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
All Open Access, Gold
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