Long-term use of psychedelic drugs is associated with differences in brain structure and personality in humans.
Open accessAbstract
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.
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There is some evidence in humans that psychoplastogens can impact brain structure.
“There is some evidence in humans that psychoplastogens can impact brain structure as well.”
From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [119]
Chronic use of the psychedelic tisane ayahuasca is associated with thickening of the anterior cingulate cortex.
“Chronic use of the psychedelic tisane ayahuasca is associated with thickening of the anterior cingulate cortex (119)”
From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [119]
Ayahuasca users equalled or outperformed matched controls on tests of neuropsychological function, suggesting that this PCC thinning is not linked to cognitive impairment.
“Interestingly, these ayahuasca users equalled or outperformed matched controls on tests of neuropsychological function, suggesting that this PCC thinning is not linked to cognitive impairment.”
From Self unbound: ego dissolution in psychedelic experience (2017) · cites this paper as Bouso et al. 2015
Thinning of the PCC has been observed in long-term ayahuasca users, with the degree of thinning correlated with both psychometric scores for trait 'self-transcendence' and the extent of prior ayahuasca use.
“Meanwhile, thinning of the PCC has been observed in long-term ayahuasca users, with the degree of thinning correlated with both psychometric scores for trait ‘self-transcendence’ and the extent of prior ayahuasca use (Bouso et al. 2015).”
From Self unbound: ego dissolution in psychedelic experience (2017) · cites this paper as Bouso et al. 2015
Ingestion of a psychedelic drug can induce rapid and persisting changes in personality traits, particularly reductions in neuroticism, in both healthy and clinical populations.
“It has been repeatedly found that ingestion of a psychedelic drug can induce rapid and persisting changes in personality traits, and particularly reductions in neuroticism, in both healthy and clinical populations (24, 35–41).”
From Decreases in State and Trait Anxiety Post-psilocybin: A Naturalistic, Observational Study Among Retreat Attendees (2022) · cites this paper as [36]
Long-term ayahuasca users demonstrated thinning of the PCC.
“while long-term ayahuasca users demonstrated thinning of the PCC (117).”
From Examining the Potential Synergistic Effects Between Mindfulness Training and Psychedelic-Assisted Therapy (2021) · cites this paper as [117]
Cortical thickness in long-term ayahuasca users has been correlated with cognitive capacities and personality traits.
“cortical thickness in long-term ayahuasca users has been correlated with cognitive capacities and personality traits (Bouso et al., 2015)”
From Psychological variables implied in the therapeutic effect of ayahuasca: A contextual approach (2018) · cites this paper as Bouso et al., 2015
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References 46 · Cited by 218
- Authors
- Bouso, J. C., Palhano-Fontes, F., Rodríguez-Fornells, A., Ribeiro, S., Sanches, R., Crippa, J. A. S., Hallak, J. E. C., de Araujo, D. B., & Riba, J.
- Affiliations
- Institut de Recerca Sant Pau (ES)
- Universidade Federal do Rio Grande do Norte (BR)
- Universidade de São Paulo (BR)
- ORCID
- Venue
- European Neuropsychopharmacology
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 25
- Issue
- 4
- Pages
- 483-492
- ISSN
- 0924-977X (ISSN-L)
- OpenAlex
- W1972616052
- Cited by
- 218
- References
- 46
- Citations by year
- 2026: 17 · 2025: 21 · 2024: 26 · 2023: 21 · 2022: 25 · 2021: 20 · 2020: 21 · 2019: 20 · 2018: 15 · 2017: 12 · 2016: 17 · 2015: 3
- FWCI
- 19.43
- Type
- journal article
- Language
- en
- Open access
- green
- repositorio.ufrn.br
- Licence
- Locations
- European Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Americanae (AECID Library) (publishedVersion, other-oa)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
- Funders
- the Beckley Foundation
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Social Psychology › Paranormal Experiences and Beliefs
- Keywords
- psychedelics, ayahuasca, N,N-dimethyltryptamine, 5-HT2A receptor agonists, cortical thickness, posterior cingulate cortex, default mode network, self-transcendence, personality, brain structure, long-term drug use, synaptic plasticity
- MeSH terms
- Adolescent, Adult, Brain, Child, Child, Preschool, Female, Hallucinogens, Humans, Functional Laterality, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Personality, Personality Disorders, Personality Inventory, Tomography, X-Ray Computed, Chi-Square Distribution, Imaging, Three-Dimensional, Banisteriopsis, Young Adult
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