The History of Ketamine

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Medically reviewed: Paloma Lehfeldt, MD
the chemical compound of ketamine

How Ketamine Went From the Battlefield to the Therapist’s OfficeKetamine has been safely used as an anesthetic in hospitals and clinics for decades. Now this well-established drug is set to revolutionize mental healthcare. Ketamine’s history of use is both long and interesting, from the Vietnam conflict’s battlefields to the mental health clinics and therapy offices of today. Ketamine has shown promise as a treatment for some mental health disorders and has been listed as an essential medicine by the World Health Organization (WHO). Research continues to show that ketamine has many potential uses in addition to anesthesia, making it one of the most promising new mental health treatments in decades.

When was Ketamine Discovered?Ketamine was initially synthesized in 1962 by Calvin L. Stevens on behalf of the Parke-Davis Company.

First researched and developed in the 1960s, ketamine is a dissociative anesthetic originally used in veterinary care. Parke-Davis was searching for a new general anesthetic that could be produced quickly and would not suppress a patient’s respiratory system.

When Did Ketamine Gain FDA Approval?Ketamine received its inaugural FDA approval in 1970. Authorized for use as a general anesthetic, medical professionals rapidly adopted ketamine in hospitals nationwide. This was due in part to ketamine’s excellent safety profile. Because ketamine does not suppress the respiratory system, it is a viable option for scenarios where someone may be at risk for respiratory failure.

Ketamine on the BattlefieldAfter ketamine received FDA approval, it spread from domestic hospitals to the battlefields of Vietnam. When ketamine became approved for human use, the U.S. military had been bogged down in vicious fighting on the Vietnamese peninsula. Due to the staggering number of casualties, the military quickly encountered growing incidents of soldiers inadvertently becoming addicted to common battlefield anesthetics and painkillers, particularly morphine. 

During their search for an easier-to-administer drug that could be used in the field by medics and non-medical military personnel, the Department of Defense procured ketamine. Ketamine would quickly be deployed to hundreds of field hospitals across the conflict zone and eventually administered to thousands of wounded military personnel. As a fast-acting, relatively safe general anesthetic, ketamine was an ideal drug for use in the fast-paced environment of a military hospital. 

a military helmet

Ketamine for Pediatric and Elder CareAs discussed above, ketamine has a reliable safety profile when used in a medical setting compared to longer-lasting anesthetics. Of particular note is ketamine’s non-depressive effect on the respiratory system. This means ketamine will not affect someone’s breathing ability when used as an anesthetic. 

Respiratory safety is one of ketamine’s most important aspects for certain patients, such as children (pediatric care) and the elderly, as well as those with a general risk of respiratory failure. When paired with ketamine’s rapid onset and ability to reduce postoperative pain,(1) ketamine is an excellent drug for patients needing specialty care. Ketamine has also been shown to reduce the need for opioids after surgery.

Ketamine, a New Mental Health TreatmentSince 1970, ketamine has enjoyed a long track record as both an effective and relatively safe anesthetic medication. As investigations into other potential uses for ketamine continued, researchers made additional discoveries regarding ketamine’s efficacy as a mental health treatment

Beginning with a study conducted in 2005, medical professionals began diving into whether ketamine could treat patients suffering from depression and other mental health conditions.(2) This initial line of work directly led to the first ketamine-derived treatment for treatment-resistant depression and suicidality in individuals with major depressive disorder, esketamine (branded as Spravato). The FDA granted esketamine approval for treating the two aforementioned conditions in 2019, making it the first and only type of ketamine approved by the FDA for mental health conditions, specifically. 

While only esketamine has received FDA approval to treat depression and suicidality, ketamine is still used for other mental health conditions. Medical providers administer ketamine for mental health treatments in what’s known as off-label status. Off-label means that a drug is being used in a capacity outside of its FDA approval. This does not mean it is illegal or unsafe. Ketamine is the only legal psychedelic medicine in the United States. 

This research has grown to include ketamine treatments for:

Ketamine may treat these conditions due to its apparent action as an N-methyl-D-aspartate receptor (NMDA) antagonist. The NMDA receptor is part of the brain’s glutamate system and is responsible for some of the effects of the neurotransmitter glutamate. 

As an NMDA receptor antagonist, ketamine alters how glutamate binds to and interacts with its receptor. This appears to change the levels of available glutamate in the brain. Scientists place importance on this because healthy glutamate levels may be a key part of the brain’s ability to regulate mood.(3) It is thought that altering glutamate levels can have a direct, beneficial effect on certain mental health conditions, such as depression.(4)
a woman in ketamine therapy

Current Ketamine ResearchDespite ketamine’s nearly five decades of medical use, research into its potential as a mental health treatment is still relatively new and will need to be explored further. However, early results are very promising. Some studies have shown that ketamine can help up to 70% of patients with treatment-resistant depression.(5) One study has shown that ketamine may also greatly benefit nearly 83% of anxiety patients.(6) Other research examining ketamine’s effectiveness for PTSD(7) shows early results with response rates as high as 80%. 

As researchers continue to delve into the vast potential range of applications for ketamine, it is essential to note that ketamine may not be suitable for everyone. If you have certain mental health conditions, such as high blood pressure, or some heart conditions, ketamine may not be right for you. You should always consult a physician or medical provider before starting ketamine or ketamine-assisted therapy. Find a ketamine clinic near you to get started with your ketamine therapy

Where to Find
Ketamine TreatmentLocate outpatient ketamine clinics and at-home ketamine service providers in the U.S. that offer care for pain, depression, anxiety, PTSD, OCD, and addiction.