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.

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.”

Authors: Isis M. Ornelas, Felipe A. Cini, Isabel Weißner, Encarni Marcos, Draulio de Araújo, Livia Goto-Silva, Juliana Nascimento, Sergio R. Silva, Marcelo Falchi, Rodolofo Olivieri, Fernanda Palhano-Fontes, Eduardo Sequerra, Daniel Martins-de-Souza, Amanda Feilding, Cesar Renno-Costa, Luis F. Tófoli, Stevens K. Rehen & Sidarta Ribeiro

Author Highlights

• LSD enhances neural plasticity signalling pathways in human brain organoids.
• LSD enhances novel object preference in rats.
• LSD enhances visuospatial memory in humans.
• LSD-induced neural plasticity explains cognitive gains in rats and humans.