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Therapeutic use of serotoninergic hallucinogens: A review of the evidence and of the biological and psychological mechanisms

dos Santos, Rafael Guimarães, Hallak, Jaime Eduardo Cecilio·2020·Neuroscience & Biobehavioral Reviews

DOI 10.1016/j.neubiorev.2019.12.001

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Abstract

Serotoninergic hallucinogens include drugs such as lysergic acid diethylamide (LSD), dimethyltryptamine (DMT) and psilocybin. Recent trials with single/few doses of these compounds show that they induce rapid and sustained antidepressive, anxiolytic, and antiaddictive effects. These effects are also observed in religious groups using the DMT-containing brew ayahuasca. The agonist action of these substances on 5-HT 2A receptors expressed in frontal and limbic areas increase glutamatergic transmission and neuroplasticity. These neurochemical effects are associated with acute alterations on self-perception and increases in introspection and positive mood, and with subacute and long-term decreases in psychiatric symptoms, increases in some personality traits such as openness, improvements in emotional processing, and increases in empathy. These are preliminary but promising results that should be further explored in controlled trials with larger sample sizes, especially considering that these compounds could be beneficial in the treatment of treatment-resistant psychiatric disorders.

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Authors: dos Santos, R. G., & Hallak, J. E. C.
Affiliations: Conselho Nacional de Desenvolvimento Científico e Tecnológico (BR)
ORCID: Hallak, Jaime Eduardo Cecilio
Venue: Neuroscience & Biobehavioral Reviews
Publisher: Elsevier BV
Published: 2020-01
Volume: 108
Pages: 423-434
ISSN: 0149-7634 (ISSN-L)
DOI: 10.1016/j.neubiorev.2019.12.001
OpenAlex: W2992322507
Cited by: 111
References: 113
Citations by year: 2026: 4 · 2025: 8 · 2024: 16 · 2023: 22 · 2022: 27 · 2021: 17 · 2020: 17
FWCI: 2.40
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Neuroscience & Biobehavioral Reviews (publishedVersion)
PubMed (publishedVersion)
Funders: Conselho Nacional de Desenvolvimento Científico e Tecnológico
Topics: Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Keywords: LSD, DMT, psilocybin, ayahuasca, 5-HT2A receptor agonism, antidepressant effects, anxiolytic effects, neuroplasticity, glutamatergic neurotransmission, self-perception, self-reflection, positive mood, personality traits, empathy, emotional processing, treatment-resistant psychiatric disorders, psychedelic therapy
MeSH terms: Social Cognition, Exploratory Behavior, Hallucinogens, Humans, Limbic System, Neuronal Plasticity, Prefrontal Cortex, Serotonin 5-HT2 Receptor Agonists

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Therapeutic use of serotoninergic hallucinogens: A review of the evidence and of the biological and psychological mechanisms

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