ayahuasca

Review Article

THE PHARMACOLOGY OF AYAHUASCA: A REVIEW Rafael Guimarães dos Santos*

ABSTRACT Ayahuasca is an Amazonian psychoactive, hallucinogenic brew used by indigenous and non-indigenous groups for magical, ritual, religious, therapeutic and political goals. The objective of this review is to describe the main pharmacological properties of ayahuasca. The potential benefits and risks of ayahuasca consumption will also be reviewed. Key words. Psychotropic drugs; hallucinogens; banisteriopsis; psychotria; pharmacology.

RESUMO A FARMACOLOGIA DA AYAHUASCA: UMA REVISÃO Ayahuasca é uma bebida psicoativa, alucinógena, utilizada por grupos indígenas e não-indígenas com objetivos mágicos, rituais, religiosos, terapêuticos e políticos. O objetivo desta revisão é o de descrever as principais propriedades farmacológicas da ayahuasca. Os potenciais benefícios e riscos do consumo da ayahuasca também serão abordados. Palavras-chave. Drogas psicotrópicas; alucinógenos; banisteriopsis; psychotria; farmacologia.

INTRODUCTION

T

he Quechua word ayahuasca combines the words aya, meaning “soul” or “dead spirit”, and waska, meaning “rope” or “vine”, and, so, could be translated as “vine of the souls”.1-3 In general terms, ayahuasca can be explained as being a psychoactive, hallucinogenic preparation, made with Amazonian plants and used originally in this region of the world by indigenous populations.1-3 Ayahuasca is usually consumed in the form of a brew, made with the vine Banisteriopsis caapi as the main ingredient, although there are many admixture plants that can be prepared together with the vine.1-3 Psychotria viridis is one of the main admixture plants used to prepare ayahuasca, especially, but not only, in Brazil.1-5 There are numerous indigenous and mestizo populations in Brazil, Colombia, Peru, and other Amazonian locations, that use ayahuasca ritually, for magical, religious, medicinal, and other social and

political objectives.1-3,5 The indigenous people of this part of the world have been using ayahuasca preparations for centuries, and this brew is a integral part of the cosmology of these people, being present in the most important moments of their lives, like birth, the passage to adulthood, disease, and death.1-3,5 In Brazil, after the encounter of Brazilian rubber workers with indigenous/mestizo uses of ayahuasca in the borders between Brazil, Peru, and Bolivia, syncretic churches that use ayahuasca as a religious sacrament developed. In the 1930’s, 1940’s, and 1960’s, respectively, the Santo Daime, the Barquinha, and the União do Vegetal, were created. The Santo Daime and the Barquinha were created in Rio Branco, in the Acre State, and the União do Vegetal was created in Porto Velho, in the Rondônia State. CEFLURIS (Centro Eclético de Fluente Luz Universal Raimundo Irineu Serra) is a Santo Daime group created in the 1970’s after the death of the Santo Daime creator, Raimundo Irineu Serra. This group was also created in Rio Branco, Acre.4

* Ph.D. candidate in Pharmacology at the Universitat Autònoma de Barcelona, Spain, and researcher of NEIP (Interdisciplinary Group for Psychoactive Studies), Brazil. Correspondence: Calle St. Antoni Maria Claret, 46, principal, 1a, Barcelona 08025, Spain. Tel.: +34 666379980. E-mail address: [email protected] Received on May 14, 2010. Accepted on June 2, 2010.

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The pharmacology of ayhuasca

The cosmology of these groups is composed by influences from Christianity, the European Esoteric ideas, the Afro-Brazilian religious manifestations, and the indigenous shamanism. In the 1970’s and 1980’s, some of these groups started to move from the Amazon to the urban centers of the Brazilian cities like São Paulo, Rio de Janeiro and Brasília. In the 1990’s, these groups started to spread to other countries. Today, some groups of the CEFLURIS or from the União do Vegetal can be found in North America, Europe, Asia and Africa.4 Nevertheless, only in some countries, like in Brazil, in the Netherlands, and in some States of the United Sates, a legal status for the use of ayahuasca by these groups has been stablished.4 There are also other more recent uses of ayahuasca, like the ones that associate ayahuasca religious rituals with various kinds of psychotherapy or oriental religions and disciplines,6 or the use of ayahuasca that is characterized by the visit to Amazonian countries of people from North America, Europe, and other parts of the world to do spiritual, existential, or healing rituals with ayahuasca.7 The use of ayahuasca analogues, in the form of combining plants with the same ayahuasca chemicals, also called anahuasca, or the pure, synthetic substances, also called pharmahuasca, has also been described.8

AIMS OF THE REVIEW

As the use of ayahuasca preparations is actually present in many parts of the world, it is important to know as many information as possible regarding these preparations. In the present work, the main pharmacological aspects of ayahuasca will be exposed. The pharmacological aspects of Banisteriopsis caapi and Psychotria viridis will be explored before describing ayahuasca in its full composition. In the present review, the main information will be about these plants and the ayahuasca made only with these plants. This decision was made because the ayahuasca consumed in the Brazilian ayahuasca religions is made with these plants,4 and most of the scientific literature regarding human studies were made with members of these groups, or with ayahuasca used by these groups.

THE PHARMACOLOGY OF AYAHUASCA

Banisteriopsis caapi (mariri, jagube) The main substances found in Banisteriopsis caapi are the β-carbolines harmine and tetrahydroharmine,

and to a lesser extent harmaline, harmol and harmalol, plus other substances.8-10 The main pharmacological effect of these substances in ayahuasca preparations is their capacity to inhibit the enzyme monoamine oxidase (MAO).8,9,11,12 Harmine, tetrahydroharmine, and harmaline are potent natural, selective, reversible, competitive inhibitors of MAO, especially MAO-A, the form of the enzyme for which norepinephrine, serotonin, and presumably other tryptamines including dimethyltryptamine (DMT, see below) are the preferred substrates.9,11,13-15 Ayahuasca was found to be an extremely effective inhibitor of MAO in vitro and the degree of inhibition was directly correlated with the concentration of MAO-inhibiting β-carbolines.13 There is also evidence that tetrahydroharmine acts as a selective inhibitor of serotonin reuptake as well as a MAO inhibitor.9 One study16 showed that before membership in an ayahuasca religion, some of the participants were diagnosed as having previously been afflicted with major depressive disorders and phobic anxiety disorders, psychiatric diagnoses that remitted following entry into the ayahuasca religion. In this context, it is interesting to mention that there is now some evidence from animal and also from human research that harmine, harmaline, and ayahuasca have or antidepressive or anxiolytic potentials.16-24 In the 1920’s and early 1930’s, harmine, then called banisterine, was used in animals and patients with symptoms similar to Parkinson disease.25 Interest in harmine died quickly, but recently, reports have described the potential use of this compound on Parkinson’s disease.26 In particular, there is a double-blind, randomized, placebo-controlled trial which demonstrated that extracts prepared from the Banisteriopsis vine improved motor function in Parkinson’s patients.27 Nevertheless, because of the serotonin agonist properties of these β-carbolines, the use of ayahuasca is not recommended to people who are under treatment with pro-serotoninergic chemicals, especially antidepressives, because of the risk of the serotonin syndrome.28 Psychotria viridis (rainha, chacrona) The main substance present in Psychotria viridis is the tryptamine dimethyltryptamine, or simply DMT.8-11 The pharmacological literature indicates that the main psychopharmacological effect of DMT in ayahuasca preparations is the production of the hallucinogenic effects, by acting at the 5-HT2A receptors.8,9,12 Brasília Med 2010;47(2):188-195

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Some studies described the human psychopharmacology of synthetic DMT, administered by the intramuscular or intravenous route.29-34 These investigations postulated that the subjective effects of DMT were qualitatively similar to those elicited by classic hallucinogens, like mescaline and LSD-25. These studies also showed that DMT administration produced temporary increases in levels of prolactin, growth hormone, cortisol, β-endorphin, corticotrophin, adrenocorticotropic hormone (ACTH), and in blood pressure, heart rate, pupillary diameter and rectal temperature, although this last variable failed to increase in a subsequent study. One of these studies did not found tolerance to the subjective effects or blood pressure increases after a dosing regime involving four doses of intravenous DMT administered at 30 minutes intervals, whereas neuroendocrine responses, such as adrenocorticotropic hormone, prolactin and cortisol levels, and heart rate, decreased from the first to the fourth administered dose. There are also more recent studies with synthetic DMT.35-39 These studies showed that DMT slowed down reaction times, produced disturbances of attention, and impaired information processing. Nevertheless, as the human pharmacology of DMT administered in all these studies previously commented deals with the synthetic form of the substance administered by the intramuscular or intravenous route, it must be considered that the effects of DMT might be pharmacologically different as they are when the substance is being administered in the natural form, orally, and together with β-carbolines. For these reasons, ayahuasca must be studied in its complete composition. Ayahuasca (daime, vegetal, hoasca) As said before, ayahuasca is composed mainly of the β-carbolines harmine and tetrahydroharmine and the tryptamine DMT.9,40 DMT does not produce psychoactive effects when taken orally, but when it is combined with the β-carbolines present in ayahuasca, that inhibit the MAO enzyme, DMT reaches systemic circulation and the central nervous system in sufficient amounts to induce psychotropic effects.9,11,41,42 Previous reviews have been published about the pharmacology of ayahuasca.9,11,41,42 So, only the main pharmacological data provided by studies done with humans will be presented here. The Hoasca Project One of the main studies done with ayahuasca

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Brazilian consumers was the Hoasca Project. Hoasca is one of the names that the members of the União do Vegetal use to name ayahuasca.4 They also name ayahuasca as vegetal.4 The Hoasca Project showed that 15 adult members of the União do Vegetal, which were members of this religion for at least 10 years, participating in church rituals utilizing ayahuasca a minimum of twice monthly, but often as frequently as several times per week, had a normal physical, psychological, neuropsychological, and psychiatric health when compared to a control group.16,43 In fact, this study showed that the ayahuasca users performed significantly better than control subjects on one of the memory tests. Also according to the study, previous cases by these members of drug abuse disorders, major depressive disorders, phobic anxiety disorders, and histories of violent behavior associated with binge drinking, had all remitted following entry into the ayahuasca religion. The Hoasca Project also found a significant upregulation in the density of the serotonin transporter in blood platelets of the ayahuasca drinkers compared to the control group,44 which could explain some of the potential therapeutic effects, according to some researchers.11,45 Other findings of the study were that after the consumption of ayahuasca, the authors described temporary increases in pupillary diameter, respiration rate, oral temperature, heart rate, blood pressure, and on plasma levels of prolactin, cortisol, and growth hormone.46 These researchers also reported that regarding the subjective effects, the duration of psychoactivity from ayahuasca was coincidental with alkaloid plasma levels. The study about the adolescents from the União do Vegetal Other group of studies was also done with members of the União do Vegetal, but the ayahuasca and control groups were adolescents in these studies. 40 adolescents from three different cities in Brazil that have been consuming ayahuasca in a regular basis in the União do Vegetal ceremonies were compared to a control group and evaluated for psychiatric and mental status, neuropsychology, and psychoactive consumption.47-49 Many of these adolescents have been consuming ayahuasca since they were in their mother’s womb, or when they were children. The study found that the ayahuasca using group was normal in all measures. In fact, it was found that


the ayahuasca consuming group showed considerable lower frequencies of positive scoring for anxiety, self image, and attentional problems. The study about the Brazilian CEFLURIS members Within the Brazilian Santo Daime context, one study evaluated personality, general health, neuropsychological functions, psychosocial wellbeing, purpose of life, and spirituality among 68 members of CEFLURIS compared to 63 control subjects.50 The participants have frequently participated in the church rituals for at least 15 years. Eight months later, the same tests were administered with the objective of assessing the stability of the results. According to the results, the long-term consumers of ayahuasca did not present any problems. In fact, they presented better results regarding their sociofamilial environment, satisfaction with the general conditions of life, on measures of psychopathology, on tests of temperament and character, on the neuropsychological tests, and on the tests of psychological well-being, spirituality, and purpose of life. The study about the North American CEFLURIS members Another group did a research with 32 (out of 40) North American members of one branch of the Santo Daime church, where the participants usually attended the religious rituals weekly (lifetime 269 ± 314.7 ceremonies; range 20-1300).51 Neurology-focused physical exam and psychological test scores revealed healthy subjects. Many subjects argued that church participation was positive for them. Participants presented lower rates of symptomatology, lower overall complains, and lower intensity and severity of complains than the general population. Most side-effects were temporal to ayahuasca ingestion, manageable, and rarely persisted beyond a day or two. Studies about the subacute and chronic effects of ayahuasca in people who consumed the brew for the first time in their lives Some studies investigated the short-term psychological and psychiatric after-effects induced by the first time use of ayahuasca in the rituals of União do Vegetal and CEFLURIS in an urban context in Brazil.52,53 They analyzed 28 subjects one to four days before their first ayahuasca experience and one to two weeks after this experience.

In the CEFLURIS group, it was observed a significant reduction in the intensity of minor psychiatric symptoms in the week after the ayahuasca experience. In the follow-up study,54 the authors assessed 23 subjects immediately before and six months after their first ayahuasca experience. Subjects had a significant reduction of minor psychiatric symptoms, improvement of mental health, and a change in attitude towards more confidence and optimism. The group also had a significant decrease in physical pain, and attitude change towards more independence. Clinical studies about the acute effects of ayahuasca In the last decade, clinical trials have been done in Barcelona, Spain, by the team of Dr. Jordi Riba and Dr. Manel Barbanoj, about the human pharmacology of ayahuasca, using the brew as encapsulated freezedried ayahuasca.9,12,41,55-62 The ayahuasca was donated by CEFLURIS.41 These studies have addressed the tolerability, subjective effects, pharmacokinetics, electrophysiological effects, cerebral blood flow effects and sleep effects of ayahuasca following its administration in single doses to healthy volunteers, using placebo-controlled and single- and double-blind protocols. These studies showed that the psychological effects produced by ayahuasca were first noted after 30-60 minutes, peaked between 60-120 minutes, and were resolved by 240 minutes. Moderate increases were observed in systolic blood pressure, diastolic blood pressure and heart rate, so the authors concluded that ayahuasca poses only a moderate risk from the cardiovascular point of view when administered to healthy volunteers. The laboratory analyses conducted after ayahuasca sessions did not find any clinically relevant alterations in hematological indices or biochemical indicators of liver function or other standard analytical parameters (cellular counting, plasmatic bilirubin, and hepatic enzymes). The results also showed that ayahuasca induces significant and dose-dependent modifications of brain electrical activity, studied by means of topographic quantitative-pharmaco-electroencephalography (q-EEG). Absolute power decreased in all frequency bands, most prominently in the theta band, and relative power decreased in the delta and theta bands, and increased in the beta band. These modifications were similar to those previously described for other serotonergic hallucinogens and also to the effects shown by pro-serotonergic and pro-dopaminergic drugs. Brasília Med 2010;47(2):188-195

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The acute administration of ayahuasca was also assessed by means of low-resolution electromagnetic tomography (LORETA). This analysis showed that ayahuasca decreased power density predominantly over the temporo-parieto-occipital junction, temporomedial cortex and in frontomedial regions. These areas play relevant roles in the neurobiology of attention, emotion and memory. When investigating the changes in blood flow following acute ayahuasca administration by means of single photon emission tomography (SPECT), ayahuasca produced activation of frontal and paralimbic brain regions, in areas implicated in somatic awareness, subjective feeling states, and emotional arousal. Ayahuasca also produced significant dose-dependent reductions of P50 suppression, indicating a decremental effect on sensory gating. Nevertheless, there was no significant effects on the prepulse inhibition of the startle reflex (PPI), indicating no distinct effects of ayahuasca on sensorimotor gating. Finally, daytime administration of ayahuasca did not induce any subjectively perceived deterioration of sleep quality or polysomnography-measured disruptions of sleep initiation or maintenance, in contrast with d-amphetamine. Polysomnography analysis also showed that, similarly to d-amphetamine, ayahuasca inhibits REM sleep, decreasing its duration. Also, slow-wave sleep (SWS) power was enhanced by ayahuasca, in contrast with d-amphetamine. Acute effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in CEFLURIS members In this study,20 standard questionnaires were used to evaluate state-anxiety, trait-anxiety, paniclike and hopelessness in 9 CEFLURIS members that ingested ayahuasca for at least 10 consecutive years. Questionnaires were administered 1 hour after ayahuasca ingestion, in a double-blind, placebo-controlled procedure. The study showed that under the acute effects of ayahuasca participants scored lower on the scales for panic and hopelessness related states. Ayahuasca ingestion did not modify state- or trait-anxiety. Once again, it is important to remember that there are increasing data suggesting antidepressive or anxiolytic potentials of ayahuasca or of some of its compounds.16-19,21-24 In fact, Brazilian researches are planning to study the potential antidepressive effects of ayahuasca in humans.21

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Of course, much work must be done to better characterize these potentials.

FINAL CONSIDERATIONS

Ayahuasca is a psychoactive, hallucinogenic preparation rich in β-carbolines and DMT. Studies of acute administration of ayahuasca support the opinion that the use of this brew, in controlled settings, by healthy individuals, is safe. Studies of the longterm ritual consumption of the beverage do not point to any mental or physical health problems in adolescents or in adults. The frequency of psychopathology in these groups seems to be low, and ayahuasca does not appear to be a toxic preparation.63,64 It is also important to acknowledge that the Brazilian government has recently reaffirmed the legitimacy of the religious use of ayahuasca in the country, and also suggested future investigations about the therapeutic potentials of ayahuasca.65 Nevertheless, and despite the possible therapeutic uses of ayahuasca, like for the treatment of substance dependence,66-68 ayahuasca has its own risks. As said before, the use of pro-serotoninergic compounds, especially antidepressives, are not indicated to be consumed with ayahuasca.28 Foods with high tyramine content are also not recommended, because of the risk of hypertension.42 People with cardiac dysfunctions should also be careful, since the cardiovascular effects of the brew, although moderate, were investigated only in healthy volunteers. Finally, persons with some predisposition to psychotic disorders may be at risk to develop psychotic episodes with the brew.69

Disclosure

No potential conflict of interest relevant to this article was reported.

REFERENCES 1. Schultes RE. El desarrollo histórico de la identificación de las malpigiáceas empleadas como alucinógenos. América Indígena. 1986;46:9-47. 2. Schultes RE, Hofmann A. Plants of the gods: their sacred, healing, and hallucinogenic powers. Rochester, Vermont: Healing Arts Press; 1992. 3. Schultes RE, Raffauf RF. Vine of the soul: Medicine men, their plants and rituals in the Colombian Amazonia. 2nd ed. New Mexico: Synergetic Press; 2004.


4. Labate BC, Rose IS, Santos RG. Ayahuasca Religions: a comprehensive bibliography and critical essays. Santa Cruz: Multidisciplinary Association for Psychedelic Studies – MAPS; 2008. 5. Dobkin de Rios M. Visionary vine: hallucinogenic healing in the Peruvian Amazon. Illinois: Waveland Press, Inc.; 1972. 6. Labate BC. A reinvenção do uso da ayahuasca nos centros urbanos. Campinas, São Paulo: Mercado de Letras; 2004. 7. Winkelman M. Drug tourism or spiritual healing? Ayahuasca seekers in Amazonia. J Psychoactive Drugs. 2005;37:209-18. 8. Ott J. Ayahuasca Analogues: Pangaean Entheogens. Kennewick, WA: Natural Books Co.; 1994. 9. Riba J. Human Pharmacology of Ayahuasca [Doctoral Thesis]: Universitat Autònoma de Barcelona: Universitat Autònoma de Barcelona; 2003. 10. Callaway JC, Brito GS, Neves ES. Phytochemical analyses of Banisteriopsis caapi and Psychotria viridis. J Psychoactive Drugs. 2005;37:145-50. 11. McKenna DJ, Callaway JC, Grob CS. The scientific investigation of Ayahuasca: a review of past and current research. The Heffter Review of Psychedelic Research. 1998;1:65-77. 12. Riba J, Valle M, Urbano G, Yritia M, Morte A, Barbanoj MJ. Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics. J Pharmacol Exp Ther. 2003;306:73-83. 13. McKenna DJ, Towers GHN, Abbott F. Monoamine oxidase inhibitors in South American hallucinogenic plants: tryptamine and β-carboline constituents of Ayahuasca. J Ethnopharmacol. 1984;10:195-223. 14. Samoylenko V, Rahman MM, Tekwani BL, Tripathi LM, Wang YH, Khan SI, et al. Banisteriopsis caapi, a unique combination of MAO inhibitory and antioxidative constituents for the activities relevant to neurodegenerative disorders and Parkinson’s disease. J Ethnopharmacol. 2010;127:357-67. 15. Wang YH, Samoylenko V, Tekwani BL, Khan IA, Miller LS, Chaurasiya ND, et al. Composition, standardization and chemical profiling of Banisteriopsis caapi, a plant for the treatment of neurodegenerative disorders relevant to Parkinson’s disease. J Ethnopharmacol. 2010;128:662-71.

18. Farzin D, Mansouri N. Antidepressant-like effect of harmane and other β-carbolines in the mouse forced swim test. Eur Neuropsychopharmacol. 2006;16:324-8. 19. Lima LM, Ferreira MS, Ávila AA, Perazzo FF, Schneedorf JM, Carvalho JC. Ayahuasca central nervous system effects: behavioral study. Ärztezeitschrift für Naturheilverfahren. 2006;47:476-80. 20. Santos RG, Landeira-Fernandez J, Strassman RJ, Motta V, Cruz AP. Effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in Santo Daime members. J Ethnopharmacol. 2007;112:507-13. 21. Coizzi J. USP testa “chá do Santo Daime” contra depressão. Folha Online [Internet]. 2008 Nov [cited 2010 Apr 22. Available from: http://www1.folha.uol.com.br/folha/ ciencia/ult306u469235.shtml. 22. Fortunato JJ, Réus GZ, Kirsch TR, Stringari RB, Stertz L, Kapczinski F, et al. Acute harmine administration induces antidepressive-like effects and increases BDNF levels in the rat hippocampus. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33:1425-30. 23. Fortunato JJ, Réus GZ, Kirsch TR, Stringari RB, Fries GR, Kapczinski F, et al. Effects of β-carboline harmine on behavioral and physiological parameters observed in the chronic mild stress model: Further evidence of antidepressant properties. Brain Res Bull. 2010;81:491-6. 24. Wu C, Jiang XL, Shen HW, Yu AM. Effects of CYP2D6 status on harmaline metabolism, pharmacokinetics and pharmacodynamics, and a pharmacogenetics-based pharmacokinetic model. Biochem Pharmacol. 2009;78:617-24. 25. Sanchez-Ramos JR. Banisterine and Parkinson’s disease. Clin Neuropharmacol. 1991;14:391-402. 26. Schwarz MJ, Houghton PJ, Rose S, Jenner P, Lees AD. Activities of extract and constituents of Banisteriopsis caapi relevant to parkinsonism. Pharmacol Biochem Behav. 2003;75:627-33. 27. Serrano-Dueñas M, Cardozo-Pelaez F, Sánchez-Ramos JR. Effects of Banisteriopsis caapi extract on Parkinson’s disease. The Scientific Review of Alternative Medicine. 2001;5:127-32. 28 - Callaway JC, Grob CS. Ayahuasca preparations and serotonin reuptake inhibitors: a potential combination for severe adverse interactions. J Psychoactive Drugs. 1998;30:367-9.

16. Grob CS, McKenna DJ, Callaway JC, Brito GS, Neves ES, Oberlaender G, et al. Human psychopharmacology of hoasca, a plant hallucinogen used in ritual context in Brazil. J Nerv Ment Dis. 1996;184:86-94.

29. Szára S. The comparison of the psychotic effect of tryptamine derivatives with the effects of mescaline and LSD25 in self-experiments. In: Garattini S, Ghetti V, editors. Psychotropic drugs. Amsterdam: Elsevier; 1957. p. 460-7.

17. Hilber P, Chapillon P. Effects of harmaline on anxietyrelated behavior in mice. Physiol Behav. 2005;86:164-7.

30. Szára S. DMT at fifty. Neuropsychopharmacol Hung. 2007;9:201-5.

Brasília Med 2010;47(2):188-195

193


31. Strassman RJ, Qualls CR. Dose-response study of N,Ndimethyltryptamine in humans: I. Neuroendocrine, autonomic, and cardiovascular effects. Arch Gen Psychiatry. 1994;51:85-97.

do chá hoasca por longo prazo e controles; avaliação fisiológica dos efeitos agudos pós–ingestão do chá hoasca). In: Labate BC, Araújo WS, eds. O uso ritual da ayahuasca. 2.ª ed. Campinas: Mercado de Letras; 2004. p. 671-80.

32. Strassman RJ, Qualls CR, Uhlenhuth EH, Kellner R. Dose-response study of N,N-dimethyltryptamine in humans: II. Subjective effects and preliminary results of a new rating scale. Arch Gen Psychiatry. 1994;51:98-108.

44. Callaway JC, Airaksinen MM, McKenna DJ, Brito G, Grob CS. Platelet serotonin uptake sites increased in drinkers of ayahuasca. Psychopharmacology (Berl). 1994;116:385-7.

33. Strassman RJ, Qualls CR, Berg LM. Differential tolerance to biological and subjective effects of four closely spaced doses of N,N-dimethyltryptamine in humans. Biol Psychiatry. 1996;39:784-95. 34. Strassman RJ. Human psychopharmacology of N,Ndimethyltryptamine. Behav Brain Res. 1996;73:121-4. 35. Gouzoulis-Mayfrank E, Heekeren K, Neukirch A, Stoll M, Stock C, Obradovic M, et al. Psychological effects of (S)-Ketamine and N,N-dimethyltryptamine (DMT): A double-blind, cross-over study in healthy volunteers. Pharmacopsychiatry. 2005;38:301-11. 36. Gouzoulis-Mayfrank E, Heekeren K, Neukirch A, Stoll M, Stock C, Daumann J, et al. Inhibition of return in the human 5HT2A agonist and NMDA antagonist model of psychosis. Neuropsychopharmacology. 2006;31:431-41. 37. Daumann J, Heekeren K, Neukirch A, Thiel Cm, MöllerHartmann W, Gouzoulis-Mayfrank E. Pharmacological modulation of the neural basis underlying inhibition of return (IOR) in the human 5-HT2A agonist and NMDA antagonist model of psychosis. Psychopharmacology (Berl) 2008;200:573-83. 38. Heekeren K, Daumann J, Neukirch A, Stock C, Kawohl W, Norra C, et al. Mismatch negativity generation in the human 5HT2A agonist and NMDA antagonist model of psychosis. Psychopharmacology (Berl). 2008;199:77-88. 39. Daumann J, Wagner D, Heekeren K, Neukirch A, Thiel C, Gouzoulis-Mayfrank E. Neuronal correlates of visual and auditory alertness in the DMT and ketamine model of psychosis. J Psychopharmacol. 2009; (in press). 40. Callaway JC. Various alkaloid profiles in decoctions of Banisteriopsis caapi. J Psychoactive Drugs. 2005;37:151-5. 41. Riba J, Barbanoj MJ. Bringing ayahuasca to the clinical research laboratory. J Psychoactive Drugs. 2005;37:219-30. 42. Santos RG. Ayahuasca: neuroquímica e farmacologia. SMAD, Rev. Eletrônica Saúde Mental Álcool Drog. (Ed. port.) [Internet]. 2007 Feb [cited 2010 Apr 22];3: [about 11 p.]. Available from: http://pepsic.bvs-psi.org.br/scielo. php?script=sci_arttext&pid=S1806-69762007000100007&lng =pt&nrm=iso&tlng=pt. 43. Andrade EN, Brito GS, Andrade EO, Neves ES, McKenna D, Cavalcante JW, et al. Farmacologia humana da hoasca: estudos clínicos (avaliação clínica comparativa entre usuários

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Brasília Med 2010;47(2): 188-195

45. McKenna DJ. Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges. Pharmacol Ther. 2004;102:111-29. 46. Callaway JC, McKenna DJ, Grob CS, Brito GS, Raymon LP, Poland RE, et al Pharmacokinetics of Hoasca alkaloids in healthy humans. J Ethnopharmacol. 1999;65:243-56. 47. Da Silveira DX, Grob CS, Dobkin de Rios M, Lopez E, Alonso LK, Tacla C, et al. Ayahuasca in adolescence: a preliminary psychiatric assessment. J Psychoactive Drugs. 2005;37:129-33. 48. Doering-Silveira E, Lopez E, Grob CS, Dobkin de Rios M, Alonso LK, Tacla C, et al. Ayahuasca in adolescence: a neuropsychological assessment. J Psychoactive Drugs. 2005;37:123-8. 49. Doering-Silveira E, Grob CS, Dobkin de Rios M, Lopez E, Alonso LK, Tacla C, et al. Report on psychoactive drug use among adolescents using ayahuasca within a religious context. J Psychoactive Drugs. 2005;37:141-4. 50. Fábregas JM. Long term effects on mental health of ayahuasca ritual use. In: Psychedelic Science in the 21st Century - An International Conference Offering Continuing Medical Education Credits. April 15-18, 2010. San Jose, California, USA. 51. Halpern JH, Sherwood AR, Passie T, Blackwell KC, Ruttenber AJ. Evidence of health and safety in American members of a religion who use a hallucinogenic sacrament. Med Sci Monit. 2008;14:SR15-22. 52. Barbosa PCR, Dalgalarrondo P. O uso ritual de um alucinógeno no contexto urbano: estados alterados de consciência e efeitos em curto prazo induzidos pela primeira experiência com a ayahuasca. J Bras Psiquiatr. 2003;52:181-90. 53. Barbosa PCR, Giglio JS, Dalgalarrondo P. Altered states of consciousness and short-term psychological after-effects induced by the first time ritual use of ayahuasca in an urban context in Brazil. J Psychoactive Drugs. 2005;37:193-201. 54. Barbosa PCR, Cazorla IM, Giglio JS, Strassman R. A six-month prospective evaluation of personality traits, psychiatric symptoms and quality of life in ayahuasca-naïve subjects. J Psychoactive Drugs. 2009;41:205-12. 55. Riba J, Rodriguez-Fornells A, Strassman RJ, Barbanoj MJ. Psychometric assessment of the Hallucinogen Rating Scale. Drug Alcohol Depend. 2001;62:215-23.


56. Riba J, Rodriguez-Fornells A, Urbano G, Morte A, Antonijoan R, Monteiro M, et al. Subjective effects and tolerability of the South American psychoactive beverage Ayahuasca in healthy volunteers. Psychopharmacology (Berl). 2001;154:85-95. 57. Riba J, Anderer P, Morte A, Urbano G, Jane F, Saletu B, et al. Topographic pharmaco-EEG mapping of the effects of the South American beverage ayahuasca in healthy volunteers. Br J Clin Pharmacol. 2002;53:613-28. 58. Riba J, Rodriguez-Fornells A, Barbanoj MJ. Effects of ayahuasca sensory and sensorimotor gating in humans as measured by P50 suppression and prepulse inhibition of the startle reflex, respectively. Psychopharmacology (Berl). 2002;165:18-28. 59. Yritia M, Riba J, Ortuno J, Ramirez A, Castillo A, Alfaro Y, et al. Determination of N,N-dimethyltryptamine and β-carboline alkaloids in human plasma following oral administration of Ayahuasca. J Chromatogr B. 2002;779:271-81. 60. Riba J, Anderer P, Jané F, Saletu B, Barbanoj MJ. Effects of the South American psychoactive beverage Ayahuasca on regional brain electrical activity in humans: a functional neuroimaging study using low-resolution electromagnetic tomography. Neuropsychobiology. 2004;50:89-101. 61. Riba J, Romero S, Grasa E, Mena E, Carrió I, Barbanoj MJ. Increased frontal and paralimbic activation following ayahuasca, the pan-amazonian inebriant. Psychopharmacology (Berl). 2006;186:93-8.

62. Barbanoj MJ, Riba J, Clos S, Giménez S, Grasa E, Romero S. Daytime Ayahuasca administration modulates REM and slow-wave sleep in healthy volunteers. Psychopharmacology (Berl). 2008;196:315-26. 63. Lima F, Naves M, Motta J, Migueli J, Brito G, et cols. Sistema de Monitoramento Psiquiátrico em Usuários do Chá Hoasca. Rev Bras Psiquiatr 2002;24(Suppl 2). [cited 2010 may 16]. Available from: