Location of Receptor Key to Psychedelic Drug Effects

It turns out that real estate and psychedelic treatments hinge on the same factor.

That is the chief takeaway from a new paper published by researchers at the University of California, Davis.

“Location, location, location is the key for psychedelic drugs that could treat mental illness by rapidly rebuilding connections between nerve cells,” read a release from the university.

In the paper, which was published last Friday, “researchers at the [university] show that engaging serotonin 2A receptors inside neurons promotes growth of new connections but engaging the same receptor on the surface of nerve cells does not,” the news release said. 

“The findings will help guide efforts to discover new drugs for depression, PTSD and other disorders, said senior author David E. Olson, associate professor of chemistry, biochemistry and molecular medicine, and director of the Institute for Psychedelics and Neurotherapeutics at UC Davis,” said the release. “Drugs such as LSD, MDMA and psilocybin show great promise for treating a wide range of mental disorders that are characterized by a loss of neural connections. In laboratory studies, a single dose of these drugs can cause rapid growth of new dendrites — branches — from nerve cells, and formation of new spines on those dendrites.”

The Institute for Psychedelics and Neurotherapeutics was launched at the university earlier this month, which the school said would “bring together scientists across a range of disciplines and partner with the pharmaceutical industry to ensure that key discoveries lead to new medicines for patients.”

The university said that the institute “will be funded in part by a contribution of approximately $5 million from the deans of the College of Letters and Science and the School of Medicine, the vice chancellor for Research, and the Office of the Provost,” which makes it different from other comparable institutions.

“While other psychedelic science centers have been formed across the country with gifts from philanthropists, the UC Davis institute is notable for also being supported by substantial university funds,” the university said in the announcement earlier this month.

Olson, the author of the paper that was published on Friday, is serving as founding director of the new institute.

“Psychedelics have a lot of therapeutic potential, but we can do better,”  Olson said in the announcement of the institute. 

“Psychedelics have a unique ability to produce long-lasting changes in the brain that are relevant to treating numerous conditions,” added Olson. “If we can harness those beneficial properties while engineering molecules that are safer and more scalable, we can help a lot of people.”

The news release accompanying his paper on Friday said that “Olson calls this group of drugs ‘psychoplastogens’ because of their ability to regrow and remodel connections in the brain.”

Olson and his team of researchers “found that the growth-promoting ability of compounds was correlated with the ability to cross cell membranes.”

“Drug receptors are usually thought of as being on the cell membrane, facing out. But the researchers found that in nerve cells, serotonin 2A receptors were concentrated inside cells, mostly around a structure called the Golgi body, with some receptors on the cell surface. Other types of signaling receptors in the same class were on the surface,” the release explained. “The results show that there is a location bias in how these drugs work,” Olson said. Engaging the serotonin 2A receptor when it is inside a cell produces a different effect from triggering it when it is on the outside.”

Olson said that the research “gives us deeper mechanistic insight into how the receptor promotes plasticity, and allows us to design better drugs.”