The History of Ketamine

In the last few years, ketamine has been making headlines as a breakthrough treatment for depression, anxiety, trauma, and chronic pain. While ketamine is a revolutionary treatment option, it is not actually new. Ketamine has a long history of therapeutic use in the setting of anesthesia.

The history of ketamine begins in the 1950s, when scientists were developing new and improved medications for anesthesia with the goal of helping patients undergo surgery without awareness or pain. Through this process, ketamine was first created by chemists working at Parke Davis Company in 1956. Initially called CI-581, ketamine has its origins in a Michigan laboratory. These days, ketamine originates from manufacturers both inside and outside the United States.

After ketamine was first synthesized, initial studies in animals were promising. The first dose of ketamine was administered to a human being in 1964 by Dr. Ed Domino and Dr. Guenter Corssen. Soon, ketamine was found to be safe and effective for inducing anesthesia. The unique properties of ketamine were discovered early in its history. In the 1960s, some of the first patients receiving ketamine reported unusual experiences, such as feeling that they were floating in outer space. In addition, patients receiving ketamine appeared to be awake and were able to breathe on their own without needing a breathing tube, yet they did not feel any pain whatsoever. This property makes ketamine one of the safest anesthetics (most other anesthetics decrease a person’s ability to breathe on their own and require a breathing tube).

This occurs because ketamine causes the mind to disconnect or “dissociate” completely from the body and its environment. Dr. Domino’s wife coined the term “dissociative anesthetic” to describe this unique mechanism of action.

Ketamine was approved by the U.S. Food and Drug Administration for use as an anesthetic beginning in 1970. Due to its fast onset of action and excellent safety profile, it was frequently used on the battlefield to treat wounded soldiers during the Vietnam War. In the decades since, ketamine has become an essential medication used every day in hospitals around the world. In hospitals, the purpose of ketamine is to provide anesthesia for surgery and other medical procedures. Because it is so safe and effective, it is also used to help children who need to undergo a procedure in the Emergency Room.

In the 1970s, ketamine also began to be used outside of medical settings. This early recreational use of ketamine led some individuals to report on the psychedelic effects of ketamine. For example, the physician and mystic John Lilly, MD self-administered ketamine and described experiences as a “peeping Tom at the keyhole of eternity.” Recreational use became more widespread throughout the 1970s. Because ketamine can cause trance-like states and induce euphoria, it became a popular rave and party drug (often called “special K”) in the 1980s and 1990s. Ketamine was eventually listed as a controlled substance in the United States in order to stop recreational use. However, thanks to decades of safe and effective use in the medical field, ketamine remained legal to use in medical settings (in contrast to psilocybin and LSD).

In 2000, a team of researchers at Yale discovered that low doses of IV ketamine produced very rapid antidepressant effects in patients with Major Depressive Disorder. This exciting finding spurred hundreds of other research studies over the past two decades. In 2014, this incredibly promising line of research led Dr. Thomas Insel, former director of the National Institute for Mental Health, to declare that ketamine "might be the most important breakthrough in antidepressant treatment in decades.” Since then, more and more research has demonstrated that ketamine is effective in treating depression, bipolar depression, post-traumatic stress disorder, anxiety, and chronic pain. Increasing evidence shows ketamine may also be helpful for treating alcohol use disorder and opioid use disorder. In 2019, a ketamine-based treatment called Spravato was approved by the Food and Drug Administration for treatment of Major Depressive Disorder.

Lower doses of ketamine are used for mental health treatment than for anesthesia. At these doses, people remain awake and aware throughout ketamine treatment. They experience a different state of consciousness which can range from mild relaxation to a psychedelic experience. Just like those first patients receiving ketamine in the 1960s, patients receiving ketamine today often report psychedelic experiences that include journeys through outer space and other galaxies, among many other possibilities.

The purpose of ketamine in treating mental health is twofold. First, during the treatment session, the effects of ketamine open a window into the subconscious, which can allow the person to process painful or traumatic events and experience psychological healing. Second, ketamine appears to increase neuroplasticity, or the brain’s ability to change and rewire itself. In chronic depression, anxiety, or trauma, neuroplasticity is decreased and the brain can become stuck in patterns of activity that lead to unhelpful thoughts, feelings, and behaviors. Ketamine helps to create new neural connections in the brain to support new and healthier ways of thinking, feeling, and being.

Ketamine shares this mechanism of action with other psychedelic medicines, such as psilocybin and LSD. Although new research shows that psilocybin and LSD are promising treatment options for certain mental health conditions, these medicines remain illegal at the federal level in the United States. Ketamine, however, is legally available in medical settings in all fifty states.

From its humble origins in a laboratory in Michigan in the 1950s, through a decades-long history of safe and effective use in anesthesia, ketamine now promises to revolutionize mental health treatment.