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Ayahuasca

Hypotheses regarding the mechanisms of ayahuasca in the treatment of addictions

Ayahuasca is a medicinal plant mixture utilized by indigenous peoples throughout the Amazon River basin for healing purposes. The “vine of the soul” or “vine of death,” as it is known in South America, contains a combination of monoamine oxidase inhibitors and N,N-dimethyltryptamine (DMT). When ingested together, these medicines produce profound alterations in consciousness. Increasingly, ayahuasca is being utilized to treat addictions. However, the mechanism of action by which ayahuasca treats addictions remains unclear. We offer four hypotheses to explain possible biochemical, physiological, psychological, and transcendent mechanisms by which ayahuasca may exert its anti-addiction effects.

Liester, M. B., & Prickett, J. I. (2012). Hypotheses regarding the mechanisms of ayahuasca in the treatment of addictions. Journal of psychoactive drugs, 44(3), 200-208. 10.1080/02791072.2012.704590
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Health status of ayahuasca users.

Abstract

Ayahuasca is a psychedelic brew originally used for magico-religious purposes by Amerindian populations of the western Amazon Basin. Throughout the last four decades, the use of ayahuasca spread towards major cities in all regions of Brazil and abroad. This trend has raised concerns that regular use of this N,N-dimethyltryptamine- and harmala-alkaloid-containing tea may lead to mental and physical health problems associated typically with drug abuse. To further elucidate the mental and physical health of ayahuasca users, we conducted a literature search in the international medical PubMed database. Inclusion criteria were evaluation of any related effect of ayahuasca use that occurred after the resolution of acute effects of the brew. Fifteen publications were related to emotional, cognitive, and physical health of ayahuasca users. The accumulated data suggest that ayahuasca use is safe and may even be, under certain conditions, beneficial. However, methodological bias of the reviewed studies might have contributed to the preponderance of beneficial effects and to the few adverse effects reported. The data up to now do not appear to allow for definitive conclusions to be drawn on the effects of ayahuasca use on mental and physical health, but some studies point in the direction of beneficial effects. Additional studies are suggested to provide further clarification.

Barbosa, P. C. R., Mizumoto, S., Bogenschutz, M. P., & Strassman, R. J. (2012). Health status of ayahuasca users. Drug testing and analysis, 4(7-8), 601-609. https://dx.doi.org/10.1002/dta.1383
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Quantitative Analysis of Narrative Reports of Psychedelic Drugs

Abstract

Background

Psychedelic drugs facilitate profound changes in consciousness and have potential to provide insights into the nature of human mental processes and their relation to brain physiology. Yet published scientific literature reflects a very limited understanding of the effects of these drugs, especially for newer synthetic compounds. The number of clinical trials and range of drugs formally studied is dwarfed by the number of written descriptions of the many drugs taken by people. Analysis of these descriptions using machine-learning techniques can provide a framework for learning about these drug use experiences.

Methods

We collected 1000 reports of 10 drugs from the drug information website Erowid.org and formed a term-document frequency matrix. Using variable selection and a random-forest classifier, we identified a subset of words that differentiated between drugs.

Results

A random forest using a subset of 110 predictor variables classified with accuracy comparable to a random forest using the full set of 3934 predictors. Our estimated accuracy was 51.1%, which compares favorably to the 10% expected from chance. Reports of MDMA had the highest accuracy at 86.9%; those describing DPT had the lowest at 20.1%. Hierarchical clustering suggested similarities between certain drugs, such as DMT and Salvia divinorum.

Conclusion

Machine-learning techniques can reveal consistencies in descriptions of drug use experiences that vary by drug class. This may be useful for developing hypotheses about the pharmacology and toxicity of new and poorly characterized drugs.

Coyle, J. R., Presti, D. E., Baggott, M. J. (2012). Quantitative Analysis of Narrative Reports of Psychedelic Drugs.
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Analytical techniques for the determination of tryptamines and β-carbolines in plant matrices and in psychoactive beverages consumed during religious ceremonies and neo-shamanic urban practices

Abstract

The consumption of ayahuasca, a hallucinogenic beverage used by indigenous communities in the Amazon, is increasing worldwide due to the expansion of syncretic religions founded in the north of Brazil in the first half of the twentieth century, such as Santo Daime and União do Vegetal. Another example is the jurema wine, a drink that originated from indigenous cultures of the northeast of Brazil. It is currently used for several religious practices throughout Brazil involving urban neo-shamanic rituals and syncretic Brazilian religions, such as Catimbó and Umbanda. Both plant products contain N,N-dimethyltryptamine which requires co-administration of naturally occurring monoamine oxidase inhibitors, for example β-carboline derivatives, in order to induce its psychoactive effects in humans. This review explores the cultural use of tryptamines and β-carbolines and focuses on the analytical techniques that have been recently applied to the determination of these compounds in ayahuasca, its analogues, and the plants used during the preparation of these beverages.

Gaujac, A., Navickiene, S., Collins, M. I., Brandt, S. D., & Andrade, J. B. (2012). Analytical techniques for the determination of tryptamines and β‐carbolines in plant matrices and in psychoactive beverages consumed during religious ceremonies and neo‐shamanic urban practices. Drug testing and analysis, 4(7-8), 636-648. https://dx.doi.org/10.1002/dta.1343
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Metabolism and disposition of N,N-dimethyltryptamine and harmala alkaloids after oral administration of ayahuasca

Abstract

Ayahuasca is an Amazonian psychotropic plant tea obtained from Banisteriopsis caapi, which contains β-carboline alkaloids, chiefly harmine, harmaline and tetrahydroharmine. The tea usually incorporates the leaves of Psychotria viridis or Diplopterys cabrerana, which are rich in N,N-dimethyltryptamine (DMT), a psychedelic 5-HT2A/1A/2C agonist. The β-carbolines reversibly inhibit monoamine-oxidase (MAO), effectively preventing oxidative deamination of the orally labile DMT and allowing its absorption and access to the central nervous system. Despite increased use of the tea worldwide, the metabolism and excretion of DMT and the β-carbolines has not been studied systematically in humans following ingestion of ayahuasca. In the present work, we used an analytical method involving high performance liquid chromatography (HPLC)/electrospray ionization (ESI)/selected reaction monitoring (SRM)/tandem mass spectrometry(MS/MS) to characterize the metabolism and disposition of ayahuasca alkaloids in humans. Twenty-four-hour urine samples were obtained from 10 healthy male volunteers following administration of an oral dose of encapsulated freeze-dried ayahuasca (1.0 mg DMT/kg body weight). Results showed that less than 1% of the administered DMT dose was excreted unchanged. Around 50% was recovered as indole-3-acetic acid but also as DMT-N-oxide (10%) and other MAO-independent compounds. Recovery of DMT plus metabolites reached 68%. Harmol, harmalol, and tetrahydroharmol conjugates were abundant in urine. However, recoveries of each harmala alkaloid plus its O-demethylated metabolite varied greatly between 9 and 65%. The present results show the existence in humans of alternative metabolic routes for DMT other than biotransformation by MAO. Also that O-demethylation plus conjugation is an important but probably not the only metabolic route for the harmala alkaloids in humans.

Riba, J., McIlhenny, E. H., Valle, M., Bouso, J. C., & Barker, S. A. (2012). Metabolism and disposition of N, N‐dimethyltryptamine and harmala alkaloids after oral administration of ayahuasca. Drug testing and analysis, 4(7-8), 610-616. 10.1002/dta.1344
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Ayahuasca scientific literature overview

iceers3

In response to claims made in 2010 by the United Nations International Narcotics Control Board (INCB) regarding the serious health risks that would entail the use of ayahuasca, psychologist and ayahusaca researcher Jose Carlos Bouso has compiled a document with all the scientific studies into the short, medium and long term effects of ayahuasca. No study supports the claims of the INCB, and some of these studies even indicate a possible therapeutic potential of ayahuasca.

The document was published by the International Center for Ethnobotanical Education, Research and Service (ICEERS), and can be downloaded here.

Seeing with the eyes shut: Neural basis of enhanced imagery following ayahuasca ingestion

Abstract

The hallucinogenic brew Ayahuasca, a rich source of serotonergic agonists and reuptake inhibitors, has been used for ages by Amazonian populations during religious ceremonies. Among all perceptual changes induced by Ayahuasca, the most remarkable are vivid “seeings.” During such seeings, users report potent imagery. Using functional magnetic resonance imaging during a closed-eyes imagery task, we found that Ayahuasca produces a robust increase in the activation of several occipital, temporal, and frontal areas. In the primary visual area, the effect was comparable in magnitude to the activation levels of natural image with the eyes open. Importantly, this effect was specifically correlated with the occurrence of individual perceptual changes measured by psychiatric scales. The activity of cortical areas BA30 and BA37, known to be involved with episodic memory and the processing of contextual associations, was also potentiated by Ayahuasca intake during imagery. Finally, we detected a positive modulation by Ayahuasca of BA 10, a frontal area involved with intentional prospective imagination, working memory and the processing of information from internal sources. Therefore, our results indicate that Ayahuasca seeings stem from the activation of an extensive network generally involved with vision, memory, and intention. By boosting the intensity of recalled images to the same level of natural image, Ayahuasca lends a status of reality to inner experiences. It is therefore understandable why Ayahuasca was culturally selected over many centuries by rain forest shamans to facilitate mystical revelations of visual nature.

de Aurojo, D. B., Ribeiro, S., Cecchi, G. A., Carvalho, F. M., Sanchez, T. A., Pinto, J. P., … Santos, A. C. (2011). Seeing with the eyes shut: Neural basis of enhanced imagery following ayahuasca ingestion. Human Brain Mapping, 33(11), 2550-2560. http://dx.doi.org/10.1002/hbm.21381
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Reassessing the cultural and psychopharmacological significance of Banisteriopsis caapi: preparation, classification and use among the Piaroa of Southern Venezuela

Recent attention to the monoamine oxidase inhibiting properties of Banisteriopsis caapi‘s harmala alkaloids has precluded a balanced assessment of B. caapi‘s overall significance to indigenous South American societies. Relatively little attention has been paid to the cultural contexts, local meanings and patterns of use of B. caapi among snuff-using societies, such as the Piaroa, who do not prepare decoctions containing N,N-dimethyltryptamine (DMT) admixtures. This article reviews the psychopharmacological literature on B. caapi in light of recent ethnographic work conducted among the Piaroa of southern Venezuela. Piaroa shamans use only B. caapi’s cambium, identify at least five distinct varieties of B. caapi, and emphasise the plant’s importance for heightening empathy. Some Piaroa people also attribute a range of extra-shamanic uses to B. caapi, including as a stimulant and hunting aid. In light of the psychopharmacological complexity of harmala alkaloids, and ethnographic evidence for a wide range of B. caapi uses, future research should reconsider B. caapi‘s cultural heritage and psychopharmacological potential as a stimulant and antidepressant-like substance.

Rodd, R. (2008). Reassessing the cultural and psychopharmacological significance of Banisteriopsis caapi: preparation, classification and use among the Piaroa of Southern Venezuela. Journal of psychoactive drugs, 40(3), 301-307. 10.1080/02791072.2008.10400645
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Phytochemical analyses of Banisteriopsis caapi and Psychotria viridis

A total of 32 Banisteriopsis caapi samples and 36 samples of Psychotria viridis were carefully collected from different plants on the same day from 22 sites throughout Brazil for phytochemical analyses. A broad range in alkaloid distribution was observed in both sample sets. All B. caapi samples had detectable amounts of harmine, harmaline and tetrahydroharmine (THH), while some samples of P. viridis had little or no detectable levels of N,N-dimethyltryptamine (DMT). Leaves of P. viridis were also collected from one plant and analyzed for DMT throughout a 24-hour cycle.

Callaway, J. C., Brito, G. S., & Neves, E. S. (2005). Phytochemical analyses of Banisteriopsis caapi and Psychotria viridis. Journal of psychoactive drugs, 37(2), 145-150. 10.1080/02791072.2005.10399795
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Bringing Ayahuasca to the Clinical Research Laboratory

Since the winter of 1999, the authors and their research team have been conducting clinical studies involving the administration of ayahuasca to healthy volunteers. The rationale for conducting this kind of research is twofold. First, the growing interest of many individuals for traditional indigenous practices involving the ingestion of natural psychotropic drugs such as ayahuasca demands the systematic study of their pharmacological profiles in the target species, i.e., human beings. The complex nature of ayahuasca brews combining a large number of pharmacologically active compounds requires that research be carried out to establish the safety and overall pharmacological profile of these products. Second, the authors believe that the study of psychedelics in general calls for renewed attention. Although the molecular and electrophysiological level effects of these drugs are relatively well characterized, current knowledge of the mechanisms by which these compounds modify the higher order cognitive processes in the way they do is still incomplete, to say the least. The present article describes the development of the research effort carried out at the Autonomous University of Barcelona, commenting on several methodological aspects and reviewing the basic clinical findings. It also describes the research currently underway in our laboratory, and briefly comments on two new studies we plan to undertake in order to further our knowledge of the pharmacology of ayahuasca.

Riba, J., & Barbanoj, M. J. (2005). Bringing ayahuasca to the clinical research laboratory. Journal of Psychoactive Drugs, 37(2), 219-230. 10.1080/02791072.2005.10399804
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