LSD drug appears to treat depression in mice without the psychedelic trip: NPR

Scientists have identified a drug that appears to produce the antidepressant effects of LSD without the psychedelic side effects – at least in mice.


Drugs like magic mushrooms and LSD can act as powerful antidepressants, but they also produce mind-blowing side effects. Well, NPR’s Jon Hamilton reports on an LSD-based drug 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. Just like psychedelic drugs. But with psychedelics, the effect can occur within hours instead of weeks and last for months. Brian Shoichet of the University of California, San Francisco, says the best evidence to date involves people with depression taking psilocybin, the active ingredient in magic mushrooms.

BRIAN SHOICHET: There are some really interesting reports of people getting great results after just a few doses.

HAMILTON: A study has found results can last a year or more, possibly because the drug causes brain rewiring. Psychedelic drugs, however, require medical supervision and a therapist to guide a patient through their hallucinatory experience. Shoichet says it’s an inconvenient way to treat millions of people with depression.

SHOICHET: The company 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 this molecule. They started from a virtual collection of about 75 million hypothetical drugs that could act on the brain’s serotonergic system. Shoichet says that 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 entered the brain in high concentrations.

HAMILTON: A test of one of these drugs found that it seemed to relieve depression in mice. A depressed mouse tends to give up quickly when placed in an awkward situation, such as hanging from its tail. But the same mouse will continue to struggle if given 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 LSD-based molecule had a similar effect.

BRYAN ROTH: We found our compound to have essentially the same antidepressant activity, at least acutely – so a day later.

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

ROTH: We were, I would say, surprised that they didn’t have any psychedelic drug-like action.

HAMILTON: People studies are still far from complete. 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 compounds that we’re passionate about is that it’s basically one and done. Patients basically take one dose and then everything is fine.

HAMILTON: It’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 think they’re getting us closer to a cure, rather than just treating the symptoms of the disease.

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

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

HAMILTON: The new research appears in the journal Nature.

Jon Hamilton, NPR News.

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