Background and aims: Ayahuasca is a psychedelic decoction prepared from two (or more) plants containing monoamine oxidase inhibitors, N, N-dimethyltryptamine, and other chemicals. Ayahuasca has apparently been used for centuries in the Amazon basin of South America, and in recent years has increasingly been used internationally in diverse contexts. This study aims to elucidate differences between cross-cultural ceremonial and psychonautic contexts of ayahuasca use. Methods: This study systematically examines subjective differences across contexts for contemporary ayahuasca-drinking practices. User reports of ayahuasca experiences were subjected to textual analysis to compare use in cross-cultural ceremonial contexts that attempt to include elements of traditional Amazonian practices, with psychonautic use that does not formally integrate traditional ceremonial aspects. The experience reports were collected from an online database. Results: The use of ayahuasca in a cross-cultural ceremonial context is associated with prominence of affective and motivational features, whereas psychonautic use was associated with an emphasis on cognitive processes. Conclusions: The beneficial effects of ayahuasca may operate via affective processing and integration and as such, cross-cultural ceremonial use may have advantages relative to psychonautic use. Findings are considered in light of the importance of context on experiences with ayahuasca and other psychedelic substances.