The History of Ketamine: Uses, Origin, & More

April 28, 2022

Nue Life

Nue Life

Ketamine is a drug with a long-standing history. Kemaine uses in clinical practice have proven to be an essential part of modern medical treatment in numerous ways. After 50 years, ketamine has proven itself to be nothing short of amazing.

As time goes on, more and more applications for ketamine have come about. Scientists are still discovering unique ways that it affects the brain and how it can be useful in assisting treating specific conditions. 

As these new discoveries are being made, it is important to look back on the historical impact ketamine has had, so we can better understand its safety and efficacy and look forward with excitement to the promise ketamine holds.  

What is the Origin of Ketamine? 

Ketamine was first created in 1962 by a chemist named Calvin Stevens. Due to its many side effects, the anesthetic of the day, phencyclidine, needed an alternative. Ketamine came forth as a perfect alternative for phencyclidine. 

After first being used in humans in 1965, ketamine was introduced into clinical practice in 1970.


Historically Ketamine primary use was as an anesthetic. Its appeal was great because it was the first anesthetic that could provide adequate sedation while also taking away the patient’s ability to feel pain, all the while not compromising any respiratory function. 

Vietnam War

Following its release, ketamine’s first instance of widespread use was on the battlefields of the Vietnam War. Because it can sedate people and prevent pain without affecting respiratory function, it was beneficial on the battlefield as it was often difficult or impossible to hook a patient up to a respirator during an operation. 

In this way, ketamine allowed many life-saving operations on the battlefield, helping to save the lives of hundreds of people.
It became so essential, especially in conflict zones, that, in 1985, the World Health Organization declared ketamine to be an “Essential Medicine.” Because of this, ketamine became incredibly popular in clinical use and is now one of the most common anesthesia medicines globally.


One of ketamine’s most common uses is in pediatrics for surgery. One of the primary reasons for this is that ketamine can be administered intramuscularly or with a shot instead of with an IV, unlike some anesthetics. IVs are difficult for many children to handle, so a simple shot is often a more practical method of delivering anesthesia. 

Ketamine has also been shown to be an incredibly safe option for children. Children actually metabolize ketamine faster than adults do, so their bodies can handle it well with minimal side effects. 

For these reasons, ketamine has become one of the most popular anesthetic choices for children in emergency departments.

Traumatic Brain Injury

Ketamine has also proven to have great application for patients who have suffered a severe brain injury. In the early 2000s, it was discovered that ketamine was safe for use in this application, unlike certain other anesthesia medications. 

But, going beyond that, because of ketamine’s effect on the brain, it may prove to be helpful in more ways than just as an anesthetic. Scientists are also discovering that it may be able to protect patients from seizures and secondary brain injuries.

Patients with Lung Problems

Ketamine’s ability to provide sufficient anesthesia without inhibiting lung function makes it particularly useful in conducting surgery on patients with lung conditions like asthma. 

Ketamine opens the airways and allows for safe breathing, so it is a much safer option for those with acute bronchial constriction. 

In addition to that, ketamine has favorable cardiovascular characteristics, so it is a good option for patients who have unstable blood flow. 

The lack of adverse effects makes ketamine an incredibly versatile anesthetic that is safe for use in a variety of patients with various pre-existing health problems. 


Ketamine is also one of the few anesthetics that is approved for use in cesarean sections. It allows for healthy breathing, which is important for this surgery. But most importantly, because of how well children can handle ketamine and how safe it is for them, ketamine has proven to be a safe choice for this particular procedure. 

Pain Management

Ketamine, when used for anesthesia, has incredible analgesic effects. This means that it can prohibit people from feeling any pain. This concept has been built upon in the years following ketamine’s introduction, and it is now used in practice for treating pain. 

Burn Victims

Ketamine has been used specifically for burn victims since about 1978. Its analgesic effects allow doctors to change patients’ bandages without causing a great deal of pain. 

Ketamine is also used as an anesthetic for burn victims when performing painful surface surgeries like skin grafts. In this context, ketamine has proven incredibly useful for decades.

Cancer and Post-Operative Pain

But it took doctors a few more decades to figure out that ketamine could also help reduce chronic pain. The first instances of this took place in the nineties when ketamine was used to help enhance the performance of opioids in pain management. 

Many patients suffering from intense pain from conditions like cancer following a surgery would normally require a very high dose of opioids to get their pain to a manageable level. But high opioid doses can also bring the risk of addiction and should be avoided. 

Ketamine can help limit that risk. Cancer often causes hyperalgesia, a condition where patients are overly sensitive to pain, which can require high opioid doses. 

When ketamine and opioids are administered together, ketamine can actually work to prevent the development of hyperalgesia. In addition, it reduces opioid tolerance. These together can allow for better pain management at lower opioid doses, which is incredibly valuable. 

Acute Pain

In the early 2000s, ketamine showed that it was also effective for use in the case of acute, isolated pain when combined with other pain medicines. When combined with other pain treatments, ketamine can reduce the risk of side effects of the pain treatment but maintain its effectiveness. 

For example, when combined with a reduced dose of hydromorphone in the emergency department, ketamine can produce profound, rapid pain relief without significant side effects when combined with reduced dose hydromorphone in the emergency departments. It can have this effect of pain relief in all sorts of different pain cases, making it a known practice to treat acute pain in the emergency department setting. 

Chronic Pain

When given at lower doses, ketamine can produce sufficient pain relief for patients struggling with chronic pain. It proves especially helpful in the case of neuropathic pain, which is the result of nervous system malfunction. The pain relief ketamine can provide in this case is very strong.

Ketamine’s effect on NMDA receptors in the brain is likely the root cause of pain relief. 

In addition, getting a ketamine infusion multiple days in a row at a low dose showed great pain relief effects in the case of chronic pain due to spinal cord injury. And the pain relief lasted for two weeks after the infusions had ended. 

Ketamine can also be of great help in amputees who struggle with phantom pain: feelings of pain in a limb no longer there. This type of neuropathic pain is well treated by ketamine. 

It can also be used as a good alternative in treating chronic pain from cancer, fibromyalgia, and ischemia. 

Depression and Mental Illnesses

Over the past twenty years, ketamine has been studied to treat depression and other mental health disorders. In 2019, a particular form of ketamine called esketamine was approved by the FDA for use against treatment-resistant depression.

Mechanism of Action

Ketamine works as an NMDA antagonist. It binds to the NMDA receptors in the brain, triggering the production of an important neurotransmitter called glutamate. This creates a significant chain reaction in the brain that ends with prompting your brain to form new neural pathways and connections, what we commonly refer to as “neuroplasticity.” 

By increasing your neuroplasticity and making the brain more adaptable, ketamine gives people a chance to develop new, positive, helpful thought patterns and behaviors, and to release the hold that the negative thought pathways have had on them. 

This treatment is incredibly effective, and it works incredibly fast. Many patients improve their symptoms within two hours of treatment, and 50 percent of patients see improvements within the first 24 hours.

Ketamine’s fast-acting nature can be incredibly important, especially in severe depression that causes the patient to struggle with thoughts of suicide. The immediate relief provides much-needed safety and gives people a chance to find healing quickly. 

Treatment-Resistant Depression

Ketamine is specifically effective in cases of treatment-resistant depression. Treatment-resistant depression is diagnosed when an individual has not responded to two or more antidepressants for the recommended dose and duration of treatment. 

Many people struggle with the effectiveness of traditional antidepressants. One study, looking into the efficacy of SSRIs and SNRIs, found that these antidepressants only provided meaningful relief in about 20 percent of the cases studied. 

The people who have experienced the ineffectiveness of antidepressants firsthand are likely experiencing treatment-resistant depression. This can be a tough battle, but ketamine can be the treatment that spurs you on to victory. 

One study showed that, in cases of treatment-resistant depression, ketamine provides relief up to 70 percent of the time. That is far more effective than traditional antidepressants. 


As of 2014, the medical community has begun to look into ketamine for treating post-traumatic stress disorder. 

Midazolam is a common medicine used to treat PTSD. When compared to midazolam, ketamine can reduce symptom severity faster.  

Ketamine’s mechanism of action for PTSD is similar to its mechanism for depression. By increasing the brain’s neuroplasticity, ketamine can give people a chance to establish healthy patterns of thought surrounding their trauma to manage it effectively. 


The most recent development in the world of ketamine has been with ALS (or amyotrophic lateral sclerosis, also called Lou Gehrig’s disease). In August of 2021, ketamine was given the orphan drug designation by the FDA to treat ALS. This means that a pharmaceutical company called PharmaTher has been approved to pursue ketamine to treat this disease. 

In a preclinical study, ketamine was shown to safely preserve muscle function and extend survival in animal models of ALS. This may indicate that the same success could be seen in humans. 

ALS patients suffer from calcium damage to neurons caused by excess levels of glutamate attaching to NMDA receptors. Ketamine can help to block the NMDA receptors and reduce glutamate toxicity. 

In this way, ketamine could prove to be a neuroprotective agent that could help treat ALS. Time will tell if this treatment will be effective or not, but it looks very promising. 


The history of ketamine has proven that it has earned its place in modern medicine, and it continues to do so in new ways. From providing groundbreaking anesthesia to remarkable relief from depression, ketamine has proven to be effective again and again. 

Treatment at Nue Life

Nue Life believes in holistic treatment. We offer at-home ketamine therapy programs that address multiple aspects of wellness. What happens after your ketamine experience is equally as important as the experience itself. We want to ensure you have meaningful takeaways from your experiences and help you establish positive new neural pathways. 

That’s why we provide one-on-one health coaching and integration group sessions with each of our programs. We’re here to help map out the mind and body connections in your brain and help you discover the real insights that lead to real relief.


Depression: How effective are antidepressants? | Informed Health

FDA approves new nasal spray medication for treatment-resistant depression; available only at a certified doctor’s office or clinic | The FDA

​​How New Ketamine Drug Helps with Depression | Yale Medicine

Ketamine: 50 Years of Modulating the Mind | National Institutes of Health

Ketamine: A Review of an Established Yet Often Underappreciated Medication | Anesthesia Patient Safety Foundation

Ketamine Earns FDA’s Orphan Drug Designation for ALS Treatment | ALS News Today

Ketamine use in current clinical practice | National Institutes of Health

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