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What is Ketamine?

What do I need to know?

Learn More About Ketamine

Ketamine was first synthesized in 1962 and soon approved by the FDA for use as an anesthetic/analgesic medication. For over 40 years it has been used safely in emergency departments and operating rooms across the world. Ketamine has become the go-to anesthetic/analgesic for pediatric patients. Why?

The safety of using ketamine lies in its ability to relieve pain while not causing a decrease in heart rate, blood pressure, or respiration. Unlike opioids such as morphine or fentanyl, the risk for overdose with ketamine is almost nonexistent. This is why the US armed forces have used ketamine in field trauma since the Vietnam War.

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In the last 15 years, studies from Yale, the National Institute of Health, the Veterans Administration, Harvard, John Hopkins, Oxford University, and many others have shown the usefulness of sub-anesthetic, or low-dose, ketamine infusions in treating multiple mood disorders and chronic pain. These studies have focused on the most severe forms of these conditions, and the results have been astonishing. Over the years the vast majority of research published point to ketamine providing rapid relief while also having a success rate of 70% in even the most severe forms of depression.

For those who have been suffering from mental illness for many years, the claims of a drug being faster and more effective than traditional mood disorder medications may sound too good to be true. But the fact still remains, ketamine is not only the first rapid-acting antidepressant, it is the most effective medication we have today. Ketamine is even being used in rescuing individuals from suicidal ideation.

Traditional medications such as SSRIs, SNRIs, and MAOIs have to be taken every day, have success rates below 50%, and have many undesirable side effects which can even include depression and suicidal thoughts. This is not the case with low-dose ketamine infusions. Ketamines side effects are minimal and are only experienced during the infusion. Some side effects may include a “light” or “floating on air” sensation, a mild increase in blood pressure and heart rate, light-headedness, temporary blurred vision, euphoria, and nausea. At our clinic, each patient is monitored continuously during infusions. Patients are also preemptively treated for sides effects such as nausea. Currently, there is no data documenting long-term side effects with low doses of ketamine administered for short periods of time.

So how exactly does ketamine work?

Ketamine is known as an NMDA receptor antagonist. Many researchers are still searching for exactly how the medication can affect mood so rapidly and effectively, but what we do know is that ketamine works on glutamate, one of the most numerous neurotransmitters in the body. This increase in glutamate can cause a cascade effect of increased neural activity and communication in the brain. The areas of the brain which have shut down due to over-anxiety and depression, are suddenly awakened. Ketamine causes neuroplasticity, or new neural growth, a “rewiring” of the brain believed to play a big part in the lasting anti-depressant effects.

We know that ketamine is not only working on the NMDA receptor, but ketamine is also working on other receptors such as GABA receptors, G protein-coupled receptors, and a small effect on cholinergic Mu receptors. Along with reversing neuronal atrophy, ketamine also has an anti-inflammatory effect. Interestingly, the dissociative effects of ketamine are believed to play a part in the healing process as well. When given appropriately and titrated in the right doses by a trained provider, ketamine’s multiple mechanisms of action create a powerful, effective treatment for a variety of chronic mental illness and pain conditions.

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A picture of a neuron. The neuron below shows new dendritic formations, or new neural growth, within just 2 hours of receiving ketamine.

History of Ketamine

  • Ketamine was synthesized in 1962
  • FDA approved anesthetic agent since 1970
  • Given safely every day to pediatrics to geriatrics in ERs and ORs for light to heavy sedation and pain relief.
  • In the past 7-10 years, low dose ketamine infusions have been proven highly effective in treatment-resistant depression (TRD), PTSD, and chronic pain.


  • Ketamine hydrochloride is a high-affinity, noncompetitive N-methyl-D-aspartic acid (NMDA) glutamate receptor antagonist.
  • Glutamate is a major excitatory neurotransmitter, a chemical substance, in the brain. Ketamine is currently approved by the U.S. Food and Drug Administration (FDA) as an anesthetic agent.

Ketamine’s Effects

  • Ketamine increases neurotransmitter activity
  • Improved cell signaling
  • Increases translation of neurotrophic proteins (BDNF)
  • Increased generation of synapses (Synaptogenesis)
  • Reversal of neuronal atrophy
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Quick Facts

  • In 1985 ketamine was added to the World Health Organizations list of Essential Medicines
  • Neurologists were the first to use ketamine for the treatment of complex regional pain syndrome (CRPS)
  • Over 41 million Americans are taking antidepressants
  • Traditional antidepressants are ineffective in up to 50% of patients
  • When they do work, they take weeks to months to take effect
  • Ketamine as a therapy achieved FDA Breakthrough Therapy Designation for Treatment-Resistant Depression
  • Ketamine is 70-80% effective at treating the most difficult cases of depression

In Summary

  • Major benefits of ketamine for depression
    • The worlds only rapid-acting antidepressant
    • Highly effective, rapid termination of suicidal ideation
  • Limitations of ketamine
    • Not covered by most insurances
    • Inconvenient route of administration
66709 by Midwest Ketafusion in Iowa City, IA
A CT scan of a human brain. After ketamine treatments, the depressed brain is almost identical to the non depressed picture as new neural activity has awakened the depressed areas.

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