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Psychedelic medicine allows new brain cells in mice to develop

Research in mice has shown that N,N-dimethyltryptamine (DMT), one of the active ingredients in ayahuasca psychedelic tea, can stimulate the development of new nerve cells and enhance spatial learning and memory efficiency.

Ayahuasca is made from Psychotria viridis leaves.

Psychotria viridis leaves
Image credit: Alison Wright/Getty Images

The researchers behind the new study speculate that neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, may be handled by the treatment.

The gradual loss of nerve cells in damaged areas of the brain or in some cases, in other locations of the nervous system includes neurodegenerative diseases. Restoring the ability to create new nerve cells, which is known as neurogenesis, may be one way to reverse the damage.

Before birth, the development of most nerve cells in the human body takes place. Some studies, however, indicate that the development of new neurons is possible in adulthood, although the results have been questioned by other researchers.

Ayahuasca, a tea which shamans use for ritual and healing purposes in several South American countries, is emerging as a surprising potential source of drugs that could stimulate neurogenesis.

The psychedelic brew has antidepressant effects, preliminary studies have shown. These results can partly be explained by its newly identified possible ability to encourage the development of new nerves in the brain.

Ayahuasca is made from Psychotria viridis berries, a DMT-containing shrub, and the Banisteriopsis caapi stem, a vine containing chemicals called beta-carbolines. These chemicals prevent DMT in the gut from breaking down.

Researchers at the Instituto de Investigaciones Biomédicas and the Network Center for Neurodegenerative Disease Biomedical Research, both in Madrid, recently conducted a study that showed that ayahuasca beta-carbolines induce neurogenesis in cultures of mouse cells.

They have now found that in mice, DMT induces neurogenesis as well. Moreover it improves their performance in spatial learning and memory tests.

Brain plasticity

Together the results show that DMT raises “plasticity,” which is the brain’s capacity to rewire in order to learn new things.

“For a wide variety of psychological and neurological disorders, including neurodegenerative diseases, this ability to modulate brain plasticity indicates that it has great therapeutic potential,” says José Ángel Morales, who led the study.

Morales adds, “The challenge is to activate our dormant ability to form neurons and thus replace the neurons that die from the disease.” “This research shows that DMT can stimulate neural stem cells and shape new neurons.”

Stem cells are precursor cells that as the body demands, can transform into a number of different specialized cells.

DMT also stimulated stem cells in cell cultures to divide into three groups of nervous system cells: neurons, astrocytes, and oligodendrocytes. All three cells will be required in a possible therapy to repair circuitry in the brain.

The thesis appears in Translational Psychiatry, a journal.

Encoding memories

The researchers showed that DMT activates neurogenesis in the hippocampus, the part of the brain that consolidates new memories, in adult mice.

DMT binds to several receptors, including serotonin receptors, on nerve cells in the brain. When it binds to one called the serotonin 5-HT2A receptor, the drug is known to cause its psychedelic effects.

Scientists injected mice with DMT, either alone or in combination with many different agents that block particular receptors, to find out which receptor is responsible for the effects of DMT on neurogenesis.

This process showed that when DMT binds to a receptor called sigma-1, rather than the serotonin 5-HT2A receptor, it only activates neurogenesis.

For drug developers, this is good news because it means it is possible to block the hallucinogenic effects of DMT while retaining the capacity of the drug to boost neurogenesis.

In a second round of experiments, the researchers administered daily injections of DMT to mice for 21 days, either alone or in combination with the sigma-1 receptor blocking agent. On spatial perception and memory tests, they then assessed the abilities of the animals.

The animals receiving DMT on their own performed better than those injected with DMT plus the receptor blocker by the team. This result indicates that for learning, the brain puts the newly formed brain cells to use in the hippocampus.

Cause for optimism

To test whether DMT can increase neurogenesis in humans and whether it can reverse or slow the progression of neurodegenerative diseases, much more research is needed.

The potential antidepressant effects of ayahuasca, however, offer cause for optimism. Scientists have speculated that by boosting neurogenesis, many antidepressants work, which may explain why their effects can take up to a month to become apparent.

As with DMT, the antidepressant fluvoxamine binds to the sigma-1 receptor, the authors note. Therefore in diseases such as Alzheimer’s and Parkinson’s, activating the same receptor might also be the key to boosting neurogenesis.

They write:

“[T]he stimulation of neurogenesis has already been proposed as a new therapeutic strategy for psychiatric and neurological diseases, and several studies have reported that the clinical efficacy of antidepressant drugs is frequently linked to the capacity of these drugs to induce neurogenesis.”

However, nerve cells can start to die off decades before the symptoms of neurodegenerative disorders become evident. So it remains to be seen if the brains of people who have obtained a diagnosis of one of these disorders still possess the potential to produce new functional brain cells.

For now in common with other classic psychedelics, such as psilocybin and LSD, DMT is a Schedule 1 drug. This classification means that regulators consider it to have no approved medical usage and high potential for violence.

As clinical trials gradually add evidence to prove that psychedelics are highly effective antidepressants, however, their schedule is likely to alter.

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