Introduction: Psychedelics, which are currently considered to lack medical efficacy and to be, as a rule, dangerous, were once used as therapeutic adjuncts in the so-called psycholytic and psychedelic therapies of the years between 1950 and 1970. The expansion of religious use of the psychedelic drink ayahuasca in Brazil and elsewhere has been increasing interest in the investigation of ostensible therapeutic properties which are attributed to this drink by its users. Objectives: To explore the therapeutic potential of first experiences with ayahuasca. Methods: Case study, in which in-depth interview techniques were used to elicit the parameters and meaning of first experiences with ayahuasca in Santo Daime (CEFLURIS branch) and its behavioral consequences in the following week. Conclusions: The states of consciousness induced by first experiences with ayahuasca point to therapeutic potential because, according to the subject’s self- report, they stimulated processes of self-knowledge and insight about aspects of the subject’s biography. It was noteworthy that, unlike psycholytic and psychedelic therapies, this insight occurred in association with feelings of peace and in the absence of the visionary experiences typical of psychedelics. The tranquilizing properties of ayahuasca, as well as aspects of the ritual and environmental setting, contribute to the elaboration of interpretive hypotheses about the experience.