• Isha Team

How Does Ketamine Work?

Your doctor has just recommended ketamine assisted therapy and you want to know more about it. Ketamine has been used as a surgical anesthetic since 1970, 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 extremely effective in the treating of mood disorders, 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 therapy for mental illness requires a much lower dosage (about 1/10 of what is used for surgery) and it is administered either as a slow intravenous infusion, intranasally, or as an oral medication. It is thought that the ketamine works by helping the depressed patient relax and forming new neuronal connections in their brain that leads to an improvement in their mood.

how ketamine works

Ketamine Pills

The first thing to note is that ketamine assisted therapy utilizes sub-dissociative doses of ketamine in an oral pill form. This means that patients are not expected to hallucinate or dissociate from reality during their sessions. This is very different from what is used during surgery where doctors want their patients to dissociate from their bodies so that they won’t feel any pain from the procedures. It is also different from the street version of ketamine, often called Special K, where the illicit drug is obtained so that the user can hallucinate and dissociate and to experience a “drug trip.”

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 medication without much success. Ketamine can also help people who are acutely suicidal or suffering from anxiety or PTSD.

Oral ketamine differs from traditional treatments for depression by working much faster. Traditional methods for treating depression like psychotherapy and psychiatric medications can take weeks or months before a difference is felt. For people with acute suicidality or deep depression, studies have shown that the effect of ketamine can be seen within hours or days. Ketamine also has the advantage of working for patients who haven’t responded to other depression treatments.

Types of Ketamine

There are two types of ketamine employed for the treatment of major depression: racemic ketamine and esketamine. These two drugs are molecules that are mirror images of each other. Esketamine is the S form of ketamine and comes as a nasal spray. 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 most 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, like anxiety and PTSD, are very stressful for your brain. In response to that stress, your brain may erase important connections (called pruning) 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 regrow those pruned connections, and as a result, allow you to improve your mood. With the formation of the new receptors, the traditional forms of treatment may also become more effective.

Besides reactivating specific connections, ketamine also helps you to comprehend your consciousness and will help you work through therapy to improve your mood. This may explain why many patients who have successfully completed ketamine treatments for depression see such an improvement in their overall moods and abilities to overcome all aspects of depression.

ketamine treatment increases neuroplasticity

The Nitty Gritty

The mechanics of ketamine are somewhat complicated, but in the simplest terms: ketamine binds to receptors called NMDA receptors. 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 helps create new pathways for communication.

Ketamine also affects your mTOR pathway. 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 will talk you through the process of taking the ketamine and help you from the comfort of your home. While everyone’s reaction may vary slightly, you should start to feel an improvement in the days following your first treatment.

Contact us for more information on breaking out of your depression and seeing the world through different eyes.




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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