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Other meanings of Ketamine

Medicine & Pharmacology

Ketamine

Ketamine is a dissociative anesthetic and analgesic medication also used recreationally. It acts primarily as an NMDA receptor antagonist, producing a trance-like state, pain relief, and amnesia. Developed in 1962, it is on the WHO Model List of Essential Medicines and has seen a resurgence in psychiatric use for treatment-resistant depression.

1962
Year synthesized
First synthesized by Calvin Stevens
0.5–2 mg/kg
IV anesthetic dose
Typical induction dose
~3 min
Onset (IV)
Rapid onset of action
~45 min
Duration (IV)
Anesthetic effects last about 45 minutes
1

Medical uses

Ketamine is primarily used as an anesthetic for induction and maintenance of general anesthesia, particularly in emergency and field settings due to its favorable safety profile, preserving airway reflexes and cardiovascular stability.1 It is also a potent analgesic at sub-anesthetic doses, effective for acute pain, and is increasingly used for chronic pain conditions.2 In 2019, the FDA approved esketamine (the S-enantiomer) nasal spray for treatment-resistant depression, marking a paradigm shift in psychiatric pharmacotherapy. Off-label, ketamine is used for rapid suicide ideation reduction and in palliative care.

2

Pharmacology and mechanism

Ketamine's primary mechanism is non-competitive antagonism of the N-methyl-D-aspartate (NMDA) receptor, a subtype of glutamate receptor, which leads to decreased excitatory neurotransmission.3 This action disrupts thalamocortical signaling, producing the characteristic dissociative state. Ketamine also interacts with opioid receptors, monoaminergic systems, and voltage-gated sodium channels, contributing to its analgesic and psychotropic effects.4 The drug is a racemic mixture of two enantiomers; esketamine has higher affinity for the NMDA receptor and is more potent. Its metabolites, including norketamine, also contribute to its effects, particularly in prolonged analgesia.

3

Recreational use and risks

Ketamine is used recreationally for its dissociative and hallucinogenic effects, often at parties or in club scenes, where it is known as "Special K".5 At sub-anesthetic doses, users experience euphoria, altered perception, and out-of-body experiences, but higher doses can lead to the "K-hole", a state of profound dissociation and immobility. Chronic use is associated with significant health risks, including ulcerative cystitis (ketamine-induced cystitis), cognitive impairment, and dependence.6 Acute toxicity can cause hypertension, tachycardia, and respiratory depression, especially when combined with other depressants. The drug is a Schedule III controlled substance in the US and a Class B drug in the UK.

4

Lesser-known aspects

Ketamine was developed by Calvin Stevens at Parke-Davis while searching for a safer alternative to phencyclidine (PCP), and it was first tested on humans in 1964.7 It was used extensively as a battlefield anesthetic during the Vietnam War, earning a reputation for safety. In veterinary medicine, ketamine is widely used for anesthesia in animals, including horses and cats. A lesser-known fact is that ketamine has been studied for its potential to reduce PTSD symptoms and as a neuroprotective agent in traumatic brain injury. Additionally, it is used in low doses as an adjunct to opioid therapy to reduce opioid tolerance. The drug's rapid antidepressant effect, occurring within hours, is unique among antidepressants and has sparked research into its effects on synaptic plasticity and the default mode network.

Glossary

NMDA receptor
A glutamate receptor that plays a key role in synaptic plasticity and memory; ketamine blocks it.
Dissociative
A state of feeling disconnected from one's body or surroundings.
Esketamine
The S-enantiomer of ketamine, used as a nasal spray for depression.
K-hole
A colloquial term for a state of intense dissociation and immobility caused by high doses of ketamine.

Ketamine is a versatile drug with a complex history, balancing clinical utility and potential for abuse.