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)
Study at a glance
AI-extracted from the abstract| 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 Novelty Agonist Cognition Downregulation and upregulation Receptor Pharmacology Hallucinogen Biochemistry |
| Citations | 9 |
| Key findings | 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.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
Cited by 7
- Repeated lysergic acid diethylamide (LSD) reverses stress-induced anxiety-like behavior, cortical synaptogenesis deficits and serotonergic neurotransmission decline Neuropsychopharmacology March 17, 2022
- Psychedelics, Sociality, and Human Evolution Frontiers in Psychology September 29, 2021
- Psychedelics as a Treatment for Alzheimer’s Disease Dementia Frontiers in Synaptic Neuroscience August 21, 2020
- Unraveling psilocybin's therapeutic potential: behavioral and neuroplasticity insights in Wistar-Kyoto and Wistar male rat models of treatment-resistant depression. Psychopharmacology July 4, 2024
- A Brief Review on the Potential of Psychedelics for Treating Alzheimer’s Disease and Related Depression International Journal of Molecular Sciences August 7, 2023
and 2 more in the library
Cites 20
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
and 15 more in the library