New World Tryptamine Hallucinogens and the Neuroscience of Ayahuasca
This book chapter (2016) provides an overview of major tryptamine-containing New World hallucinogens with a special focus on ayahuasca, for which the authors propose a model of brain effects in which ayahuasca reduces top-down constraints and facilitates bottom-up information transfer.
Authors
- Jordi Riba
Published
Abstract
New World indigenous peoples are noted for their sophisticated use of psychedelic plants in shamanic and ethnomedical practices. The use of psychedelic plant preparations among New World tribes is far more prevalent than in the Old World. Yet, although these preparations are botanically diverse, almost all are chemically similar in that their active principles are tryptamine derivatives, either DMT or related constituents. Part 1 of this paper provides an ethnopharmacological overview of the major tryptamine-containing New World hallucinogens. Part 2 focuses on ayahuasca and its effects on the human brain. Using complementary neurophysiological and neuroimaging techniques, we have identified brain areas involved in the cognitive effects induced by this complex botanical preparation. Initial SPECT data showed that ayahuasca modulated activity in higher order association areas of the brain. Increased blood perfusion was observed mainly in anterior brain regions encompassing the frontomedial and anterior cingulate cortices of the frontal lobes, and in the medial regions of the temporal lobes. On the other hand, applying spectral analysis and source location techniques to cortical electrical signals, we found changes in neuronal activity that predominated in more posterior sensory-selective areas of the brain. Now, using functional connectivity analysis of brain oscillations we have been able to reconcile these seemingly contradictory findings. By measuring transfer entropy, a metric based on information theory, we have shown that ayahuasca temporarily modifies the ordinary flow of information within the brain. We propose a model in which ayahuasca reduces top-down constraints and facilitates bottom-up information transfer. By simultaneously enhancing endogenous cortical excitability and reducing higher-order cognitive control, ayahuasca temporarily disrupts neural hierarchies allowing inner exploration and a new outlook on reality.
Research Summary of 'New World Tryptamine Hallucinogens and the Neuroscience of Ayahuasca'
Introduction
Halberstadt and colleagues open by framing classic serotonergic hallucinogens as powerful probes of perception, cognition and consciousness. They note three major structural chemotypes that have dominated the literature — tryptamines, ergolines and phenethylamines — and stress that most modern understanding springs from molecular pharmacology that identifies serotonin 5-HT2A receptor agonism as the critical proximal mechanism. The authors emphasise that much early human work was limited, that many compounds remain pharmacologically characterised only in vitro or in animals, and that renewed clinical and neuroscientific interest in the past decades motivates a synthesis of structure–activity relationships (SAR), receptor signalling, and systems neuroscience relevant to human effects and potential therapeutic uses. The chapter sets out to: survey the chemistry and SAR of tryptamine hallucinogens (with comparisons to ergolines and phenethylamines); summarise molecular and cellular receptor pharmacology (including functional selectivity or "biased agonism"); and integrate electrophysiological, neuroimaging and behavioural data on how 5-HT2A agonists perturb cortical and thalamocortical circuitry. The introduction frames the material as an interdisciplinary review with direct relevance to clinical research and to the interpretation of experimental human studies (imaging, psychophysiology and gene-expression work).
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McKenna, D., & Riba, J. (2016). New World Tryptamine Hallucinogens and the Neuroscience of Ayahuasca. Current Topics in Behavioral Neurosciences, 283-311. https://doi.org/10.1007/7854_2016_472
References (129)
Papers cited by this study that are also in Blossom
Bogenschutz, M. P., Forcehimes, A. A., Pommy, J. A. et al. · Journal of Psychopharmacology (2015)
Karst, M., Halpern, J. H., Bernateck, M. et al. · Cephalalgia (2010)
Ray, T. S. · PLOS ONE (2010)
Fantegrossi, W. E., Murnane, K. S., Reissig, C. J. · Biochemical Pharmacology (2007)
Gonza ´lez-Maeso, J., Weisstaub, N. V., Zhou, M. et al. · Neuron (2007)
Green, A. R. · British Journal of Pharmacology (2009)
Halberstadt, A. L. · Behavioural Brain Research (2014)
Hanks, J. B., González-Maeso, J. · ACS Chemical Neuroscience (2012)
Krebs, T. S., Johansen, P. Ø. · Journal of Psychopharmacology (2012)
Moreno, F. A., Wiegand, C. B., Taitano, E. K. et al. · Journal of Clinical Psychiatry (2006)
Show all 129 referencesShow fewer
King, C., Nichols, D. E. · Nature Reviews Neuroscience (2013)
Preller, K. H., Pokorny, D., Hock, A. et al. · PNAS (2016)
Preller, K. H., Herdener, M., Pokorny, T. et al. · Current Biology (2017)
Schmid, Y., Enzler, F., Gasser, P. et al. · Biological Psychiatry (2015)
Sewell, R. A. · Neurology (2006)
Vollenweider, F. X., Vollenweider-Scherpenhuyzen, M. F. I., Bäbler, A. et al. · NeuroReport (1998)
Carhart-Harris, R. L., Erritzoe, D., Williams, T. et al. · PNAS (2012)
Geyer, M. A., Vollenweider, F. X. · Trends in Pharmacological Sciences (2008)
Kometer, M., Pokorny, T., Seifritz, E. et al. · Psychopharmacology (2015)
McKenna, D. · ACS Chemical Neuroscience (2004)
McKenna, D., Towers, G. H., Abbott, F. · Journal of Ethnopharmacology (1984)
Muthukumaraswamy, S. D., Carhart-Harris, R. L., Moran, R. J. et al. · Journal of Neuroscience (2013)
Páleníček, T., Fujáková, M., Brunovský, M. et al. · Psychopharmacology (2012)
Riba, J., Anderer, P., Morte, A. et al. · British Journal of Clinical Pharmacology (2002)
Riba, J., Anderer, P., Jané, F. et al. · Neuropsychobiology (2004)
Schenberg, E. E., Alexandre, J. F. M., Filev, R. et al. · PLOS ONE (2015)
Vollenweider, F. X., Kometer, M. · Nature Reviews Neuroscience (2010)
Vollenweider, F. X., Leenders, K. L., Maguire, P. et al. · Neuropsychopharmacology (1997)
Berman, R. M., Cappiello, A., Anand, A. et al. · Biological Psychiatry (2000)
Carhart-Harris, R. L., Williams, T. M., Sessa, B. et al. · Journal of Psychopharmacology (2010)
Griffiths, R. R., Richards, W. A., Mccann, U. et al. · Journal of Psychopharmacology (2006)
Griffiths, R. R., Johnson, M. W., Richards, W. A. et al. · Psychopharmacology (2011)
Grob, C. S., Danforth, A. L., Chopra, G. S. et al. · JAMA Psychiatry (2011)
Halpern, J. H., Pope Jr, H. G. · Drug and Alcohol Dependence (2003)
Johnson, M. W., Garcia-Romeu, A., Cosimano, M. P. et al. · Journal of Psychopharmacology (2014)
Johnson, M. W., Garcia-Romeu, A., Griffiths, R. R. · The American Journal of Drug and Alcohol Abuse (2016)
Nau, F., Miller, J., Saravia, J. et al. · American Journal of Physiology (2015)
Halberstadt, A. L., Geyer, M. A. · Neuropharmacology (2011)
Moya, P. R., Berg, K. A., Gutiérrez-Hernandez, M. A. et al. · Journal of Pharmacology and Experimental Therapeutics (2007)
Quednow, B. B., Kometer, M., Geyer, M. A. et al. · Neuropsychopharmacology (2011)
Riba, J., Rodríguez-Fornells, A., Barbanoj, M. J. · Psychopharmacology (2002)
Shen, H. W., Jiang, X. L., Winter, J. C. et al. · Current Drug Metabolism (2010)
Vollenweider, F. X., Csomor, P. A., Knappe, B. et al. · Neuropsychopharmacology (2007)
Winter, J. C. · Psychopharmacology (2008)
Aronson, H., Silverstein, A. B., Klee, G. D. · JAMA Psychiatry (1980)
Brogaard, B. · Frontiers in Human Neuroscience (2013)
Carhart-Harris, R. L., Leech, R., Williams, T. M. et al. · British Journal of Psychiatry (2018)
Carhart-Harris, R. L., Leech, R., Erritzoe, D. et al. · Schizophrenia Bulletin (2012)
Carhart-Harris, R. L., Leech, R., Shanahan, M. et al. · Frontiers in Human Neuroscience (2014)
Carhart-Harris, R. L., Kaelen, M., Whalley, M. G. et al. · Psychopharmacology (2014)
Carter, O., Burr, D. C., Pettigrew, J. D. et al. · Journal of Cognitive Neuroscience (2006)
Carter, O. L., Hasler, F. ;., Pettigrew, J. D. et al. · Psychopharmacology (2007)
Gasser, P., Holstein, D., Michel, Y. et al. · Journal of Nervous and Mental Disease (2014)
Kirchner, K. · Journal of Psychopharmacology (2014)
Griffiths, R. R. · Journal of Psychopharmacology (2008)
Harman, W. W., McKim, R. H., Mogar, R. E. et al. · Psychological Reports (1966)
Hasler, F., Grimberg, U., Benz, M. A. et al. · Psychopharmacology (2004)
Johnson, M. W., Richards, W. A., Griffiths, R. R. · Journal of Psychopharmacology (2008)
Kaelen, M., Roseman, L., Kahan, J. et al. · European Neuropsychopharmacology (2016)
Kometer, M., Cahn, B. R., Andel, D. et al. · Biological Psychiatry (2011)
Kometer, M., Schmidt, A., Bachmann, R. et al. · Biological Psychiatry (2012)
Kraehenmann, R., Preller, K. H., Scheidegger, M. et al. · Biological Psychiatry (2015)
Leary, T., Litwin, G. H., Metzner, R. · Journal of Nervous and Mental Disease (1977)
Lienert, G. A., Netter, P. · Personality and Individual Differences (1996)
Maclean, K. A., Johnson, M. W., Griffiths, R. R. · Journal of Psychopharmacology (2011)
MacLean, K. A., Leoutsakos, J. S., Johnson, M. W. et al. · Journal for the Scientific Study of Religion (2012)
Osmond, H. · Annals of the New York Academy of Sciences (2010)
Passie, T., Seifert, J., Schneider, U. et al. · Addiction Biology (2002)
Schmidt, A., Kometer, M., Bachmann, R. et al. · Psychopharmacology (2012)
Sessa, B. · Journal of Psychopharmacology (2008)
Sinke, C., Halpern, J. H., Zedler, M. et al. · Consciousness and Cognition (2012)
Spitzer, M., Thimm, M., Hermle, L. et al. · Biological Psychiatry (1996)
Studerus, E., Gamma, A., Vollenweider, F. X. · PLOS ONE (2010)
Studerus, E., Kometer, M., Hasler, F. et al. · Journal of Psychopharmacology (2010)
Studerus, E., Gamma, A., Kometer, M. et al. · PLOS ONE (2012)
ten Berge, J. T. · Journal of Psychoactive Drugs (2002)
Umbricht, A., Vollenweider, F. X., Schmid, L. et al. · Neuropsychopharmacology (2003)
Wittmann, M., Hasler, F., Vollenweider, F. X. · Neuroscience Letters (2008)
Wittmann, M., Carter, O., Hasler, F. et al. · Journal of Psychopharmacology (2007)
Bernasconi, F. ;., Schmidt, A. ;., Pokorny, T. ;. et al. · Cerebral Cortex (2013)
Krippner, S. · Journal of Psychoactive Drugs (1985)
Luke, D. P., Terhune, D. B. · Frontiers in Psychology (2013)
Rolland, B., Jardri, R., Amad, A. et al. · BioMed Research International (2014)
Bouso, J. C., González, D., Fondevila, S. et al. · PLOS ONE (2012)
Bouso, J. C., Fábregas, J. M., Antonijoan, R. M. et al. · Psychopharmacology (2013)
De Araujo, D. B., Ribeiro, S., Cecchi, G. A. et al. · Human Brain Mapping (2011)
Sessa, B. · British Journal of Psychiatry (2018)
Abraham, H. D., Aldridge, A. M., Gogia, P. · Neuropsychopharmacology (1996)
Baggott, M. J., Coyle, J. R., Erowid, E. et al. · Drug and Alcohol Dependence (2011)
Strassman, R. J. · Journal of Nervous and Mental Disease (1984)
Barbosa, P., Mizumoto, S., Bogenschutz, M. P. et al. · Drug Testing and Analysis (2012)
Tracy, D., Baumeister, D., Barnes, G. et al. · Therapeutic Advances in Psychopharmacology (2014)
Bogenschutz, M. P., Pommy, J. A. · Drug Testing and Analysis (2012)
Bogenschutz, M. P., Johnson, M. W. · Progress in Neuro-Psychopharmacology and Biological Psychiatry (2016)
Carhart-Harris, R. L., Nutt, D. J. · Journal of Substance Use (2010)
Carhart-Harris, R. L., Bolstridge, M., Rucker, J. et al. · Lancet Psychiatry (2016)
Cohen, S. · Journal of Nervous and Mental Disease (1980)
Doering-Silveira, E., Grob, C. S., Dobkin de Rios, M. et al. · Journal of Psychoactive Drugs (2005)
Dyck, E. · Social History of Medicine (2006)
Fábregas, J. M., González, D., Fondevila, S. et al. · Drug and Alcohol Dependence (2010)
Gable, R. S. · Addiction (2006)
Garcia-Romeu, A., Griffiths, R. R., Johnson, M. W. · Current Drug Abuse Reviews (2015)
Grof, S., Soskin, R. A., Richards, W. A. et al. · Pharmacopsychiatry (1973)
Halpern, J. H., Sherwood, A. R., Hudson, J. I. et al. · Biological Psychiatry (2005)
Halpern, J. H., Sherwood, A. R., Passie, T. et al. · Medical Science Monitor (2008)
Krebs, T. S., Johansen, P. ˚. Ø. · PLOS ONE (2013)
Liester, M. B., Prickett, J. I. · Journal of Psychoactive Drugs (2012)
Litjens, R. P. W., Brunt, T. M., Alderliefste, G. et al. · European Neuropsychopharmacology (2014)
Ludwig, A., Levine, J., Stark, L. et al. · American Journal of Psychiatry (1969)
Mangini, M. · Journal of Psychoactive Drugs (2011)
Ross, S., Bossis, A. P., Guss, J. et al. · Journal of Psychopharmacology (2016)
Serafini, G., Howland, R. H., Rovedi, F. et al. · Current Neuropharmacology (2014)
Strassman, R. J., Qualls, C .R. · JAMA Psychiatry (1994)
Thomas, G., Lucas, P., Rielle Capler, N. et al. · Current Drug Abuse Reviews (2013)
Tomsovic, M., Edwards, R. V. · Journal of Studies on Alcohol and Drugs (1970)
Bouso, J. C., Pedrero-Pérez, E. J., Gandy, S. · Human Psychopharmacology (2016)
Carbonaro, T. M., Bradstreet, M. P., Barrett, F. S. et al. · Journal of Psychopharmacology (2016)
Doblin, R. · Journal of Transpersonal Psychology (1991)
Gouzoulis-Mayfrank, E., Schreckenberger, M., Sabri, O. et al. · Neuropsychopharmacology (1999)
Lebedev, A. V., Kaelen, M., L€ Ovd En, M. et al. · Human Brain Mapping (2016)
Lebedev, A. V., L€ Ovd En, M., Rosenthal, G. et al. · Human Brain Mapping (2015)
Liechti, M. E., Dolder, P. C., Schmid, Y. · Psychopharmacology (2016)
Majic, T., Schmidt, T. T., Gallinat, J. · Journal of Clinical Psychopharmacology (2015)
Nichols, D. E. · Pharmacological Reviews (2016)
Nour, M. R., Evans, J., Nutt, D. J. et al. · Frontiers in Human Neuroscience (2016)
Richards, W. A., Rhead, J. C., Dileo, F. B. et al. · Journal of Psychedelic Drugs (1997)
Roseman, L., Leech, R., Feilding, A. et al. · Frontiers in Human Neuroscience (2014)
Speth, J., Speth, C., Kaelen, M. et al. · Journal of Psychopharmacology (2016)
Tagliazucchi, E., Roseman, L., Kaelen, M. et al. · Current Biology (2016)
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