ketamine, general anesthetic agent related structurally to the hallucinogen phencyclidine (PCP). Ketamine was first synthesized in 1962 at Parke Davis Laboratories by American scientist Calvin Stevens, who was searching for a new anesthetic to replace PCP, which was not suitable for use in humans because of the severe hallucinogenic effects it produced upon recovery of consciousness. Ketamine was originally patented in Belgium in 1963 and was approved for use in humans by the U.S. Food and Drug Administration in 1970. Soon after, it was put to use to treat American soldiers fighting in the Vietnam War. Today, since ketamine can produce minor hallucinogenic side effects in humans, it is used most often as a veterinary anesthetic. However, the drug does have valuable applications in human medicine, especially as an anesthetic for children and for individuals undergoing minor surgery. It may also be used to treat depression and chronic pain.

Unlike inhalation anesthetics or sedative anesthetics (e.g., narcotics and benzodiazepines), ketamine does not depress respiration or other basic functions of the central nervous system. Thus, ketamine has a relatively wide margin of safety. In addition, it is distinct from other anesthetics because it has three major effects: analgesia (pain relief), hypnosis (sedation), and amnesia. The drug is known particularly for its ability to induce a dissociative (cataleptic) state, which is characterized by a lack of pain sensation, unconsciousness, and increased muscle tone. These characteristics are often accompanied by open eyes, jumping eye movements (nystagmus), and involuntary limb movements.

Ketamine works by altering the activity of neurons in the brain. This is accomplished through the drug’s inhibition of neuronal uptake of various neurotransmitters, including serotonin, glutamate, and dopamine. The net effect is a depression of neural communication between the thalamus and the cerebral cortex, resulting in an uncoupling of brain activity associated with memory, motor function, sensory experience, and emotion. Ketamine also stimulates activity in the limbic system, a region of the brain involved in controlling certain autonomic functions and in integrating various brain activities, including those associated with motivation and emotion.

In clinical use ketamine is administered intramuscularly or intravenously. Minor side effects of the drug include tearing (lacrimation) when emerging from the dissociative anesthetic state. Patients can sometimes experience severe and troubling hallucinogenic effects, such as intense dreams and delirium, upon waking; these effects are more common in adults than in children. Hallucinations are directly related to dose. Thus, higher doses produce more pronounced delirium and other symptoms of hallucination than do lower doses.

Ketamine’s ability to produce hallucinogenic effects within minutes after administration has led to its abuse as a recreational drug. The dissociative effect of ketamine that is produced by high doses is often described by recreational users as the “K hole”—a separation of the mind and body, or a hallucinatory “out of body” experience. Ketamine is known by various street names, including K, special K, jet, super acid, and cat valium. It may be snorted, injected, or taken orally, and its effects may last from 30 minutes to more than an hour. However, for one or more days after taking the drug, users may display symptoms of amnesia, schizophrenia, impaired judgment, and lack of coordination. In addition, long-term abuse can lead to paranoia, depression, and other evidence of cognitive dysfunction. Many individuals appear to be in a stupor when the drug has been taken in low doses; however, high doses can cause unconsciousness, cardiovascular depression, and death.