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Eur Neuropsychopharmacol. 2015 Apr;25(4):483-92. doi: 10.1016/j.euroneuro.2015.01.008. Epub 2015 Jan 16.

Long-term use of psychedelic drugs is associated with differences in brain structure and personality in humans.

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Human Neuropsychopharmacology Group, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), C/Sant Antoni María Claret, 167, 08025 Barcelona, Spain; International Center for Ethnobotanical Education, Research & Service, Barcelona, Spain.
Brain Institute/Hospital Universitario Onofre Lopes, Federal University of Rio Grande do Norte, Natal, Brazil.
Cognition and Brain Plasticity Group, IDIBELL (Bellvitge Biomedical Research Institute), L'Hospitalet de Llobregat, Barcelona 08097, Spain; Department of Basic Psychology, University of Barcelona, Barcelona 08035, Spain; Catalan Institution for Research and Advanced Studies, ICREA, Barcelona, Spain.
Neuroscience and Behaviour Department, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
Human Neuropsychopharmacology Group, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), C/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, Barcelona, Spain; Departament de Farmacologia i Terapèutica, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain. Electronic address:


Psychedelic agents have a long history of use by humans for their capacity to induce profound modifications in perception, emotion and cognitive processes. Despite increasing knowledge of the neural mechanisms involved in the acute effects of these drugs, the impact of sustained psychedelic use on the human brain remains largely unknown. Molecular pharmacology studies have shown that psychedelic 5-hydroxytryptamine (5HT)2A agonists stimulate neurotrophic and transcription factors associated with synaptic plasticity. These data suggest that psychedelics could potentially induce structural changes in brain tissue. Here we looked for differences in cortical thickness (CT) in regular users of psychedelics. We obtained magnetic resonance imaging (MRI) images of the brains of 22 regular users of ayahuasca (a preparation whose active principle is the psychedelic 5HT2A agonist N,N-dimethyltryptamine (DMT)) and 22 controls matched for age, sex, years of education, verbal IQ and fluid IQ. Ayahuasca users showed significant CT differences in midline structures of the brain, with thinning in the posterior cingulate cortex (PCC), a key node of the default mode network. CT values in the PCC were inversely correlated with the intensity and duration of prior use of ayahuasca and with scores on self-transcendence, a personality trait measuring religiousness, transpersonal feelings and spirituality. Although direct causation cannot be established, these data suggest that regular use of psychedelic drugs could potentially lead to structural changes in brain areas supporting attentional processes, self-referential thought, and internal mentation. These changes could underlie the previously reported personality changes in long-term users and highlight the involvement of the PCC in the effects of psychedelics.


Ayahuasca; Cortical thickness; N,N-dimethyltryptamine; Personality; Psychedelics

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