Nootropic effects of LSD: Behavioral, molecular and computational evidence

Autor: Isis M. Ornelas, Felipe A. Cini, Isabel Wießner, Encarni Marcos, Dráulio B. Araújo, Livia Goto-Silva, Juliana Nascimento, Sergio R.B. Silva, Marcelo N. Costa, Marcelo Falchi, Rodolfo Olivieri, Fernanda Palhano-Fontes, Eduardo Sequerra, Daniel Martins-de-Souza, Amanda Feilding, César Rennó-Costa, Luis Fernando Tófoli, Stevens K. Rehen, Sidarta Ribeiro
Přispěvatelé: Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Brasil), Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brasil), Sao Paulo Research Foundation, Universidade Federal do Rio Grande do Norte, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Royal Society (UK)
Rok vydání: 2022
Předmět:
Zdroj: Experimental Neurology. 356:114148
ISSN: 0014-4886
DOI: 10.1016/j.expneurol.2022.114148
Popis: 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.
This project was supported by the Beckley Foundation; Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) – Finance Code 001, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (grants 308775/2015-5 and 408145/2016-1), São Paulo Research Foundation grants (2013/07699-0, 2014/10068-4, 2017/25588-1 and 2019/00098-7), intramural grants from D'Or Institute and Federal University of Rio Grande do Norte, and a Juan de la Cierva-Incorporación Scholarship (IJCI-2016-27864) from the Spanish Ministry of Science, Innovation and Universities, and a Newton International Fellowship from the Royal Society.
Databáze: OpenAIRE
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