How Ketamine is Helping us Better Understand Depression and the Brain

Ketamine is a dissociative anesthetic medication that was first synthesized in 1962 by a chemist searching for a novel compound with the anesthetic efficacy of older dissociative anesthetics such as PCP but with a much greater safety profile and lower incidence of “emergence reactions.” Emergence reactions are untoward, uncomfortable reactions that may be experienced while the medication wears off, causing hallucinations, anxiety, and other unpleasant psychic symptoms.

A dissociative anesthetic can, at higher doses, cause a sense of the patient being dissociated or “out of body” for a time, hence the name. This effect is not typical at the lower doses used for mental health disorders, but milder side effects such as altered perceptions or a sensation of floating frequently occur.

How is Ketamine Used?

Due to Ketamine’s favorable safety profile, it rapidly replaced morphine as the “buddy drug” given by soldiers to their wounded comrades in pain during the Vietnam War. It is still being used on battlefields today. Ketamine was found to be a much safer and more effective analgesic than the previously used opiate medications, as it did not lower the blood pressure or slow the patient’s breathing and did not require cardiac monitoring.

Ketamine is used extensively in emergency departments for analgesia and sedation in children. More recently, Ketamine has been administered to adults who are about to undergo painful or delicate procedures—creating a favorable dissociative, amnestic state. As a result, Ketamine is the anesthetic of choice for pediatric analgesia and sedation in the ED.

Most recently, the administration of intravenous low-dose Ketamine has been surprisingly effective in rapidly improving the symptoms of depression, posttraumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), and other mental health conditions such as chronic pain syndromes. This effect is supported by numerous studies conducted at reputable research centers from 2000 to the present.

Ketamine as a Quick Treatment for Depressive Disorder

Ketamine has been shown to improve symptoms of depression in as little as several hours after the first treatment. This lifting of the depressive symptoms seems to last anywhere from several days to weeks or months and typically lasts longest after a series of six infusions over two weeks. In addition, single-dose “booster” treatments for two weeks to months after the initial infusion have been shown to prolong the antidepressant effect of the medication in many patients.


For depressive disorder, typically, antidepressants are prescribed. Antidepressants work in line with what’s called the monoamine hypothesis of depression. The hypothesis, which emerged in the 1950s, says that depression is caused by low levels of chemical messengers in the brain called monoamine neurotransmitters, which include serotonin, dopamine, and noradrenaline. The idea is if you can increase levels of these neurotransmitters in the brain, you can reverse depression.

These drugs fall into several categories, including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and the older tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). They all affect one or more of the monoamine neurotransmitters. These drugs cause monoamines to remain in the synaptic cleft — the space between neurons — for longer. Their success at treating depression is thought to be related to the birth of new neurons in a part of the brain called the hippocampus (an area responsible for learning, memory, and emotion) and the increased production of proteins such as brain-derived neurotrophic factor (BDNF), which is known to build neural connections. These processes take time and may account for the slow relief typically associated with antidepressants. It can take anywhere from weeks to months to alleviate depression symptoms.

How Ketamine Differs

Research suggests that one of Ketamine’s significant actions is as an N-methyl-D-aspartate (NMDA) receptor antagonist. That is, it blocks the activation of the NMDA receptor. This action leads to increased release of glutamate, which is involved in neuronal plasticity and synaptic growth and repair. These effects through complex pathways lead to the release of Brain-derived neurotrophic factor (BDNF), a substance responsible for maintaining healthy neurons and their connections, known as synapses.

Increased BDNF has been shown to bring about the repair and regrowth of damaged synapses and their neuronal connections caused by chronic stress in animal models. Likewise, in humans, Ketamine is thought to lead to the creation of new neuronal circuits and/or repair of the healthy neuronal connections that existed in the brain before the patient suffered from depression, PTSD, OCD, and/or chronic anxiety.

In 2014, Thomas Insel, former Director of the National Institute of Mental Health, stated, “Recent data suggest that ketamine, given intravenously, might be the most important breakthrough in antidepressant treatment in decades.”

If you or someone you know could benefit from Ketamine Infusion Therapy, please contact Tranquility Ketamine by clicking here or calling (505) 639-4973.