Nootropic effects of LSD: Behavioral, molecular and computational evidence

• Autor(a) principal: Ornelas, Isis M
• Data de Publicação: 2022
• Outros Autores: Silva, Felipe Augusto Cini da, Wießner, Isabel, Marcos, Encarni, Araujo, Draulio Barros de, Goto-Silva, Livia, Nascimento, Juliana, Silva, Sérgio Ruschi Bergamachi, Costa, Marcelo N, Falchi, Marcelo, Olivieri, Rodolfo, Fontes, Fernanda Palhano Xavier de, Sequerra, Eduardo Bouth, Martins-de-Souza, Daniel, Feilding, Amanda, Costa, César Rennó, Tófoli, Luis Fernando, Rehen, Stevens K, Ribeiro, Sidarta Tollendal Gomes
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFRN
• Texto Completo: https://repositorio.ufrn.br/handle/123456789/48767
• topic: Cognition; Computational model; Human brain organoids; Lysergic Acid Diethylamide (LSD); Memory; Neuroplasticity; Psychedelic

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