Ayahuasca is a South American psychoactive decoction prepared from Banisteriopsis caapi vine and a dimethyltryptamine (DMT)-containing plant, used by Indigenous cultures in the Amazon and Orinoco basins as part of traditional medicine and shamanism. The word ayahuasca, originating from Quechuan languages spoken in the Andes, refers both to the B. caapi vine and the psychoactive brew made from it, with its name meaning "spirit rope" or "liana of the soul."

The specific ritual use of ayahuasca was widespread among Indigenous groups by the 19th century, though its precise origin is uncertain. Ayahuasca is traditionally prepared by macerating and boiling B. caapi with other plants like Psychotria viridis during a ritualistic, multi-day process. Ayahuasca has been used in diverse South American cultures for spiritual, social, and medicinal purposes, often guided by shamans in ceremonial contexts involving specific dietary and ritual practices, with the Shipibo-Konibo people playing a significant historical and cultural role in its use. It spread widely by the mid-20th century through syncretic religions in Brazil. In the late 20th century, ayahuasca use expanded beyond South America to Europe, North America, and elsewhere, leading to legal cases, non-religious adaptations, and the development of ayahuasca analogs using local or synthetic ingredients.

While DMT is internationally classified as a controlled substance, the plants containing it—including those used to make ayahuasca—are not regulated under international law, leading to varied national policies that range from permitting religious use to imposing bans or decriminalization. The United States patent office controversially granted, challenged, revoked, reinstated, and ultimately allowed to expire a patent on the ayahuasca vine, sparking disputes over intellectual property rights and the cultural and religious significance of traditional Indigenous knowledge.

Ayahuasca produces intense psychological and spiritual experiences with potential therapeutic effects. Ayahuasca’s psychoactive effects primarily result from DMT, rendered orally active by harmala alkaloids in B. caapi, which act as reversible inhibitors of monamine oxidase; B. caapi and its β-carbolines also exhibit independent contributions to ayahuasca’s effects, acting on serotonin and benzodiazepine receptors. Systematic reviews show ayahuasca has strong antidepressant and anxiolytic effects with generally safe traditional use, though higher doses of ayahuasca or harmala alkaloids may increase risks.

Ayahuasca is the hispanicized spelling (i.e., spelled according to Spanish orthography) of a word that originates from the Quechuan languages, which are spoken in the Andean states of Ecuador, Bolivia, Peru, and Colombia. Speakers of Quechuan languages who use modern Quechuan orthography spell it ayawaska. The word refers both to the liana Banisteriopsis caapi, and to the brew prepared from it. In the Quechua languages, aya means "spirit, soul", or "corpse, dead body", and waska means "rope" or "woody vine", "liana". The word ayahuasca has been variously translated as "liana of the soul", "liana of the dead", and "spirit liana". In the cosmovision of its users, the ayahuasca is the vine that allows the spirit to wander detached from the body, entering the spiritual world, otherwise forbidden for the alive.

Although ayahuasca is the most widely used term in Peru, Bolivia, Ecuador and Brazil, the brew is known by many names throughout northern South America:

In the last decades, two new important terminologies emerged. Both are commonly used in the Western world in neoshamanic, recreative or pharmaceutical contexts to address ayahuasca-like substances created without the traditional botanical species, due to it being expensive and/or hard to find in these countries. These concepts are surrounded by some controversies involving ethnobotany, patents, commodification and biopiracy:

Archaeological evidence of the use of psychoactive plants in northeastern Amazon dates back to 1500–2000 BCE. Anthropomorphic figurines, snuffing trays and pottery vessels, often adorned with mythological figures and sacred animals, offer a glimpse of the pre-Columbian culture regarding use of the sacred plants, their preparation and ritual consumption [citar naranjo 86].^{[citation needed]} Although several botanical specimens (like tobacco, coca and Anadenanthera spp.) were identified among these objects, there is no unequivocal evidence of this date referring directly to ayahuasca. Banisteriopsis caapi use is suggested from a pouch containing carved snuffing trays, bone spatulas and other paraphernalia with traces of harmine and DMT, discovered in a cave in southwestern Bolivia in 2008, and chemical traces of harmine in the hair of two mummies found in northern Chile. Both cases are linked to Tiwanaku people, circa 900 CE. There are several reports of oral and nasal use of Anadenanthera spp. (rich in bufotenin) ritualistically and therapeutically during labor and infancy, and researchers suggest that addition of Banisteriopsis spp. to catalyze its psychoactivity emerged later, due to contact between different groups of Amazon and Altiplano.