Ketamine has come a long way from its reputation as a party drug and veterinary anesthetic. In recent years, it has been used in medical treatments for conditions like depression and post-traumatic stress disorder (PTSD).
However, its use remains controversial, especially after the 2024 death of actor Matthew Perry from a ketamine overdose. His passing reignited debates over the safety of prescribing a hallucinogenic drug to patients with mental health conditions.
Despite these concerns, ketamine’s effects on the brain are not fully understood. Scientists have long suspected that it works by blocking a specific brain receptor called GluN1-2B-2D, a type of NMDA receptor (NMDAR) involved in brain signaling. However, there was a major gap in research—scientists weren’t even sure if GluN1-2B-2D existed in the human brain.
Now, researchers at Cold Spring Harbor Laboratory (CSHL) have solved the mystery. A new study led by Professor Hiro Furukawa and postdoctoral researcher Hyunook Kang, published in Neuron, confirms that GluN1-2B-2D does exist in the mammalian brain and sheds light on how ketamine interacts with it.
Unraveling the Brain’s Ketamine Response
Using advanced imaging techniques like electron cryo-microscopy (cryo-EM), the researchers reconstructed a human version of GluN1-2B-2D and observed how it behaves. They identified a tension-and-release mechanism that controls how the receptor’s ion channel opens and closes.
This breakthrough allowed them to map how ketamine binds to GluN1-2B-2D. The team discovered four different ways the drug can attach to the receptor, shutting down its channel like a mesh that blocks signals. However, they believe there may be many more binding patterns yet to be discovered.
What This Means for Ketamine Therapy
Scientists think ketamine relieves depression and anxiety by altering GluN1-2B-2D’s movements, but the effects can vary widely among patients. Some experience mild relief, while others may develop severe side effects like hallucinations or even psychosis.
One major question remains: How long should the receptor remain open or closed to provide effective treatment without harmful side effects?
“Each patient likely needs a different duration,” says Furukawa. If researchers can determine how GluN1-2B-2D movements influence mental health, they may be able to develop safer, more effective ketamine-based treatments—ones that provide the benefits without the risks.
The Future of Ketamine Research
Furukawa’s team now plans to focus on designing new versions of ketamine that minimize side effects while still offering relief for patients with depression and anxiety. This research could bring hope to millions of people struggling with mental health conditions, potentially leading to safer and more targeted therapies.
By uncovering how ketamine interacts with brain receptors at a molecular level, this study marks a significant step forward in neuroscience and psychiatric medicine. While there is still much to learn, these findings could shape the future of ketamine therapy—and mental health treatment as a whole.
If you care about depression, please read studies about how dairy foods may influence depression risk, and B vitamins could help prevent depression and anxiety.
For more information about mental health, please see recent studies that ultra-processed foods may make you feel depressed, and extra-virgin olive oil could reduce depression symptoms.
The research findings can be found in Neuron.
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