How Does Ketamine Affect The Brain? New Research Is Shedding Light On Why The Drug Is Helpful For Depression

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For a few years, there's been a new drug on everybody's lips when it comes to depression treatment: ketamine. Ketamine is used both as an anesthetic and as a hallucinogenic drug, but has held promise as a potential therapy for treatment-resistant depression — only, scientists haven't been able to figure out why. But new research has shed new light on how ketamine affects your brain to help bust depression. And that's great news for depression sufferers, because the more we understand ketamine, the more we can test its wider use.

In 2014, Oxford scientists tested ketamine on 28 people whose depression had totally refused to lift despite every conventional treatment on the books — therapy, selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs) and everything else currently legalized for treating depression. The results were seriously promising: 30 percent of the patients felt a considerable lift in their symptoms that lasted at least a couple of weeks.

And other studies have produced some pretty interesting results. We've discovered that ketamine is incredibly fast-acting — which is part of the reason it became so popular as a party drug, with its swift "high" — and wears off quickly. But beyond some vague theories that ketamine may help severely depressed people because it targets an area of brain signaling called the N-methyl-D-aspartate (NMDA) receptor, which seems to function oddly in depressed people, we haven't known why ketamine does what it does. Until now.

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The new science, from researchers at Zhejiang University, reveals that ketamine works on depression because of a bit of your brain you may not have realized was there: the lateral habenula. Aside from being a magnificent name for a science fiction villain, it's also an important part of brain functioning when it comes to emotional processing. The lateral habenula is related to "anti-reward" feelings. In other words, it deals with emotions and feelings we find difficult and want to stay away from. A 2017 study found that the lateral habenula's functioning goes wrong in animals with depression, whether they're lab mice, primates, or humans. The "wrongness" isn't quite understood yet, but it has something to do with the neurons, or brain cells, in the lateral habenula, and how they "fire." And when ketamine gets involved, it seems to fix things.

Basically, the Zhejiang University scientists found that in animals with depression, including humans, the neurons in the lateral habenula, or LHb, "burst" into activity in a particular way, and very often. That seems to signal a depressive episode. When people and animals are given ketamine, those "bursts" stop and the neurons function in a more normal way. Why? Because the "bursts" appear to be dependent on the NMDA receptor, and ketamine cuts those right out. Ketamine basically acts as a traffic cop, swiftly blocking off signals to the negative-emotion bit of the brain, and stopping it from going haywire.

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This is a big deal. Understanding how ketamine works in the brain means it's less risky to test it out on humans or to create trials for its potential as a drug that could go to market. But ketamine has only been tested for this use in lab settings, and for now should not be used to treat depression without a doctor's supervision. For one, it's only been tested on people with treatment-resistant depression in clinical settings; for another, it's also been associated with the development of depressive symptoms, among other potential negative side effects. You'd not only put yourself in danger, you'd also risk your depression getting worse.

Now that we know a bit more about ketamine as a potential treatment for depression, researchers are still facing a few problems — including the well-known issue that it wears off very fast. This new insight into the brain can help us potentially understand how to extend its beneficial effects.

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