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Increased frontal and paralimbic activation following ayahuasca, the pan-amazonian inebriant

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Abstract

Rationale

Ayahuasca is a South American psychoactive plant tea which contains the serotonergic psychedelic N,N-dimethyltryptamine (DMT) and monoamine-oxidase inhibitors that render DMT orally active. Previous investigations with ayahuasca have highlighted a psychotropic effect profile characterized by enhanced introspective attention, with individuals reporting altered somatic perceptions and intense emotional modifications, frequently accompanied by visual imagery. Despite recent advances in the study of ayahuasca pharmacology, the neural correlates of acute ayahuasca intoxication remain largely unknown.

Objectives

To investigate the effects of ayahuasca administration on regional cerebral blood flow.

Methods

Fifteen male volunteers with prior experience in the use of psychedelics received a single oral dose of encapsulated freeze-dried ayahuasca equivalent to 1.0 mg DMT/kg body weight and a placebo in a randomized double-blind clinical trial. Regional cerebral blood flow was measured 100–110 min after drug administration by means of single photon emission tomography (SPECT).

Results

Ayahuasca administration led to significant activation of frontal and paralimbic brain regions. Increased blood perfusion was observed bilaterally in the anterior insula, with greater intensity in the right hemisphere, and in the anterior cingulate/frontomedial cortex of the right hemisphere, areas previously implicated in somatic awareness, subjective feeling states, and emotional arousal. Additional increases were observed in the left amygdala/parahippocampal gyrus, a structure also involved in emotional arousal.

Conclusions

The present results suggest that ayahuasca interacts with neural systems that are central to interoception and emotional processing and point to a modulatory role of serotonergic neurotransmission in these processes.

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References

  • Anonymous (2000) Ayahuasca: from the Amazon to the urban jungles. In: The world geopolitics of drugs 1998/1999. Observatoire géopolitique des drogues, Paris, pp 103–107

  • Buckholtz NS, Boggan WO (1977) Monoamine oxidase inhibition in brain and liver produced by beta-carbolines: structure–activity relationships and substrate specificity. Biochem Pharmacol 26:1991–1996

    Article  CAS  PubMed  Google Scholar 

  • Callaway JC, Airaksinen MM, McKenna DJ, Brito GS, Grob CS (1994) Platelet serotonin uptake sites increased in drinkers of ayahuasca. Psychopharmacology (Berl) 116:385–387

    Article  CAS  Google Scholar 

  • Callaway JC, McKenna DJ, Grob CS, Brito GS, Raymon LP, Poland RE, Andrade EN, Andrade EO, Mash DC (1999) Pharmacokinetics of Hoasca alkaloids in healthy humans. J Ethnopharmacol 65:243–256

    Article  CAS  PubMed  Google Scholar 

  • Check E (2004) Psychedelic drugs: the ups and downs of ecstasy. Nature 429:126–128

    Article  CAS  PubMed  Google Scholar 

  • Craig AD (2002) How do you feel? Interoception: the sense of the physiological condition of the body. Nat Rev Neurosci 3:655–666

    CAS  PubMed  Google Scholar 

  • Craig AD (2003) Interoception: the sense of the physiological condition of the body. Curr Opin Neurobiol 13:500–505

    Article  CAS  PubMed  Google Scholar 

  • Critchley HD, Wiens S, Rotshtein P, Ohman A, Dolan RJ (2004) Neural systems supporting interoceptive awareness. Nat Neurosci 7:189–195

    Article  CAS  PubMed  Google Scholar 

  • Damasio AR (2003) Looking for Spinoza: joy, sorrow, and the feeling brain. Harcourt, Orlando, FL

    Google Scholar 

  • Damasio AR, Grabowski TJ, Bechara A, Damasio H, Ponto LL, Parvizi J, Hichwa RD (2000) Subcortical and cortical brain activity during the feeling of self-generated emotions. Nat Neurosci 3:1049–1056

    Article  CAS  PubMed  Google Scholar 

  • Devinsky O, Morrell MJ, Vogt BA (1995) Contributions of anterior cingulate cortex to behaviour. Brain 118:279–306

    Article  PubMed  Google Scholar 

  • Dobkin de Rios M (1984) Visionary vine: hallucinogenic healing in the Peruvian Amazon. Waveland, Prospect Heights, IL

    Google Scholar 

  • Gouzoulis-Mayfrank E, Schreckenberger M, Sabri O, Arning C, Thelen B, Spitzer M, Kovar KA, Hermle L, Büll U, Sass H (1999) Neurometabolic effects of psilocybin, 3,4-methylenedioxyethylamphetamine (MDE) and d-methamphetamine in healthy volunteers. A double-blind, placebo-controlled PET study with [18F]FDG. Neuropsychopharmacology 20:565–581

    Article  CAS  PubMed  Google Scholar 

  • Greenhouse L (2005) Supreme court to hear case of dispute over religious group’s use of banned drug. The New York Times (April 19), p 15

  • Grob CS, McKenna DJ, Callaway JC, Brito GS, Neves ES, Oberlaender G, Saide OL, Labigalini E, Tacla C, Miranda CT, Strassman RJ, Boone KB (1996) Human psychopharmacology of hoasca, a plant hallucinogen used in ritual context in Brazil. J Nerv Ment Dis 184:86–94

    Article  CAS  PubMed  Google Scholar 

  • Halpern JH (2004) Hallucinogens and dissociative agents naturally growing in the United States. Pharmacol Ther 102:131–138

    Article  CAS  PubMed  Google Scholar 

  • Hamann S (2003) Nosing in on the emotional brain. Nat Neurosci 6:106–108

    Article  CAS  PubMed  Google Scholar 

  • Hermle L, Fünfgeld M, Oepen G, Botsch H, Borchardt D, Gouzoulis E, Fehrenbach RA, Spitzer M (1992) Mescaline-induced psychopathological, neuropsychological, and neurometabolic effects in normal subjects: experimental psychosis as a tool for psychiatric research. Biol Psychiatry 32:976–991

    Article  CAS  PubMed  Google Scholar 

  • Kotler S (2005) Psychedelics in rehab. Psychology Today (Mar/Apr)

  • Labate B, Araújo W (2002) O Uso Ritual da Ayahuasca. Mercado de Letras, Sao Paulo

    Google Scholar 

  • Lamas X, Farré M, Llorente M, Camí J (1994) Spanish version of the 49-item short form of the Addiction Research Center Inventory. Drug Alcohol Depend 35:203–209

    Article  CAS  PubMed  Google Scholar 

  • Lazar SW, Kerr CE, Wasserman RH, Gray JR, Greve DN, Treadway MT, McGarvey M, Quinn BT, Dusek JA, Benson H, Rauch SL, Moore CI, Fischl B (2005) Meditation experience is associated with increased cortical thickness. Neuroreport 16:1893–1897

    Article  PubMed  Google Scholar 

  • Martin WR, Sloan JW, Sapira JD, Jasinski DR (1971) Physiologic, subjective, and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazine, and methylphenidate in man. Clin Pharmacol Ther 12:245–258

    CAS  PubMed  Google Scholar 

  • McKenna DJ (2004) Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges. Pharmacol Ther 102:111–129

    Article  CAS  PubMed  Google Scholar 

  • McKenna DJ, Towers GH, Abbott F (1984) Monoamine oxidase inhibitors in South American hallucinogenic plants: tryptamine and beta-carboline constituents of ayahuasca. J Ethnopharmacol 10:195–223

    Article  CAS  PubMed  Google Scholar 

  • McKenna DJ, Repke DB, Lo L, Peroutka SJ (1990) Differential interactions of indolealkylamines with 5-hydroxytryptamine receptor subtypes. Neuropharmacology 29:193–198

    Article  CAS  PubMed  Google Scholar 

  • Melton L (2004) Dream drug or demon brew. New Sci 182(2453):42–43

    Google Scholar 

  • Paus T (2001) Primate anterior cingulate cortex: where motor control, drive and cognition interface. Nat Rev Neurosci 2:417–424

    Article  CAS  PubMed  Google Scholar 

  • Phan KL, Wager T, Taylor SF, Liberzon I (2002) Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI. Neuroimage 16:331–348

    Article  PubMed  Google Scholar 

  • Pierce PA, Peroutka SJ (1989) Hallucinogenic drug interactions with neurotransmitter receptor binding sites in human cortex. Psychopharmacology (Berl) 97:118–122

    Article  CAS  Google Scholar 

  • Rabin RA, Regina M, Doat M, Winter JC (2002) 5-HT2A receptor-stimulated phosphoinositide hydrolysis in the stimulus effects of hallucinogens. Pharmacol Biochem Behav 72:29–37

    Article  CAS  PubMed  Google Scholar 

  • Reichel-Dolmatoff G (1990) The cultural context of an aboriginal hallucinogen: Banisteriopsis caapi. In: Furst P (ed) Flesh of the Gods: the ritual use of hallucinogens. Waveland, Prospect Heights, IL, pp 84–113

    Google Scholar 

  • Reiman EM, Lane RD, Ahern GL, Schwartz GE, Davidson RJ, Friston KJ, Yun LS, Chen K (1997) Neuroanatomical correlates of externally and internally generated human emotion. Am J Psychiatry 154:918–925

    CAS  PubMed  Google Scholar 

  • Riba J, Rodriguez-Fornells A, Strassman RJ, Barbanoj MJ (2001a) Psychometric assessment of the hallucinogen rating scale. Drug Alcohol Depend 62:215–223

    Article  CAS  PubMed  Google Scholar 

  • Riba J, Rodriguez-Fornells A, Urbano G, Morte A, Antonijoan R, Montero M, Callaway JC, Barbanoj MJ (2001b) Subjective effects and tolerability of the South American psychoactive beverage Ayahuasca in healthy volunteers. Psychopharmacology (Berl) 154:85–95

    Article  CAS  Google Scholar 

  • Riba J, Valle M, Urbano G, Yritia M, Morte A, Barbanoj MJ (2003) Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics. J Pharmacol Exp Ther 306:73–83

    Article  CAS  PubMed  Google Scholar 

  • Salak K (2004) The vision seekers. The New York Times (September 12)

  • Schultes RE, Hofmann A (1980) The botany and chemistry of hallucinogens. Thomas, Springfield, IL

    Google Scholar 

  • Schultes RE, Hofmann A (1987) Plants of the gods: origins of hallucinogenic use. A. van der Marck Editions, New York

    Google Scholar 

  • Spruce R (1908) Notes of a botanist on the Amazon and Andes. Macmillan, London

    Google Scholar 

  • Strassman RJ, Qualls CR (1994) Dose–response study of N,N-dimethyltryptamine in humans. I. Neuroendocrine, autonomic and cardiovascular effects. Arch Gen Psychiatry 51:85–97

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Titeler M, Lyon RA, Glennon RA (1988) Radioligand binding evidence implicates the brain 5-HT2 receptor as a site of action for LSD and phenylisopropylamine hallucinogens. Psychopharmacology (Berl) 94:213–216

    Article  CAS  Google Scholar 

  • Villavicencio M (1858) Geografía de la República del Ecudador. Craighead, New York

    Google Scholar 

  • Vollenweider FX, Leenders KL, Øye I, Hell D, Angst J (1997) Differential psychopathology and patterns of cerebral glucose utilisation produced by (S)- and (R)-ketamine in healthy volunteers using positron emission tomography (PET). Eur Neuropsychopharmacol 7:25–38

    Article  CAS  PubMed  Google Scholar 

  • Vollenweider FX, Vollenweider-Scherpenhuyzen MF, Babler A, Vogel H, Hell D (1998) Psilocybin induces schizophrenia-like psychosis in humans via serotonin-2 agonist action. Neuroreport 9:3897–3902

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by grant SAF 2002-02746 from the Spanish Ministry of Education and Science and a private donation by Richard Wolfe.

We wish to thank Araceli Cabrero, Sylvie Cotxet, David Martínez, and Llúcia Benito for their help in data collection. The experiment reported in the present article complies with the Spanish law.

Author information

Author notes

  1. Jordi Riba

    Present address: Department of Neuropsychology, Otto-von-Guericke University, Magdeburg, Germany

Authors and Affiliations

  1. Centre d’Investigació de Medicaments, Institut de Recerca, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, St. Antoni Maria Claret, 167, Barcelona, 08025, Spain

    Jordi Riba, Sergio Romero, Eva Grasa & Manel J. Barbanoj

  2. Departament de Farmacologia i Terapèutica, Universitat Autònoma de Barcelona, Barcelona, Spain

    Jordi Riba, Sergio Romero, Eva Grasa & Manel J. Barbanoj

  3. Servei de Medicina Nuclear, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    Esther Mena & Ignasi Carrió

  4. Departament ESAII, Centre de Recerca en Enginyeria Biomèdica, Universitat Politècnica de Catalunya (UPC), Barcelona, Spain

    Sergio Romero

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  1. Jordi Riba
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  2. Sergio Romero
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  6. Manel J. Barbanoj
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Corresponding author

Correspondence to Jordi Riba.

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Riba, J., Romero, S., Grasa, E. et al. Increased frontal and paralimbic activation following ayahuasca, the pan-amazonian inebriant. Psychopharmacology 186, 93–98 (2006). https://doi.org/10.1007/s00213-006-0358-7

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  • DOI: https://doi.org/10.1007/s00213-006-0358-7

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