SIU research may aid ketamine’s approval as antidepressant

By Tyler Crotzer, @TylerCrotzer_DE

Thirty-two percent of college students in 2014 admitted they felt so depressed that it was difficult to function, according to the National College Health Assessment involving 94,197 students from 168 universities.  

Researchers at SIU are working to better understand ketamine, which could potentially be a more effective antidepressant drug in preventing suicide.

Xiang Cai, who works in the department of physiology, hopes with more research into how ketamine works that a safely regulated fast-acting antidepressant can be manufactured and distributed to patients suffering from depression. Not only has ketamine been used to treat major depression disorder, but it has had success in suicide prevention because of its near immediate ability to curb suicidal thoughts. 


Without proper approval by the FDA, many people will not have access to ketamine as a way to treat their mental illness. There is only a select number of clinics in the U.S. that administer ketamine as an antidepressant, according to the Ketamine Advocacy Network, and because the drug is not FDA-approved, patients cannot use insurance to help pay for the expensive medication. 

In the four years Cai has researched ketamine, he has concluded it alleviates depression symptoms through enhancing excitatory synaptic transmissions in the brain. The hippocampus, the region of the brain responsible for emotions and memory, and the prefrontal cortex, the region that dictates critical thinking and decision making, are the main areas of the brain where Cai has detected the most excited neurons after administering ketamine to his subjects.

He injects five to 10mg/kg to a control group of mice or rats and a genetically modified group of mice or rats, and uses a variety of methods to analyze the rodents’ neurological transmissions, protein compositions and behaviors.

When dealing with neurons, one of the methods Cai uses is called patch clamp. This method records the intensity of ions as they pass through cells, which allows Cai to indicate what areas of the brain are being affected when ketamine is administered, according to the Leica Microsystems website. 

Cai’s research, which was funded by the National Institute of Mental Health’s research project grant and SIU start-up money, also consists of behavioral tests on rodents, such as the sucrose-preference test, novelty suppressed feeding test, forced-swim test and Morris water maze test.

The forced-swim test is one of the most widely used behavioral tests for examining potential antidepressants. The test is based on the notion that when a rodent is placed in an inescapable cylinder filled with water it will become immobile, expressing a depressive state of despair, according to National Center for Biotechnological Information website.

After administering this test, Cai noted the rodents that had been administered ketamine struggled to escape for longer periods of time than rodents in the control group, expressing a non-depressive state.   


Ketamine is in a different class of drugs than the most commonly prescribed antidepressants and affects the brain in a differently, allowing it to work for patients that have had unsuccessful treatments with other drugs, according the WebMD. 

There has been controversy about Ketamine’s use as an antidepressant, as it already holds a place in society as a party drug, producing dissociative and hallucinogenic effects on the user. It can also have sedative effects when administered in high doses or in combination with alcohol, creating use as a date-rape drug on unsuspecting party-goers, according to the Drug Enforcement Agency. 

MORE: Carbondale group fights the use of ketamine as date-rape drug

There are not any active cases involving ketamine in Carbondale, said Carbondale police Sgt. Corey Kemp, but a lack of cases does not indicate an absence of the drug. 

No cases involving ketamine have been investigated by the DEA based in Carbondale either.

Ke Zhang, a graduate student conducting research with Cai for the past 2 years, said she was excited about the opportunity to research ketamine as an antidepressant.   

“However, the psychotomimetic properties and abuse potential of ketamine necessitate caution in promoting this compound as a general treatment for depression,” she said. “Understanding the underlying mechanism of action of ketamine linked to behavioral improvement is of significant importance for developing novel, safe and fast-acting antidepressants.”  

Tyler Crotzer can be reached at [email protected] or 618-536-3325.