A Brief History of Ketamine

The unique story of ketamine began in 1956 with the synthesis of the drug, phencyclidine. Found to be a remarkable anesthetic for monkeys, phencyclidine was then used on humans after numerous animal testings. Unfortunately, the side effects that researchers observed in some patients were concerning. Instead of waking peacefully from anesthesia, some patients experienced acute emergence delirium lasting hours after their operation was over. They described feeling sensory deprived and the loss of sensations in their limbs. Further studies concluded that phencyclidine produced a sensory deprivation syndrome.

Phencyclidine was found to be an unsuitable anesthetic after more clinical studies. In a study with nine schizophrenic patients and nine normal patients, phencyclidine increased the hostility and unmanageability in the former.  The psychiatrist in charge of the study, Dr. Elliot Luby described that the state of both groups had “an impressive similarity to the schizophrenic syndrome…” These findings in addition to the prolonged emergence delirium caused by phencyclidine lead researchers to conclude that a better anesthetic should be found elsewhere.

Hoping to find a short-acting alternative, Dr. Calvin Lee Stevens of Wayne State University synthesized a sequence of phencyclidine derivatives. The compounds he synthesized were sent to pharmacological testing in animals, and one compound in particular was found to be a successful, short-acting anesthetic. Selected for human testing, it was titled CI-581 and is what we now call ketamine.  Ketamine was named because of the ketone and the amine group in its chemical structure.

On August 3, 1964, the first human was given intravenous ketamine. Subjects administered ketamine had minimal emergence delirium. They described the experience like floating in space, as if they were disconnected from their body and environment with a loss of feeling in their limbs. Because of this strange sensation, ketamine is called a dissociative anesthetic. After Food and Drug Administration approval in 1970, ketamine was used on injured soldiers during the Vietnam War because of its large margin of safety. Since 1994, many clinical studies have found that ketamine is not only useful to relieve pain short term, but can be an effective way to treat certain chronic pain syndromes such as fibromyalgia, migraines and burns.

In addition to relieving physical pain, ketamine was found to ease pain of a psychological nature. An unexpected finding occurred during a study observing the effects of ketamine in low doses as a model for schizophrenia. In depressed patients, ketamine had an antidepressant effect. In 2000, the first randomized, double-blinded study was published in Biological Psychiatry. In this study, Dr. Berman et al. reported the antidepressant effects of ketamine in patients suffering from depression.  And in 2012, researchers called ketamine, “the biggest breakthrough in depression research in a half century.” Other studies are showing that ketamine may be effective in OCD, PTSD, anxiety, and suicidal ideation as well.

Ketamine’s complex history has lead to the current understanding that it is a safe, multi-purpose, and miraculous drug.  Further research will shed light on the mysteries of this remarkable substance.  In the meantime, please contact us know if you have any questions about ketamine.

Reference:

Domino, E. F. (2010). Taming the Ketamine Tiger. Anesthesiology,1. doi:10.1097/aln.0b013e3181ed09a2

Berman, R. M., Cappiello, A., Anand, A., Oren, D. A., Heninger, G. R., Charney, D. S., & Krystal, J. H. (2000). Antidepressant effects of ketamine in depressed patients. Biological Psychiatry,47(4), 351-354. doi:10.1016/s0006-3223(99)00230-9