Ketamine

Summary sheet: Ketamine

Ketamine
Chemical Nomenclature
Common names	Ketamine, K, Ket, Kitty, "Special K", "Cat Tranquilizer", Ketaset, Ketalar, Ketanest
Substitutive name	Ketamine
Systematic name	(RS)-2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone
Class Membership
Psychoactive class	Dissociative
Chemical class	Arylcyclohexylamine
Routes of Administration
WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section. ⇣ Oral Dosage Bioavailability 17% Threshold 50 mg Light 50 - 100 mg Common 100 - 300 mg Strong 300 - 450 mg Heavy 450 mg+ Duration Onset 10 - 30 minutes Peak 45 - 90 minutes After effects 4 - 8 hours ⇣ Sublingual Dosage Bioavailability 20% - 29% Duration ⇣ Insufflated Dosage Bioavailability 45% Threshold 5 mg Light 10 - 30 mg Common 30 - 75 mg Strong 75 - 150 mg Heavy 150 mg + Duration Total 1 - 1.5 hours Onset 2 - 5 minutes Come up 5 - 10 minutes Peak 30 - 60 minutes After effects 2 - 12 hours ⇣ Intramuscular Dosage Bioavailability 93% Duration DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.
Interactions
Amphetamines
Cocaine
Benzodiazepines
MAOIs
Alcohol
GHB
GBL
Opioids
Tramadol

Ketamine (also known as ket, K, special K, kitty, and others) is a classical dissociative substance of the arylcyclohexylamine class. It is one of the most well-known and widely-used dissociatives, a diverse group that includes phencyclidine (PCP), methoxetamine (MXE), dextromethorphan (DXM), and nitrous oxide. It principally acts as an NMDA receptor antagonist; however, its precise mechanism is poorly understood.

Ketamine was developed in 1963 by Parke-Davis Laboratories as a replacement for the surgical anesthetic phencyclidine (PCP). It became available by prescription in 1969 under the name Ketalar. Today, ketamine is widely used in human and veterinary medicine, primarily for general anesthesia for surgical procedures. Recreational use is associated with dance parties, electronic dance music, and the club and rave scenes.

Subjective effects include motor control loss, internal hallucinations, conceptual thinking, euphoria, and dissociation. Dissociation is a complex mental state characterized by perceptual distortions and feelings of detachment from the environment and one's self. Ketamine's effects are similar to dissociatives like PCP and DXM but with a shorter duration and rapid onset. The effects of ketamine are highly dose-dependent. At lower doses, users report disinhibition and relaxation effects similar to those of alcohol. Higher doses exceeding a certain threshold colloquially known as a "k-hole") are capable of inducing a trance-like state that is commonly described as an out-of-body or near-death experience.

Ketamine is considered to have moderate to high abuse potential and the health effects of chronic use are not well-known. There is significant evidence that abuse causes bladder and urinary tract dysfunction. Additionally, some studies have found cognitive deficits in chronic users, which suggests it may have neurotoxic properties. As a result, it is highly advised to use harm reduction practices if using this substance.

Contents

History and culture

Ketamine was first synthesized at Parke Davis Laboratories by the American scientist Calvin Stevens. Stevens was searching for a new anesthetic to replace PCP, which was deemed not suitable for use in humans because of the severe hallucinogenic effects it produced upon recovery of consciousness.

Ketamine began as a veterinary anaesthetic when it was patented in Belgium in 1963. After being patented by Parke-Davis for human and animal use in 1966, ketamine became available by prescription in 1969 in the form of ketamine hydrochloride, under the name of Ketalar. It was officially approved for human consumption by the United States Food and Drug Administration in 1970 and, because of its sympathomimetic properties and its wide margin of safety, was administered as a field anaesthetic to soldiers during the Vietnam War.

Ketamine is on the World Health Organization’s “Essential Drugs List”, a list of the safest and most effective drugs needed in a modern health system.

Street names include "special K", "kitty", and "horse/dog/cat tranquilizer", which refers to its use in veterinary medicine.

Chemistry

Ketamine, or (RS)-2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone, is a member of the arylcyclohexylamine chemical class. Arylcyclohexylamines are named for their chemical structures which include a cyclohexane ring bound to an aromatic ring along with an amine group. Ketamine is comprised of a phenyl ring with a chlorine substituent at R₂ bonded to a cyclohexane ring substituted with an -Oxo group (cyclohexanone). An amino methyl chain (-N-CH₃) is bound to the same location (R₁) of the cyclohexanone ring.

Ketamine is a chiral molecule and is typically produced as a racemate. Enantiopure versions such as esketamine (S-ketamine) and arketamine (R-ketamine) are sometimes used.

Pharmacology

Further information: NMDA receptor antagonist

Ketamine acts as a non-competitive antagonist of the NMDA receptor, an ionotropic glutamate receptor. NMDA receptors allow for electrical signals to pass between neurons in the brain and spinal column; for the signals to pass, the receptor must be open. Dissociatives close the NMDA receptors by blocking them. This disconnection of neurons leads to loss of feeling, difficulty moving, and eventually the notorious state known as the “K-hole”.

At high, fully anesthetic level doses, ketamine has also been found to bind to μ-opioid receptors type 2 in cultured human neuroblastoma cells without agonist activity and to sigma receptors in rats. Also, ketamine interacts with muscarinic receptors, descending monoaminergic pain pathways and voltage-gated calcium channels. At subanesthetic and fully anesthetic doses, ketamine has been found to block serotonin depletion in the brain by inhibiting 5-HT receptors rather than through monoamine oxidase inhibition.

Subjective effects

This subjective effects section is a stub. As such, it is still in progress and may contain incomplete or wrong information. You can help by expanding or correcting it.

Disclaimer: The effects listed below are cited from the Subjective Effect Index (SEI), which relies on assorted anecdotal reports and the personal experiences of PsychonautWiki contributors. As a result, they should be taken with a healthy amount of skepticism. It is worth noting that these effects will not necessarily occur in a consistent or reliable manner, although higher doses (common+) are more likely to induce the full spectrum of reported effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.

Physical effects

• • Sedation - Ketamine is considered to have a light to moderate sedative effect. It discourages physical activity and can render the user immobile at higher doses.
  • Spontaneous bodily sensations - The ketamine "body high" is a sharp, pleasurable tingling sensation which is location-specific to the hands, feet and head. This regularly results in an out-of-body sensation or a general disconnection between the mind and body, which can be accompanied by states of euphoria.
  • Physical euphoria - This results in feelings of physical euphoria which range between mild pleasure to powerfully all-encompassing bliss.
  • Perception of bodily lightness - This creates the sensation that the body is floating and has become entirely weightless. This effect is oddly stimulating and encourages physical activities at low to moderate doses by making the body feel light and effortless to move.
  • Changes in felt bodily form
  • Changes in felt gravity
  • Motor control loss - A loss of gross and fine motor control alongside balance and coordination is commonly produced by ketamine and becomes especially strong at higher dosages. This means that one should be sitting down before the onset in case of falling over and injuring oneself.
  • Tactile suppression - This partially to entirely suppresses one's sense of touch, creating feelings of numbness within the extremities. It is responsible for the anesthetic properties of this substance.
  • Pain relief
  • Optical sliding
  • Dizziness - Although uncommon, some people report dizziness while under the influence of ketamine.
  • Increased salivation
  • Nausea - Higher doses of ketamine can sometimes result in nausea and vomiting at the peak of the experience.
  • Decreased libido
  • Gustatory hallucination
  • Orgasm suppression
  • Physical autonomy

Visual effects

• Suppression

  • Double vision - Prevalent at moderate to heavy doses and makes reading text impossible unless one closes an eye.
  • Pattern recognition suppression - Generally occurs at higher doses and makes one unable to recognize and interpret perceivable visual data.
  • Acuity suppression
  • Frame rate suppression

  Distortions

  • Perspective distortion
  • Environmental cubism
  • Environmental orbism
  • Scenery slicing

  Geometry

  The visual geometry produced by ketamine can be described as very brightly colored in scheme when compared to that of other, less visually disconnecting dissociatives like MXE and PCP, but not as complex as the geometry evoked by DXM or any psychedelic. 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 its depth and consistent in its intensity.

  Hallucinatory states

  Higher doses of ketamine can produce a full range of high level hallucinatory states in a fashion that is less consistent and reproducible than that of many common psychedelics. These effects include:

  • Machinescapes
  • Internal hallucination (autonomous entities; settings, sceneries, and landscapes; perspective hallucinations and scenarios and plots) - This effect can be comprehensively described through its variations as delirious in believability, fixed in style, equal in new experiences and memory replays in content, autonomous in controllability and solid in style.
  • External hallucination (autonomous entities; settings, sceneries, and landscapes; perspective hallucinations and scenarios and plots) - This effect can be comprehensively described through its variations as delirious in believability, autonomous in controllability and solid in style. The most common theme for this effect to follow is one of experiencing and talking to friends when they are not actually present.

Cognitive effects

• • Analysis suppression
  • Anxiety suppression
  • Compulsive redosing
  • Conceptual thinking
  • Déjà vu
  • Delusion
  • Depersonalization & Derealization
  • Disinhibition
  • Dream potentiation
  • Ego inflation
  • Focus suppression
  • Immersion enhancement
  • Increased music appreciation
  • Introspection
  • Memory suppression
    • Amnesia
  • Personal bias suppression
  • Spatial disorientation
  • Suggestibility enhancement
  • Thought deceleration
  • Time distortion

Auditory effects

• • Auditory suppression
  • Auditory distortion
  • Auditory hallucinations

Disconnective effects

• • Cognitive disconnection
  • Physical disconnection
  • Visual disconnection - This eventually results in the experience of the notorious "k-hole" or, more specifically, holes, spaces and voids alongside of structures.

Multi-sensory effects

• • Synaesthesia

Transpersonal effects

• • Existential self-realization
  • Identity alteration
  • Spirituality enhancement

Experience reports

Anecdotal reports which describe the effects of this compound within our experience index include:

• Experience:260 mg Ketamine (insufflated) - Lost in Paisley
• Experience:300mg Ketamine (Insufflated) - The Void: Finding peace in death
• Experience:50mg Ketamine (esketamine) i.m. - Exploring space heights and ocean depths
• Experience:75mg Ketamine (insufflated) - Wandering through the winter night
• Experience:Date: MM/YYYY Age: Sex: Height: Weight: kg / lb (include both if possible) Misc:
• Experience:Ketamine (200mg nasal) Quasi sexual experience
• Experience:Ketamine (unknown dosage) - States of unity and interconnectedness

Additional experience reports can be found here:

• Erowid Experience Vaults: Ketamine

Medical uses

Novel antidepressant

It has been demonstrated that ketamine, even if taken in small doses, is effective for patients suffering from chronic depression and bipolar disorder. Studies have shown that the effect of the drug is immediate or within 2 hours and consistent in relieving a patient’s depressive and/or suicidal symptoms, lasting up to 3 days after a single dose. In comparison, common antidepressants such as Prozac, are entirely ineffective for 40% of the population and can take weeks to show effects. This gives ketamine the potential to become an indispensable tool in the treatment of depression and bipolar disorder, which is currently being held back by institutionalized drug prohibition.

Ketamine is a racemate that comprises the R-(−)-ketamine enantiomer (arketamine) and the S-(+)-ketamine enantiomer (esketamine). Esketamine inhibits the reuptake of the dopamine transporter about 8-fold more potently than does arketamine, and so is about 8 times more potent as a dopamine reuptake inhibitor. Arketamine appears to be more effective as a rapid-acting antidepressant than esketamine.

A study conducted in mice found that ketamine's antidepressant activity is not caused by ketamine inhibiting NMDAR, but rather by sustained activation of a different glutamate receptor, the AMPA receptor, by a metabolite, (2R,6R)-hydroxynorketamine; as of 2017 it was unknown if this was happening in humans. Arketamine is a AMPA receptor agonist.

Anesthetic does may not produce an antidepressant effect. While the research is limited, between .5 and 1mg/kg IV given over about 40 mins seems to be the optimal dose. A typical anesthetic dose is 1-2 mg/kg given over 2 minutes, followed by .5-1.8mg/kg/hr. Benzodiazepines and GABA agonist (both of which are often used alongside ketamine in anesthesia) may mitigate the antidepressant effect of ketamine.

Psychedelic therapy

Ketamine psychedelic therapy (KPT) is used for preparation for death (thanatological, Death-Rebirth Psychotherapy)

Toxicity and harm potential

This toxicity and harm potential section is a stub. As such, it may contain incomplete or even dangerously wrong information. You can help by expanding or correcting it. We also recommend that you conduct independent research and use harm reduction practices when using this substance.

This radar plot shows relative physical harm, social harm, and dependence of ketamine.

The first large-scale, longitudinal study of ketamine users found that frequent ketamine users (at least 4 days/week, averaging 20 days/month) had increased depression and impaired memory by several measures, including verbal, short-term memory and visual memory. However, infrequent (1–4 days/month, averaging 3.25 days/month) ketamine users and former ketamine users were not found to differ from controls in memory, attention and psychological well-being tests. This suggests the infrequent use of ketamine does not cause cognitive deficits and that any deficits that might occur may be reversible when ketamine use is discontinued. However, abstinent, frequent, and infrequent users all scored higher than controls on a test of delusional symptoms.

Neurotoxicity

Short-term exposure of cultures of GABAergic neurons to ketamine at high concentrations led to a significant loss of differentiated cells in one study, and non-cell death-inducing concentrations of ketamine (10 μg/ml) may still initiate long-term alterations of the dendritic arbor in differentiated neurons.

More recent studies of ketamine-induced neurotoxicity have focused on primates in an attempt to use a more accurate model than rodents. One such study administered daily ketamine doses consistent with typical recreational doses (1 mg/kg IV) to adolescent cynomolgus monkeys for varying periods of time. Decreased locomotor activity and indicators of increased cell death in the prefrontal cortex were detected in monkeys given daily injections for six months, but not those given daily injections for one month.

Urinary tract effects

According to a 2010 systematic review, 110 documented reports of irritative urinary tract symptoms from ketamine dependence exist. Urinary tract symptoms have been collectively referred to as "ketamine-induced ulcerative cystitis" or "ketamine-induced vesicopathy" and they include urge incontinence, decreased bladder compliance, decreased bladder volume and painful haematuria (blood in urine).

The time of onset of lower urinary tract symptoms varies depending, in part, on the severity and chronicity of ketamine use; however, it is unclear whether the severity and chronicity of ketamine use corresponds linearly to the presentation of these symptoms. All reported cases where the user consumed greater than 5 grams per day reported symptoms of the lower urinary tract.

Overdose

Fatal ketamine overdoses are particularly rare, but not unheard of. However, the exact toxic dosage is unknown.

Dependence and abuse potential

As with other NMDA receptor antagonists, ketamine produces dependence with chronic use and has high abuse potential. When dependence has developed, cravings and withdrawal effects may occur if a person suddenly stops their usage.

Tolerance to the main effects of ketamine develops with prolonged and repeated use. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about 3 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to be back at baseline (in the absence of further consumption). Ketamine presents cross-tolerance with all dissociatives, meaning that after the consumption of ketamine all dissociatives will have a reduced effect.

It is strongly advised to use harm reduction practices when using this substance.

Dangerous interactions

Although many psychoactive substances are reasonably safe to use on their own, they can quickly become dangerous or even life-threatening when combined with other substances. The list below includes some known dangerous combinations (although it cannot be guaranteed to include all of them). Independent research (e.g. Google, DuckDuckGo) should always be conducted to ensure that a combination of two or more substances is safe to consume. Some interactions listed have been sourced from TripSit.

• Amphetamines - No unexpected interactions, though likely to increase blood pressure but not an issue with sensible doses. Moving around on high doses of this combination may be ill advised due to risk of physical injury.
• Cocaine - No unexpected interactions, though likely to increase blood pressure but not an issue with sensible doses. Moving around on high doses of this combination may be ill advised due to risk of physical injury.
• Benzodiazepines - Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position.
• MAOIs - MAO-B inhibitors appear to increase the potency of Ketamine. MAO-A inhbitors have some negative reports associated with the combination but there isn't much information available
• Alcohol - Both substances cause ataxia and bring a very high risk of vomiting and unconsciousness. If the user falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position.
• GHB - Both substances cause ataxia and bring a risk of vomiting and unconsciousness. If the user falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position.
• GBL - Both substances cause ataxia and bring a risk of vomiting and unconsciousness. If the user falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position.
• Opioids - Both substances bring a risk of vomiting and unconsciousness. If the user falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position.
• Tramadol
• Grapefruit - Grapefruit juice significantly increases oral absorption of ketamine. This may result in the user having double the concentration of ketamine in their system compared to normal. The ketamine may also have a longer duration of effect. This is likely to apply to oral, sublingual, and intranasal administration.

Legal status

• Australia: Ketamine is a Schedule 8 drug in Australia, meaning that possession, manufacture or supply without authority is illegal.
• Austria: Ketamine is legal for medical and veterinary use and illegal when sold or possessed without a prescription under the NPSG (Neue-Psychoaktive-Substanzen-Gesetz Österreich).
• Belgium: Ketamine is legal for medical and veterinary use and illegal when sold or possessed without a prescription.
• Brazil: Ketamine is legal for veterinary use and illegal when sold or possessed for human use.
• Canada: Ketamine is a Schedule I drug.
• China: Ketamine is a Schedule II drug.
• Czech Republic: Ketamine is legal for medical and veterinary use and illegal when sold or possessed without a prescription.
• Denmark: Ketamine is legal for medical and veterinary use and illegal when sold or possessed without a prescription.
• France: Ketamine is a Schedule IV drug in France.
• Germany: Ketamine is a prescription medicine, according to Anlage 1 AMVV.
• Hong Kong: Ketamine is a Schedule I drug in Hong Kong.
• Malaysia: Ketamine is illegal to sell and possess in Malaysia.
• Mexico: Ketamine is a Category 3 drug in Mexico.
• New Zealand: Ketamine is a Class C drug in New Zealand.
• Norway: Ketamine is a Class A drug in Norway.
• Singapore: Ketamine is a Class A drug in Singapore.
• Slovakia: Ketamine is a Schedule II drug in Slovakia.
• South Korea: Ketamine is illegal to possess and sell in South Korea.
• Spain: Ketamine is a Schedule IV drug in Spain.
• Sweden: Ketamine is a Schedule IV drug in Sweden.
• Taiwan: Ketamine is a Schedule III drug in Taiwan.
• United Kingdom: Ketamine is a Class B drug in the United Kingdom.
• United States: Ketamine is a Schedule III drug in the United States.

See also

• Responsible use
• Dissociatives
• Arylcyclohexylamines
• MXE
• PCP

External links

• Ketamine (Wikipedia)
• Ketamine (Erowid Vault)
• Ketamine (Isomer Design)
• Ketamine (DrugBank)

Media

• Interview with a Ketamine Chemist (VICE)
• The Experimental Ketamine Cure for Depression (VICE)
• Ketamine: Dreams and Realities (Jansen 2000, 2004)

Literature

• Durieux, M., & Kohrs, R.T. (1998). Ketamine: teaching an old drug new tricks. Anesthesia and A nalgesia, 87 5, 1186-93. PMID: 9806706
• Mion, G. (2017). History of anaesthesia: The ketamine story–past, present and future. European Journal of Anaesthesiology (EJA), 34(9), 571-575. https://doi.org/10.1097/EJA.0000000000000638
• Krystal, J. H., Karper, L. P., Seibyl, J. P., Freeman, G. K., Delaney, R., Bremner, J. D., . . . Charney, D. S. (1994). Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans: Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Archives of General Psychiatry, 51(3), 199-214. http://dx.doi.org/10.1001/archpsyc.1994.03950030035004
• Morris, H., & Wallach, J. (2014). From PCP to MXE: A comprehensive review of the non-medical use of dissociative drugs. Drug Testing and Analysis, 6(7–8), 614–632. https://doi.org/10.1002/dta.1620