We Now Know Why Ketamine Is So Effective At Treating Depression

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Ketamine, the veterinary anesthetic turned party drug, has previously been shown to rapidly and radically reduce symptoms of depression in some people. However, until now, scientists have been uncertain about how it actually does this.

A new study might just have the answer. As reported in the Nature journal Molecular Psychiatry, researchers from the University of Illinois at Chicago (UIC) have detailed the mechanism of how ketamine dampens the symptoms of depression and keeps it at bay. It turns out, it works in a remarkably similar fashion to SSRIs, the most commonly prescribed class of antidepressants.

It’s all to do with things called "G proteins" that produce cyclic AMP, a messenger which nerve cells need to signal properly. As earlier studies have shown, people with depression have higher numbers of G proteins packed into their cell membranes. This appears to dampen the signals of cells and may contribute to symptoms of depression, most notably the feeling of emotional numbness.

Their previous work has detailed how SSRIs help to move G proteins off of "lipid rafts" on the cell membrane, freeing them up and allowing them to work again. Ketamine appears to do the exact same thing, however, it manages to do so within just 15 minutes. Furthermore, the G proteins were very sluggish when moving back onto the lipid rafts, perhaps explaining why ketamine has such a profound and long-lasting effect on people.

Previously, scientists thought ketamine worked solely by blocking a cellular receptor called the NMDA receptor, however, this study suggests that this is not the whole story.

"When G proteins move out of the lipid rafts, it allows for better communication among brain cells, which is known to help alleviate some of the symptoms of depression," Mark Rasenick, distinguished professor of physiology and psychiatry at the UIC College of Medicine, said in a statement.

“This further illustrates that the movement of G proteins out of lipid rafts is a true biomarker of the efficacy of antidepressants, regardless of how they work," Rasenick explained. "It confirms that our cell model is a useful tool for showing the effect of potential new antidepressant drug candidates on the movement of G proteins and the possible efficacy of these drugs in treating depression."

Science and society at large are starting to relax their attitudes about using illicit drugs to treat health problems. Numerous studies have shown how ketamine could be used to treat a range of mental health problems, including severe depression, post-traumatic stress disorder (PTSD), and even obsessive-compulsive disorder (OCD).

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