Psychedelics without hallucinations? Study identifies possible antidepressants in LSD-like molecules

According to a scientific study published Wednesday in Nature, a group of computational biologists may have found therapeutic potential in a handful of molecules adjacent to LSD. They generated 3D iterations of more than 75 million related molecules that don't actually exist but could, STAT reported. They found that these "synthetic quasi-psychedelic molecules appeared to have distinct antidepressant activity" in mice, without the hallucinations traditionally associated with psychedelics.

Brian Roth, a psychiatrist and pharmacology researcher at the University of North Carolina, explained that determining whether patients are fit for psychedelic therapies to ward off "bad trips" can be time-consuming and complex (and costly process). "This can significantly increase the cost and complexity of these treatments," Roth said.

"You're looking at thousands and thousands of dollars that a typical person would have to pay out of pocket. If you're thinking about deploying these treatments for the world's population, there will never be enough therapists for anyone suffering from depression."

The research was first discussed at a conference by Brian Shoichet, a scientist from the University of California, San Francisco, who co-led the research, and the chemist from Yale Jon Ellman. They contacted Roth, who received $26.9 million in DARPA (Defense Advanced Research Projects Agency - DOD) funding to develop better psychiatric drugs for depression, anxiety, and drug use disorders. of substances.

Researchers built 75 million compounds and tasked a computer to fit them into a 3D rendering of the serotonin 5-HT2A receptor that interacts with LSD. 17 of these compounds have been synthesized. "It's like the computer is trying to figure out a 3D puzzle," Shoichet said.

"We were very surprised that the compound had antidepressant activity similar to ketamine and psilocybin, two fast-acting antidepressant psychedelic drugs," added Roth, who is also professor emeritus of Pharmacology Michael Hooker at the UNC School of Medicine. “We were basically running a chemistry experiment to see if we could create a compound to activate 5-HT2A. Once we got there, we decided to experiment with mice."

"Two of them seemed to interact with serotonin receptors and were tested on mice. The molecules had antidepressant activity: they were just as effective in mice as fluoxetine or Prozac, but at a dose that was 40 times lower. And despite the small amount that was administered, the antidepressant effect...lasted for several weeks," STAT reported. "Scientists are now trying to make the molecules better and more selective for serotonin. They're also trying to remove unnecessary portions that might have off-target effects or toxicities.

"UCSF, Yale and UNC-Chapel Hill have a patent on the particular molecules for depression (...), but the overall library is supposed to be publicly available."

Image by Okan Caliskan On