LSD, MDMA, and psilocybin hold great potential for the treatment of various mental disorders marked by neural disconnection. Research conducted in laboratories has shown that a single dosage of these drugs can stimulate the growth of new dendrites, or branches, from nerve cells, along with the formation of new spines on those dendrites.
LSD, MDMA, and psilocybin are just a few of the drugs that have shown significant promise in treating a number of mental diseases that are marked by a loss of neural connections.
A single dosage of these medications has been shown in laboratory trials to rapidly increase the number of new dendrites, or branches, from nerve cells as well as the development of new spines on those dendrites.
Because of their capacity to rebuild and remodel neural connections in the brain, the senior author David E. Olson, an associate professor of chemistry, biochemistry, and molecular medicine at UC Davis, and the director of the Institute for Psychedelics and Neurotherapeutics, refers to this class of drugs as “psychoplastogens.”
Previous research from Olson’s and other laboratories shown that psychedelic drugs function by activating the serotonin 2A receptor (5-HT2AR). However, serotonin and other medications that target the same receptor do not have the same growth-promoting benefits.
This new study suggests that the key to psychedelic drugs’ potential to heal mental disease by speedily re-establishing connections between nerve cells is location.
In a report published in Science today, researchers demonstrate that activating serotonin 2A receptors inside neurons stimulates the formation of new connections, but activating the same receptor on the surface of nerve cells does not.
According to the study’s senior author, their results will serve as a roadmap for the development of future treatments for mental health issues including depression, PTSD, and others.
Maxemiliano Vargas, a graduate student in Olson’s lab, Olson, and others tried changing drugs chemically and using transporters to make it easier or harder for compounds to move across cell membranes. Polar molecules like serotonin are readily dissolved in water but have a hard time passing across the lipid membranes that separate different cell types. On the other hand, psychedelics are much less polar and can easily get inside a cell.
They found that a compound’s ability to help cells grow was linked to its ability to pass through cell membranes.
Typically, drug receptors are shown as being on the cell membrane and facing out. Serotonin 2A receptors, however, were discovered by the researchers to be concentrated within nerve cells, mostly surrounding a structure known as the Golgi body, with some receptors being present on the cell surface. On the surface, there were other kinds of signaling receptors of the same class.
Olson said that the findings confirm that there is a bias in how these drugs work based on where they are used. When the serotonin 2A receptor is located inside of a cell, activating it generates a different impact than when it is triggered when it is located outside of the cell.
“It gives us deeper mechanistic insight into how the receptor promotes plasticity, and allows us to design better drugs,” Olson adds.
Source: 10.1126/science.adf0435
Image Credit: Getty