Ketamine to treat depression: A new study highlights the effects of “special K”


“Depression is the second most expensive health problem that we face worldwide, but this fact is not very well known because there is a stigma attached to depression and people don’t like to talk about it. About 17 percent of Americans will be treated for depression at some point in their lives, but there are limited treatment options and about one-third of patients do not respond to these treatments,” according to Bernhard Lüscher, the author of a recently published 2016 study in Biological Psychiatry.  

Dozens of antidepressant pharmacological treatments include selective serotonin reuptake inhibitors (SSRIs), which are the most commonly prescribed and the first-line treatment for depression. Antidepressants on average take approximately four to six weeks to have any effect on the individual’s mood and, as a result, this is the most common reason for noncompliance.  

A delicate balance

A recent study released in May 2016 tested the efficacy of ketamine on mice to determine how ketamine influences gamma-aminobutyric acid (GABA) and glutamate signaling in the brain. Ketamine is a well-known anesthetic used in procedures and operations in the hospital setting. Ketamine is also widely used on the street illegally and is commonly known as “special K.” A common party drug, ketamine produces a euphoric state but not without adverse side-effects.  

GABA and glutamate are well-known neurotransmitters in the brain that help regulate mood and emotions. Certain drugs such as benzodiazepines and alcohol work specifically on the GABA receptors. GABA is known as an inhibitory neurotransmitter, meaning that it slows the activity of nerve cells. Glutamate, on the other hand, has opposite effects and is known to increase activity in nerve cells. GABA and glutamate are in a strict equilibrium with one another, meaning that if one is increased or a decreased, it can tip the table, having a profound effect on mood stability.  

In this study, the experimenters reduced the activity of GABA in mice and discovered that glutamate was also reduced as a result. Ketamine was introduced to mice who expressed the knockout/mutation gene for GABA. This experimental antidepressant is known to decrease glutamate in normal active nerve cells.  

More research needed

In this experiment ketamine normalized the activity of glutamate receptors and also restored GABA activity in these mice. This effect was only true for the mice who expressed the knockout mutation and not for the control (normal) mice. This experiment has led researchers to believe that depression is regulated by both GABA and glutamate, not just serotonin and norepinephrine. By exploring the effects of ketamine on both GABA and glutamate, future research can be performed to understand more clearly the antidepressive effects of ketamine.  

Ketamine has shown to have antidepressive properties and this drug acts much faster than the alternative antidepressant agents. It has been administered in many different forms such as oral, intranasal and intravenous with intravenous and intranasal having the fastest-acting effects. This is a relatively new treatment for depression and many more studies and research must be done. It is known that ketamine has a high addiction potential due to the fact that it is a popular street drug, therefore caution must be taken before using this drug for any type of long-term treatment. Although this is a relatively new approach to treating depression, like any new drug therapy, a long road ahead awaits before this drug takes precedence over SSRIs.  

White River Academy is a therapeutic boarding school for adolescent males from age 12 to 17 that treats substance abuse, numerous mental health conditions including depression and anxiety, and co-occurring conditions. For more information about our programs, please call our 24/7 helpline.  

About the author

Kristen Fuller, M.D., is a senior staff writer and enjoys writing about evidence-based topics in the cutting-edge world of medicine. She is a physician and author, who also teaches, practices medicine in the urgent care setting and contributes to medicine board education. She is also an outdoor and dog enthusiast. 

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