A group of computational biologists might have found therapeutic potential in a handful of LSD-adjacent molecules, according to a study published Wednesday in Nature. They generated 3 D iterations of more than 75 million related molecules that don't 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.
Brian Roth, a psychiatrist and pharmacology researcher at the University of North Carolina, said that determining if patients are fit for psychedelic therapies to ward off bad trips can be a long and complex process. Roth said that this can greatly increase the cost and complexity of these treatments.
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 population, there will never be enough therapists for everyone who is depressed. The research was first discussed at a conference hosted by Brian Shoichet, a scientist at the University of California, San Francisco, who co-managed 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.
The researchers built 75 million compounds and tasked a computer with fitting them against a 3 D rendering of the 5 HT 2 A serotonin receptor that interacts with LSD. 17 of those compounds were synthesized. It is like the computer is trying to figure out a 3 D jigsaw puzzle, Shoichet said.
The compound had no anti-depressant activity similar to ketamine and psilocybin, both rapidly acting antidepressant psychedelic drugs, according to Roth, who is also Michael Hooker Distinguished Professor of Pharmacology at the UNC School of Medicine. We were running a chemistry experiment to see if we could create a compound to activate 5 HT 2 A. We decided to run experiments in mice once we reached that goal. Two of these seemed to 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. Despite the small amount administered, the antidepressant effect lasted several weeks, STAT reported. Scientists are trying to make the molecules more selective and better for serotonin. They are 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 specific molecules for depression, but the overall library is meant to be available to the public.