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A drug based on LSD appears to treat depression in mice without the psychedelic trip

AILSA CHANG, HOST:

Drugs like magic mushrooms and LSD can act as powerful antidepressants, but they also produce mind-bending side effects. Well, NPR's Jon Hamilton reports on a drug based on LSD that appears to treat depression in mice without taking the animals on a trip.

JON HAMILTON, BYLINE: Antidepressants like Prozac act on the brain's serotonin system. So do psychedelic drugs. But with psychedelics, the effect can occur in hours instead of weeks and last for months. Brian Shoichet from the University of California, San Francisco, says the best evidence so far involves people with depression who take psilocybin, the active ingredient in magic mushrooms.

BRIAN SHOICHET: There's really interesting reports about people getting great results out of this after just a few doses.

HAMILTON: One study found the results can last a year or more, perhaps because the drug causes the brain to rewire. Psychedelic drugs, though, require medical supervision and a therapist to guide a patient through their hallucinatory experience. Shoichet says that's an impractical way to treat millions of people with depression.

SHOICHET: The society would like a molecule that you can, you know, get prescribed and just take - you know, go home and take, and you don't need a guided tour for your trip.

HAMILTON: So Shoichet and a large team of researchers are looking for that molecule. They started with a virtual collection of about 75 million hypothetical drugs likely to act on the brain's serotonin system. Shoichet says ultimately, the scientists focused on just two.

SHOICHET: They had the best properties. They were the most potent, and when you gave them to a mouse, they got into the brain at high concentrations.

HAMILTON: A test of one of these drugs found it did seem to relieve depression in mice. A depressed mouse tends to give up quickly when placed in an uncomfortable situation like being dangled from its tail. But the same mouse will keep struggling if it gets an antidepressant drug like Prozac, ketamine or psilocybin. Dr. Bryan Roth, a psychiatrist at UNC-Chapel Hill and another member of the team, says the molecule based on LSD had a similar effect.

BRYAN ROTH: We found our compound had essentially the same antidepressant activity, at least acutely - so one day later.

HAMILTON: But were those mice tripping? Apparently not. Psychedelic drugs cause mice to twitch frequently in a distinctive way. And Roth says that wasn't the case with mice that got the team's LSD-based compound.

ROTH: We were, I would say, surprised to see that they had no psychedelic drug-like actions at all.

HAMILTON: Studies in people are still a ways off. Even so, Roth says the approach points to a class of depression drugs that would have a huge advantage over products like Prozac and Zoloft, which are taken every day.

ROTH: The difference with psychedelics and the compounds that we're excited about is that it's basically one and done. Patients basically take one dose, and then they're fine.

HAMILTON: That's an optimistic view, says David Olson of the University of California, Davis. Olson, who helped create a non-psychedelic version of the drug Ibogaine, says he's skeptical that a single dose of these new compounds can eliminate depression.

DAVID OLSON: But I do think they take us a step closer to a cure, rather than simply treating disease symptoms.

HAMILTON: Olson says drugs based on psychedelics have the potential to help people who haven't responded to existing antidepressants. And because they work immediately, he says, they could be integrated into a psychotherapy session.

OLSON: You might imagine a day where a patient could take one of these drugs at home and then interact with their therapist via virtual platform like Zoom.

HAMILTON: The new research appears in the journal Nature.

Jon Hamilton, NPR News. Transcript provided by NPR, Copyright NPR.

Jon Hamilton is a correspondent for NPR's Science Desk. Currently he focuses on neuroscience and health risks.