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Effects vary widely by individual, dose, and context.
The subjective physical effects of ketamine can be broken down into eight components all of which progressively intensify proportional to dosage.
In comparison to other dissociatives, the cognitive effects of ketamine are often described as particularly forceful towards introspection and with more analytical thought process when compared to that of DXM and MXE.
This substance does not enhance visual stimuli; instead it tends to degrade and decrease visual aptitude in a variety of ways.
Ketamine exhibits a full array of dissociative distortions and alterations in visual perception.
The visual geometry found within ketamine can be described as very brightly coloured in scheme when compared to that of MXE but not as complex or psychedelic as that of DXM. It does not extend beyond level 4 and can be comprehensively described through its variations as simplistic in complexity, algorithmic in style, synthetic in feel, unstructured in organization, dimly lit in lighting, multicoloured in scheme, glossy in shading, soft in edges, large in size, fast in speed, smooth in motion, equal in rounded and angular corners, immersive in depth and consistent in intensity.
At high dosages, ketamine can produce a full range of high level hallucinatory states in a fashion that is less consistent and reproducible than that of many other commonly used psychedelics.
The auditory effects of ketamine are common in their occurrence and exhibit a range of effects.
Ketamine principally acts as a noncompetitive, open-channel, voltage-dependent antagonist of the NMDA receptor, an ionotropic glutamate receptor. It exists as a racemic mixture of two enantiomers, S-ketamine and R-ketamine, with S-ketamine displaying approximately 3- to 4-fold greater NMDA receptor affinity (Ki 0.30 μM) compared to R-ketamine (Ki 1.4 μM). In the presence of physiological magnesium concentrations, ketamine shows a degree of subunit selectivity, with its affinity for GluN2C- and GluN2D-containing receptors being less reduced by magnesium than its affinity for GluN2A- and GluN2B-containing receptors. Acute NMDA receptor blockade results in increased glutamate release, which in turn activates AMPA receptors and modulates downstream signaling pathways including upregulation of BDNF, activation of mTOR, and inhibition of eEF2 kinase phosphorylation, facilitating rapid synaptic protein synthesis and neuroplasticity. Ketamine is considered a psychoplastogen, a compound capable of promoting rapid and sustained neuroplasticity. Beyond NMDA receptor antagonism, ketamine interacts with opioid receptors, monoaminergic receptors, muscarinic receptors, and voltage-gated calcium channels, though a broad screening study found that at 10 μM, ketamine primarily affected NMDA receptors and did not meaningfully displace binding at muscarinic receptors, opioid receptors, sigma receptors, serotonin receptors, or monoamine transporters. Whether ketamine acts as a D2 receptor agonist is controversial, with early research suggesting partial agonist activity while later studies found affinity exceeding 10 μM.
Ketamine undergoes extensive hepatic metabolism primarily via CYP3A4 and CYP2B6, yielding norketamine through N-demethylation. Norketamine is subsequently converted by CYP2A6 and CYP2B6 into hydroxynorketamines and dehydronorketamine. Conjugated hydroxylated derivatives account for approximately 80% of urinary metabolites, with dehydronorketamine comprising about 16%. Overall, 85–95% of the administered dose is recovered in urine, primarily as metabolites, with a small fraction (approximately 3% after intravenous dosing) eliminated in feces. Oral bioavailability is low (16–24%) due to substantial first-pass metabolism, while intramuscular bioavailability is high at approximately 93%. Ketamine distributes rapidly, with a distribution half-life of approximately 2 minutes, and has a clearance rate of approximately 95 L/h/70 kg.
These combinations are considered extremely harmful and should always be avoided. Reactions to these drugs taken in combination are highly unpredictable and have a potential to cause death.
These combinations are not usually physically harmful, but may produce undesirable effects, such as physical discomfort or overstimulation. Extreme use may cause physical health issues. Synergistic effects may be unpredictable. Care should be taken when choosing to use this combination.
Moderate to high abuse potential with risk of psychological dependence developing with chronic use. Compulsive redosing is commonly reported, particularly with insufflation. The short duration of effects promotes bingeing patterns.
Physical dependence can develop with daily use. Withdrawal symptoms reported include anxiety, tremor, sweating, and palpitations following attempts to stop.
Fatal ketamine overdoses are rare when ketamine is the sole substance involved. Deaths from recreational use are more commonly associated with accidents such as drowning, combinations with respiratory depressants, or positional asphyxia rather than direct toxicity. More than 90 deaths were recorded in England and Wales between 2005-2013, including accidental poisonings, drownings, and traffic accidents.
| Species | Route | Value |
|---|---|---|
| mouse | unspecified | 224 mg/kg |
| rat | unspecified | 229 mg/kg |
Frequent heavy use can cause ketamine-induced cystitis, reduced bladder capacity, urge incontinence, and painful haematuria; these effects are strongly associated with chronic abuse patterns, with 20-30% of frequent users reporting bladder complaints.
Liver toxicity has been reported with higher doses and repeated administration; in chronic high-dose users, the frequency of liver injury is approximately 10%.
Chronic heavy use has been associated with kidney damage ranging from hydronephrosis to acute kidney injury; rhabdomyolysis causing kidney failure has been reported in overdose cases.
Chronic heavy use is associated with cognitive deficits in memory and learning, with imaging studies showing reductions in white and grey matter and brain atrophy in frequent users; infrequent users do not appear to differ from controls on cognitive measures.
Some evidence suggests ketamine may have antibiotic properties at higher doses, though how this affects normal human use is unclear.
At anesthetic doses, 10-20% of adults experience adverse psychiatric reactions during emergence, ranging from dysphoria to hallucinations and emergence delirium. Regular use is associated with paranoia, egocentrism, and increased delusional symptoms. Chronic heavy use may lead to persistent psychotic symptoms.
Seizures are rare but have been reported at very high or overdose-level doses. Tonic-clonic movements occur commonly at anesthetic doses but are distinct from true epileptic seizures.
Ketamine was first synthesized in 1962 by American scientist Calvin Stevens at Parke Davis Laboratories, initially designated "CI581." Stevens sought a safer anesthetic to replace phencyclidine, which produced severe and prolonged hallucinogenic effects upon recovery from anesthesia. By 1965,…
Not under international control (WHO Expert Committee on Drug Dependence recommended against scheduling in January 2016)
WHO Essential Medicines List
Possession, manufacture, or supply without authority is illegal. Classified as a controlled drug requiring strict regulation.
Legal for medical and veterinary use. Possession without prescription can result in arrest.
Not legal to possess without a prescription. Some pharmacies may sell ketamine, though most consider it forbidden.
Classified as a class II psychiatric drug. Trade is limited to licensed wholesalers and retail sales are prohibited.
Available exclusively with a prescription under Nařízení vlády č. 463/2013 Sb. Sales and distribution controlled under the Medicines Act.
Listed as a narcotic in Annexe IV of the Liste des substances classées comme stupéfiants. Injectable preparations classified as Médicine - List I and subject to strict controls.
Classified as a dangerous drug with strict controls on possession, manufacture, and distribution.
Listed in Tabella I of Tabelle delle sostanze stupefacenti e psicotrope. Illegal to possess, purchase, or sell.
Prohibited substance for recreational use under national drug legislation.
Classified under Mexico's General Health Law as having therapeutic value but constituting a problem for public health. Acquisition restricted to licensed veterinarians only under Medicines Administration Regulations.
Reclassified as a Class C substance in February 2008, the same category as cannabis and codeine.
Illegal to possess, manufacture, and sell except for authorized medical purposes.
Added to Schedule II (Grade 2) in October 2009, aligned with the 1971 United Nations Convention on Psychotropic Substances.
Classified as a Schedule IV substance under Spanish drug control legislation.
Specifically named under Verzeichnis B. Possession or handling without a license is illegal. Medicinal use is permitted.
Available only with a 'green prescription' designation. Illegal when sold or possessed without a prescription.
Emergency scheduled by the DEA on August 12, 1999. Previously unscheduled with FDA-regulated sales. Possession without prescription or license is illegal. Esketamine nasal spray (Spravato) was FDA-approved in March 2019 for treatment-resistant depression under restricted distribution.
Legal for medical and veterinary use. Repeated dispense prohibited. Illegal when sold, possessed, or produced without a prescription under the Neue-Psychoaktive-Substanzen-Gesetz (NPSG).
Legal for veterinary use only. Illegal when sold or possessed for human use.
Controlled under the Controlled Drugs and Substances Act as an analogue of phencyclidine (PCP). Sale, possession, and production are illegal unless authorized for medical, scientific, or industrial purposes.
Possession and distribution regulated under national drug legislation.
Illegal except for scientific and medicinal uses as of February 8, 2008.
Available by prescription for medical and veterinary use. Illegal when sold or possessed without a prescription.
Not listed under the Narcotic Drugs and Psychotropic Substances Act, 1985. Reportedly available over-the-counter in many pharmacies.
Classified as a narcotic under the Narcotic and Psychotropic Drugs Control Act (麻薬及び向精神薬取締法).
Controlled under Section 39b of the Dangerous Drugs Act. Possession and sale are illegal.
Treated as a medication rather than a controlled substance. Not listed in List 1 or 2 of the Opium Act. Sales require appropriate pharmaceutical licensing.
Classified as a Class A drug since 1999. Sold under the brand name Ketalar for authorized medical use.
Class A controlled drug. Traffickers face 5-20 years imprisonment and 5-15 strokes of the cane. Possession of more than 113g is deemed trafficking.
Controlled substance as of January 2005. Possession and sale are illegal.
Scheduled as of July 1, 2005 following increased reports of recreational misuse.
Controlled under national narcotics legislation with restrictions on possession and distribution.
Reclassified as a Class B drug under the Misuse of Drugs Act 1971 on June 10, 2014. Previously classified as Class C from January 1, 2006. Prior to 2006, possession was legal though sales required licensing.
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