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Psychedelics, once reported as the preserve of “college campuses and in beatnik dives in California,” have recently seen something of a resurgence in scientific research. They have been shown to help treat depression, help to heal trauma, and they may even be useful in fighting COVID-19. A new study, published in the journal Experimental Neurology, has found evidence of another benefit of LSD – promoting brain plasticity.

“My main research topics are the neural plasticity mechanisms underlying the cognitive benefits of sleep and dreaming,” study author Sidarta Ribeiro, a professor of neuroscience at the Brain Institute of the Federal University of Rio Grande do Norte, told PsyPost. 

“I became interested in psychedelics because they produce dream-like states with major cognitive impacts.”

So, to see the effect of LSD on the brain's ability to learn and take in new information, the team dosed two groups of rats – one with the psychedelic drug, and the other with a saline control. 

A few days later, the rats were given a novel object preference test – which is pretty much what it sounds like: the rodents were shown a selection of objects, some new and some familiar, and the researchers measured which the critters preferred.

This is a pretty standard cognitive test for lab rats and mice, as it’s an efficient way to measure learning and memory in the animals. Generally speaking, the better the rats’ memory and cognition, the more time they will spend exploring novel items – and indeed, the rats which had been given LSD spent significantly more time investigating the new items. 

“Our results show that LSD pre-treatment can substantially increase novelty preference in rats several days after dosing, with a significant single dose effect,” the researchers said. “The results imply that LSD-induced plasticity enhanced novelty-seeking.”

The same effect was found when the investigators tested humans: 25 healthy volunteers who had previously used LSD – albeit not within the two weeks preceding the study – were recruited into a randomized, double-blind, placebo-controlled study in which they received 50 μg of LSD, and 50 μg of an inactive placebo, over two test sessions. While all participants were given one of each dose, the order in which they occurred was randomized.

Novel object preference tasks are a little easy for humans, so the subjects were instead given a visuospatial 2D object-location task and a Rey-Osterrieth Complex Figure test – in which the aim is to reproduce a line drawing – to complete. Both of these are common ways to assess memory encoding and consolidation, processes that require neuroplasticity.

Again, the researchers found that subjects who had consumed LSD in the days preceding the tests performed better than those given a placebo – showing that “even a single dose of LSD can promote neural plasticity and enhance cognition in healthy adults, several days after the LSD administration,” Ribeiro told PsyPost. 

However, while the effects of psychedelics are fairly easy to study – as we’ve seen, you can pretty much just give a bunch of volunteers a measured dose and see what happens – the mechanisms that cause those effects have proved more mysterious. So, to investigate what was happening at the cellular level, the researchers tested the drug on brain organoids: tissue formed from stem cells that can approximate the structure and function of the brain.

The results appeared to confirm something suggested by previous studies: that the therapeutic effects of LSD are caused by an increase in neural plasticity – that is, the brain’s ability to learn, change and adapt throughout life. 

“Analysis of human brain organoids showed that LSD affected metabolic pathways associated with neural plasticity, including mTOR,” explains the paper. mTOR, or the mechanistic Target Of Rapamycin, is a key protein in many cellular and physiological processes controlling growth, and acts as a hub between plasticity, learning, and memory, the researchers explain.

So, while there’s still more research to be done before we all start tripping balls while we study – “we still need to learn more about age differences, potential gender differences and the role of the context (setting) in the modulation of the effects,” noted Ribeiro – the research suggests that there might be a place for psychedelics not just in the therapist’s office, but in everyday life.

“Psychedelics have been demonized since the 1960s, and in the past decade they have returned to biology and medicine through the front door,” Ribeiro told PsyPost. “However, the utility of psychedelics is not restricted to the treatment of patients with a pathological condition. They can also be very useful to improve the cognition of healthy individuals, i.e., they should be seen not just as medicine, but also as part of human life at large.”

Katie has a PhD in maths, specializing in the intersection of dynamical systems and number theory.

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