The history or ketamine as a medication begins in 1970, when the drug is approved by the United States Food and Drug Administration [FDA], which has been used predominantly to start and maintain anesthesia but was first used in the treatment of battlefield injuries to American soldiers during the Vietnam War.
First discovered in 1956, and synthesized by Calvin L. Stevens in 1962, ketamine is used to induce a dissociative amnesia which puts patients into a trance-like state, and provides them relief from pain in addition to sedation.
What sets ketamine apart from the rest as an anesthetic is that the patient’s airway and breathing reflexes are preserved, their blood pressure is increased to stimulate heart function, and their bronchodilation is modulated. It is a dissociative drug which intercepts between the brain receptors and chemicals. It relaxes the muscles that are causing pain, and produces visual and auditory distortion which eventually causes detachment from reality. Once the mind is away from reality, it automatically forgets the trauma or any past experience, thus offering a state of complete relaxation.
Ketamine was first discovered because of phencyclidine—an anesthetic which would prove to be unsuitable for use on humans. Chemists at Parke-Davis began experimenting, and searching for anesthetic agents in the organic compound known as cyclohexylamine. The main purpose was to find analgesic properties in these agents.
Through different processes and experiments, chemist Maddox discovered a process which led to the synthesis of phencyclidine. Before being synthesized, it was being administered on different animals, including monkeys, pigeons, dogs, and rodents to see the effects it had on pain receptors, and how the different animals’ minds reacted to pain with the help of the chemical compound. Even though the drug did ease their pain and relaxed the muscles, it caused the animals to appear drunk and delirious.
A similar side effect was unfortunately observed in the human patients on whom the drug was tested. They would wake from their amnesia in a state of acute emergence delirium, one that would last long hours even after the operation was completed.
Undeterred by the results, scientists and chemists redirected their energy toward other analogs of the drug—those which were short-acting, and began attempts to synthesize them so they could be acceptable for human use. Most of these would prove to have similar anesthetic reactions.
However, in 1962, Dr. Calvin Lee Stevens of Wayne State University managed to synthesize a sequence of phencyclidine derivatives which he hoped would work as short-acting anesthetics. He sent off the different compounds for pharmalogical testing on animals, and one of them—originally titled C1-581—was found to be so successful it was selected for testing on humans. The compound is known today as ketamine: from the ketone and the amine group found in its chemical structure.
The first human dose for anesthetic purposes was administered in 1964 by Dr. Guenter Corssen and Dr. Edward Domino. The professors used the drug on a sample size of 130 patients, and the results concluded that this drug agent could actually have profound analgesia and alters the state of mind of the patients. These effects were short lived but could be increased with an increased dose or repeated administration.
There were minimal side effects of the drug, especially compared to its parent drug phencyclidine, and there was also a complete lack of, or only minimal, emergence delirium. Ketalar became the first preparation of ketamine to be approved, in 1970, by the FDA for human use.
The history of ketamine would not be the same without the Vietnam War where the drug was administered clinically as a surgical anesthetic because of its safety. It has been listed on the World Health Organization’s List of Essential Medicines.
More recent research, particularly since 1994, has shown that ketamine, when used properly under medical supervision, can help treat—and even prevent—certain mental distresses, including depression, anxiety, suicidal ideation, obsessive-compulsive disorder [OCD], and post traumatic stress disorder [PTSD]. It is also an effective method of treating several chronic pain syndromes, including burns, migraines, and fibromyalgia. In 2012, ketamine was identified as “the biggest breakthrough in depression research in a half century” by researchers. The introduction of Ketamine IV treatments has streamlined the dosage and onset of ketamine so it can be administered consistently with the guidance of specialists.
It has proven to be particularly effective when used to manage treatment-resistant depression because it possesses an anti-depressant activity, and can also help improve the postoperative state of patients who suffer from depression.
However, a single dose of ketamine is not enough because the anti-depressant activity wears off after a little while. Repeated administration has shown promise to solve this problem.
Today, Ketamine is an exciting new form of treatment for a myriad of ailments and new research is pushing further understanding of how ketamine treatments are not only safe but one of the staples of future psychedelic therapies.
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