Nootropic effects of LSD: Behavioral, molecular and computational evidence
This double-blind placebo-controlled study (n=25) assessed the effects of LSD on metabolic pathways associated with neural plasticity, to gain insight into the relationship between neural plasticity, ageing and LSD-induced cognitive gains in both humans and rodents. LSD treatment in humans (50μg) enhanced performance in a visuospatial memory task, and in a novel object recognition task in rodents indicating that LSD has nootropic effects.
Authors
- Fernanda Palhano-Fontes
- Luiz Tófoli
- Amanda Feilding
Published
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 ageing. 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 visuospatial memory task in humans. Proteomic analysis of human brain organoids showed that LSD affected metabolic pathways associated with neural plasticity, including mTOR. To gain insight into the relationship between neural plasticity, ageing 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.
Research Summary of 'Nootropic effects of LSD: Behavioral, molecular and computational evidence'
Introduction
Psychedelics such as LSD, psilocybin, DMT, and 5-MeO-DMT are potent agonists at the serotonin 5-HT2A receptor and have long been associated with intense perceptual and cognitive experiences. Beyond their acute phenomenological effects, accumulating evidence from rodent studies suggests that these compounds also promote structural neuroplasticity — including increased dendritic spine density and synaptic protein synthesis — via downstream activation of mTOR pathways. The hypothesis that such plasticity could translate into lasting cognitive enhancement, or nootropic effects, in humans had not been systematically examined in an integrated cross-species framework. This study aimed to test the nootropic potential of LSD across four levels of analysis — molecular (human brain organoids), behavioural (rats across age groups), behavioural (healthy adult humans), and computational (a cortico-hippocampal neural network model) — to determine whether LSD-induced plasticity translates into measurable improvements in memory and novelty processing.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Ornelas, I. M., Cini, F. A., Wießner, I., Marcos, E., Araújo, D. B., Goto-Silva, L., Nascimento, J., Silva, S. R., Costa, M. N., Falchi, M., Olivieri, R., Palhano-Fontes, F., Sequerra, E., Martins-de-Souza, D., Feilding, A., Rennó-Costa, C., Tófoli, L. F., Rehen, S. K., & Ribeiro, S. (2022). Nootropic effects of LSD: Behavioral, molecular and computational evidence. Experimental Neurology, 356, 114148. https://doi.org/10.1016/j.expneurol.2022.114148
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