Nootropic effects of LSD: Behavioral, molecular and computational evidence

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Ornelas, Isis M. ; Cini, Felipe A. ; Wiessner, Isabel ; Marcos, Encarni ; Araujo, Draulio B. ; Goto-Silva, Livia ; Nascimento, Juliana ; Silva, Sergio R. B. ; Costa, Marcelo N. ; Falchi, Marcelo ; Olivieri, Rodolfo ; Palhano-Fontes, Fernanda ; Sequerra, Eduardo ; Martins-de-Souza, Daniel ; Feilding, Amanda ; Renno-Costa, Cesar ; Tofoli, Luis Fernando ; Rehen, Stevens K. ; Ribeiro, Sidarta

• Tipo de documento: Artigo Científico
• Fonte: Experimental Neurology; v. 356, p. 14-pg., 2022-07-12.

Resumo

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 per-formance 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 plas-ticity, 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. (AU)

• Processo FAPESP: 14/10068-4 - EMU concedido no processo 13/08711-3: espectrômetro de massas Waters SYNAPT G2-Si HDMs + nanoACQUITY UPLC
• Beneficiário: Daniel Martins-de-Souza
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• Processo FAPESP: 17/25588-1 - Da compreensão básica a biomarcadores clínicos para a esquizofrenia: um estudo multidisciplinar centrado na neuroproteômica
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• Modalidade de apoio: Auxílio à Pesquisa - Temático
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• Processo FAPESP: 19/00098-7 - EMU concedido no processo 2017/25588-1: cromatógrafo Acquity UPLC I-Class
• Beneficiário: Daniel Martins-de-Souza
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários