Nootropic effects of LSD: Behavioral, molecular and computational evidence
| Author | Ornelas, Isis M; 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 | |
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| Publisher | Elsevier BV | |
| Date | 2022-06-19 | |
| Keywords | Cognition Computational model Human brain organoids Lysergic Acid Diethylamide (LSD) Memory Neuroplasticity Psychedelic | |
| Citation | ||
| Abstract | 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 | |
| URI | https://repositorio.ufrn.br/handle/123456789/48767 | |
| Collections | ICe - Artigos publicados em periódicos |
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