The present work reconstructs two routes from the ayahuasca historically built: the one that moves from banipsteriosis caapi to the DMT molecule and the one who invests DMT as a spiritual molecule. We say here that through these appropriations of the ayahuasca, the ritual contexts that shelter it has become increasingly reduced. We propose that a reconstruction of the historical density of the drug triad, provision [set] and environment should be made better to understand the complexes of psychoactive experience in particular context. The routes studied here put molecules and plants on the side and inside amateur psychonauts, scientists and a wide network of substrates that activate them in different times and spaces. Among ethical, cultural and medical aspects there is an epistemological reflection to be carried out: this epistemology can be helpfully directed towards addressing the narratives of the drug, set & setting which relate to the historical practices of the ayahuasca field. Key words: Ayahuasca; DMT; Drug, set & setting; Epistemology; Itineraries.