LSD-like compounds found to have potent antidepressant and anti-anxiety effects without hallucinogenic effects

Researchers have announced that they have designed a new compound that activates the 5-HT2A receptor, which is thought to be involved in anxiety and depression. Synthetic narcotics 'LSD' is known as a substance that activates the same receptor, but it seems that LSD promotes hallucinations, while new compounds promote antidepressant and anxiolytic effects.

Bespoke library docking for 5-HT2A receptor agonists with antidepressant activity | Nature

LSD-Like Molecules Counter Depression Without the Trip | UC San Francisco

The 5-HT2A receptor is thought to be involved in schizophrenia and other psychiatric disorders, anxiety and depression, and many antipsychotics and antidepressants inhibit its activity. A research team led by Brian Shoishet of the University of California, San Francisco has developed an antipsychotic drug that does not inhibit the activity of the 5-HT2A receptor but activates the 5-HT2A receptor in the same way as LSD. We conducted research with the aim of

It has been known for several decades that the 5-HT2A receptor activates various intracellular signaling pathways, but various symptoms such as hallucinations may occur with activation. . In this study, it was discovered that the receptor activates two different pathways: the ``pathway of hallucinogenic action'' and the ``pathway of antidepressant/anxiety action.'' In addition, Mr. Shoishet et al. optimized a compound called tetrahydropyridine for 5-HT2A and succeeded in activating the antidepressant/anxiety pathway.

Until now, there have been no compounds that are highly selective enough to confirm the action of each pathway. Recent studies have shown that high doses of hallucinogens such as MDMA and psilocybin in combination with psychotherapy can have long-term effects on anxiety and depression, but hallucinations brought about as side effects are known to be effective. is viewed as a problem. For this reason, there has been a demand for the discovery of compounds with less risk.

When the compound designed by Mr. Shoische et al. was tested on mice, it was said that the effect of improving symptoms similar to human anxiety and depression was enormous. Also, it seems that almost no head spasm reaction, which is a sign of hallucinogenic action, was confirmed.

The team's next project is to further optimize the compound and make it selective enough to be used in clinical trials.

in Science, Posted by log1p_kr