Ayahuasca has probably been used in the western Amazon for millennia.
In 1841 Harmaline was first isolated from Syrian Rue seeds. First Western records of the psychoactive effects of Banisteriopsis caapi are dating back to 1851 (in Peru) Around the 1850s several reports about the use of Banisteriopsis Caapi were published.
In 1922-1923 a film that was shot at a traditional Yage ceremony was shown to the annual American Pharmaceutical Association meeting. During the late 20th Century Ayahuasca gained more and more popularity which lead to a real "entheotourism" - many Europeans and North Americans traveled to South America to experience the effects of Ayahausca in a "traditional" setting. And it was this industry that caused a shift in how Ayahuasca use is viewed and rated in its native regions.
Amazonian Perú, Ecuador, Colombia, Bolivia, Western Brazil and certain regions of the Río Orinoco basin are known as the areas where this drink is widely employed nowadays.
The growth of organized syncretic religious movements such as Santo Daime, União do Vegetal (UDV) and Barquinia promote the use of Ayahuasca and it is rapidly gaining popularity throughout South America today.
Ayahuasca is the basis of traditional medicine practice for at least 75 different indigenous tribes across the Amazon region, but the history of Ayahuasca itself is relatively unknown. Due to a lack of data and evidence, no one can say where the preparation and use of the Ayahuasca brew originates, although several archaeological evidences such as pottery vessels, figurines, snuffing trays and tubes more or less indicate that plant hallucinogens have been used in the Ecuadorian Amazon since 1500 – 2000 B.C. A ceremonial cup found in Ecuador which is believed to be well over 2,500 years old, contained traces of Ayahuasca. There are no written records from back then and it is suspected that the Spanish conquistadors who invaded the Amazon region in the 16th Century destroyed tons upon tons of books of the indigenous tribes because of the blasphemous content (just like they did with the Mayan literature).
Jesuits traveling the Amazon were the earliest Europeans to mention Ayahuasca and in a report dating back to 1737 it was described as an intoxicating potion, which is ingested to get in touch with the gods and other purposes and that it has the potential to unhitch one from all his senses and sometimes, even his life. Other early explorers also referred to Ayahuasca, Yagé and Caapi, but did not mention any details.
In the 1850s, the English botanist Richard Spruce explored the Amazon region and described the sources and preparation of Ayahuasca and its effects upon himself. 1851, while he explored the upper Rio Negro, he observed that the Tukano Indians used Yagé and collected some samples of the Banisteriopsis which he then send home for chemical anlysis . Two years later in Peru, he observed the use of Banisteriopsis two more times. In 1860 he encountered Banisteriopsis in use among the Guahibo Indians of Colombia and Venezuela and later the same year, he found it was used by the Záparo Indians in Peru. Watching how the "diabolical potion" was prepared, Spruce suspected that the admixture plants caused the psychedelic effcts of the brew and noted that Banisteria Caapi (the name of the species turned out to be wrong later; subsequent botanical studies showed that it actually belonged to the genus Banisteriopsis) was considered an active ingredient of Ayahuasca. More than a century after he had send samples of Banisteriopsis Caapi to England, the probes were finally examined in 1966 and were found to be still psychoactive. The discoveries of Richard Spruce were not published until 1873 and it took 35 more years before his notes would be published in full. Also in the 19th century, various ethnographers, botanists and explorers report on their encounters of the use of a divining brew prepared by various indigenous tribes in the Amazon region and mentioned the "roots" or "vines" used in this procedure, but they rarely collected specimen of the plants. But the fact that several diverse admixtures were being used for Ayahuasca was established.
In 1905 and 1923 alkaloids were isolated from "Yagé" and both were called "telepathine"; a Colobian team obtained another alkaloid and named it Yageine. Yageine, Telepathine and Banisterine were ther names given to the alkaloids isolated between 1926 and 1928, but it turned out to be always the same alkaloid and that it was identical with Harmine, an alkaloid isolated from Peganum harmala in 1847. In 1939 it was established that the different terms Caapi, Yagé, and Ayahuasca were all different names for the same beverage and that the used source material was (nearly) identical; Banisteriopsis caapi or Banisteriopsis inebriens.
Richard Evans Schultes, later a professor at Harvard and author of many books, explored especially the Colombian Amazon from 1941 to 1953 and researched the plant knowledge of the Amazonian peoples. He observed the use importance of Ayahuasca brews in indigenous cultures in the Upper Amazon region and documented the use of over 2,000 medicinal plants, which gave him the title "father of modern ethnobotany." He also documented and underpinned that the admixture plants varied greatly, whereas the use of Banisteriopsis caapi or one of its close relatives was the one constant in the brews. Schultes and his students published their initial findings on the DMT-containing admixture plants in the Ayahuasca brew in 1968 and 1969.
In 1955, the potent, but short-acting hallucinogen N,N-dimethyltryptamine (DMT) was obtained from these species; a surprise because DMT had been known as a synthetic since 1931. Harmine, Harmaline and Tetrahydroharmine were isolated from Banisteriopsis caapi in 1957 and firmly established as the active alkaloids of Banisteriopsis caapi and its related species in 1965. The first detailed reports about the use of admixture plants as a frequent components of Ayahuasca began to emerge in the late 1960s.
In the 1980s, Luis Eduardo Luna worked among Mestizos of the Amazon region in Peru, near the cities of Iquitos and Pucallpa. Luna was the first to enunciate the importance of the strict diet, apprentice shamans had to follow, as well as the use of some of the rather unusual admixture plants. He also reported on the concept of "plant teachers," which is how many of the admixture plants are viewed by the Mestizos.
In 1984, Dennis McKenna (yes, the brother of Terrance McKenna, the guy who traveled the globe to explore the world of magic mushrooms) and others published the results of their ethnobotanical, chemical and pharmacological investigations, underpinning the theory that the active substance of Ayahuasca was DMT, which itself is orally inactive, was rendered orally active by the ß-carboline-mediated blockade of peripheral MAO.
In recent years, the brew has gained popularity in the Western world for recreational use after some reports on the hallucinogenic effects and scientific studies that affirmed that the ritualized use of the Ayahuasca brew may improve mental and physical health. In 2008, psychology professor Benny Shanon published a controversial hypothesis that in early Judaism they used a brew analogue to Ayahuasca and that the effects of this brew were responsible for some of the most significant events of Moses' life, including and particularly his vision of the burning bush talking to him.