Ketamine is known to be able to reverse the symptoms of depression very quickly. It has been shown to treat depression in a matter of hours. Most antidepressant medications take a number of weeks or months for results to be reached. Sadly, the drug comes with many major side effects, such as hallucinations or even dissociation. Thankfully, researchers recently discovered a metabolite of ketamine that has successfully reversed depression within mice, with zero side effects.

Todd Gould, a researcher at the Department of Psychiatry within the University of Maryland’s School of Medicine says this new information has the potential of becoming a major breakthrough that may offer the fast help of ketamine to sufferers of depression without all the risks. Most depression medications increase neurochemical levels in the brain. Most commonly, SSRIs are used but these drugs are only helpful to about half the patients they are prescribed to. Moreover, when the drugs do work properly, they do not take effect for up to two months. Ketamine does not work by increasing serotonin or norepinephrine levels, and offers help within just a few hours following first treatment.

Work for the project was done by scientists at the University of Maryland School of Medicine (UM SOM), the NIH National Institute of Mental Health (NIMH) , the NIH National Center for Advancing Translational Sciences, the NIH National Institute on Aging and the University of North Carolina.

Scott Thompson, co-author and UM SOM researcher says the team has been working for years to try to find ways to treat depression more effectively. He has spent over ten years studying the link between glutamate and depression and calls these results exciting vistas for a new generation of antidepressant compounds. It has been 30 years since the last generation of such meds were introduced.









Mice were used in these new tests to see how different ketamine metabolites effected the body. Metabolites are chemicals that are created when ketamine is broken down. Hydroxynorketamine ended up being the main focus of the study, which is shocking because it was previously believed to not have any psychoactive effects. When the transformation from ketamine to this metabolite was stopped, so were ketamine’s antidepressant actions. Hydroxynorketamine also showed antidepressant effects with zero of the side effects previously associated with treatment via ketamine.

Co-author and NIMH researcher, Carlos Zarate says thanks to the newest research ketamine has been reverse-engineered to better understand its properties. He says this holds great promise for future developments of a much safer and wider scale treatment of depression. Ketamine is known to block the NMDA glutamate receptor. In the past researchers believed ketamine probably worked as an antidepressant in a very similar way. This was proven false upon the finding that hydroxynorketamine actually stimulates a glutamate receptor called the AMPA receptor. Whether or not the metabolite does so directly or indirectly is not certain at this time.

There are plans to continue testing of hydroxynorketamine and how safe it would be in human trials. Gould believes the metabolite will prove to be safe as it has already been in humans for years after administration by ketamine.

The study was published this month in Nature journal.