Opinion – Psychedelic Turn: Brazilian study suggests LSD may reactivate cognition

National research makes new contribution to 21st century psychedelic science renaissance, now with LSD. A study from three public universities suggests that lysergic acid diethylamide, a former star of psychiatry now half-forgotten, makes mice and humans smarter and may yield clues about what happens in the brains of the elderly.

The article “Nootropic Effects of LSD: Behavioral, Molecular and Computational Evidence” appeared in the journal Experimental Neurology. As the title suggests, the study went beyond observing the cognitive performance of rodents and members of our species, adding biochemical data and a computational model to explain it.

The main authors are Sidarta Ribeiro and César Rennó-Costa, from the Brain Institute at UFRN, alongside Steven Rehen, from UFRJ, and Luis Fernando Tófoli and Daniel Martins-de-Souza, from Unicamp. Several other researchers from these universities also participated, such as Isis Ornelas and Felipe Cini, as well as Encarni Marcos, from the Institute of Neurosciences in Alicante, Spain.

The term “nootropic” comes from the Greek word for intellect and refers to substances thought to sharpen cognition, in functions such as creativity and memory. It’s the hypothesis behind the use of LSD known as microdosing, ingesting amounts that don’t trigger a lysergic trip and have gained a reputation for boosting mental performance.

Many people are unaware that, until prohibition in the 1960s/70s, LSD was the subject of studies and clinical use in the treatment of alcohol abuse and in so-called psycholytic therapy. In the current renaissance, it lost prominence in research for psilocybin (mushrooms) and MDMA (base of ecstasy) and even for DMT from ayahuasca.

The widespread recreational use of “candy”, as it is known in the nightlife scene, and the practice of microdosing would warrant more attention from psychedelic science, but the stigma is strong. Not so much for this Brazilian group and for the British countess Amanda Feilding, who kept the flame burning in her Beckley Foundation and also appears as a co-author of the article.

The notion that LSD can act as a type of vitamin for the brain is not new. The staff from UFRN, UFRJ and Unicamp decided to test it using two types of organisms, one endowed with consciousness (humans), which can be altered by the psychedelic, and the other not (rats).

In the first case, several cognitive tests were applied by the German researcher living in Brazil Isabel Wießner. For her doctoral thesis at Unicamp, she subjected 25 volunteers (9 women and 16 men) to two experimental sessions, one with a median dose of LSD (50 mcg) and the other with a placebo, to compare their performance on tasks such as a memory game. with pairs of figures and a drawing that should be reproduced after a certain interval.

“To the best of our knowledge, this is the first study to show that LSD improves subacute memory in humans,” the article highlights.

The 76 mice treated with LSD, in turn, faced a test of preference for new objects in Ribeiro’s laboratory at UFRN, such as arrangements of lego pieces with a few more edges than those they were familiar with. In this case, there is the permanence of the memory of known objects and the motivation to investigate novelties.

In addition to these organisms and their behaviors, Rehen’s team at UFRJ investigated the biochemical effect of LSD on mini-brains, or, as experts prefer, brain organoids. They are spheres of neural cells cultured for 45 days from stem cells created with the manipulation of cells obtained from human urine.

These cell clusters differentiate to the point of developing structures similar to a tiny nervous system. After bathing for 24 hours with LSD, they were dissolved and had their proteins analyzed in an exhaustive way, for comparison with control organoids, which had not received the acid.

A total of 3,448 proteins were identified in both groups, of which 234 (6.8%) had expression significantly altered by LSD. That is, the psychedelic-treated mini-brains produced them in varying amounts from the control batch, many times greater.

The analysis revealed a strong influence on processes such as axon targeting, synaptic recycling and long-term depression (nothing to do with mental disorder), cellular activities that clearly point to synapse reorganization. In other words, for neuroplasticity, the formation of new neural connections that underlie memory fixation and learning.

“We were able to conclusively demonstrate that the prior administration of LSD increases neural plasticity in the organoids of human neurons, increases the preference for new objects in rats and improves visuospatial memory in humans”, summarizes Ribeiro. “These effects are significant and substantial.”

There is more. At the request of reviewers of the scientific article, the group added computational models that simulated the effect of the substance on neural networks and showed that LSD-induced neural plasticity satisfactorily explains cognitive gains in rats and humans.

These four lines of evidence finally made it possible, after three years of attempts, to publish the work in a respected journal (Experimental Neurology has an impact factor of 5.62, that is, each article edited there receives an average of 5.62 citations in the scientific literature) .

The work had already been publicly presented in 2019, in the form of a pre-print, in the open access repository bioRxiv, as reported by Folha. Still without data from the experiment with humans and without the computational model, it was submitted to eight journals, which ended up refusing it. With the new parts, there were four submissions until acceptance.

“Given the importance of the topic and the broad scope of the study, we tried to publish the article in scientific journals with maximum international impact, such as Science and Nature”, says Ribeiro. “This process is known to be very competitive, and for that reason we were very pleased with the publication in Experimental Neurology, which has a lot of prestige, tradition and capillarity in the biomedical field.”

The researcher gave an interview by e-mail in upstate New York (USA), where he would give lectures on dreams, on Tuesday and Wednesday (2 and 3), at the Chautauqua Institution, which is in the town of the same name. The American edition of his book “The Night Oracle: The History and Science of the Dream” prompted the invitation.

The laboratory at UFRN is also exploring the interaction between LSD and the enriched environment for rats, in order to verify whether such a combination would result in cognitive results as good in elderly animals as those observed in adult and young animals. Thus, one of the initial motivations of the research is resumed: to investigate whether psychedelics could contribute to the cognitive rescue of elderly minds.

“The results that we already have indicate that it is”, adds the neuroscientist (in addition, one of the biochemical pathways affected by LSD is mTOR, as the article shows, known to be involved in plasticity, memory, aging and dementia). Ribeiro explains that this part was left out of the article because there were an excessive number of females in the rodent sample, which could distort findings.

“We are preparing to initiate a lifetime follow-up study of the rodents to test the effects and interactions of regular lifetime LSD administration every 15 days and exposure to the enriched environment.” “The topic of psychedelics has grown a lot in my lab over the last five years.”

Her group has a study in the final stages of completion on the electrophysiological effects on the hippocampus and cortex of rats using LSD and 5-MeO-DMT (a substance originally extracted from frogs and related to DMT from ayahuasca), the basis of the former’s doctoral thesis. -student Annie da Costa Souza. He points out that there are similarities between the electrophysiological patterns induced by psychedelics and those observed during sleep.

“Under the effect of psychedelics, animals are awake, moving, but their brains are sleeping, from a certain point of view”, summarizes Ribeiro.

Rats may not have consciousness or mental disorders, like humans, but apparently they share with us the ability to walk through the world, with psychedelics, perceiving it in a different way. A good way to learn and discover new perspectives, whatever the organism.

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To learn more about the history and new developments of science in this area, including in Brazil, look for my book “Psiconautas – Travels with Brazilian Psychedelic Science”.

Be sure to also see the reports from the series A Ressurreição da Jurema:

https://www1.folha.uol.com.br/ilustrissima/2022/07/reporter-conta-experiencia-de-inalar-dmt-psicodelico-em-teste-contra-depressao.shtml

https://www1.folha.uol.com.br/ilustrissima/2022/07/da-caatinga-ao-laboratorio-cientistas-investigam-efeito-antidepressivo-de-psicodelico.shtml

https://www1.folha.uol.com.br/ilustrissima/2022/07/cultos-com-alucinogeno-da-jurema-florescem-no-nordeste.shtml

It is always worth remembering that psychedelics are still experimental therapies and certainly do not constitute a panacea for all mental disorders, nor should they be self-medicated. Talk to your therapist or doctor before venturing into the area.