Research Suggests LSD May Enhance Learning and Memory

LSD may hold beneficial nootropic properties, according to a new study published in the journal Experimental Psychology. 

By studying human brain organoids — tissue cultures grown from stem cells that can mimic the developing brain — researchers have found that LSD regulates numerous processes related to neuroplasticity in the human brain. The study also revealed that LSD increases novelty preference in rats and improves visuospatial memory performance in humans.

LSD affects key processes in the brain

Although psychedelics administered alongside traditional psychotherapy have recently shown promise as a treatment for depression and addiction, the exact cellular mechanisms behind such effects have remained unclear.

Recent research has hypothesized that these beneficial effects may stem from the ability of psychedelics to promote neurogenesis and neuroplasticity in the brain. In this new study, the researchers set out to investigate whether these psychedelic-induced changes in neuroplasticity could also be harnessed to enhance learning and memory.

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

To study the effects of LSD at the cellular level, the researchers created brain organoids which were aged to the point where they were able to mimic certain aspects of patterning, organizations, and connectivity observed in the human embryonic brain. These organoids were then exposed to either LSD or a vehicle for 24 hours before being analyzed via liquid chromatography mass spectrometry (LC-MS).

The researchers found several brain processes involved in neural plasticity that were affected by exposure to LSD, including DNA replication, neural pathfinding and dopamine neurotransmitter release cycling.

Notably, significant LSD-induced changes were also seen in the mTOR pathway. As the researchers explain, mTOR is a protein kinase which is involved in multiple neural plasticity events and which acts as a central hub between plasticity, learning, and memory. mTOR disturbance is also a typical pathophysiological finding in neurodegenerative disorders, such as Alzheimer’s disease.

LSD promotes novelty-seeking behaviors in rats

To further investigate the effects of LSD on memory processes and whether this changes with age, the researchers carried out another experiment using young and old rats dosed with either LSD or an inert saline solution.

In this novel object preference task, the rats first participated in a training session where they were placed in an enclosure with two objects and allowed time to explore them. Then, in the test session, one of the objects would be replaced by a new, novel object. Spending more time investigating the novel object would indicate that the memory of the familiar object still remains, and that there is more curiosity about foreign stimuli.

In this experiment, rats pre-treated with LSD several days before the task spent significantly more time exploring the novel object and less time with the familiar object. Young animals tended to spend more time investigating the novel object than older animals, but no significant associations between age and LSD dosing were found.

These results would imply that LSD-induced chances in neuroplasticity enhance novelty-seeking behaviors. Alternatively, the researchers also theorize that exposure to psychedelics could be affecting salience processing, thus increasing the time it takes for the rat to become familiar with a new object.

Similar effects seen in humans

To further examine the effects of LSD on memory, the researchers recruited 25 healthy adult volunteers to complete two tasks designed to assess memory consolidation, encoding, and recall. Each volunteer attended two experimental sessions, one where they would be given a placebo and one where they were given a low dose of LSD.

Memory consolidation was assessed by a 2D object-location task, where the participants were asked to learn the locations of various card pairs presented in a grid. After learning, the dose of LSD or placebo was given, with the participant returning 24 hours later to test whether they could still locate the correct card pairs.

A complex figure test was also used to test memory encoding and recall. In this task, conducted at least 24 hours after dosing, participants were given a sheet of paper displaying a complex geometric figure and asked to copy it as accurately as possible onto a second sheet of paper. Then, after both sheets were removed, the participants were given a third sheet of paper and asked to draw the same figure again from memory.

The researchers found that participants who had consumed LSD in the days prior to the visuospatial testing performed better than those given the placebo, suggesting 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, he also added that “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.”

The researchers also note that although the effects of the LSD application were not particularly strong, this could be down to the low doses used in the study. Overall, the researchers say that these new findings may help to explain some of the beneficial effects of psychedelics, identifying several processes affected by LSD that may enhance neuroplasticity and subsequently, cognitive performance.

“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.”