Ketamine may rebuild broken brain synapses, according to new research

Unfounded blame game.
Unfounded blame game.
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The body of science showing that ketamine, the drug best known for its recreational use, might one day become a prominent treatment for depression is growing.

A new study published April 11 in the journal Science shows that not only does ketamine offer fast-acting and temporary relief for depression, but the drug appears to actively repair damaged brain circuits, as well. So far, evidence of such reparative effects has only been tested in mice, but if it winds up proving to have a similar effect in humans it may constitute a breakthrough in treating the mental illness.

A team of researchers administered a stress hormone to lab mice that causes them to exhibit depressive symptoms: They lose interest in eating foods that typically excites them, and stop engaging in normal activities, such as walking through lab-made mazes. After giving the mice the hormone, the scientists used laser-scanning microscopy to examine the animals’ brains to note any changes to their brain synapses, the connections between neurons. They noticed the animals lost a bunch of synapses when they were stressed.

So then the researchers gave the mice ketamine before performing the same microscopic inspection. According the study, the ketamine worked in two steps. First it temporarily gets broken brain circuits to function better. Then it actually repairs those circuits by rebuilding the synapses around them that serve as the connectors between cells. Ultimately, this helps the cells in the brain communicate more effectively as a network.

Though this study was in mice, the overall body of evidence behind the medical benefits of ketamine is not exclusive to the lab animals. In April 2018, a study published by the American Journal of Psychiatry found that in human subjects the drug offered temporary and rapid relief for symptoms of depression. That built upon work published a year earlier in the journal Nature, which showed that a metabolite in the drug pinpointed and blocked the NMDA receptor, known to be associated with the effects of depression, in lab mouse brains.

According to the US Centers for Disease Control and Prevention, about one in six adults will have depression at some point in their life. The condition affects close to 16 million Americans every year and it can occur across the entire age spectrum.

In March, the US Food and Drug Administration approved esketamine, a drug derived from ketamine. It will be formally marketed as Spravato and will come in the form of a nasal spray released by Janssen Pharmaceuticals, a branch of Johnson & Johnson.