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Ketamine treatment has helped fill in details that the serotonin model of depression missed

Ketamine helps treat depression by creating neuroplasticity

The Serotonin model of depression missed a lot, ketamine treatment for depression helped fill in some of the gaps


The serotonin model of depression has been outdated for decades. This theory came out in the early 1960’s and was the best explanation for depression with the resources of that era. The original model assumed that people experiencing depression were deficient in Serotonin, a neurotransmitter that our bodies use to send signals between cells in our brain.  There are different types of receptors for this important chemical and they are found in different parts of the body. In the brain, these serotonin receptors help different parts of the brain communicate with each other. What we’ve learned recently is that this molecule and it’s receptors are only a small piece of the puzzle.

The old model has been helpful in furthering the understanding of depression and other mental health problems.

This model has been helpful in helping us understand depression and other mental health problems. This is because the model was one of the early explanations of mental illness that introduced a biological cause based in actual physiology. In the 1960’s it was found that

The old model says that depression and anxiety are caused by the lack of serotonin, a neurotransmitter that’s part of your brains everyday function.

The old model of depression says that depression and anxiety are caused by the lack of this important neurotransmitter that’s part of your bodies everyday function.

As we said earlier, serotonin is a chemical that communicates between neurons—the cells in your brain that carry messages between different parts of the brain and nervous system. These different parts of the brain make up what we call “networks” which are areas of the brain that work together to accomplish different tasks.

We previously thought that being depressed or anxious was caused by, low serotonin levels. Causing your brain to not have enough of this molecule to help regulate your moods or make decisions about what to do next. This model did expand to include other important neurotransmitters like dopamine and norepinephrine. So for many years medications were designed to help increase the availability or improve the effects of these three chemicals in the brain.

Then research on ketamine came in – ketamine helps your brain to create neuroplasticity or the ability to form new pathways between the brains networks. We’ve learned that the brain does this by increasing another neurotransmitter glutamate which results in an increase in BDNF or Brain Derived Neurotropic factor encourages the brain to grow new connections and strengthen existing connections. See our blog on the Default Mode Network and Glutamate model of mental illness.

So how does ketamine do all of this and what is Glutamate? It turns out that ketamine is an NMDA receptor antagonist. An NMDA receptor is a protein in the brain which interacts with glutamate, a neurotransmitter involved in learning and memory. Glutamate also plays an important role in regulating mood and anxiety.

In fact, when you take ketamine you block this interaction between glutamate and your brain’s receptors for it! That’s why people who take ketamine say they feel so “at peace” or detached from their bodies—the drug stops them from being able to access these memories. At the same time, ketamine creates the ability of your brain to form new pathways of communication between those important brain networks.

The reason that disconnecting from those memories is important, is that we think that trauma causes a disruption of the brains network communication. In an effort to protect us from things we see as harmful, our brains create faster pathways to those traumatic or “dangerous” experiences. As we get older, our brains try to save energy by following those shortcuts to the protective information. Even if it that information is no longer helpful! These shortcuts are why people in depression often have the same negative thoughts at rest, or struggle to think clearly and make decisions or process emotional information quickly. This causes our brains communication to be out of balance, and prewired for negative or scary thoughts.

Ketamine helps restore the balance between the default mode network and other areas of the brain in depressed patients

Ketamine and its ability to block those negative pathways temporarily while giving the opportunity to create new and healthier pathways is a big part of why ketamine is so effective at treating depression and other mental illness. The effects of ketamine on the NMDA, Glutamate, BDNF, and many other portions of the brain give us an opportunity to help restore the balance of those brain networks communication. Which gives the person receiving ketamine treatment a chance to heal from depression, anxiety, PTSD and more.

In our clinic located in Aurora just outside of Denver, we’ve seen huge improvements in patients suffering from depression, anxiety, and PTSD with ketamine treatment.


Ketamine is an important breakthrough that has helped us to study how depression works in a way that wasn’t possible before. It’s also a potential treatment for people who have tried everything else without success. We’re excited about what this means for the future of psychiatry and mental health care in Aurora and Denver!

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