The Clinician’s Guide to Ketamine Therapy: A Brief History | Part 1
Synopsis: In Part 1 of our Clinician’s Guide to Ketamine Therapy, we explore the history of ketamine—from its roots in pharmaceutical chemistry to its rise as a battlefield anesthetic and eventual reputation as a recreational drug. Understanding this history is key to appreciating ketamine’s legitimacy as a medical tool and its evolving role in interventional mental health and chronic pain care.
Key takeaway: Ketamine’s complex past—from clinical innovation to public misconception—shapes how patients, providers, and the public perceive it today. By understanding its medical origins and FDA-approved uses, clinicians can more effectively educate patients and confidently integrate ketamine therapy into modern care.
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A powerful tool, decades in the making. Discover how ketamine evolved from battlefield anesthetic to breakthrough mental health treatment in this 3-part guide for clinicians.
A Clinician’s Guide To Ketamine Therapy: A 3-Part Series
Welcome to Part 1 of our three-part blog series designed for clinicians seeking a deeper understanding of ketamine therapy.
Whether you're a budding ketamine therapy specialist, exploring treatment options for your patients, or simply need a refresher on the science and protocols, this series offers a clear and comprehensive foundation.
In Part 1, we’ll explore the current state of mental health, the historical journey of ketamine, and how this decades-old anesthetic has reemerged as a powerful mental health intervention.
In Part 2, we’ll take a closer look at how ketamine works, types of patient experiences, and key scientific studies.
Finally, Part 3 will cover patient selection, dosing strategies, treatment scheduling, and side effect management.
Let’s begin by understanding why ketamine therapy is more relevant than ever in today’s mental health landscape.
Prefer listening over reading? Check out Episode 31 of our podcast: The Clinician’s Guide to Ketamine Therapy: History, Science & Real-World Protocols and jump to 2:17 to dive right in.
The episode is on Apple Podcasts, Spotify, Overcast, or on your favorite podcast platform. Watch the discussion on YouTube here.
The Current State of Mental Health
We’re facing a major mental health crisis. Rates of depression, post-traumatic stress disorder (also known as post-traumatic stress injury), anxiety, and suicide are all on the rise. In fact, depression is now the leading cause of disability worldwide, affecting more than 300 million people. Globally, one in five people are living with a mental health condition. So whether that’s you, a friend, or one of your patients, it impacts a tremendous number of people.
Traditional medications for mood disorders such as antidepressants can take weeks or even months to take effect and reach therapeutic levels. For many patients, that delay can feel unbearable.
In addition to mood disorders, more than 17 million people in the U.S. live with debilitating chronic pain. And here's where physical and emotional suffering intersect: when people are in extreme distress—whether mental or physical—the risk of suicide increases dramatically.
Between 1999 and 2017, suicide rates in the U.S. rose by 33%. Suicide is now the second leading cause of death for Americans between the ages of 10 and 34. Globally, nearly 800,000 people die by suicide every year. And in the U.S., there are twice as many suicides as homicides.
This is a growing crisis and it demands new and effective tools in our mental health arsenal. That’s where ketamine therapy comes in.
So let's explore the origins of this medication, as it is not a new drug but a rather old one.
From lab bench to operating room: Ketamine’s early development aimed to replace PCP with a safer alternative - uncover the story behind its complex legacy.
A Brief History of Ketamine
Why care about the history of this medication? Understanding its origins helps explain why ketamine remains a widely used and trusted medication in hospitals around the world today.
But just as importantly, it sheds light on its storied and sometimes confusing past, including the misinformation and stigma tied to its reputation as a drug of abuse.
From Phencyclidine to Ketamine
Ketamine belongs to the arylcyclohexylamine group, which is a class of compounds you might recall from your days in organic chemistry (fond memories, or maybe not!).
It was originally developed as a safer alternative to phencyclidine (PCP), which was patented by Parke-Davis in 1956 as a general anesthetic. Unfortunately, PCP caused prolonged psychotic reactions, therefore by 1965, its clinical use was discontinued.
Parke-Davis then tasked Dr. Calvin Stevens at Wayne State University with developing a safer version. In 1962, he created multiple derivatives of PCP, one of them stood out. Which was CI-58. That compound would later be named ketamine.
From Human Trials to FDA Approval
Once tested in rodents and non-human mammals, CI-581 progressed to human trials.
In 1964, Dr. Edward Domino led a study at Jackson Prison in Michigan, administering IV ketamine to 20 volunteers. Participants reported hallucinations, feelings of floating, and other “non-ordinary states of consciousness.” Despite the psychedelic effects, at high doses, ketamine proved to be a powerful anesthetic.
Because it appeared to separate the mind from the body without compromising respiration, it earned the label “dissociative anesthetic.” In 1970, the FDA officially approved ketamine for anesthetic use in adults and children during surgical and diagnostic procedures
However, despite ketamine’s clinical utility, it also gained popularity as a recreational drug in the 1970s and 1980s. Known by street names like “Special K” and “Kit Kat,” it became associated with party scenes and club culture.
Unfortunately, this reputation has overshadowed ketamine’s therapeutic origins in the eyes of the general public even though it has continued to be used safely and effectively in hospitals
From the frontlines of war to emergency departments worldwide, ketamine’s journey as a versatile, life-saving anesthetic has stood the test of time.
From the Hospital to the Battlefield
During the Vietnam War, ketamine quickly became the go-to battlefield anesthetic. Combat medics favored it because it could be administered safely intramuscularly (IM) and patients maintained their ability to breathe on their own.
This allowed wounded soldiers to be stabilized in the field and evacuated to military hospitals without the need for intubation. Its versatility and reliability earned ketamine a permanent place in military medicine.
Out of the OR and Into the Emergency Department
In 1990, a landmark study published in the Annals of Emergency Medicine demonstrated ketamine’s safety and efficacy for procedural sedation in pediatric emergency patients.
The research, conducted at Loma Linda University in Southern California (where we both completed our residency training - Sam in emergency medicine and Kim in ophthalmology), helped expand ketamine’s use beyond the operating room and into emergency departments across the country.
Today, ketamine has been in clinical use for over 50 years. It’s recognized globally and is listed on the World Health Organization’s List of Essential Medicines - a designation reserved for medications that are critical to any basic healthcare system.
From Battlefields to Breakthroughs
Understanding ketamine’s history is essential for anyone working in the evolving fields of interventional mental health and chronic pain treatment. Why? Because knowing where ketamine came from—how it was developed, how it’s been used both legally and illegally, and how public perception has shifted—equips us not only to provide safer, more informed care, but also to hold space for patient experiences and educate a still-uncertain public.
In Part 2 of this blog series, we’ll explore how ketamine works, its shift from procedural sedation to mental health treatment, what patients commonly experience during therapy, and more.
Related Questions:
Where did ketamine come from originally?
Ketamine is a derivative of phencyclidine (PCP), a compound developed in the 1950s. Because PCP caused prolonged psychotic symptoms, researchers sought safer alternatives. One of those alternatives was CI-581, which later became known as ketamine. It was designed to maintain the anesthetic benefits of PCP while minimizing its side effects.
When did ketamine receive FDA approval and what was it approved for?
Ketamine received FDA approval in 1970 for use as an anesthetic in adults and children during surgical and diagnostic procedures. It was originally used in operating rooms and later expanded to emergency departments following a landmark 1990 study showing its safety in pediatric patients.
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In Part 1 of our Clinician’s Guide to Ketamine Therapy, we explore the history of ketamine—from its roots in pharmaceutical chemistry to its rise as a battlefield anesthetic and eventual reputation as a recreational drug. Understanding this history is key to appreciating ketamine’s legitimacy as a medical tool and its evolving role in interventional mental health and chronic pain care.
Explore the origins of ketamine therapy—from its development as an anesthetic to its evolution into a promising mental health treatment.