Ketamine is effective in treating depression in patients with depression and bipolar disorder who have not responded to antidepressants. It produces a rapid antidepressant effect, acting within two hours as opposed to the several weeks taken by typical antidepressants to work.
Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist. At high, fully anesthetic level doses, ketamine has also been found to bind to μ-opioid receptors type 2 in cultured human neuroblastoma cells – however, without agonist activity – and to sigma receptors in rats. Also, ketamine interacts with muscarinic receptors, descending monoaminergic pain pathways and voltage-gated calcium channels.
Ketamine is a chiral compound. Most pharmaceutical preparations of ketamine are racemic; however, some brands reportedly have (mostly undocumented) differences in enantiomeric proportions. The more active enantiomer, (S)-ketamine, is also available for medical use under the brand name Ketanest S.
Ketamine was originally developed in 1962 as a derivative of phencyclidine (PCP), which was synthesized in 1926, a feat made possible by the discovery of a new organic Grignard reaction by Parke-Davis scientist Harold Maddox. Initially known as CI-581, ketamine was first synthesized by Parke-Davis scientist Calvin Stevens. Pharmacological investigations in human subjects began in 1964. These investigations demonstrated that ketamine’s shorter duration of action and lesser psychotomimetic profile made it favorable over PCP as a “dissociative” anesthetic. Following FDA approval in 1970, ketamine anesthesia was first given to American soldiers during the Vietnam War.
Nonmedical use of ketamine was documented in the early 1970s in underground literature (see The Fabulous Furry Freak Brothers). It was used in psychiatric and other academic research through the 1970s, culminating in 1978 with the publishing of psychonaut John Lilly’s The Scientist and Marcia Moore and Howard Alltounian’s Journeys into the Bright World, which documented the unusual phenomenology of ketamine intoxication. The incidence of nonmedical ketamine use increased through the end of the century, especially in the context of raves and other parties. However, its emergence as a club drug differs from other club drugs (e.g. MDMA) due to its anesthetic properties (e.g., slurred speech, immobilization) at higher doses; in addition, reports of ketamine being sold as “ecstasy” are common. The use of ketamine as part of a “post-clubbing experience” has also been documented. Ketamine’s rise in the dance culture was most rapid in Hong Kong by the end of the 1990s.