Dimethyltryptamine (DMT), the main psychedelic compound found in ayahuasca, which is used by indigenous peoples of the Amazon in therapeutic and ceremonial practices, has shown potential to encourage the generation of new neurons in the brain.
Historical Context and Scientific Discoveries
Historically, it was believed that the number of neurons was fixed after birth and tended to decrease. However, current research indicates that many animals, including humans, possess a reserve of neural stem cells in adulthood capable of replicating and forming new neurons, although they usually remain in a latent state.
DMT, or N,N-dimethyltryptamine, is a fast-acting psychedelic known for causing profound changes in perception, sense of time, and identity, often described as the dissolution of the boundaries of the self. Although ayahuasca has been used for centuries by Amazonian peoples, DMT was first synthesized in 1931 by Canadian chemist Richard Manske. Later, in 1946, Oswaldo Gonçalves de Lima, from Pernambuco, isolated a substance from jurema-preta (Mimosa tenuiflora) that proved to be DMT, based on studies of the traditional indigenous 'jurema wine' of Northeast Brazil.
The psychedelic effects of DMT in humans were experimentally characterized only in the 1950s, through the work of psychiatrist Stephen Szára. More recently, the scientific focus shifted from the mind to the cell, identifying that the acute effects of DMT derive mainly from its interaction with the serotonin receptor 5-HT2A. However, much of this initial knowledge was obtained in rodents, whose brains differ from human brains.
Study in Human Cells
The central question raised was what DMT specifically does to human neural cells, focusing on neural progenitor cells. To investigate this, researchers used cell reprogramming technology, a technique awarded the Nobel Prize in 2012. This method allows transforming an adult human cell, such as one from the skin, into an immature, embryonic-like state, creating induced pluripotent stem cells, which serve as a biological model for testing.
When exposed to DMT for one day, a larger portion of these cells began to multiply, which was measured by a marker that incorporates into DNA during cell replication. Furthermore, DMT influenced the production of essential molecules for neuronal survival and adaptation. Brain-Derived Neurotrophic Factor (BDNF) showed a notable increase, both in gene expression and protein quantity, reaching about five times. A significant surprise was Nerve Growth Factor (NGF), whose gene expression increased almost tenfold.
Results and Future Perspectives
The day after exposure, the DMT-treated cells were grouped into neurospheres, without the presence of the molecule. These spheres were found to be larger and metabolically more active in the first few days. Even though DMT was not present, its influence remained. The results showed that DMT seemed to predispose the cells to multiplication without altering their maturation pathway. If extrapolated to a living brain, this would represent a significant advance.
Similar clues have emerged in animal models: in 2020, a Spanish group observed that DMT stimulates neurogenesis in rodents with repeated doses. More recently, Brazilian researchers demonstrated that a single dose was sufficient to restore neurogenesis markers in mice under chronic stress, a finding that echoes the results in human cells after a single 24-hour exposure.
It is important to note that the process of neuron formation is complex, involving birth, multiplication, survival, maturation, and integration into existing circuits. The petri dish study observed only the first stage—cell proliferation and a persistent growth signal. There are still open questions about whether this reserve reacts the same way in a living brain and whether these new neurons would be functional or have therapeutic value.
However, the study suggests that a molecule associated with the dissolution of the boundaries of the self was capable of awakening dormant aspects. It is relevant to mention that treatments with DMT are being tested by scientists at UFRN, indicating rapid relief of depressive symptoms after a single dose, and synthetic oral formulations are in clinical trials for treatment-resistant depression. The therapeutic capacity of DMT may, therefore, be linked to its ability to promote the multiplication of neural stem cells and the creation of new connections.
