Scientists in Shanghai have developed rapid antidepressant compounds that do not have hallucinogenic effects

Traditional antidepressants currently on the market often take up to weeks or even months to take effect and have no improving effect on one-third of people with refractory depression. On January 28, the international academic journal Science published a research result by Wang Sheng's research group at the Center for Excellence in Molecular and Cell Science of the Chinese Academy of Sciences and the Cheng Jianjun research group of the iHuman Institute of ShanghaiTech University, who completed the design of a new rapid antidepressant compound that was oriented to the structure of hallucinogens and their targets.

In recent years, multiple hallucinogens have shown some potential in the treatment of depression. A class of natural hallucinogens, psilocybin extracted from "magic mushrooms" (collectively known as mushrooms that can produce hallucinogenic effects), was awarded a breakthrough therapy for the treatment of major depression and drug-resistant depression by the U.S. Food and Drug Administration in 2019. The results of the phase II clinical study show that psilocybin can greatly improve the symptoms of depressed patients in one day, and the effect can last for more than three months. However, the hallucinogenic side effects of hallucinogens greatly limit their clinical research and widespread application. Therefore, scientists around the world have been working to find and develop new antidepressants that are non-hallucinogenic and can work quickly.

Psilocybin is metabolized in humans to dephosphate psilocybin, and Wang Sheng's research group found through structural analysis that in addition to the classical mode of binding to serotonin 2A receptors previously predicted, there is another lipid-regulated binding mode. Based on the second binding mode, the researchers designed and synthesized a series of preferred agonists for serotonin 2A receptor β-arrestin signals, and experimentally verified in animals that the series of compounds had no hallucinogenic effect and had a rapid antidepressant effect. The research results point the way for the development of a new generation of non-hallucinogenic antidepressants that act quickly.

It should be pointed out that compounds are not equivalent to drugs, and researchers also need to conduct a lot of experimental verification to strive to make them drugs that benefit patients as soon as possible.