psychedelic substances.