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 might have found therapeutic potential in a handful of LSD-adjacent molecules. They generated 3D iterations of more than 75 million related molecules that don’t actually exist but could, reported STAT. They found that these “synthetic, near-psychedelic molecules seemed to have distinct antidepressant activity” in mice, without the hallucinations traditionally associated with psychedelics.

No More Bad Trips?

Brian Roth, a psychiatrist and pharmacology researcher at the University of North Carolina, explained that determining if patients are fit for psychedelic therapies to ward away “bad trips” can be a long and complex (and costly) process. “This can dramatically 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 think about rolling out these treatments for the world’s population, there will never be enough therapists for everyone who is depressed.”

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

A ‘3D Jigsaw Puzzle’

Researchers built 75 million compounds and tasked a computer with fitting them against a 3D rendering of the 5-HT2A serotonin receptor which interacts with LSD. 17 of those compounds were synthesized. “It’s like the computer’s trying to figure out a 3D jigsaw puzzle,” Shoichet said.

“We were very surprised the compound had any anti-depressant activity similar to ketamine and psilocybin, both rapidly acting antidepressant psychedelic drugs,” added Roth who is also Michael Hooker Distinguished Professor of Pharmacology 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 achieved that, we decided to run experiments in mice."

STAT Weighs In

"Two of these seemed to actually interact with the serotonin receptors and were tested in 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 quantity that was administered, the antidepressant effect (...) lasted several weeks,” STAT reported. “Scientists are now trying to make the molecules better, and more selective for serotonin. They’re also trying to carve away unnecessary portions that could 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 meant to be available to the public.” 

Image By Okan Caliskan On Pixabay.