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Ketamine

Group: Dissociatives
Nicknames: Ket, K, Special K, Spravato
Last reviewed: October 2026

Pharmacology

Ketamine interacts with a vast number of receptors, channels and enzymes in the central and peripheral nervous systems (CNS and PNS) which produce the varying and dose-dependent effects associated with ketamine use. Ketamine functions in pain perception, the cardiovascular, gastrointestinal and respiratory systems by interacting with the related signalling molecules in the nervous system.

Ketamine is primarily known for interacting with NMDA (N-methyl-D-aspartate) receptors, where it acts as a non-competitive antagonist. This means it binds to and then blocks the NMDA receptors from functioning. The predominant sought-after effect of ketamine is the ‘dissociative’ effect, similar to other NMDA receptor antagonists such as dextromethorphan (DXM) and memantine.

Interactions of ketamine within the CNS results in this state of ‘dissociative anaesthesia’ – sensory loss and analgesia but without actual loss of consciousness. While some of these interactions are explored below, note that the research is constantly evolving and non-NMDA receptor effects of ketamine are disputed.

In the CNS, ketamine may interact with

  • Nitric oxide synthase (NOS): ketamine inhibits NOS, and therefore the production of nitric oxide or NO (not to be confused with nitrous oxide or N2O, aka laughing gas) which plays a role in pain perception.
  • Sigma receptors: ketamine has a low affinity for the sigma receptors 1 and 2 and it is thought that the analgesic effects of the sigma receptor are not activated by ketamine.
  • Opioid receptors: ketamine has a preference for the mu and kappa receptors, but its affinity for these receptors is 10 times less than that for NMDA. Reports show that naloxone (the opioid antagonist which counteracts the effects of opioids) does not work in countering the effects of ketamine, suggesting that ketamine’s interaction with opioid receptors does not have a significant impact on its effects. (See the Morphine section for a fuller explanation of opioid receptors).
  • Calcium channels: ketamine blocks calcium channels, which again contributes to the analgesic effects.
  • Sodium channels: ketamine has shown to have local anaesthetic properties possibly due to its interaction with sodium channels found in nerve endings of pain perceiving fibres.
  • Cholinergic, noradrenergic and serotonergic neurotransmission: in the spinal cord, ketamine acts to inhibit uptake of neurotransmitters involved in the pain perception. Simply put, it increases certain transmitters that work to inhibit pain.

In the peripheral nervous system, it increases catecholamines (which include adrenaline) in the cardiovascular system to increase heart rate and blood pressure (this is dose-related) and in the respiratory system which causes bronchodilation (relaxation of certain airway walls, causing them to open).

Intravenously, the onset of action is a few seconds, intramuscularly (injected into muscle/fat) it is 4 minutes, and intranasally (snorted) it is 1–3 minutes. When taken intranasally, ketamine’s effects last for around 1–2 hours.

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