How Does Ketamine Work for Depression

How ketamine works for depression is not fully understood but viable theories exist. On HealthyPlace, see how ketamine affects the brain and reduces depression.

Thousands have now tried ketamine treatment for major depressive disorder and bipolar depression leaving many people asking, “How does ketamine work for depression?” Because ketamine is a medication that acts on the brain, understanding how ketamine works is a little complicated and even a little unknown.

What Is Ketamine?

Ketamine is considered a general anesthetic. It has been used as anesthesia for surgery as well as in pain management. Ketamine is not the most common anesthetic for human use, although it is common in veterinary medicine. Typically, ketamine is administered via intravenous drip although other administration routes such as oral or intranasal are also available.

While ketamine is not Food and Drug Administration (FDA) approved to treat major depressive disorder or bipolar depression, these uses do occur due to the promising efficacy rates of ketamine for depression.

How Does Ketamine Affect the Brain?

Cells that specialize in nerve impulses are called neurons. There are over 100 billion neurons in the human brain. According to an article in eLife, a biology periodical out of Cambridge University in the United Kingdom,

“Neurons communicate with one another by releasing chemicals known as neurotransmitters, which transfer information by binding to receptor proteins on the surface of other neurons. Drugs such as ketamine also bind to these receptors. Ketamine works by blocking a specific receptor called the n-methyl d-aspartate (NMDA) receptor. . .”

Because ketamine restricts the activation of these NMDA receptors, it is theorized that normal levels of protein synthesis are restored and neuron communication is improved in the brain’s cortex. This, in turn, is thought to reduce depression.

However, while it is understood that ketamine creates a rapid increase in protein synthesis, it is unclear how a drug like ketamine actually does this.

How Does Ketamine Help Depression?

Ketamine is a rapid-acting medication in the treatment of depression, both in major depressive disorder and in the depressive phase of bipolar disorder. Positive effects of ketamine are often seen within hours of intravenous administration. This makes it very valuable in the treatment of severe depression, and suicidality is also decreased with ketamine treatment. Ketamine has also been shown to be very effective even in those with treatment-resistant depression. This development is important as those who are treatment resistant now have very few viable treatment options.

The Technical Details of How Ketamine Helps Depression

How ketamine helps with depression is currently under debate. One theory suggests that a particular subunit of a cortical MNDA receptor known as GluN2B, acts to suppress signaling and repress protein synthesis. Once ketamine, a GluN2B antagonist is applied, these changes are reversed. This results in antidepressant effects in both human and rodent models.

Knowing How Ketamine Works

While there are theories on how ketamine works on the brain to produce an antidepressant response, it is not completely understood. Nevertheless, many trials and even clinical practice show the usefulness of this medication in the treatment of depression. And while researchers will continue their quest to fully understand this medication, a full understanding is not needed to help those with major depressive disorder or bipolar depression.

APA Reference
Tracy, N. (2022, January 4). How Does Ketamine Work for Depression, HealthyPlace. Retrieved on 2024, July 15 from

Last Updated: January 11, 2022

Medically reviewed by Harry Croft, MD

More Info