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Assessing the Psychedelic “After-Glow” in Ayahuasca Users: Post-Acute Neurometabolic and Functional Connectivity Changes Are Associated with Enhanced Mindfulness Capacities

BACKGROUND: Ayahuasca is a plant tea containing the psychedelic 5-HT(2A) agonist N,N-dimethyltryptamine and harmala monoamine-oxidase inhibitors. Acute administration leads to neurophysiological modifications in brain regions of the default mode network, purportedly through a glutamatergic mechanism...

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Autores principales: Sampedro, Frederic, de la Fuente Revenga, Mario, Valle, Marta, Roberto, Natalia, Domínguez-Clavé, Elisabet, Elices, Matilde, Luna, Luís Eduardo, Crippa, José Alexandre S, Hallak, Jaime E C, de Araujo, Draulio B, Friedlander, Pablo, Barker, Steven A, Álvarez, Enrique, Soler, Joaquim, Pascual, Juan C, Feilding, Amanda, Riba, Jordi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5581489/
https://www.ncbi.nlm.nih.gov/pubmed/28525587
http://dx.doi.org/10.1093/ijnp/pyx036
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author Sampedro, Frederic
de la Fuente Revenga, Mario
Valle, Marta
Roberto, Natalia
Domínguez-Clavé, Elisabet
Elices, Matilde
Luna, Luís Eduardo
Crippa, José Alexandre S
Hallak, Jaime E C
de Araujo, Draulio B
Friedlander, Pablo
Barker, Steven A
Álvarez, Enrique
Soler, Joaquim
Pascual, Juan C
Feilding, Amanda
Riba, Jordi
author_facet Sampedro, Frederic
de la Fuente Revenga, Mario
Valle, Marta
Roberto, Natalia
Domínguez-Clavé, Elisabet
Elices, Matilde
Luna, Luís Eduardo
Crippa, José Alexandre S
Hallak, Jaime E C
de Araujo, Draulio B
Friedlander, Pablo
Barker, Steven A
Álvarez, Enrique
Soler, Joaquim
Pascual, Juan C
Feilding, Amanda
Riba, Jordi
author_sort Sampedro, Frederic
collection PubMed
description BACKGROUND: Ayahuasca is a plant tea containing the psychedelic 5-HT(2A) agonist N,N-dimethyltryptamine and harmala monoamine-oxidase inhibitors. Acute administration leads to neurophysiological modifications in brain regions of the default mode network, purportedly through a glutamatergic mechanism. Post-acutely, ayahuasca potentiates mindfulness capacities in volunteers and induces rapid and sustained antidepressant effects in treatment-resistant patients. However, the mechanisms underlying these fast and maintained effects are poorly understood. Here, we investigated in an open-label uncontrolled study in 16 healthy volunteers ayahuasca-induced post-acute neurometabolic and connectivity modifications and their association with mindfulness measures. METHODS: Using (1)H-magnetic resonance spectroscopy and functional connectivity, we compared baseline and post-acute neurometabolites and seed-to-voxel connectivity in the posterior and anterior cingulate cortex after a single ayahuasca dose. RESULTS: Magnetic resonance spectroscopy showed post-acute reductions in glutamate+glutamine, creatine, and N-acetylaspartate+N-acetylaspartylglutamate in the posterior cingulate cortex. Connectivity was increased between the posterior cingulate cortex and the anterior cingulate cortex, and between the anterior cingulate cortex and limbic structures in the right medial temporal lobe. Glutamate+glutamine reductions correlated with increases in the “nonjudging” subscale of the Five Facets Mindfulness Questionnaire. Increased anterior cingulate cortex-medial temporal lobe connectivity correlated with increased scores on the self-compassion questionnaire. Post-acute neural changes predicted sustained elevations in nonjudging 2 months later. CONCLUSIONS: These results support the involvement of glutamate neurotransmission in the effects of psychedelics in humans. They further suggest that neurometabolic changes in the posterior cingulate cortex, a key region within the default mode network, and increased connectivity between the anterior cingulate cortex and medial temporal lobe structures involved in emotion and memory potentially underlie the post-acute psychological effects of ayahuasca.
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spelling pubmed-55814892017-09-06 Assessing the Psychedelic “After-Glow” in Ayahuasca Users: Post-Acute Neurometabolic and Functional Connectivity Changes Are Associated with Enhanced Mindfulness Capacities Sampedro, Frederic de la Fuente Revenga, Mario Valle, Marta Roberto, Natalia Domínguez-Clavé, Elisabet Elices, Matilde Luna, Luís Eduardo Crippa, José Alexandre S Hallak, Jaime E C de Araujo, Draulio B Friedlander, Pablo Barker, Steven A Álvarez, Enrique Soler, Joaquim Pascual, Juan C Feilding, Amanda Riba, Jordi Int J Neuropsychopharmacol Regular Research Articles BACKGROUND: Ayahuasca is a plant tea containing the psychedelic 5-HT(2A) agonist N,N-dimethyltryptamine and harmala monoamine-oxidase inhibitors. Acute administration leads to neurophysiological modifications in brain regions of the default mode network, purportedly through a glutamatergic mechanism. Post-acutely, ayahuasca potentiates mindfulness capacities in volunteers and induces rapid and sustained antidepressant effects in treatment-resistant patients. However, the mechanisms underlying these fast and maintained effects are poorly understood. Here, we investigated in an open-label uncontrolled study in 16 healthy volunteers ayahuasca-induced post-acute neurometabolic and connectivity modifications and their association with mindfulness measures. METHODS: Using (1)H-magnetic resonance spectroscopy and functional connectivity, we compared baseline and post-acute neurometabolites and seed-to-voxel connectivity in the posterior and anterior cingulate cortex after a single ayahuasca dose. RESULTS: Magnetic resonance spectroscopy showed post-acute reductions in glutamate+glutamine, creatine, and N-acetylaspartate+N-acetylaspartylglutamate in the posterior cingulate cortex. Connectivity was increased between the posterior cingulate cortex and the anterior cingulate cortex, and between the anterior cingulate cortex and limbic structures in the right medial temporal lobe. Glutamate+glutamine reductions correlated with increases in the “nonjudging” subscale of the Five Facets Mindfulness Questionnaire. Increased anterior cingulate cortex-medial temporal lobe connectivity correlated with increased scores on the self-compassion questionnaire. Post-acute neural changes predicted sustained elevations in nonjudging 2 months later. CONCLUSIONS: These results support the involvement of glutamate neurotransmission in the effects of psychedelics in humans. They further suggest that neurometabolic changes in the posterior cingulate cortex, a key region within the default mode network, and increased connectivity between the anterior cingulate cortex and medial temporal lobe structures involved in emotion and memory potentially underlie the post-acute psychological effects of ayahuasca. Oxford University Press 2017-06-13 /pmc/articles/PMC5581489/ /pubmed/28525587 http://dx.doi.org/10.1093/ijnp/pyx036 Text en © The Author 2017. Published by Oxford University Press on behalf of CINP. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Regular Research Articles
Sampedro, Frederic
de la Fuente Revenga, Mario
Valle, Marta
Roberto, Natalia
Domínguez-Clavé, Elisabet
Elices, Matilde
Luna, Luís Eduardo
Crippa, José Alexandre S
Hallak, Jaime E C
de Araujo, Draulio B
Friedlander, Pablo
Barker, Steven A
Álvarez, Enrique
Soler, Joaquim
Pascual, Juan C
Feilding, Amanda
Riba, Jordi
Assessing the Psychedelic “After-Glow” in Ayahuasca Users: Post-Acute Neurometabolic and Functional Connectivity Changes Are Associated with Enhanced Mindfulness Capacities
title Assessing the Psychedelic “After-Glow” in Ayahuasca Users: Post-Acute Neurometabolic and Functional Connectivity Changes Are Associated with Enhanced Mindfulness Capacities
title_full Assessing the Psychedelic “After-Glow” in Ayahuasca Users: Post-Acute Neurometabolic and Functional Connectivity Changes Are Associated with Enhanced Mindfulness Capacities
title_fullStr Assessing the Psychedelic “After-Glow” in Ayahuasca Users: Post-Acute Neurometabolic and Functional Connectivity Changes Are Associated with Enhanced Mindfulness Capacities
title_full_unstemmed Assessing the Psychedelic “After-Glow” in Ayahuasca Users: Post-Acute Neurometabolic and Functional Connectivity Changes Are Associated with Enhanced Mindfulness Capacities
title_short Assessing the Psychedelic “After-Glow” in Ayahuasca Users: Post-Acute Neurometabolic and Functional Connectivity Changes Are Associated with Enhanced Mindfulness Capacities
title_sort assessing the psychedelic “after-glow” in ayahuasca users: post-acute neurometabolic and functional connectivity changes are associated with enhanced mindfulness capacities
topic Regular Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5581489/
https://www.ncbi.nlm.nih.gov/pubmed/28525587
http://dx.doi.org/10.1093/ijnp/pyx036
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