new study suggests that a metabolite of ketamine — not the drug itself — fights depression. Inside the body,
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, ketamine gets converted into a slew of related molecules. One of these breakdown molecules,
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, a chemical called (2R,6R)-hydroxynorketamine, is behind the benefits,
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, neuropharmacologist Todd Gould of the University of Maryland School of Medicine in Baltimore and colleagues found.
On its own,
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, a single dose of (2R,6R)-HNK reduced signs of depression in mice,
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, restoring their drive to search for a hidden platform in water, to try to escape a shock and to choose sweet water over plain. A type of ketamine that couldn’t be broken down easily into HNKs didn’t ease signs of depression in mice. Finding that a breakdown product, and not ketamine itself, was behind the results was a big surprise,
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, Gould says.
That surprise could turn out to be valuable. Ketamine comes with serious side effects for people — hallucinations, floating sensations and clumsiness, for example. And at high enough doses, the drug is an anesthetic. But (2R,6R)-HNK may avoid these problems,
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, experiments on mice movement indicate. “It’s actually pretty amazing how high a dose we went up to and didn’t see any ill effects,” Gould says. And since ketamine has already been used to treat depression, he says, the breakdown product has been inside people with no apparent ill effects.
Gould says that the behavioral improvements and lack of side effects make him optimistic that (2R,
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,6R)-HNK can be developed into a safe and effective antidepressant. He and his colleagues plan to test the ketamine

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