Ayahuasca History
Among the many hallucinogenic plants employed by indigenous communities in the Amazon Basin, there is a particularly captivating and intricate beverage that stands out both botanically and ethnographically. Referred to by different names such as ayahuasca, caapi, or yagé, this hallucinogenic concoction holds immense fascination. The term most commonly used to describe this brew is ayahuasca, derived from the Quechua language, meaning "vine of the souls".
Banisteriopsis caapi or"Vine of The Souls"
It encompasses both the beverage itself and one of its key ingredients, the Banisteriopsis caapi, a vine from the Malpighiaceae family (Schultes 1957). In Brazil, the Portuguese adaptation of the Quechua term gives rise to the name hoasca. Ayahuasca, or hoasca, assumes a central role in mestizo ethnomedicine. Given its active constituents and usage patterns, studying it becomes pertinent to contemporary matters in fields like neuropharmacology, neurophysiology, and psychiatry.
What is Ayahuasca?
In a traditional setting, ayahuasca is a brew created by boiling or steeping the bark and stems of Banisteriopsis caapi together with various companion plants. The most commonly used companion plant is Psychotria, specifically P. viridis from the Rubiaceous genus. The leaves of P. viridis contain essential alkaloids for the psychoactive effect.
P. viridis
Ayahuasca's uniqueness lies in its pharmacological activity, which relies on a synergistic interplay among the active alkaloids present in the plants. One of these components is the bark of Banisteriopsis caapi, containing potent MAO inhibitors known as ß-carboline alkaloids. The other components are the leaves of Psychotria viridis or related species, containing the potent short-acting psychoactive compound called N,N-dimethyltryptamine (DMT). DMT itself is not orally active when ingested alone, but in the presence of a peripheral MAO inhibitor, it becomes orally active, forming the basis of ayahuasca's psychotropic action (McKenna, Towers, and Abbott 1984).
N,N-dimethyltryptamine (DMT) and beta-carboline formulas (MAO inhibitor)
Reports (Schultes 1972) suggest that other Psychotria species are similarly utilized in different parts of the Amazon. In the northwest Amazon, particularly in the Colombian Putumayo and Ecuador, the leaves of Diplopterys cabrerana, a jungle liana from the same family as Banisteriopsis, are used instead of Psychotria leaves. However, the alkaloid present in Diplopterys is identical to the one found in Psychotria, resulting in similar pharmacological effects. In Peru, various companion plants are frequently added to ayahuasca alongside Psychotria or Diplopterys, depending on the magical, medical, or religious purposes for which the brew is intended. While a wide range of companion plants may be employed, the most commonly used ones (in addition to Psychotria, which is a constant element) are various genera from the Solanaceous family, including tobacco (Nicotiana sp.), Brugmansia sp., and Brunfelsia sp. (Schultes 1972; McKenna et al. 1995). These Solanaceous plants are known to contain alkaloids such as nicotine, scopalamine, and atropine, which affect both central and peripheral adrenergic and cholinergic neurotransmission. The interactions of these agents with serotonergic agonists and MAO inhibitors remain largely unknown in modern medicine.
Ancient Origins of Ayahuasca
The ancient roots of ayahuasca usage in the Amazon Basin remain shrouded in the mysteries of prehistoric times. The exact origins and original practitioners of this practice remain uncertain, but it is evident that by the mid-nineteenth century, ayahuasca was already prevalent among various indigenous tribes throughout the Amazon Basin when Western ethnographers first encountered it. This fact alone indicates its ancient lineage, although the specifics remain largely unknown. Plutarco Naranjo, an ethnographer from Ecuador, has compiled the limited available information on the prehistory of ayahuasca (Naranjo 1979, 1986).
“Ground zero” of Ayahuasca usage is the northwestern region of the Amazon Basin
Archaeological findings, including pottery vessels, anthropomorphic figurines, snuffing trays, and tubes, provide ample evidence of established plant hallucinogen use in the Ecuadorian Amazon between 1500 and 2000 B.C. Unfortunately, most of the tangible evidence, such as vegetable powders, snuff trays, and pipes, pertains to the use of psychoactive plants other than ayahuasca, such as coca, tobacco, and the hallucinogenic snuff derived from Anadenanthera species, known as vilka or by various other names. There is no definitive iconographic evidence or preserved botanical remains specifically establishing the prehistoric use of ayahuasca. However, it is probable that these pre-Columbian cultures, with their sophisticated knowledge of various psychotropic plants, were familiar with ayahuasca and its preparation. The lack of comprehensive data is frustrating, particularly considering the fascination it has generated among ethnopharmacologists since the late 1960s, when its significance was first illuminated by the work of Richard Schultes and his students. As mentioned earlier, ayahuasca is distinct among plant hallucinogens as it requires a combination of two plants: the bark or stems of Banisteriopsis species, along with the leaves of Psychotria species or other DMT-containing companion plants. The beverage's efficacy relies on this unique combination. The probability of accidentally discovering the precise combination for an active preparation, when neither plant alone is particularly potent, seems unlikely. Yet, at some point in prehistory, this fortunate combination was discovered, leading to the "invention" of ayahuasca.
A shaman leads an Ayahuasca ritual.
The exact circumstances and individuals responsible for this discovery may forever elude us, although there are intriguing myths surrounding the topic. Mestizo ayahuasqueros in Peru maintain that this knowledge was directly transmitted by "plant teachers" (Luna 1984), while the mestres of the Brazilian syncretic cult, the UDV, firmly believe that the knowledge was bestowed upon the Inca king by "the first scientist," King Solomon, during an ancient and relatively unknown visit to the New World. In the absence of concrete evidence, these explanations serve as the only narratives available. What we can assert with certainty is that the knowledge of ayahuasca preparation techniques, including the appropriate companion plants, had disseminated throughout the Amazon by the time modern researchers became aware of its usage.
The Scientific Unveiling of Ayahuasca—The 19th Century
The archaeological origins of ayahuasca will forever intertwine with its mythical beginnings, unless a discovery is made that definitively establishes its ancient usage.In contrast, the modern or scientific history of ayahuasca traces back to 1851 when the renowned British botanist Richard Spruce encountered the consumption of an intoxicating beverage among the Tukano people of the Rio Uapes in Brazil (Schultes 1982). Spruce collected flowering specimens of the large jungle liana used in the beverage, forming the basis for his classification of the plant as Banisteria caapi. In 1931, taxonomist Morton revised the generic concepts within the Malpighiaceae family and reclassified it as Banisteriopsis caapi.
Seven years later, Spruce encountered the same liana among the Guahibo people in the upper Orinoco region of Colombia and Venezuela. During the same year, he discovered the Záparo people of Andean Peru consuming a narcotic beverage prepared from the same plant, which they referred to as ayahuasca. Although Spruce's discovery predates other published accounts, he did not publish his findings until 1873, when they were mentioned in a popular account of his Amazon explorations (Spruce 1873). A more detailed account was published in 1908 as part of Spruce's contribution to A. R. Wallace's anthology, "Notes of a Botanist on the Amazon and Andes" (Spruce 1908). The credit for the earliest published reports on ayahuasca usage goes to Manuel Villavicencio, an Ecuadorian geographer who wrote about its sorcery and divination use on the upper Rio Napo in 1858 (Villavicencio 1858). Although Villavicencio did not provide botanical details about the source plant, his personal account of intoxication left no doubt in Spruce's mind that they were referring to the same substance.
Throughout the remainder of the 19th century, various ethnographers and explorers documented encounters with indigenous Amazonian tribes using an intoxicating beverage prepared from various "roots" (Crévaux 1883), "shrubs" (Koch-Grünberg 1909), or "lianas" (Rivet 1905) with uncertain botanical origins. Unlike Spruce, who had the foresight to collect botanical specimens and materials for future chemical analysis, these later investigators did not gather plant samples, rendering their accounts of historical significance only. One notable exception was Simson's (1886) publication of ayahuasca usage among Ecuadorians, mentioning the consumption of ayahuasca mixed with yage, sameruja leaves, and guanto wood, which often resulted in conflicts among those partaking in the beverage. The ingredients were not identified, and no voucher specimens were collected, but this report provides the earliest indication of additional admixture species used in ayahuasca preparation.
While Richard Spruce and other intrepid explorers of the Amazon collected the initial field reports on ayahuasca from 1851 onwards, groundwork was being laid for significant research on the chemistry of ayahuasca in the early 20th century. The 19th century witnessed the birth of natural products chemistry, starting with the isolation of morphine from opium poppies by German pharmacist Sertüner in 1803. During this period, many natural products, particularly alkaloids, were isolated for the first time. This was partly due to the relative ease of obtaining pure forms of alkaloids and the notable pharmacological properties of the plants containing them. In this period of fervent alkaloid discovery, German chemist H. Göbel isolated harmaline from the seeds of Syrian rue, Peganum harmala. Six years later, his colleague J. Fritsch isolated harmine from the same seeds in 1847. Over fifty years later, Fisher isolated another alkaloid, harmalol, from Syrian rue seeds in 1901. Harmine, one of the ß-carbolines named after the species epithet of Peganum harmala, would eventually be identified as the major ß-carboline present in Banisteriopsis caapi. However, the definitive establishment of the equivalence between ayahuasca's ß-carboline and harmine from Syrian rue occurred in the 1920s after multiple researchers independently isolated harmine and assigned various names to it. The final significant event in the scientific history of ayahuasca during the 19th century took place in 1895, with the first investigations into the effects of harmine on the central nervous system in laboratory animals by Tappeiner.
While Richard Spruce and other intrepid explorers of the Amazon collected the initial field reports on ayahuasca from 1851 onwards, groundwork was being laid for significant research on the chemistry of ayahuasca in the early 20th century. The 19th century witnessed the birth of natural products chemistry, starting with the isolation of morphine from opium poppies by German pharmacist Sertüner in 1803. During this period, many natural products, particularly alkaloids, were isolated for the first time. This was partly due to the relative ease of obtaining pure forms of alkaloids and the notable pharmacological properties of the plants containing them. In this period of fervent alkaloid discovery, German chemist H. Göbel isolated harmaline from the seeds of Syrian rue, Peganum harmala. Six years later, his colleague J. Fritsch isolated harmine from the same seeds in 1847. Over fifty years later, Fisher isolated another alkaloid, harmalol, from Syrian rue seeds in 1901. Harmine, one of the ß-carbolines named after the species epithet of Peganum harmala, would eventually be identified as the major ß-carboline present in Banisteriopsis caapi. However, the definitive establishment of the equivalence between ayahuasca's ß-carboline and harmine from Syrian rue occurred in the 1920s after multiple researchers independently isolated harmine and assigned various names to it. The final significant event in the scientific history of ayahuasca during the 19th century took place in 1895, with the first investigations into the effects of harmine on the central nervous system in laboratory animals by Tappeiner.
Ayahuasca in The Early Twentieth Century (1900–1950)
The initial decades of the twentieth century saw Spruce's extensive descriptions of his explorations in the Amazon and his observations on the use of the mind-altering drink among various tribes he encountered. While brief reports had been published earlier by Spruce and others, it was Spruce's travel account published in 1908, edited by the renowned naturalist and co-discoverer of evolution A. R. Wallace, that potentially saved the knowledge of ayahuasca from being forgotten by academics and brought it to the attention of educated individuals.
During this period in the early twentieth century, advancements in the comprehension of ayahuasca primarily occurred in two areas: taxonomy and chemistry. With a few notable exceptions, research on the pharmacological properties of ayahuasca remained relatively inactive during this time.
The botanical history of ayahuasca during this era is a blend of impressive taxonomic detective work by some researchers and a series of errors made by others. In 1917, Safford claimed that ayahuasca and the beverage known as caapi were identical and derived from the same plant. The French anthropologist Reinberg (1921) added to the confusion by stating that ayahuasca was associated with Banisteriopsis caapi, while yagé was prepared from a genus called Haemadictyon amazonicum, now correctly classified as Prestonia amazonica. This error, which seems to have originated from an uncritical reading of Spruce's original field notes, persisted and spread through the literature on ayahuasca for the next forty years. It was finally debunked when Schultes and Raffauf published a paper specifically refuting this misidentification (Schultes and Raffauf 1960), although it still occasionally appears in technical literature.
Among the researchers who contributed to clarifying the taxonomic understanding of ayahuasca botany, rather than adding to the confusion, are the works of Rusby and White in Bolivia in 1922 (White 1922), as well as Morton's publication in 1930 of the field notes made by botanist Klug in the Colombian Putumayo. From Klug's collections, Morton described a new species of Banisteriopsis, B. inebriens, which was used as a hallucinogen. He also suggested that at least three species, B. caapi, B. inebriens, and B. quitensis, were used similarly, and that two other species, Banisteria longialata and Banisteriopsis rusbyana, might have been used as additional ingredients in the preparation. Interestingly, it was two chemists, Chen and Chen (1939), who made significant contributions to resolving the early taxonomic confusion surrounding the source plants of ayahuasca. While isolating the active components of yagé and ayahuasca, these investigators supported their research with authentic botanical voucher specimens (a rare practice at that time). After reviewing the literature, they concluded that caapi, yagé, and ayahuasca were all different names for the same beverage, and that their source plant was identical: Banisteriopsis caapi. Subsequent work by Schultes and others in the 1950s established that Malpighiaceous species other than B. caapi were involved in the preparation of the beverage. Nevertheless, considering the prevailing confusion at the time, Chen and Chen's contribution was a rare source of clarity. Based on subsequent fieldwork, it is now well established that the two primary botanical sources of the beverage known as caapi, ayahuasca, yagé, natéma, and pinde are the barks of B. caapi and B. Inebriens.
During this period in the early twentieth century, advancements in the comprehension of ayahuasca primarily occurred in two areas: taxonomy and chemistry. With a few notable exceptions, research on the pharmacological properties of ayahuasca remained relatively inactive during this time.
The botanical history of ayahuasca during this era is a blend of impressive taxonomic detective work by some researchers and a series of errors made by others. In 1917, Safford claimed that ayahuasca and the beverage known as caapi were identical and derived from the same plant. The French anthropologist Reinberg (1921) added to the confusion by stating that ayahuasca was associated with Banisteriopsis caapi, while yagé was prepared from a genus called Haemadictyon amazonicum, now correctly classified as Prestonia amazonica. This error, which seems to have originated from an uncritical reading of Spruce's original field notes, persisted and spread through the literature on ayahuasca for the next forty years. It was finally debunked when Schultes and Raffauf published a paper specifically refuting this misidentification (Schultes and Raffauf 1960), although it still occasionally appears in technical literature.
Among the researchers who contributed to clarifying the taxonomic understanding of ayahuasca botany, rather than adding to the confusion, are the works of Rusby and White in Bolivia in 1922 (White 1922), as well as Morton's publication in 1930 of the field notes made by botanist Klug in the Colombian Putumayo. From Klug's collections, Morton described a new species of Banisteriopsis, B. inebriens, which was used as a hallucinogen. He also suggested that at least three species, B. caapi, B. inebriens, and B. quitensis, were used similarly, and that two other species, Banisteria longialata and Banisteriopsis rusbyana, might have been used as additional ingredients in the preparation. Interestingly, it was two chemists, Chen and Chen (1939), who made significant contributions to resolving the early taxonomic confusion surrounding the source plants of ayahuasca. While isolating the active components of yagé and ayahuasca, these investigators supported their research with authentic botanical voucher specimens (a rare practice at that time). After reviewing the literature, they concluded that caapi, yagé, and ayahuasca were all different names for the same beverage, and that their source plant was identical: Banisteriopsis caapi. Subsequent work by Schultes and others in the 1950s established that Malpighiaceous species other than B. caapi were involved in the preparation of the beverage. Nevertheless, considering the prevailing confusion at the time, Chen and Chen's contribution was a rare source of clarity. Based on subsequent fieldwork, it is now well established that the two primary botanical sources of the beverage known as caapi, ayahuasca, yagé, natéma, and pinde are the barks of B. caapi and B. Inebriens.
The first half of the twentieth century also witnessed the commencement of serious chemical investigations into the active constituents of ayahuasca. Similar to the early taxonomic research of that period, progress on this front initially suffered from confusion arising from the simultaneous investigations of multiple independent groups of researchers. Gradually, as these studies found their way into scientific literature, a clearer understanding began to emerge from what was initially a murky picture.
Harmine, eventually recognized as the primary ß-carboline alkaloid of Banisteriopsis species, had been isolated from the seeds of Peganum harmala in 1847 by the German chemist Fritsch. Its definitive identification, however, would still take several decades. In 1905, an alkaloid named "telepathine" was obtained from unvouchered botanical material called "yajé" by Zerda and Bayón, although its true identity was uncertain at the time (quoted in Perrot and Hamet 1927). In 1923, another alkaloid was isolated from unvouchered botanical materials by the Colombian chemist Fisher Cardenas (1923) and was also named telepathine. Concurrently, a Colombian team of chemists, Barriga-Villalba and Albarracin (1925), isolated an alkaloid named yageine. This compound may have been an impure form of harmine, but its assigned formula and melting point were inconsistent with a ß-carboline structure. To further complicate matters, the vine studied by Barriga-Villalba had been "identified" as Prestonia amazonica, but he later corrected this identification to Banisteriopsis caapi. The lack of botanical reference specimens undermined the value of these studies.
From 1926 to the 1950s, the situation gradually improved. Michaels and Clinquart (1926) isolated an alkaloid they called yageine from unvouchered materials. Shortly after, Perrot and Hamet (1927) isolated a substance they referred to as telepathine, suggesting it was identical to yageine. In 1928, Lewin isolated an alkaloid named banisterine, which was later shown by chemists from E. Merck and Co. (Elger 1928; Wolfes and Rumpf 1928) to be identical to harmine, previously known from Syrian rue. Elger worked with vouchered botanical materials identified as Banisteriopsis caapi at Kew Gardens. Based on Lewin's animal studies, pharmacologist Kurt Beringer (1928) used samples of "banisterine" donated by Lewin in a clinical study of fifteen post-encephalitic Parkinson's patients and reported significant positive effects (Beringer 1928). This marked the first evaluation of a reversible MAO inhibitor for the treatment of Parkinson's disease, although harmine's activity as a reversible MAOI would not be discovered until nearly thirty years later. It also represents one of the few instances where a hallucinogenic drug has been clinically assessed for the treatment of any disease (Sanchez-Ramos 1991).
Harmine, eventually recognized as the primary ß-carboline alkaloid of Banisteriopsis species, had been isolated from the seeds of Peganum harmala in 1847 by the German chemist Fritsch. Its definitive identification, however, would still take several decades. In 1905, an alkaloid named "telepathine" was obtained from unvouchered botanical material called "yajé" by Zerda and Bayón, although its true identity was uncertain at the time (quoted in Perrot and Hamet 1927). In 1923, another alkaloid was isolated from unvouchered botanical materials by the Colombian chemist Fisher Cardenas (1923) and was also named telepathine. Concurrently, a Colombian team of chemists, Barriga-Villalba and Albarracin (1925), isolated an alkaloid named yageine. This compound may have been an impure form of harmine, but its assigned formula and melting point were inconsistent with a ß-carboline structure. To further complicate matters, the vine studied by Barriga-Villalba had been "identified" as Prestonia amazonica, but he later corrected this identification to Banisteriopsis caapi. The lack of botanical reference specimens undermined the value of these studies.
From 1926 to the 1950s, the situation gradually improved. Michaels and Clinquart (1926) isolated an alkaloid they called yageine from unvouchered materials. Shortly after, Perrot and Hamet (1927) isolated a substance they referred to as telepathine, suggesting it was identical to yageine. In 1928, Lewin isolated an alkaloid named banisterine, which was later shown by chemists from E. Merck and Co. (Elger 1928; Wolfes and Rumpf 1928) to be identical to harmine, previously known from Syrian rue. Elger worked with vouchered botanical materials identified as Banisteriopsis caapi at Kew Gardens. Based on Lewin's animal studies, pharmacologist Kurt Beringer (1928) used samples of "banisterine" donated by Lewin in a clinical study of fifteen post-encephalitic Parkinson's patients and reported significant positive effects (Beringer 1928). This marked the first evaluation of a reversible MAO inhibitor for the treatment of Parkinson's disease, although harmine's activity as a reversible MAOI would not be discovered until nearly thirty years later. It also represents one of the few instances where a hallucinogenic drug has been clinically assessed for the treatment of any disease (Sanchez-Ramos 1991).
Ayahuasca boiling pot
Working with vouchered botanical materials supplied by Llewellyn Williams of the Chicago Field Museum, Chen and Chen (1939) successfully confirmed the work of Elger, Wolfes, and Rumpf. They isolated harmine from the stems, leaves, and roots of B. caapi and confirmed its identity as banisterine, previously isolated by Lewin. In 1957, Hochstein and Paradies analyzed vouchered ayahuasca material collected in Peru and isolated harmine, harmaline, and tetrahydroharmine. The investigation of constituents in other Banisteriopsis species was not undertaken until 1953 when O'Connell and Lynn (1953) confirmed the presence of harmine in the stems and leaves of vouchered specimens of B. inebriens supplied by Schultes. Subsequently, Poisson (1965) confirmed these results by isolating harmine and a small amount of harmaline from "natema" from Peru, identified by Cuatrecasas as B. inebriens.
Mid 20th Century (1950–1980)
The first part of the 1900s observed the initial scientific investigations into ayahuasca, shedding some illumination on the botanical origins of this intriguing hallucinogen and the nature of its active components. Throughout the three decades spanning from 1950 to 1980, botanical and chemical studies progressed steadily, yielding new revelations that laid the foundation for a future understanding of the distinctive pharmacological effects of ayahuasca.
On the chemical front, the research conducted by Hochstein and Paradies (1957) substantiated and expanded upon the earlier work of Chen and Chen (1939) and other researchers. The active alkaloids found in Banisteriopsis caapi and related species were now firmly identified as harmine, tetrahydroharmine, and harmaline. However, in the late 1960s, detailed reports emerged indicating that admixtures were regularly, if not always, included in the ayahuasca brew (Pinkley 1969). It became evident that at least two of these admixtures, Banisteriopsis rusbyana (later reclassified as Diplopterys cabrerana by Bronwen Gates) and Psychotria species, particularly P. viridis (Schultes 1967), were added to enhance and prolong the visionary experiences. Another surprise came when the alkaloid fractions derived from these species were found to contain the potent, short-acting (but inactive when taken orally) hallucinogen N,N-dimethyltryptamine (DMT) (Der Marderosian et al. 1968). Although DMT had been synthesized artificially and known for some time, its occurrence in nature and hallucinogenic properties had only recently been discovered when Fish, Johnson, and Horning (1955) isolated it as the presumed active constituent in Piptadenia peregrina (later reclassified as Anadenanthera peregrina), a source of hallucinogenic snuff used by indigenous peoples of the Caribbean and the Orinoco basin in South America.
The pharmacological rationale behind the late 1960s discoveries by Schultes, Pinkley, and others, which suggested that the activity of ayahuasca depended on a synergistic interaction between the MAO-inhibiting ß-carbolines in Banisteriopsis and the psychoactive but peripherally inactivated tryptamine DMT, had already been established in 1958 by Udenfriend and colleagues (Udenfriend et al. 1958). These researchers at the Laboratory of Clinical Pharmacology at the NIH were the first to demonstrate that ß-carbolines were potent, reversible inhibitors of MAO. During the same period, the Hungarian psychiatrist and pharmacologist Stephen Szara (1957), through clinical work and self-experimentation with the newly synthesized DMT, published the first reports on its profound hallucinogenic effects in humans. Szara's experiments also led to the realization that the compound was not active when taken orally, although the mechanisms behind its inactivation through oral administration were not fully understood. Ironically, several decades later, Szara, the pioneer of DMT, would be appointed as the head of the NIDA (National Institute on Drug Abuse).
In 1967, during the peak of the Summer of Love in Haight-Ashbury, a remarkable symposium took place in San Francisco under the auspices of what was then the U.S. Department of Health, Education, and Welfare. Titled "Ethnopharmacologic Search for Psychoactive Drugs" (later published as U.S. Public Health Service Publication No. 1645 by the U.S. Government Printing Office) (Efron et al. 1967), this conference brought together prominent figures in the emerging field of psychedelic ethnopharmacology. Participants included toxicologist Bo Holmstedt from the Karolinska Institute in Stockholm, ethnobotanist Richard Evans Schultes, chemist Alexander Shulgin, newly accredited M.D. and marijuana researcher Andrew Weil, and others. It marked the first-ever conference dedicated to the botany, chemistry, and pharmacology of psychedelics and, coincidentally, the last conference of its kind to receive government sponsorship. This pivotal event and its subsequent publication, which became a seminal work in psychedelic literature, provided the world with an overview of the state of knowledge on ayahuasca from various disciplines. The symposium volume featured chapters on the chemistry of ayahuasca (Deulofeu 1967), the ethnography of its use and preparation (Taylor 1967), and the human psychopharmacology of ayahuasca's ß-carbolines (Naranjo 1967). Ironically, considering the limited understanding of ayahuasca at the time, the utilization of tryptamine-containing admixtures and their activation through MAO inhibition were not even discussed; the prevailing assumption was that the psychoactive effects of ayahuasca were primarily, if not exclusively, attributed to the ß-carbolines.
In the five years following the conference, progress was made in comprehending the pharmacology and chemistry of ayahuasca. Schultes and his students Pinkley and der Marderosian published their initial findings on the DMT-containing admixture plants (Der Marderosian et al. 1968; Pinkley 1969), fueling speculation that DMT, when orally activated by ß-carbolines, played a significant role in the brew's effects. However, this notion, though plausible, would only be scientifically confirmed a decade later.
In 1972, Rivier and Lindgren (1972) published one of the early interdisciplinary papers on ayahuasca, reporting on the alkaloid profiles of ayahuasca brews and source plants collected among the Shuar people of the upper Rio Purús in Peru. Their paper, at the time, represented one of the most comprehensive chemical investigations into the composition of ayahuasca brews and source plants, citing verified botanical collections. It also discussed numerous admixture plants apart from the Psychotria species and Diplopterys cabrerana, providing evidence for the complexity of ayahuasca admixture practices and the occasional use of various species.
In the late 1970s, a team of Japanese phytochemists became interested in the chemistry of Banisteriopsis and documented the isolation of several new ß-carbolines, as well as the pyrrolidine alkaloids shihunine and dihydroshihunine (Hashimoto and Kawanishi 1975, 1976; Kawanishi et al. 1982). Most of the newly reported ß-carbolines were found in minuscule amounts, and it was later suggested that they might be artifacts resulting from the isolation procedures (McKenna et al. 1984).
On the chemical front, the research conducted by Hochstein and Paradies (1957) substantiated and expanded upon the earlier work of Chen and Chen (1939) and other researchers. The active alkaloids found in Banisteriopsis caapi and related species were now firmly identified as harmine, tetrahydroharmine, and harmaline. However, in the late 1960s, detailed reports emerged indicating that admixtures were regularly, if not always, included in the ayahuasca brew (Pinkley 1969). It became evident that at least two of these admixtures, Banisteriopsis rusbyana (later reclassified as Diplopterys cabrerana by Bronwen Gates) and Psychotria species, particularly P. viridis (Schultes 1967), were added to enhance and prolong the visionary experiences. Another surprise came when the alkaloid fractions derived from these species were found to contain the potent, short-acting (but inactive when taken orally) hallucinogen N,N-dimethyltryptamine (DMT) (Der Marderosian et al. 1968). Although DMT had been synthesized artificially and known for some time, its occurrence in nature and hallucinogenic properties had only recently been discovered when Fish, Johnson, and Horning (1955) isolated it as the presumed active constituent in Piptadenia peregrina (later reclassified as Anadenanthera peregrina), a source of hallucinogenic snuff used by indigenous peoples of the Caribbean and the Orinoco basin in South America.
The pharmacological rationale behind the late 1960s discoveries by Schultes, Pinkley, and others, which suggested that the activity of ayahuasca depended on a synergistic interaction between the MAO-inhibiting ß-carbolines in Banisteriopsis and the psychoactive but peripherally inactivated tryptamine DMT, had already been established in 1958 by Udenfriend and colleagues (Udenfriend et al. 1958). These researchers at the Laboratory of Clinical Pharmacology at the NIH were the first to demonstrate that ß-carbolines were potent, reversible inhibitors of MAO. During the same period, the Hungarian psychiatrist and pharmacologist Stephen Szara (1957), through clinical work and self-experimentation with the newly synthesized DMT, published the first reports on its profound hallucinogenic effects in humans. Szara's experiments also led to the realization that the compound was not active when taken orally, although the mechanisms behind its inactivation through oral administration were not fully understood. Ironically, several decades later, Szara, the pioneer of DMT, would be appointed as the head of the NIDA (National Institute on Drug Abuse).
In 1967, during the peak of the Summer of Love in Haight-Ashbury, a remarkable symposium took place in San Francisco under the auspices of what was then the U.S. Department of Health, Education, and Welfare. Titled "Ethnopharmacologic Search for Psychoactive Drugs" (later published as U.S. Public Health Service Publication No. 1645 by the U.S. Government Printing Office) (Efron et al. 1967), this conference brought together prominent figures in the emerging field of psychedelic ethnopharmacology. Participants included toxicologist Bo Holmstedt from the Karolinska Institute in Stockholm, ethnobotanist Richard Evans Schultes, chemist Alexander Shulgin, newly accredited M.D. and marijuana researcher Andrew Weil, and others. It marked the first-ever conference dedicated to the botany, chemistry, and pharmacology of psychedelics and, coincidentally, the last conference of its kind to receive government sponsorship. This pivotal event and its subsequent publication, which became a seminal work in psychedelic literature, provided the world with an overview of the state of knowledge on ayahuasca from various disciplines. The symposium volume featured chapters on the chemistry of ayahuasca (Deulofeu 1967), the ethnography of its use and preparation (Taylor 1967), and the human psychopharmacology of ayahuasca's ß-carbolines (Naranjo 1967). Ironically, considering the limited understanding of ayahuasca at the time, the utilization of tryptamine-containing admixtures and their activation through MAO inhibition were not even discussed; the prevailing assumption was that the psychoactive effects of ayahuasca were primarily, if not exclusively, attributed to the ß-carbolines.
In the five years following the conference, progress was made in comprehending the pharmacology and chemistry of ayahuasca. Schultes and his students Pinkley and der Marderosian published their initial findings on the DMT-containing admixture plants (Der Marderosian et al. 1968; Pinkley 1969), fueling speculation that DMT, when orally activated by ß-carbolines, played a significant role in the brew's effects. However, this notion, though plausible, would only be scientifically confirmed a decade later.
In 1972, Rivier and Lindgren (1972) published one of the early interdisciplinary papers on ayahuasca, reporting on the alkaloid profiles of ayahuasca brews and source plants collected among the Shuar people of the upper Rio Purús in Peru. Their paper, at the time, represented one of the most comprehensive chemical investigations into the composition of ayahuasca brews and source plants, citing verified botanical collections. It also discussed numerous admixture plants apart from the Psychotria species and Diplopterys cabrerana, providing evidence for the complexity of ayahuasca admixture practices and the occasional use of various species.
In the late 1970s, a team of Japanese phytochemists became interested in the chemistry of Banisteriopsis and documented the isolation of several new ß-carbolines, as well as the pyrrolidine alkaloids shihunine and dihydroshihunine (Hashimoto and Kawanishi 1975, 1976; Kawanishi et al. 1982). Most of the newly reported ß-carbolines were found in minuscule amounts, and it was later suggested that they might be artifacts resulting from the isolation procedures (McKenna et al. 1984).
Late Twentieth Century (1980–2000)
Following the publication by Rivier and Lindgren, there was minimal advancement in scientific research throughout the remainder of the 1970s. It wasn't until Terence McKenna et al. (1984) published their investigations into ayahuasca that significant progress was made. Their study, which encompassed chemistry, ethnobotany, and pharmacology, utilized authenticated botanical specimens and brew samples obtained from mestizo ayahuasqueros in Peru. This groundbreaking paper provided experimental confirmation of the theory explaining the oral activity of ayahuasca. It revealed that the active component, DMT, becomes orally active due to the blockade of peripheral MAO by ß-carbolines. Tests conducted on rat-liver MAO systems demonstrated the potent MAO-inhibiting properties of ayahuasca brews, even when significantly diluted. Another important discovery was the significant disparity in alkaloid levels between the mestizo ayahuasca brews and the upper Rio Purús ayahuasca analyzed by Rivier and Lindgren. McKenna and colleagues showed that a typical dose of the mestizo ayahuasca contained enough DMT to produce psychoactive effects. They speculated that the differences in alkaloid concentration between the two studies could be attributed to variations in preparation methods, particularly the boiling and reduction of the final extract commonly practiced by mestizos but not by the Shuar people studied by Rivier and Lindgren.
During the 1980s, anthropologist Luis Eduardo Luna made notable contributions to the field. His work among mestizo ayahuasqueros near Iquitos and Pucallpa in Peru shed light on the significance of the apprentice shamans' strict diets and the specific uses of uncommon admixture plants. Luna was the first to introduce the concept of "plant teachers" (plantas que enseñan) as perceived by mestizo ayahuasqueros. In collaboration with McKenna and Towers, Luna compiled a comprehensive list of admixture species and their biodynamic constituents, emphasizing the potential of these understudied plants as sources for novel therapeutic agents.
In 1985, while conducting fieldwork together in the Peruvian Amazon, McKenna and Luna began discussing the possibility of conducting a biomedical investigation of ayahuasca. The remarkable health of ayahuasqueros, even at advanced ages, intrigued them and sparked the idea of scientific study. However, logistical challenges in Peru, including limited storage facilities for plasma samples and local beliefs in witchcraft that discouraged medical procedures, hindered their plans. A turning point came in 1991 when they were invited to a conference in São Paulo organized by the União do Vegetal (UDV), a Brazilian syncretic religion that incorporated ayahuasca into their rituals. Many UDV members were medical professionals and expressed openness to a biomedical study proposed by Luna and McKenna. The UDV sought to demonstrate the long-term safety of hoasca tea (ayahuasca) to Brazilian health authorities and eagerly enlisted foreign scientists to collaborate. The challenge of funding the study remained unanswered.
Following the 1991 conference, McKenna returned to the United States and drafted a proposal outlining the objectives of the study, later known as the Hoasca Project. Initially, they considered submitting the proposal to the National Institute on Drug Abuse (NIDA), but it became apparent that government funding was unlikely. Securing NIH funds for a study in Brazil was complicated by legal, logistical, and political issues. Additionally, the NIH's focus on highlighting harmful consequences of psychedelic drug use did not align with the proposed study's aims. Fortunately, through his affiliation with Botanical Dimensions, a nonprofit organization dedicated to investigating ethnomedically significant plants, McKenna secured generous grants from private individuals.
With sufficient funding for a modest pilot study, McKenna assembled a diverse team of collaborators from medical and academic institutions worldwide. The international, interdisciplinary team consisted of scientists from UCLA, the University of Miami, the University of Kuopio, the University of Rio de Janeiro, the University of Campinas, and the Hospital Amazonico. In the summer of 1993, the team embarked on the field phase of the research in Manaus, Brazil. They worked with volunteers from the Nucleo Caupari, one of the largest and oldest UDV congregations in Brazil. Over five weeks, the team administered test doses of hoasca tea, collected plasma and urine samples for analysis, and conducted various physiological and psychological assessments.
The result was one of the most comprehensive investigations of a psychedelic drug conducted in the twentieth century. The study encompassed chemistry, psychological effects, psychopharmacology, acute and long-term effects of regular hoasca tea ingestion, and assessments of participants' physical and mental health. Extensive psychological evaluations and structured psychiatric interviews were conducted. The study also measured and characterized the serotonergic response to ayahuasca and provided the first measurement of major hoasca alkaloids in human plasma. The findings were published in peer-reviewed papers and summarized in a comprehensive review. Notable discoveries included the positive and profound life-changing experiences reported by long-time UDV members and the persistent elevation of serotonin uptake receptors in platelets, suggesting potential long-term serotonergic modulation and adaptive changes in brain function. The study established the safety of regular hoasca use within the UDV ritual context, refuting concerns of adverse long-term toxicity and demonstrating lasting positive influences on physical and mental health.
During the 1980s, anthropologist Luis Eduardo Luna made notable contributions to the field. His work among mestizo ayahuasqueros near Iquitos and Pucallpa in Peru shed light on the significance of the apprentice shamans' strict diets and the specific uses of uncommon admixture plants. Luna was the first to introduce the concept of "plant teachers" (plantas que enseñan) as perceived by mestizo ayahuasqueros. In collaboration with McKenna and Towers, Luna compiled a comprehensive list of admixture species and their biodynamic constituents, emphasizing the potential of these understudied plants as sources for novel therapeutic agents.
In 1985, while conducting fieldwork together in the Peruvian Amazon, McKenna and Luna began discussing the possibility of conducting a biomedical investigation of ayahuasca. The remarkable health of ayahuasqueros, even at advanced ages, intrigued them and sparked the idea of scientific study. However, logistical challenges in Peru, including limited storage facilities for plasma samples and local beliefs in witchcraft that discouraged medical procedures, hindered their plans. A turning point came in 1991 when they were invited to a conference in São Paulo organized by the União do Vegetal (UDV), a Brazilian syncretic religion that incorporated ayahuasca into their rituals. Many UDV members were medical professionals and expressed openness to a biomedical study proposed by Luna and McKenna. The UDV sought to demonstrate the long-term safety of hoasca tea (ayahuasca) to Brazilian health authorities and eagerly enlisted foreign scientists to collaborate. The challenge of funding the study remained unanswered.
Following the 1991 conference, McKenna returned to the United States and drafted a proposal outlining the objectives of the study, later known as the Hoasca Project. Initially, they considered submitting the proposal to the National Institute on Drug Abuse (NIDA), but it became apparent that government funding was unlikely. Securing NIH funds for a study in Brazil was complicated by legal, logistical, and political issues. Additionally, the NIH's focus on highlighting harmful consequences of psychedelic drug use did not align with the proposed study's aims. Fortunately, through his affiliation with Botanical Dimensions, a nonprofit organization dedicated to investigating ethnomedically significant plants, McKenna secured generous grants from private individuals.
With sufficient funding for a modest pilot study, McKenna assembled a diverse team of collaborators from medical and academic institutions worldwide. The international, interdisciplinary team consisted of scientists from UCLA, the University of Miami, the University of Kuopio, the University of Rio de Janeiro, the University of Campinas, and the Hospital Amazonico. In the summer of 1993, the team embarked on the field phase of the research in Manaus, Brazil. They worked with volunteers from the Nucleo Caupari, one of the largest and oldest UDV congregations in Brazil. Over five weeks, the team administered test doses of hoasca tea, collected plasma and urine samples for analysis, and conducted various physiological and psychological assessments.
The result was one of the most comprehensive investigations of a psychedelic drug conducted in the twentieth century. The study encompassed chemistry, psychological effects, psychopharmacology, acute and long-term effects of regular hoasca tea ingestion, and assessments of participants' physical and mental health. Extensive psychological evaluations and structured psychiatric interviews were conducted. The study also measured and characterized the serotonergic response to ayahuasca and provided the first measurement of major hoasca alkaloids in human plasma. The findings were published in peer-reviewed papers and summarized in a comprehensive review. Notable discoveries included the positive and profound life-changing experiences reported by long-time UDV members and the persistent elevation of serotonin uptake receptors in platelets, suggesting potential long-term serotonergic modulation and adaptive changes in brain function. The study established the safety of regular hoasca use within the UDV ritual context, refuting concerns of adverse long-term toxicity and demonstrating lasting positive influences on physical and mental health.
The Future of Ayahuasca Research
The Hoasca Project, encompassing both field and laboratory phases, has reached its conclusion, and with the recent publication of the final major paper, its objectives have been fulfilled. From its inception, the hoasca study was designed as a pilot investigation, aiming to provide guidance for future research endeavors. In this aspect, the study has achieved remarkable success. Like any robust scientific inquiry, it has generated more inquiries than it has resolved, presenting numerous promising avenues for future investigation. With the unequivocal demonstration of ayahuasca's safety, lack of toxicity, and therapeutic potential as medicine, it is optimistic that forthcoming researchers will exhibit sufficient interest and allocate necessary resources toward exploring its healing capacities.
Some Speculative Considerations
Following the completion of the Hoasca Project, a strong groundwork of fundamental data has been established, serving as the basis for future scientific inquiries that will shift their focus from the field to the laboratory and the clinic. However, beyond the realm illuminated by scientific investigation and its rational illumination, certain matters pertaining to ayahuasca persist, unlikely to be fully resolved through scientific means alone, at least not by current scientific methodologies. Ayahuasca shares a symbiotic relationship with humanity, a connection that can be traced back to New World prehistory. The wisdom accumulated over millennia of coevolution with this visionary vine holds profound implications for our understanding of what it means to be human and to exist as an inquisitive and sentient species within the interconnected community of life on Earth.
While definitive answers elude us, questions regarding the nature and significance of the bond between humanity and this plant ally, and by extension, the entire realm of plant teachers, continue to intrigue us. Why do plants possess alkaloids that closely resemble our own neurotransmitters, allowing them to "communicate" with us? What might be the underlying "message" they seek to convey, if indeed there is one? Was it a mere coincidence or happenstance that led an early, curious shaman to combine the ayahuasca vine and the chacruna leaf, giving birth to the tea that unveiled the "invisible landscape" for the first time? This seems improbable, considering that neither of these key ingredients is particularly appealing as food. Yet, what other explanation could there be? Ayahuasqueros themselves simply attest to the calling of the vine. Others, attempting to adopt a more sophisticated and rational stance, without offering a more satisfying elucidation, propose that plant alkaloids serve as interspecies pheromonal messengers and carriers of sensoritropic cues, enabling early humans to select and utilize biodynamic plants within their environment.
While definitive answers elude us, questions regarding the nature and significance of the bond between humanity and this plant ally, and by extension, the entire realm of plant teachers, continue to intrigue us. Why do plants possess alkaloids that closely resemble our own neurotransmitters, allowing them to "communicate" with us? What might be the underlying "message" they seek to convey, if indeed there is one? Was it a mere coincidence or happenstance that led an early, curious shaman to combine the ayahuasca vine and the chacruna leaf, giving birth to the tea that unveiled the "invisible landscape" for the first time? This seems improbable, considering that neither of these key ingredients is particularly appealing as food. Yet, what other explanation could there be? Ayahuasqueros themselves simply attest to the calling of the vine. Others, attempting to adopt a more sophisticated and rational stance, without offering a more satisfying elucidation, propose that plant alkaloids serve as interspecies pheromonal messengers and carriers of sensoritropic cues, enabling early humans to select and utilize biodynamic plants within their environment.
On the other hand, individuals such as my brother Terence McKenna and myself, in our early endeavors, as well as anthropologist Jeremy Narby in his recent reformulation of a similar theory (McKenna and McKenna 1975; Narby 1998), argue that the visionary experiences facilitated by plants like ayahuasca, through some yet obscure mechanism, grant us an intuitive understanding and insight into the molecular foundation of biological existence. According to this perspective, this intuitive knowledge, now being gradually unveiled to the scientific worldview through the crude tools of molecular biology, has always been accessible as direct experience to shamans and seers courageous enough to form symbiotic bonds with our speechless yet infinitely ancient and wise plant allies.
Undoubtedly, such notions delve into the realm of speculation and lie outside the boundaries of science. Nonetheless, as an observer deeply engaged with ayahuasca both scientifically and personally for many years, I find it intriguing that these "wild" conjectures resurface persistently, regardless of our attempts to strip the tea of its sacredness and reduce it to mere chemistry, botany, receptor sites, and pharmacology. While all of these aspects hold significance, none of them can fully explain the undeniable and profound enigma that is ayahuasca.
Undoubtedly, such notions delve into the realm of speculation and lie outside the boundaries of science. Nonetheless, as an observer deeply engaged with ayahuasca both scientifically and personally for many years, I find it intriguing that these "wild" conjectures resurface persistently, regardless of our attempts to strip the tea of its sacredness and reduce it to mere chemistry, botany, receptor sites, and pharmacology. While all of these aspects hold significance, none of them can fully explain the undeniable and profound enigma that is ayahuasca.