Nootropic effects of LSD: Behavioral, molecular and computational evidence.

Autor: Ornelas IM; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil., Cini FA; Brain Institute, Federal University of Rio Grande do Norte (UFRN), Natal, Brazil., Wießner I; Brain Institute, Federal University of Rio Grande do Norte (UFRN), Natal, Brazil; Interdisciplinary Cooperation for Ayahuasca Research and Outreach (ICARO), School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil., Marcos E; Instituto de Neurociencias de Alicante, Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández de Elche, San Juan de Alicante, Spain., Araújo DB; Brain Institute, Federal University of Rio Grande do Norte (UFRN), Natal, Brazil., Goto-Silva L; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil., Nascimento J; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil; Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil., Silva SRB; Brain Institute, Federal University of Rio Grande do Norte (UFRN), Natal, Brazil., Costa MN; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil; Institute of Biology, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil., Falchi M; Interdisciplinary Cooperation for Ayahuasca Research and Outreach (ICARO), School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil., Olivieri R; Interdisciplinary Cooperation for Ayahuasca Research and Outreach (ICARO), School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil., Palhano-Fontes F; Brain Institute, Federal University of Rio Grande do Norte (UFRN), Natal, Brazil., Sequerra E; Brain Institute, Federal University of Rio Grande do Norte (UFRN), Natal, Brazil., Martins-de-Souza D; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil; Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil; Instituto Nacional de Biomarcadores em Neuropsiquiatria (INBION), Conselho Nacional de Desenvolvimento Científico e Tecnológico, São Paulo, Brazil; Experimental Medicine Research Cluster (EMRC), University of Campinas, Campinas, Brazil., Feilding A; The Beckley Foundation, Oxford, UK., Rennó-Costa C; Digital Metropolis Institute, Federal University of Rio Grande do Norte (UFRN), Natal, Brazil. Electronic address: cesar@imd.ufrn.br., Tófoli LF; Interdisciplinary Cooperation for Ayahuasca Research and Outreach (ICARO), School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil. Electronic address: tofoli@unicamp.br., Rehen SK; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil; Institute of Biology, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil. Electronic address: srehen@lance-ufrj.org., Ribeiro S; Brain Institute, Federal University of Rio Grande do Norte (UFRN), Natal, Brazil. Electronic address: sidartaribeiro@neuro.ufrn.br.
Jazyk: angličtina
Zdroj: Experimental neurology [Exp Neurol] 2022 Oct; Vol. 356, pp. 114148. Date of Electronic Publication: 2022 Jun 19.
DOI: 10.1016/j.expneurol.2022.114148
Abstrakt: The therapeutic use of classical psychedelic substances such as d-lysergic acid diethylamide (LSD) surged in recent years. Studies in rodents suggest that these effects are produced by increased neural plasticity, including stimulation of the mTOR pathway, a key regulator of metabolism, plasticity, and aging. Could psychedelic-induced neural plasticity be harnessed to enhance cognition? Here we show that LSD treatment enhanced performance in a novel object recognition task in rats, and in a visuo-spatial memory task in humans. A proteomic analysis of human brain organoids showed that LSD affected metabolic pathways associated with neural plasticity, including mTOR. To gain insight into the relation of neural plasticity, aging and LSD-induced cognitive gains, we emulated the experiments in rats and humans with a neural network model of a cortico-hippocampal circuit. Using the baseline strength of plasticity as a proxy for age and assuming an increase in plasticity strength related to LSD dose, the simulations provided a good fit for the experimental data. Altogether, the results suggest that LSD has nootropic effects.
(Copyright © 2022. Published by Elsevier Inc.)
Databáze: MEDLINE
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