Assessing the psychedelic "after-glow" in ayahuasca users: Post-acute neurometabolic and functional connectivity changes are associated with enhanced mindfulness capacities


Por: Sampedro F., Revenga M.D.L.F., Valle M., Roberto N., Domínguez-Clavé E., Elices M., Luna L.E., Crippa J.A.S., Hallak J.E.C., Araujo D.B.D., Friedlander P., Barker S.A., Álvarez E., Soler J., Pascual J.C., Feilding A., Riba J.

Publicada: 1 ene 2017
Resumen:
Background: Ayahuasca is a plant tea containing the psychedelic 5-HT2A 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 1H-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. ©2017 The Author.

Filiaciones:
Sampedro F.:
 School of Medicine, Autonomous University of Barcelona, Barcelona, Spain

Revenga M.D.L.F.:
 Human Neuropsychopharmacology Research Group, Sant Pau Institute of Biomedical Research, C/Sant Antoni Mariá Claret 167, Barcelona, 08025, Spain

Valle M.:
 Pharmacokinetic and Pharmacodynamic Modelling and Simulation, Sant Pau Institute of Biomedical Research, Barcelona, Spain

 Centre d'Investigació de Medicaments, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

 Department of Pharmacology and Therapeutics, Autonomous University of Barcelona, Barcelona, Spain

Roberto N.:
 Human Neuropsychopharmacology Research Group, Sant Pau Institute of Biomedical Research, C/Sant Antoni Mariá Claret 167, Barcelona, 08025, Spain

Domínguez-Clavé E.:
 Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain

 Department of Psychiatry, Hospital de la Santa Creu ISant Pau, Barcelona, Spain

 Department of Psychiatry and Forensic Medicine, School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain

Elices M.:
 Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain

 Department of Psychiatry, Hospital de la Santa Creu ISant Pau, Barcelona, Spain

 Department of Psychiatry and Forensic Medicine, School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain

Luna L.E.:
 Research Center for the Study of Psychointegrator Plants, Visionary Art and Consciousness, Santa Catarina, Brazil

Crippa J.A.S.:
 Department of Neuroscience and Behavior, Medical School of Ribeiraõ Preto, University of Saõ Paulo, Saõ Paulo, Brazil

Hallak J.E.C.:
 Department of Neuroscience and Behavior, Medical School of Ribeiraõ Preto, University of Saõ Paulo, Saõ Paulo, Brazil

Araujo D.B.D.:
 National Institute for Translational Medicine, Ribeiraõ Preto, Brazil

 Department of Clinical and Health Psychology, School of Psychology, Autonomous University of Barcelona, Barcelona, Spain

Friedlander P.:
 Brain Institute, Hospital Universitario Onofre Lopes, Natal, Brazil

Barker S.A.:
 Brain Institute, Hospital Universitario Onofre Lopes, Natal, Brazil

 Beckley Foundation, Beckley Park, Oxford, United Kingdom

Álvarez E.:
 Department of Psychiatry, Hospital de la Santa Creu ISant Pau, Barcelona, Spain

Soler J.:
 Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain

 Department of Psychiatry, Hospital de la Santa Creu ISant Pau, Barcelona, Spain

 Beckley Foundation, Beckley Park, Oxford, United Kingdom

Pascual J.C.:
 Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain

 Department of Psychiatry, Hospital de la Santa Creu ISant Pau, Barcelona, Spain

 Department of Psychiatry and Forensic Medicine, School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain

Feilding A.:
 Brain Institute, Hospital Universitario Onofre Lopes, Natal, Brazil

 Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Skip Bertman Drive at River Road, Baton Rouge, United States

 Department of Clinical and Health Psychology, School of Psychology, Autonomous University of Barcelona, Barcelona, Spain

Riba J.:
 Human Neuropsychopharmacology Research Group, Sant Pau Institute of Biomedical Research, C/Sant Antoni Mariá Claret 167, Barcelona, 08025, Spain

 Centre d'Investigació de Medicaments, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

 Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain
ISSN: 14611457
Editorial
OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND, Reino Unido
Tipo de documento: Article
Volumen: 20 Número: 9
Páginas: 698-711
WOS Id: 000412072200003
ID de PubMed: 28525587
imagen All Open Access, Gold

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