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 N. 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 (opens in new tab) via OpenAlex
Summary
AI-generated from the abstractA single dose of d-LSD, a potent serotonergic agonist, increased preference for novel objects in young and adult rats several days after treatment, but did not increase preference in old animals unless followed by a 6-day exposure to enriched environment, which rescued novelty preference to young levels. 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, and that better pattern separation within enriched environment explains its synergy with d-LSD in rescuing novelty preference in old animals. These results advance the use of d-LSD in cognitive enhancement.
Study at a glance
| Characteristics | Experimental study |
|---|---|
| Population | Young, adult, and old rats; human brain organoids |
| Interventions | d-LSD enriched environment |
| Dose | a single dose |
| Duration | Several days after treatment; 6-day exposure to enriched environment |
| Topics | LSD Neuroplasticity Psilocybin Serotonin |
| Keywords | Prefrontal cortex Hippocampus Neuroscience Novelty |
| Citations | 9 |
| Key finding | A single dose of d-LSD increased novel object preference in young and adult rats several days after treatment, and could rescue novelty preference in old animals to young levels when followed by a 6-day exposure to 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.