Ketamine
Anesthetic and antidepressant with dissociative and hallucinogenic properties.
Ketamine is a cyclohexanone-derived general anesthetic and NMDA receptor antagonist with analgesic and hallucinogenic properties. It is used medically for anesthesia, depression, and pain management, and is on the World Health Organization's List of Essential Medicines. First synthesized in 1962, ketamine was developed from phencyclidine in an effort to create a safer anesthetic with fewer hallucinogenic effects. It received approval for medical use in the United States in 1970 and was extensively employed for surgical anesthesia during the Vietnam War, as well as in veterinary medicine. A major breakthrough occurred in 2000 with the discovery of its rapid antidepressant effects, which marked a significant advance in treating depression. The drug exists as two enantiomers: S-ketamine (esketamine) and R-ketamine (arketamine), and its antidepressant action is believed to involve NMDA antagonism along with other mechanisms.
At anesthetic doses, ketamine induces dissociative anesthesia—a trance-like state that provides pain relief, sedation, and amnesia. Unlike most other anesthetics, it preserves breathing and airway reflexes, stimulates heart function with increased blood pressure, and produces moderate bronchodilation. These characteristics make it especially useful in trauma, emergency, and pediatric cases, as well as for individuals with asthma or chronic obstructive pulmonary disease. It is a drug of choice for short procedures where muscle relaxation is not required, and it is frequently used in severely injured people, including those in traumatic shock at risk of hypotension. Protective airway reflexes are maintained, and it can sometimes be administered without airway protective measures. Psychotomimetic side effects can be reduced by co-administration of lamotrigine, nimodipine, benzodiazepines, or propofol; a combination of ketamine and propofol is known as ketofol.
At lower, sub-anesthetic doses, ketamine is used for pain management and treatment-resistant depression. In emergency departments and perioperative settings, ketamine infusions reduce morphine use, pain levels, nausea, and vomiting after surgery, and are especially beneficial for opioid-tolerant patients or those expected to have severe post-operative pain. It is also effective for acute pain in pre-hospital settings due to its low risk of respiratory depression. For chronic pain, parti
- field
- Medicine, Anesthesiology, Psychiatry
- known_for
- Dissociative anesthesia, rapid antidepressant effects, recreational use as 'Special K'
- forms
- Racemic ketamine, esketamine (S-enantiomer), arketamine (R-enantiomer)
Lore & Background
It has been regularly used in veterinary medicine and was extensively used for surgical anesthesia in the Vietnam War. At anesthetic doses, ketamine induces a state of dissociative anesthesia, providing pain relief, sedation, and amnesia while preserving breathing and airway reflexes, stimulating heart function, and causing moderate bronchodilation. It is used especially in trauma, emergency, and pediatric cases. At lower, sub-anesthetic doses, it is used as a treatment for pain and treatment-resistant depression. Racemic ketamine, especially at higher doses, may be more effective and longer-lasting than esketamine in reducing depression severity.
Reader's Guide
Ketamine's significance lies in its unique pharmacological profile as an NMDA receptor antagonist that provides dissociative anesthesia with minimal respiratory depression, making it valuable in emergency and field settings such as the Vietnam War. The drug is tightly controlled due to recreational use for its hallucinogenic and dissociative effects, with long-term effects of repeated use largely unknown and under active investigation. Liver and urinary toxicity have been reported among regular recreational users. Ketamine is contraindicated in severe heart or liver disease and uncontrolled psychosis. Its clinical and antidepressant effects can be influenced by co-administration of other drugs, though these interactions are variable and not yet fully understood.
Did You Know?
- It was extensively used for surgical anesthesia in the Vietnam War.
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