Psychedelics may improve mental health by getting inside nerve cells

Psychedelics enter below the cell surface and exert their potential therapeutic effects.

These drugs have shown promise in clinical trials as treatments for mental health disorders (SN: 12/3/21). Well, scientists may know why.these substances can enter cortical neurons — regions of the brain critical to consciousness — and instructing neurons to grow, researchers report Feb. 17 chemistry.

Several mental health conditions, including depression and post-traumatic stress disorder, have been linked to chronic stress that degrades neurons in the cortex over time. It has been thought that therapeutic effects such as reducing anxiety and improving mood can be obtained.

Psylocin, derived from magic mushrooms, and hallucinogens such as LSD repair by promoting the growth of information-receiving nerve cell branches called dendrites (SN: 11/17/20). This behavior may explain the drugs’ positive results in the study.However, how they cause cell proliferation has been a mystery.

Psychedelics were already known to receive signals in cortical neurons and activate specific proteins that give instructions to the cells. This protein, called the 5-HT2A receptor, is made in the body and is also stimulated by the mood-related chemical serotonin. However, a 2018 study found that Serotonin doesn’t make these neurons growThe discovery “was really scratching my head,” said chemical neuroscientist David Olson, director of the Institute for Psychedelics and Neurotherapy at the University of California, Davis.

To understand why these two chemicals affect neurons differently, Olson and colleagues tweaked some to alter the degree of receptor activation. But those with better equipment to turn it on didn’t grow neurons. I noticed that the substance caused branching of neurons.

Polar chemicals such as serotonin, which cannot enter cells due to uneven distribution of charge, did not induce growth. Further experiments showed that the 5-HT2A receptors of most cortical neurons are located inside the cell, rather than on the surface, where scientists have mostly studied.

However, once serotonin gained access inside cortical neurons via gateways artificially added to the cell surface, it also led to growth. bottom. The day after receiving a serotonin surge, animals whose brain cells contained unnatural entry points did not give up as quickly as normal mice when forced to swim. Longer duration is predicted to be more effective for antidepressants, indicating that internal access to 5-HT2A receptors is key to therapeutic efficacy.

“It seems to undermine a lot of what we think should be true about how these drugs work,” says Cornell University neuroscientist Alex Kwan said he was not involved in the study. [psychedelics] It acts on receptors on the cell surface. ”

Biochemist Javier Gonzalez Maeso of Virginia Commonwealth University in Richmond, where most receptors that function like 5-HT2A are found, was also not involved in the study.

Because serotonin cannot reach 5-HT2A receptors in typical cortical neurons, Olson proposes that the receptors might respond to another chemical produced in the body. “If it’s there, it must have some role,” he says. For example, DMT is a naturally occurring psychedelic made by plants and animals, including humans, that can reach inside cells.

Kwan disagrees. “It’s interesting that hallucinogens act on them, but I don’t know if they need to be used when the brain performs its normal functions.” It is a reserve pool, suggesting that it may be ready to replace degraded receptors on the cell surface.

Either way, understanding the cellular mechanisms behind the potential therapeutic effects of psychedelics could help scientists develop safer and more effective treatments for mental health disorders.

“Ultimately, we hope this will lead to better drugs,” says Olson.