Ketamine for Mental Health Conditions: New Findings

The new discovery could lead to a ketamine treatment for depression that has all the benefits without the drug's side effects.

Researchers have figured out a way to reformat the party drug ketamine that could enable them to utilize the drug’s powerful properties for treating depression without opening patients to a host of negative side effects.

Hydroxynorketamine, a chemical byproduct of ketamine created as the body breaks the drug down, has been shown in the past to reverse depressive symptoms in mice. The new research, published in the journal Nature, found that this metabolite blocks the NMDA receptor in the brain, which ketamine has also been shown to block.

Lisa Monteggia, a neuroscientist at the Peter O’Donnell Jr. Brain Institute at the University of Texas-Southwestern, who led the research, said that this finding is instrumental in understanding how ketamine and related compounds can be used to treat mental health issues.

“It pinpoints the fact that it is this receptor we need to engage or block to trigger a rapid antidepressant effect,” she told Quartz. “This is the target; this is the pathway.”

Ketamine has been praised for its ability to quickly alleviate the symptoms of depression, providing a potentially life-saving options for the sickest patients with treatment-resistant depression.

“Those [who don’t respond to existing antidepressants] are the ones who become most at risk of suicide,” Monteggia said. “If you could identify more rapid antidepressants, it could have very real implications for people not only with depression, but who are potentially suicidal.”

Despite its promise, studying ketamine has been complicated by the drug’s powerful side effects, which can include hallucinations, panic attacks and nausea. This makes many doctors and researchers wary of using the drug.

“As a physician, you take an oath to do no harm,” said Carolyn Rodriguez, MD, PhD, an assistant professor of psychiatry and behavioral sciences at Stanford’s School of Medicine. “There are caveats with ketamine. People can feel disassociated, like they are floating; some feel nauseated.”

Monteggia said that she hopes using a metabolite of ketamine will lead to treatments that have the benefits without the strong side effects. She also said that studying the way that ketamine and related compounds work on the brain could lead to a better understanding of depression and related mental health issues, as well as their treatments.

“Can we use this ketamine finding to understand how widely prescribed antidepressants work? Is there a point where they [the effects of Prozac and ketamine] intercept?” she questioned. “This has been one of the most exciting developments in the field of psychiatry in a long time.”