New Study Shows How Ketamine Could Treat Chronic Depression

Originally approved by the FDA as an anesthetic in 1970, ketamine is a dissociative drug that can produce visual and auditory distortion as well as dissociation. However, studies have found that with a low dosage, the drug can be used to treat intractable depression.

Recently, the FDA approved use of a nasal spray called esketamine as a safe treatment for depression. However, researchers were unsure about the molecular mechanisms of the drug and how it directly affected the brain's response to depression. Many hypothesized the drug increased production of a neurotransmitter called glutamate, but researchers at the Karolinska Institutet in Sweden found the opposite to be true. The study, which was published last week by Molecular Psychiatry, shines a light on the molecular mechanisms that allow ketamine to employ its anti-depressive characteristics.

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Ketamine, which is used as a medical aesthetic but also as a recreational party drug, could ease the symptoms of depressions, according to a new study. The World Health Organization estimates that more than 264 million people suffer from depression worldwide. Getty Images

The World Health Organization estimates that more than 264 million people suffer from depression worldwide and that close to 800,000 people die due to suicide each year. Of these sufferers, many claim that common treatment does not relieve their depression.

The most commonly prescribed anti-depressant is a class of drugs known as SSRIs, or selective serotonin reuptake inhibitors. SSRIs work by increasing the production of serotonin in the brain. Serotonin's primary responsibility is regulating anxiety and stabilizing mood. However, over 30 percent of patients treated with SSRIs experience little to no relief, according to neuroscientist Per Svenningsson from the Karolinska Institutet.

Unlike these common anti-depressants, ketamine directly affects the body's glutamate neurotransmitter, which is closely related to overall mental health. Used as a treatment for depression, ketamine can relieve suicidal thoughts and other symptoms of depression quickly.

Using experiments on mice and cells, researchers found ketamine actually reduces activity within the glutamate system, the opposite of what researchers initially believed to be true. "Elevated glutamate release has been linked to stress, depression and other mood disorders, so lowered glutamate levels may explain some of the effects of ketamine," explained Svenningsson.

Researchers also found that ketamine directly affects AMPA receptors which increases the release of a particular neurotransmitter that inhibits glutamate release. This decrease in glutamate happens almost immediately and many treated with ketamine say they feel the results within hours.

"These effects could contribute to the efficacy of ketamine to instantly alleviate depressive symptoms and suicidal ideation, taking into account that excessive glutamate levels have been linked to MDD and other mood disorders," according to the study.​​

Now that scientists can explain how ketamine affects the brain, many believe that this will allow for more breakthroughs in depression treatments.

"Understanding the mechanisms of ketamine's rapid-onset anti-depressant action may aid the development of novel antidepressant medications that have fewer side effects," the researchers wrote in the study.