d-Lysergic acid diethylamide has major potential as a cognitive enhancer
Felipe Augusto Cini da Silva, Isis M. Ornelas, Encarni Marcos, Livia Goto‐silva, Juliana Nascimento, Sérgio Ruschi, José Alexandre Salerno, Karina Karmirian, Marcelo Costa, Eduardo Bouth Sequerra, Dráulio Barros de Araújo, Luís Fernando Tófoli, César Rennó‐costa, Daniel Martins‐de‐souza, Amanda Feilding, Stevens K. Rehen, Sidarta Ribeiro
bioRxiv (Cold Spring Harbor Laboratory) December 6, 2019 preprint DOI: 10.1101/866814 via OpenAlex
Summary
A single dose of d-LSD increased novel object preference in young and adult rats, but not in old rats unless followed by a 6-day enriched environment exposure. In human brain organoids, d-LSD treatment led to upregulation of proteins related to synaptic function. A model indicates that d-LSD enhances novelty preference through local and long-range synaptic changes, with improved pattern separation in enriched environments aiding older animals. These findings suggest potential for d-LSD in cognitive enhancement.
Study at a glance
| Population | young and adult rats, old rats, human brain organoids |
|---|---|
| Key finding | d-LSD increased novel object preference in young and adult rats and could restore this preference in old rats when combined with an enriched environment. |
Abstract
Abstract Psychedelic agonists of serotonin receptors induce neural plasticity and synaptogenesis, but their potential to enhance learning remains uncharted. Here we show that a single dose of d-LSD, a potent serotonergic agonist, increased novel object preference in young and adult rats several days after treatment. d-LSD alone did not increase preference in old animals, but could rescue it to young levels when followed by a 6-day exposure to enriched environment (EE). Mass spectrometry-based proteomics in human brain organoids treated with d-LSD showed upregulation of proteins from the presynaptic active zone. A computational model of synaptic connectivity in the hippocampus and prefrontal cortex suggests that d-LSD enhances novelty preference by combining local synaptic changes in mnemonic and executive regions, with alterations of long-range synapses. Better pattern separation within EE explained its synergy with d-LSD in rescuing novelty preference in old animals. These results advance the use of d-LSD in cognitive enhancement.