Ketamine

(RS)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone

Overview

Ketamine belongs to Dissociatives / Arylcyclohexylamines.

Key safety note: Ketamine's stand-out long-term harm is ketamine-induced uropathy ('ketamine bladder', ulcerative cystitis): regular heavy use inflames and scars the bladder wall, causing severe urinary urgency, frequency, pain and bleeding, and in advanced cases irreversible bladder shrinkage that can require surgery or bladder removal, and it can develop in young, frequent users.^[5]^[4]

Effects

Subjective effects vary. What a substance feels like depends on dose, individual physiology, mindset, and setting. The points below describe commonly reported effects, not guaranteed, uniform, or desirable outcomes.

Dissociation (detachment from body and surroundings)
Time & space distortion
Euphoria
Dreamlike / floaty
Reduced pain sensitivity
Reduced coordination
Immersive dissociation (k-hole)

Dosing & duration

Harm-reduction note: These are commonly cited reference ranges, not a recommendation or a “safe” dose. Potency, purity, body chemistry, tolerance, and drug combinations vary widely. Start low, go slow, wait for full effects before redosing, and never assume an unknown product matches these figures. Missing data is not evidence of safety.

Insufflated (snorted). Values below are for snorting. Doses differ markedly by route: oral and rectal need more, intramuscular much less, so never assume equivalence. These are reference ranges, not a 'safe' dose. Key harm-reduction points: ketamine's biggest long-term risk is bladder damage, so frequency matters more than any single dose: space use out and avoid daily or binge use. Stay somewhere physically safe with a sober sitter (dissociation causes falls, and vomiting while dissociated can cause choking), and do not combine it with alcohol, benzodiazepines, opioids or GHB.

Dose ranges

Threshold

5 mg

Light

10–30 mg

Common

30–75 mg

Strong

75–150 mg

Heavy

150 mg +

Duration

onset

1–3 min

peak

15–45 min

total

1–2 h

after effects

2–12 h

Chemical & Physical Properties

Formula	C13H16ClNO
Molar mass	237.73 g/mol
State	Solid
Melting point	92.5 °C
Boiling point	Not reported
Density	Not reported
Vapor pressure	Not reported
pKa	7.5
LogP	3.12
Solubility	Soluble, White crystals, mp 262–263 °C. Solubility in water: 20 g/100 mL. Freely soluble in methanol. Soluble in alcohol. Sparingly soluble in chloroform (ketamine hydrochloride)., 4.64×10⁻² g/L
Refractive index	Not reported

Identifiers & Synonyms

CAS	6740-88-1
CAS (enantiomer)
PubChem CID	3821
InChIKey	YQEZLKZALYSWHR-UHFFFAOYSA-N
InChI	InChI=1S/C13H16ClNO/c1-15-13(9-5-4-8-12(13)16)10-6-2-3-7-11(10)14/h2-3,6-7,15H,4-5,8-9H2,1H3
SMILES	CNC1(CCCCC1=O)C2=CC=CC=C2Cl

Synonyms

Ketamine
Ketalar
ketamine HCl
dl-Ketamine
Special K
Ket
Vitamin K

Pharmacodynamics & Biochemistry

Ketamine is a dissociative anaesthetic and, at lower doses, a rapid-acting antidepressant and analgesic. Its primary action is non-competitive, open-channel ('use-dependent') blockade of the NMDA glutamate receptor at the PCP binding site: it enters the open channel and blocks cation (including Ca²⁺) flux, reducing excitatory glutamatergic transmission, which underlies the dissociative, anaesthetic and analgesic effects. It is used as the racemate, but the two enantiomers differ: esketamine (S-ketamine) is roughly three to four times the more potent NMDA blocker and is the approved antidepressant nasal spray (Spravato), whereas arketamine (R-ketamine) is investigational and may have a distinct, possibly more sustained antidepressant profile. Ketamine is metabolised (CYP2B6/CYP3A4) to the active metabolite norketamine and then to hydroxynorketamine (HNK). There is evidence that HNK contributes to the antidepressant effect through an NMDA-independent, AMPA-receptor-dependent mechanism. The rapid antidepressant action is thought to involve a downstream glutamate surge, AMPA-receptor activation and rapid synaptogenesis (BDNF/mTOR signalling), rather than the slow monoamine changes of conventional antidepressants. Beyond NMDA, ketamine interacts with HCN1 channels (contributing to hypnosis), opioid receptors, monoamine transporters, muscarinic and nicotinic receptors and voltage-gated sodium/calcium channels. These secondary actions shape its analgesic, sympathomimetic and psychotomimetic effects. Uniquely among anaesthetics it tends to preserve airway reflexes and breathing and to raise (rather than lower) heart rate and blood pressure.

Biological targets

NMDA

Binding & functional measurements

Target	Measurement	Species
NMDA receptor	Ki 324 ± 19 nM	Rat

Pharmacokinetics

Bioavailability	Not reported
T_max	Not reported
Half-life	text: ≈2.5 h (redistribution, IV). low: 2.5. high: 2.5. unit: h. approx: true. note: redistribution half-life after IV
V_d	Not reported
Protein binding	Not reported
Metabolism	N-dealkylation to active norketamine primarily via CYP2B6 and CYP3A4
Excretion	elimination reflects redistribution plus hepatic biotransformation

Toxicology & Safety

Harm-reduction note: Toxicity and risk depend on dose, route, purity, combinations, setting, and individual health factors. Missing harms should never be interpreted as evidence of safety.

224 mg/kg (mouse, i.p.)

Ketamine's stand-out long-term harm is ketamine-induced uropathy ('ketamine bladder', ulcerative cystitis): regular heavy use inflames and scars the bladder wall, causing severe urinary urgency, frequency, pain and bleeding, and in advanced cases irreversible bladder shrinkage that can require surgery or bladder removal, and it can develop in young, frequent users. Heavy use also causes 'K-cramps' (severe abdominal pain), tolerance and psychological dependence with a compulsive redosing pattern, and cognitive and memory problems. Acutely, the dissociative, immobilising state (especially the 'k-hole') carries a high risk of accidents, falls, aspiration (vomiting while dissociated) and drowning (for example in a bath), so physical setting and a sober sitter matter. It raises heart rate and blood pressure and can cause confusion or frightening emergence experiences. Although ketamine alone depresses breathing less than most anaesthetics, combining it with alcohol, benzodiazepines, opioids or GHB markedly increases the risk of unconsciousness, vomiting and respiratory depression. Repeated nasal use damages the nasal lining.^[5]^[4]

Legal Status

Legal note: Legal status can change over time and may vary by country, region, formulation, analogue status, prescription context, and enforcement practice. Always confirm with current official sources before relying on this section.

US: Schedule III. UK: Class B. DE: Prescription only (Rx)

Interactions & Contraindications

Drug interactions

Alcohol, Benzodiazepines, Opioids, GHB / GBL Additive sedation and a greater risk of unconsciousness, vomiting or aspiration, and respiratory depression.^[4]^[6]

Stimulants (amphetamines, cocaine) Added cardiovascular strain (tachycardia and hypertension).^[4]

CYP2B6 / CYP3A4 inhibitors or inducers Can raise or lower ketamine and norketamine levels.^[4]

Drugs that raise blood pressure or heart rate Compound ketamine's sympathomimetic effects, caution in cardiovascular disease.^[4]

Contraindications

Cardiovascular disease, hypertension or arrhythmia poorly controlled hypertension, severe disease, or where a rise in blood pressure is dangerous (e.g. aneurysm).^[4]

Pre-existing bladder or urinary-tract disease, or drug-induced cystitis or active ketamine-induced cystitis.^[5]^[4]

Personal or family history of psychosis, schizophrenia or bipolar disorder ketamine can provoke or worsen psychotic symptoms.^[4]

Combining with alcohol or other CNS depressants^[4]^[5]

Settings where impairment or dissociation risks injury (driving, water, heights)^[4]^[5]

Usage & Context

A widely used anaesthetic and analgesic: valued in emergency, trauma, paediatric and veterinary medicine and in low-dose pain management because it preserves breathing and airway reflexes and supports blood pressure.
An established rapid-acting antidepressant: racemic ketamine is used off-label and esketamine (Spravato) is approved for treatment-resistant depression, acting within hours rather than weeks.
A popular recreational dissociative ('K', 'Special K') used for its dissociative, euphoric and psychedelic-like effects, common in nightlife and chemsex settings: where heavy, frequent use drives the bladder and dependence harms.

Sources & Evidence

Further Information

More in this subclass