Medical study materials with ketamine indication on desk. Medical study materials with ketamine indication on desk.

Ketamine’s Effects on the Brain – And What to be Wary About

Ketamine is a medicine used as an anesthetic that works by blocking a specific receptor in the brain called the N-methyl-d-aspartate (NMDA) receptor, and recently, people have been exploring ketamine as a potential treatment for depression. When given through a vein, it has shown a significant reduction in depression symptoms within just four hours.

However, despite its positive effects in the short term, ketamine is now being misused as a recreational drug. In the United Kingdom in 2008/2009, about 1.7% of people were found to have a ketamine addiction. 

When used regularly and in large amounts, ketamine abuse has been linked to lasting problems with thinking mood, and even experiencing brain activity like psychosis and feeling disconnected from reality.

1. What is Treatment-Resistant Depression?

Major Depressive Disorder (MDD) is a very serious and widespread condition. Treatment-Resistant Depression (TRD), which means not responding well to at least two standard antidepressant treatments, affects up to 30% of people with MDD.

When people with depression don’t respond to treatment, it becomes harder for them to get better with future treatments. This creates a cycle of ongoing disability. That’s why it’s crucial to find fast and effective treatments for those with Treatment-resistant depression.

One potential treatment for TRD is ketamine. Although known as an anesthetic, small doses of ketamine, different from its typical use, show promise for treating MDD.

Unlike many other psychiatric medications that take weeks to work, the effects of ketamine are quick (within hours), strong (across various symptoms), and somewhat lasting (usually up to a week) antidepressant effects, even for people with TRD.

The Icy Whiz team talked to Marcus Smith, LCPC, LPC, LCADC, Licensed Clinical Professional Counselor and Executive Director, Alpas Wellness on this. Here is what he had to say:

Marcus Smith, LCPC, LPC, LCADC
Marcus Smith, LCPC, LPC, LCADC

“Integrating ketamine treatment into psychiatric care for individuals with treatment-resistant depression represents a promising frontier in mental health interventions.
Traditional antidepressants, such as SSRIs and SNRIs, operate primarily by influencing the neurotransmitters serotonin and norepinephrine to improve mood and emotional well-being.

However, for some, these medications are not effective, leading to a classification of their condition as treatment-resistant. Ketamine, on the other hand, functions through a different mechanism.

It targets the NMDA receptors in the brain, which are involved in mood regulation and synaptic plasticity. This action can lead to rapid improvements in mood for individuals who have not responded to other treatments.

The effectiveness of ketamine in treating treatment-resistant depression has been demonstrated in various studies, showing a rapid reduction in depression symptoms, sometimes within hours or days, which is significantly quicker than traditional antidepressants that may take weeks to show effects.


This can be particularly valuable in acute situations where immediate symptom relief is crucial, such as in cases of severe depression or suicidal ideation. However, the integration of ketamine into psychiatric care is not without challenges and risks. Ketamine is known for its potential for abuse and its dissociative effects, which can include hallucinations and altered perception of time and self. These side effects necessitate careful screening, monitoring, and follow-up in clinical settings.

Additionally, the long-term effects of ketamine treatment are still under investigation, raising questions about the sustainability of its antidepressant effects and the potential for dependency or tolerance.

Given these considerations, the decision to use ketamine should be made on a case-by-case basis, carefully weighing the potential benefits against the risks and challenges. It involves a multidisciplinary approach, incorporating medical evaluation, psychological support, and continuous monitoring of the patient’s mental health status.”

2. How does Ketamine Work in the Brain?

When doctors use ketamine to treat mental health problems like depression, trauma, or anxiety, ketamine affects the brain in three main ways:

  • Brain chemistry: Ketamine helps balance natural chemicals in the brain, like a “reset button” for mood regulation. 
  • Brain flexibility: It makes the brain more flexible and able to change, allowing it to heal and adapt better. 
  • New perspectives: With ketamine and therapy, you can see things differently, leading to positive changes in behavior and values.
How Does Ketamine Affect the Brain
Source: Depositphotos

So, ketamine helps improve brain regions, flexibility, and perspective, leading to improved mental health; think of it like this:

  1. Brain chemicals: Imagine your mood like a garden with different plants. Ketamine acts like a gardener, balancing the plants so they all grow well.
  2. Brain flexibility: Imagine your brain like a piece of clay. Ketamine helps soften the clay, making molding and creating new shapes easier.
  3. New perspectives: Imagine you’re stuck in a maze. With ketamine and therapy, you can see new paths and find your way out.

Dr. Michelle Dees, board-certified Psychiatrist, Luxury Psychiatry Medical Spa talked to the Icy Whiz team about the role of ketamine. Here is what she said.

Dr. Michelle Dees
Dr. Michelle Dees

“Using ketamine in patients with treatment-resistant depression has shown promise in its psychological effects. It appears that the therapy can significantly improve depressive symptoms and anxiety levels in individuals dealing with severe depression, according to research.

The rapid antidepressant effects of ketamine – particularly when administered intravenously – have been said to work fast and produce results even after repeated administrations. Ketamine has demonstrated its efficacy in helping patients with treatment-resistant depression. However, it is crucial to consider the possible side effects associated with it.

Disassociation, intoxication, sedation, high blood pressure, dizziness, headache, blurred vision, anxiety, and nausea are some of the potential repercussions of using the substance. Despite these negative effects though, the overall mental benefits seen in patients undergoing ketamine therapy for depression have indeed been significant.

Studies on the neurocognitive effects of repeated ketamine infusions in people with treatment-resistant depression have shown that such treatments lead to long-term improvements in how depressed they feel as well as their cognitive functioning.
This means better mental health outcomes for those who live with this condition.”

3. Does Ketamine have Long-term Effects on the Brain?

A recent study by Columbia biologists and biomedical engineers has shown that long-term ketamine abuse leads to a widespread structural change in the dopamine system of the brain.

People who use ketamine for a long time, compared to those who don’t, show several differences in their brains.

https://youtube.com/watch?v=wJXHKRVMJvc%3Ffeature%3Doembed
  1. They have less gray matter (the part of the brain with nerve cell bodies) or thinner outer layers in certain areas like the prefrontal cortex, dorsal anterior cingulate cortex, and back parts.
  2. The connections between the white matter (the part of the brain responsible for communication between different areas) in the front and sides are not as strong.
  3. The connections between the thalamus (a part deep inside the brain) and the outer layers and the connections between different outer layers are not working normally.
  4. Parts of the brain that are responsible for remembering where things are, and controlling movement are not as active.
  5. There is stronger communication between two specific areas in the front part of the brain, and the overall amount of white matter is bigger.

We interviewed Elvis Rosales, LCSW, Clinical Director, Align Recovery Centers and asked him about the role of ketamine in depression. Since he deals with a recovery center, he does see a lot of people dealing with it. Here is what he said:

Elvis Rosales, LCSW
Elvis Rosales, LCSW

“Receiving a diagnosis of depression is hard enough. But for those who are struggling to get better and not having any luck with their treatments, the situation only gets worse. However, all hope is not lost for those with treatment-resistant depression (TRD), because of the potentially helpful effects of ketamine.

In 2019, Esketamine — a ketamine-derived nasal spray — was approved by the U.S. Food and Drug Administration (FDA). Research shows that it provides fast-acting results as early as 40 minutes after administration. This is in stark contrast to most antidepressants, which take weeks.

As an antidepressant, Esketamine works differently than other drugs do. Traditional medications increase levels of native substances like serotonin, norepinephrine, and dopamine. These neurotransmitters work as messengers between neurons, aiding brain cell communication and uplifting mood when they’re in higher supply.

Conversely, Esketamine takes a similar route but doesn’t rev up the production of these molecules; instead, it amps up the production of glutamate — the brain’s most abundant chemical messenger — causing a broader effect on more brain cells at once. Given its ability to alter perception, Esketamine must be administered by a healthcare provider in a certified doctor’s office or clinic. Some side effects that have been linked to its use include drowsiness, high blood pressure, and headache.”

4. Other Effects on the Brain’s Ability

  • Memory: Ketamine abuse use can lead to memory problems, but studies with depressed patients showed improved memory after treatment.
  • Migraines: Some people report worsened migraines after ketamine, while others use it to treat them. This highlights the difference between recreational and therapeutic use.
  • Hallucinations: Hallucinations after ketamine are rare in therapeutic settings.
How Does Ketamine Affect the Brain
Source: Depositphotos
  • Brain benefits: Ketamine helps regulate a brain area called the lateral habenula, which plays a role in mood, sleep, pain, and behavior, thus improving symptoms of depression.
  • Traumatic brain injury: Early research suggests ketamine could increase blood flow to the brain, potentially aiding in recovery from traumatic brain injury.
  • Therapeutic ketamine seems safe for treating trauma, anxiety, and other mental health disorders, and ketamine’s antidepressant effects are effective, too. It is unlikely to cause psychosis in people without a history of it. Some people experience positive effects, like improved memory and blood flow. For optimal safety, seek professional help before starting any ketamine treatment or ketamine therapy. 

5. Side Effects of Ketamine

Here are some things that could happen if you misuse ketamine:

  • Feeling like you’re in a dream or not in your own body.
  • Seeing things that aren’t real.
  • Feeling really sleepy and drowsy.
  • Getting confused and finding it hard to think.
  • Forgetting things.
  • Getting anxious and easily annoyed. 
How Does Ketamine Affect the Brain
Source: Depositphotos

There are also some physical effects, like:

  • Breathing slower
  • Feeling sick and throwing up.
  • Higher blood pressure.
  • Slower or faster heartbeat, depending on the dose.
  • Seeing double.
  • Having seizures. 

6. Concluding Studies

Ketamine helps with depression severity and affects other receptors in the brain, like opioid receptors, adrenergic, serotonin, and norepinephrine receptors. The trippy side effects of ketamine could also be linked to its ability to fight depressive symptoms. 

However, because different studies on ketamine have small groups of people, the results might not match up. Also, the methods used in these studies and their limitations could be causing differences in the outcomes.

How Does Ketamine Affect the Brain
Source: Depositphotos

Because the results are inconsistent and ketamine has many different effects, it’s challenging to understand exactly how it quickly, strongly, and consistently helps with depression.

If you think someone has taken too much ketamine and might be in danger, call a doctor right away, and if you’re dealing with the problem of being addicted to ketamine, reach out to a medical professional. 

Guest Author: Saket Kumar

Last Updated on April 22, 2024 by soubhik

Author

Anushree Khandelwal

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