A Brief History of Ketamine

The dissociative and hallucinatory adverse effects of ketamine were first observed in the early days of its use for medical purposes.

These adverse effects were called "emergence phenomena” and described as floating sensations, delirium, hallucinations, and vivid dreams (Reich & Silvay, 1989). It was in this context that ketamine was discovered to induce an altered state of consciousness described as being disconnected (Corssen & Domino, 1966) and was then classified as an effective analgesic and anaesthetic (Domino et al., 1965).

Phencyclidine

The history of ketamine dates back to 1956 when a chemical, phencyclidine, was first synthesized (Maddox et al., 1965). This compound was tested in animals and presented an unusual pharmacological profile, leading to its continued study (Chen et al., 1959; Domino, 1964). Eventually, it came to be used for humans undergoing surgery, though some severe reactions began to emerge (Greifenstein et al., 1958). Research was also carried out with this substance in schizophrenic patients with unfavourable results for those in the trial, though it did convince the investigators that phencyclidine presented an excellent drug model of schizophrenia (Luby et al., 1962; Rosenbaum et al., 1959).

Video: A Brief History of Therapeutic Ketamine Use

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It became clear with time that phencyclidine was not a suitable choice for human anesthesia due to the prolonged delirium that accompanied its use (Domino, 2010). Related derivatives of this compound were then synthesized with the aim of creating one that would maintain the beneficial anesthetic effects of phencyclidine without its lasting delirium (Domino, 2010). One of these derivates—CI-581— showed to have excellent anesthetic capabilities and to be shorter acting than its parent compound in animal trials, eventually leading to human testing beginning in 1964; this compound later came to be named ketamine (Domino, 2010; McCarthy et al., 1965). In this video, we will learn about more key events during the history of ketamine.

Recreational Use of Ketamine

Though developed for anesthesia, ketamine's use rapidly spread, with it becoming a substance of abuse both alone and when mixed with other compounds, as well as being used as a date rape drug; it is known under a wide range of street names, such as Bump, CatValium, K, Ket, Kit Kat, Kizzo, Special K, and Vitamin K, among others, and its recreational use continues to this day, especially in association with raves and music venues (Domino, 2010; Jansen, 2000; Jansen, 2001; Lodge & Mercier, 2015). In recreational settings, strong ketamine experiences from high doses are colloquially known as the "K-hole," likely as a result of its dissociative characteristics (Lodge & Mercier, 2015). Ketamine's parent compound, phencyclidine, also came to be used as a recreational substance under street names such as Angel Dust and PeacePill, though it is now less widely used than in the past; other phencyclidine derivatives besides ketamine have likewise made their way to the recreational market (Domino, 2010; Lodge & Mercier, 2015; Moeller et al., 2008). Though ketamine is safer than phencyclidine, recreational usage can still result in death or serious physical harm, especially when used with alcohol or other illicit drugs, as well as in

Timeline

While ketamine’s history has been relatively short compared with other substances, take a look at some of the key events that led to ketamine’s use in psychedelic-assisted therapy.

Please ensure that you read through all tabs before proceeding by using the arrows to navigate through the timeline.

Cultural Safety and Humility

Although ketamine is a synthetic substance and has not been used by Indigenous Peoples for ceremonial or traditional uses, health professionals should be aware that many of the rituals and approaches to psychedelic-assisted therapy are informed by Indigenous traditional knowledge from around the world (Fotiou, 2019). Health professionals should take great care to uphold cultural safety and humility when working with synthetic psychedelic medicines and traditional plant medicines.

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