title: Inhibition of alpha oscillations through serotonin-2A receptor activation underlies the visual effects of ayahuasca in humans.
abstract: Ayahuasca is an Amazonian psychotropic plant tea typically obtained from two plants, Banisteriopsis caapi and Psychotria viridis. It contains the psychedelic 5-HT2A and sigma-1 agonist N,N-dimethyltryptamine (DMT) plus β-carboline alkaloids with monoamine-oxidase (MAO)-inhibiting properties. Although the psychoactive effects of ayahuasca have commonly been attributed solely to agonism at the 5-HT2A receptor, the molecular target of classical psychedelics, this has not been tested experimentally. Here we wished to study the contribution of the 5-HT2A receptor to the neurophysiological and psychological effects of ayahuasca in humans. We measured drug-induced changes in spontaneous brain oscillations and subjective effects in a double-blind randomized placebo-controlled study involving the oral administration of ayahuasca (0.75mg DMT/kg body weight) and the 5-HT2A antagonist ketanserin (40mg). Twelve healthy, experienced psychedelic users (5 females) participated in four experimental sessions in which they received the following drug combinations: placebo+placebo, placebo+ayahuasca, ketanserin+placebo and ketanserin+ayahuasca. Ayahuasca induced EEG power decreases in the delta, theta and alpha frequency bands. Current density in alpha-band oscillations in parietal and occipital cortex was inversely correlated with the intensity of visual imagery induced by ayahuasca. Pretreatment with ketanserin inhibited neurophysiological modifications, reduced the correlation between alpha and visual effects, and attenuated the intensity of the subjective experience. These findings suggest that despite the chemical complexity of ayahuasca, 5-HT2A activation plays a key role in the neurophysiological and visual effects of ayahuasca in humans.
authors.affiliation: Pharmacokinetic and Pharmacodynamic Modelling and Simulation, IIB Sant Pau, Sant Antoni María Claret, 167, 08025 Barcelona, Spain; Centre d'Investigació de Medicaments, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Sant Antoni María Claret, 167, 08025 Barcelona, Spain; Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Valle
authors.affiliation: Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain; Human Neuropsychopharmacology Research Group. Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Sant Antoni María Claret, 167, 08025 Barcelona, Spain.
authors.forename: Ana Elda
authors.initials: AE
authors.lastname: Maqueda
authors.affiliation: Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain; Servei de Psiquiatria, Hospital de la Santa Creu i Sant Pau, Sant Antoni María Claret, 167, 08025 Barcelona, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Rabella
authors.affiliation: Human Neuropsychopharmacology Research Group. Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Sant Antoni María Claret, 167, 08025 Barcelona, Spain.
authors.forename: Aina
authors.initials: A
authors.lastname: Rodríguez-Pujadas
authors.affiliation: Centre d'Investigació de Medicaments, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Sant Antoni María Claret, 167, 08025 Barcelona, Spain; Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain.
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Antonijoan
authors.affiliation: Biomedical Engineering Research Centre (CREB), Department of Automatic Control (ESAII), Universitat Politècnica de Catalunya (UPC), Barcelona, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Romero
authors.affiliation: Biomedical Engineering Research Centre (CREB), Department of Automatic Control (ESAII), Universitat Politècnica de Catalunya (UPC), Barcelona, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain; Barcelona College of Industrial Engineering (EUETIB), UniversitatPolitècnica de Catalunya (UPC), Barcelona 08028, Spain.
authors.forename: Joan Francesc
authors.initials: JF
authors.lastname: Alonso
authors.affiliation: Biomedical Engineering Research Centre (CREB), Department of Automatic Control (ESAII), Universitat Politècnica de Catalunya (UPC), Barcelona, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain; Barcelona College of Industrial Engineering (EUETIB), UniversitatPolitècnica de Catalunya (UPC), Barcelona 08028, Spain.
authors.forename: Miquel Àngel
authors.initials: MÀ
authors.lastname: Mañanas
authors.affiliation: Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Skip Bertman Drive at River Road, Baton Rouge, LA 70803, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Barker
authors.affiliation: The Beckley Foundation, Beckley Park, Oxford OX3 9SY, United Kingdom.
authors.forename: Pablo
authors.initials: P
authors.lastname: Friedlander
authors.affiliation: The Beckley Foundation, Beckley Park, Oxford OX3 9SY, United Kingdom.
authors.forename: Amanda
authors.initials: A
authors.lastname: Feilding
authors.affiliation: Centre d'Investigació de Medicaments, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Sant Antoni María Claret, 167, 08025 Barcelona, Spain; Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain; Human Neuropsychopharmacology Research Group. Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Sant Antoni María Claret, 167, 08025 Barcelona, Spain. Electronic address: jriba@santpau.cat.
authors.forename: Jordi
authors.initials: J
authors.lastname: Riba
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000513:Alpha Rhythm / Q000187:drug effects* / Q000502:physiology; D031581:Banisteriopsis; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006213:Hallucinogens / Q000494:pharmacology*; D006801:Humans; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D014796:Visual Perception / Q000187:drug effects* / Q000502:physiology
chemical_list: D006213:Hallucinogens; D044402:Receptor, Serotonin, 5-HT2A; D012702:Serotonin Antagonists; D007650:Ketanserin
keywords: Ayahuasca; Human; Ketanserin; Neurophysiological effects; Serotonin-(2A) receptor; Subjective effects