Exciting new research by scientists at the University of California, Davis has revealed that the location of receptors in nerve cells may be the key to the function of psychedelic drugs in treating mental illness. The team’s work, which utilized molecular and genetic techniques, found that engaging the 5-hydroxytryptamine (serotonin) 2A receptors (5-HT2ARs) inside neurons promotes the growth of new connections, while engaging the same receptor on the surface of nerve cells does not.
The study’s findings may help guide the discovery of new drugs for mental disorders such as depression and post-traumatic stress disorder (PTSD). Senior author David E. Olson, PhD, associate professor of chemistry, biochemistry, and molecular medicine and director of the Institute for Psychedelics and Neurotherapeutics at UC Davis, suggested that the research could lead to the development of new therapies for these conditions.
LSD, MDMA, and psilocybin are among the drugs that show potential for treating mental disorders by promoting the growth of new dendrites and spines on nerve cells. In laboratory studies, a single dose of these drugs can cause rapid growth of new dendrites and spines, leading Olson to refer to them as “psychoplastogens.” This rapid activity is distinct from that of selective serotonin reuptake inhibitors (SSRIs), which require longer-term administration.
The researchers found that the growth-promoting ability of these drugs was correlated with their ability to cross cell membranes. Although drug receptors are usually thought of as being on the cell membrane, serotonin 2A receptors were found to be concentrated inside nerve cells, with some receptors located on the cell surface. The team’s results suggest that there is a location bias in how these drugs work, which could provide insight into how to design better drugs.
This research sheds light on the mechanism by which psychedelic drugs promote the growth of new connections in the brain, potentially paving the way for the development of new treatments for mental illness. However, further studies are needed to determine whether intracellular signaling is distinct from signaling at the plasma membrane, and to explore the possibility that serotonin may not be the substance that binds to 5-HT2ARs found in brain cells.
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