Nootropic effects of LSD: Behavioral, molecular and computational evidence.
I. Ornelas, F. A. Cini, Isabel Wießner, Encarni Marcos, D. D. de Araujo, L. Goto-Silva, J. Nascimento, Sérgio Ruschi B. Silva, Marcelo N. Costa, Marcelo Falchi, Rodolfo Olivieri, F. Palhano-Fontes, E. Sequerra, D. Martins‐de‐souza, A. Feilding, César Rennó-costa, L. F. Tófoli, S. Rehen, S. Ribeiro
Experimental Neurology June 1, 2022 DOI: 10.1016/j.expneurol.2022.114148 via Semantic Scholar
Summary
LSD treatment improved performance in a novel object recognition task in rats and 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. Simulations using a neural network model of a cortico-hippocampal circuit, with baseline plasticity strength as a proxy for age and increased plasticity related to LSD dose, fit the experimental data well. The results suggest that LSD has nootropic effects.
Study at a glance
| Characteristics | Experimental study with rodent and human components, plus computational modeling Peer reviewed |
|---|---|
| Population | Rats and humans |
| Keywords | Medicine Computer science |
| Citations | 37 |
| Key finding | LSD treatment enhanced performance in memory tasks in rats and humans, suggesting nootropic effects. |
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.