Chemical formula of ketamine

Ketamine

How Does Ketamine Work?

Ketamine is an NMDA receptor antagonist. Its antidepressant effects are thought to come from affecting the AMPA receptor.

Written by

Isha Team

published:

April 25, 2022

updated:

January 26, 2023

Your doctor has just recommended ketamine-assisted psychotherapy and you want to know more about it. Ketamine has been used as a surgical anesthetic since its approval by the FDA in1970, mainly used for surgical procedures in both humans and animals. It may not seem like the first choice for treating depression, but recent research has shown that it can also be effective in the treatment of major depression, anxiety, and PTSD.


You might be wondering, how exactly does ketamine work? What’s the difference between the type and amount of ketamine used for depression compared to what had been traditionally used for surgery?


In fact, there is no difference between the ketamine used in surgery and the ketamine used to treat depression. The only difference is in the dosage and how it is given. Ketamine-assisted psychotherapy for mental illness requires a much lower dosage, and it is administered either as a slow intravenous infusion, intramuscularly, intranasally or as an oral medication. It is thought that ketamine works by helping the depressed patient relax and forming new neuronal connections in their brain that lead to an improvement in their mood.


Ketamine Pills


Ketamine-assisted psychotherapy is often provided with an oral pill form of ketamine. The dosage is appropriately calculated based on its bioavailability rate which is about 20-30%.  Due to the slower absorption, oral ketamine tends to produce fewer side effects than when it is given intravenously.


Ketamine taken in these small sub-dissociative doses does produce a calming sense of well-being and aids the patient in seeing their world more clearly. Studies have demonstrated these small doses of ketamine are especially helpful to people with treatment-resistant depression, those who have tried other psychiatric medications without much success. Ketamine can also help people who are suffering from general anxiety disorder, social anxiety disorder, or PTSD.


Ketamine-assisted psychotherapy differs from traditional treatments for depression because it tends to work faster. Traditional methods for treating depression like psychotherapy and psychiatric medications can take weeks or months before a difference is felt. For people with deep depression, studies have shown that the effect of ketamine can be seen within hours or days in many cases.



Types of Ketamine


There are currently two types of ketamine employed for the treatment of major depression: racemic ketamine and esketamine. Arketamine and esketamine are molecules that are mirror images of each other. Esketamine is the S form of ketamine and its nasal spray form was approved by FDA for treatment-resistant depression in 2019. Racemic ketamine is a combination of both the S and R molecules. Although the S and R molecules are mirror images, they interact differently with the receptors in your brain.


Current scientific research is still investigating which form of ketamine is the more effective in treating depression [2] Although R-Ketamine has been shown to be less effective at binding the brain’s excitatory NMDA receptors, it has been shown to obtain better therapeutic results work and have longer-lasting antidepressant effects. [5] R-Ketamine has also been shown to have fewer adverse effects, although more research is needed to confirm these findings. [3]


ketamine treatment works on nmda receptors


Brain Receptor Interactions


Ketamine is still being studied to thoroughly understand its many benefits, but in layman’s terms, it works by helping your brain create new and better connections. Some patients with long-term depression either lose or can’t form important neuronal connections. [1] This lack of connections can make it challenging for nerve cells to talk to each other.

Depression, anxiety and PTSD, are very stressful for your brain. In response to that stress, your brain may erase important connections which actually will make it harder to cope with the stress over a long period of time. When your nerve cells don’t react appropriately to your naturally released neurotransmitters, it’s hard for your brain to adjust your mood.


With ketamine, the neurons in your brain are induced to make new receptors to replace the older ones that aren’t working well anymore. In this way, Ketamine will help your brain make new connections(neuroplasticity), and as a result, allow you to improve your mood. This can also accelerate the treatment of traditional antidepressants such as SSRIs.


Besides reactivating specific connections, the ketamine experience may also help you to comprehend your consciousness and help you work through your life.



ketamine treatment increases neuroplasticity



The Nitty Gritty


The mechanics of ketamine are somewhat complicated, but in the simplest terms: ketamine blocks one of the glutamate receptors called the NMDA receptor. It’s called an NMDA antagonist which means that it stops NMDA receptors from binding with the excitatory neurotransmitter, glutamate. [4] When your brain notices that those receptors aren’t binding with glutamate, it sends a signal to increase glutamate production.


With the extra glutamate present and unable to bind to NMDA receptors, the glutamate binds to another excitatory receptor called AMPA instead. When AMPA receptors are activated, your brain releases additional molecules to help your neurons talk to each other and help create new pathways for communication.


Ketamine is also thought to affect your mTOR pathway. Some scientists believe it is the mTOR pathway effects that allow your brain to make new and better connections. [4] When your brain is capable of regrowing pathways more effectively, you may also see increased neuroplasticity, or the ability for your brain to change and adapt better to your circumstances. In terms of mood disorders, increased neuroplasticity may mean breaking out of patterns and unhealthy thoughts in favor of more productive connections.



The ISHA Difference


ISHA employs trained medical professionals who will walk you through the entire process and monitor you through our certified telehealth network. Our doctors connected with you online will talk you through the process of taking the ketamine and help you in the comfort of your home. While everyone’s reaction may vary, many start to feel an improvement in the days following your first treatment.


Contact us at info@isha.healht for more information on breaking out of your depression and seeing the world through different eyes.




References



https://www.webmd.com/depression/features/what-does-ketamine-do-your-brain

https://www.health.harvard.edu/blog/ketamine-for-major-depression-new-tool-new-questions-2019052216673

Bahji A, Vazquez GH, Zarate CA Jr. Comparative efficacy of racemic ketamine and esketamine for depression: A systematic review and meta-analysis. J Affect Disord. 2021 Jan 1;278:542-555. doi: 10.1016/j.jad.2020.09.071. Epub 2020 Sep 23. Erratum in: J Affect Disord. 2020 Nov 20;: PMID: 33022440; PMCID: PMC7704936.


Zanos P, Gould TD. Mechanisms of ketamine action as an antidepressant. Mol Psychiatry. 2018 Apr;23(4):801-811. doi: 10.1038/mp.2017.255. Epub 2018 Mar 13. PMID: 29532791; PMCID: PMC5999402.


Jelen LA, Young AH, Stone JM. Ketamine: A tale of two enantiomers. J Psychopharmacol. 2021 Feb;35(2):109-123. doi: 10.1177/0269881120959644. Epub 2020 Nov 6. PMID: 33155503; PMCID: PMC7859674.

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