In 2017 Amanda Feilding set up a collaborative programme with leading neuroscientists in Brazil to investigate how psychedelics may benefit human health, with a particular focus on LSD’s effects on neuroplasticity, anti-inflammation and neurogenesis mechanisms.
Moving between brain cells, ‘mini-brains’, animals, and humans, this translational research programme will provide the basis to develop new treatments and therapies for neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases, but also depression, ADHD and brain injury rehabilitation. Pioneering research in areas of high unmet need.
Prof Sidarta Ribeiro is vice-Director of the world-class Brain Institute at the University Federal of Rio do Norte (UFRN), member of the Academy of Sciences of Latin America and director of the Brazilian Society for the Progress of Science. He is an expert in neurobiology, neurophysiology and behavioural neuroscience.
Prof Stevens Rehen is a world-renowned neuroscientist specialized in stem cell research at the Federal University of Rio de Janeiro and at the prestigious D’Or Institute (IDOR). Stevens was a pioneer in culturing human induced pluripotent stem cells and brain organoids, or ‘minibrains’ in Brazil.
After a delay in publication caused by cuts to Brazil’s science budget following of Jair Bolsonaro’s election as President, the Beckley/Brazil team were in 2022 able to publish promising findings from three experiments testing LSD’s effects on neuroplasticity and memory.
In the first, stem cells were used to generate cerebral organoids, sometimes referred to as ‘minibrains’. These cell cultures express the same patterning, organisation and connectivity observed in human embryonic brains, and so can be used as models to test the effects of compound on protein expression in neuronal tissue.
Organoids were randomly assigned to be bathed in either control or LSD, and changes in the abundance of different proteins were analysed. Results showed that of the 3448 proteins identified in the two sets of organoids, 234 (6.8%) had their expression significantly modified by LSD.
These changes were to proteins that could potentially affect several biological processes, including DNA replication, axon guidance, synaptic vesicle cycle, and long-term depression (which is not to be confused with depression in a mental health sense; instead, long-term depression – LTD – is the process by which synaptic connections are weakened following reduced activity). These pathways are related to synaptic reorganisation and could underlie psychedelic-induced neuroplasticity.
The second experiment tested novel object preference in rats, finding that rats pretreated with LSD were more interested in exploring novel objects in their environment than rats treated with saline. This could have particular significance in the case of adult rats, who were found to be significantly less interested in novelty than younger rats, but whose novelty-seeking after LSD was restored to more youthful levels.
Finally, LSD’s effects on memory in humans were examined in a double-blind, placebo-controlled study which applied two visuospatial tasks the morning after dosing in order to assess LSD-induced overnight memory consolidation. The first task required participants to recall the location of one of 15 matching pairs of cards in a 2D grid, and the second required them to immediately draw a geometric figure from memory and again after a 30-minute delay.
Results showed that the percentage of recalled card locations was significantly increased after LSD, and improved immediate recall of the complex geometric figure compared to placebo. While effects weren’t particularly strong, the dose was only 50 micrograms, and it could be that higher doses lead to greater effects.
A computational model of neural networks was used to try to gain insights into the relation between neural plasticity and the LSD-induced novelty preference in rats and memory enhancement in humans. The model’s predictions were consistent with the data, and suggest that it’s plausible that LSD exerts its nootropic effects through changes to neuroplasticity.
These findings could provide rationale behind using LSD as a cognitive enhancer, which could be particularly important in old age, helping to restore memory and interest in new experiences.
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Psilocybin for Depression
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