Psychedelic drugs have shown promise for treating neuropsychiatric disorders such as depression and post-traumatic stress disorder. However, due to their hallucinatory side effects, some researchers are trying to identify drugs that could provide the benefits of psychedelics without causing hallucinations. In the newspaper Cell On April 28, the researchers report that they identified such a drug through the development of a genetically encoded fluorescent sensor – called psychLight – that can screen for hallucinogenic potential by indicating when a compound activates the serotonin 2A receptor.
“Serotonin reuptake inhibitors have long been used to treat depression, but we don’t know much about their mechanism. It’s like a black box, ”says lead author Lin Tian (@LinTianLab), associate professor in the Department of Biochemistry and Molecule. Medicine at the University of California, Davis School of Medicine. “This sensor allows us to visualize the dynamics of serotonin in real time when animals are learning or are stressed and to visualize the interaction between the compound of interest and the receptor in real time.”
Tian’s lab has teamed up with the lab of David E. Olson, an assistant professor in the chemistry department at UC Davis, whose lab focuses on drug discovery. “This article was an exceptional collaborative effort,” says Olson, co-author of the study. “My lab is really interested in the serotonin 2A receptor, which is the target of both psychedelic drugs and conventional antipsychotics. Lin’s lab is a leader in the development of sensors for neuromodulators like serotonin. It made perfect sense for us to tackle this problem together. “
Experts believe that one of the advantages of using psychedelic drugs over existing drugs is that they appear to promote neural plasticity – essentially allowing the brain to rewire itself. If proven effective, this approach could result in a drug that works in a single dose or in a small number of doses, rather than having to be taken indefinitely. But one thing researchers don’t know is whether patients could take full advantage of neural plasticity without going through the “psychedelic journey” part of treatment.
In the article, the researchers report that they used psychLight to identify a compound called AAZ-A-154, a previously unstudied molecule that has the potential to act on beneficial pathways in the brain without hallucinogenic effects. “One of the problems with psychedelic therapies is that they require close guidance and supervision from a medical team,” says Olson. “A medicine that does not cause hallucinations could be taken at home.”
The serotonin 2A receptor, also known as 5-HT2AR, belongs to a class of receptors called G protein coupled receptors (GPCRs). “More than a third of all drugs approved by the FDA target GPCRs, so this sensor technology has broad implications for drug development,” says Tian. “The special funding mechanisms of the National Institutes of Health BRAIN Initiative have allowed us to take a risky and radical approach to develop this technology, which could open the door to the discovery of better drugs without side effects and to study. of neurochemical signaling in the brain. “
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