Ketamine

Ketamine
The skeletal formula of Ketamine.
Chemical Nomenclature
Common names	Ketamine
Substitutive name	K, Special K
Systematic name	(RS)-2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone
Class Membership
Psychoactive class	Dissociative
Chemical class	Arylcyclohexylamine
Routes of Administration
Oral Dosage WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section. 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. Threshold 40 - 50 mg Light 50 - 100 mg Common 75 - 300 mg Strong 200 - 450 mg Heavy 500+ mg Duration Onset 5 - 20 minutes Peak 45 - 90 minutes Afterglow 4 - 8 hours Insufflated Dosage WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section. 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. Threshold 10 - 15 mg Light 15 - 30 mg Common 30 - 75 mg Strong 60 - 125 mg Heavy 100 - 250 mg Duration Onset 5 - 15 minutes Peak 45 - 60 minutes Afterglow 1 - 3 hours

Summary sheet: Ketamine

Ketamine is a hallucinogenic dissociative drug of the arylcyclohexylamine class of chemicals. It is used in human and veterinary medicine, primarily for the induction and maintenance of general anesthesia (usually in combination with a sedative). Other uses include sedation and anestheticin intensive care (particularly in emergency medicine) and treatment of bronchospasm (a sudden constriction of the muscles in the walls of the lungs bronchioles).

This substance was originally developed as a medicine in 1965 as a derivative of phencyclidine (PCP), which was synthesized in 1926. It became popular among recreational users in the 1970s, but remains a core medicine in the World Health Organization’s “Essential Drugs List”, a list of minimum medical needs for a basic healthcare system.

Like other drugs of its class such as methoxetamine and phencyclidine (PCP), it induces a state referred to as "dissociative anesthesia" and is used as a recreational drug.

Chemistry

General formula of arylcyclohexylamine molecule

Ketamine, or (RS)-2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone, is classed as an arylcyclohexylamine drug. Ayrlcyclohexylamine drugs are named for their structures which include a cyclohexane ring bound to an aromatic ring along with an amine group. Ketamine contains 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 often produced as a racemate.

Pharmacology

Main article: NMDA receptor antagonist

Ketamine acts as a competitive NMDA receptor antagonist. 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 famous “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 oxidation.

Subjective effects

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed effects will rarely (if ever) occur all at once, but heavier dosages will increase the chances and are more likely to induce a full range of effects.

Physical effects

• Spontaneous tactile sensations - The ketamine "body high" is a sharp, pleasurable tingling sensation which is location specific to the hands, feet and head.
• Tactile suppression - This partially to entirely suppresses one's sense of touch, creating feelings of numbness within the extremities. It is responsible for the anaesthetic properties of this substance.
• Motor control loss - A loss of gross and fine motor control alongside of balance and coordination is prevalent within ketamine and becomes especially strong at higher dosages. This means that one should be sitting down before the onset (unless experienced) in case of falling over and injuring oneself.
• Physical euphoria - This results in feelings of physical euphoria which range between mild pleasure to powerfully all-encompassing bliss.
• Perception of decreased weight - This creates the sensation that the body is floating and has become entirely weightless. This effect is strangely stimulating and encourages physical activities at low to moderate doses by making the body feel light and effortless to move.
• Dizziness - Although uncommon, some people report dizziness under the influence of ketamine.
• Nausea - It's worth noting that high dose ketamine trips can sometimes result in nausea and vomiting at the peak of the trip. For most people, this is surprisingly not as unpleasant as they would initially expect due to the accompanying detachment from the physical senses.
• Tactile disconnection
• Physical autonomy
• Visual sliding

Cognitive effects

The cognitive effects of ketamine are often described as particularly forceful towards introspection and with a more analytical thought process when compared to that of other dissociatives such as DXM or MXE. These effects can be broken down into several separate subcomponents which are listed and described below:

• Depersonalization
• Derealization
• Consciousness disconnection
• Memory suppression
• Immersion enhancement
• Thought deceleration
• Information processing suppression
• Time distortion
• Introspection
• Déjà vu
• Personal bias suppression
• Conceptual thinking
• Direct communication with the subconscious
• Unity and interconnectedness
• Compulsive redosing
• Anxiety suppression
• Disinhibition
• Amnesia
• Suggestibility enhancement

Visual effects

Suppression

• Visual disconnection - This eventually results in the experience of the famous "k-hole" or, more specifically, holes, spaces and voids alongside of structures.
• Double vision - This component is prevalent at moderate to heavy doses and makes reading impossible unless one closes an eye.
• Pattern recognition suppression - This effect generally occurs at higher doses and makes one unable to recognize and interpret perceivable visual data.
• Visual acuity suppression
• Frame rate suppression

Distortions

• Perspective distortions
• Environmental cubism
• Environmental orbism
• Scenery slicing

Geometry

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.

Hallucinatory states

At high doses, 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 psychedelic. These effects include:

• External hallucinations (autonomous entities; settings, sceneries, and landscapes; alterations in perspective and scenarios and plots) - In comparison to other dissociatives, this effect can occur at heavy doses, but is extremely infrequent in comparison to the same effect found within deliriants. It 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.
• Internal hallucinations (autonomous entities; settings, sceneries, and landscapes; alterations in perspective and scenarios and plots) - In comparison to other dissociatives, this effect can occur at heavy doses, but is considerably less common than the same effect found within psychedelics and deliriants. It 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.

Auditory effects

• Enhancements
• Suppression
• Distortions
• Hallucinations

Multi-sensory effects

• Synaesthesia

Antidepressant effects

It has been demonstrated that ketamine, even if taken in small doses, is very 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 institutionalised drug prohibition.

The mechanism behind this has been shown by studies to stem from the way in which ketamine triggers the release of glutamate, which is a neurotransmitter that immediately stimulates the growth of damaged synapses which have been damaged by stress and depression.

Toxicity and harm potential

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

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

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.

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 dendritic arbor in differentiated neurons. The same study also demonstrated chronic (>24 h) administration of ketamine at concentrations as low as 0.01 μg/ml can interfere with the maintenance of dendritic arbor architecture. These results raise the possibility that chronic exposure to low, subanesthetic concentrations of ketamine, while not affecting cell survival, could still impair neuronal morphology and thus might lead to dysfunctions of neural networks.

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.

Studies have shown that the serotonin systems affected by such serotonergic drugs are linked to the NMDA/glutamate systems. Tests on rats indicate that 5-HT agonists like LSD and psilocybin can prevent neurotoxicity due to NMDA receptor antagonists.

Urinary tract effects

According to a recent 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.

It is strongly recommended that one use harm reduction practices when using this drug.

Tolerance and addiction potential

As with other NMDA receptor antagonists, the chronic use of ketamine can be considered moderately addictive with a high potential for abuse and is capable of causing psychological dependence among certain users. When addiction has developed, cravings and withdrawal effects may occur if a person suddenly stops their usage.

Tolerance to many of the 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.

Dangerous interactions

Although many drugs are safe on their own, they can become dangerous and even life-threatening when combined with other substances. The list below contains some common potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses of each but still increase the potential risk of death. Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.

• Depressants - This combination potentiates the muscle relaxation, sedation and amnesia caused by one another and can lead to unexpected loss of consciousness at high doses. There is also an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it. Examples include 1,4-butanediol, 2-methyl-2-butanol, benzodiazepines, GHB, GBL, and opioids.

Legal issues

• Australia: Ketamine is a Schedule IV drug.
• Belgium: It is legal for medical and veterinary use and illegal when sold or possessed without a prescription.
• Brazil: The drug 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: It is legal for medical and veterinary use and illegal when sold or possessed without a prescription.
• Denmark: It is legal for medical and veterinary use and illegal when sold or possessed without a prescription.
• France: Ketamine is a Schedule IV drug.
• Germany: It is legal for medical and veterinary use and illegal when sold or possessed without a prescription.
• Hong Kong: Ketamine is a Schedule I drug.
• Malaysia: The possession and sale is illegal.
• Mexico: Ketamine is a Category 3 drug.
• New Zealand: Ketamine is a Class C drug.
• Norway: Ketamine is a Class A drug.
• Singapore: Ketamine is a Class A drug.
• Slovakia: Ketamine is a Schedule II drug.
• South Korea: The possession and sale is illegal.
• Sweden: Ketamine is a Schedule IV drug.
• Taiwan: Ketamine is a Schedule III drug.
• U.K.: Ketamine is a Class C drug.
• U.S.: Ketamine is a Schedule III drug.

Experience reports

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

• Experience:Unknown dosage - States of unity and interconnectedness

See also

• Responsible use
• Dissociatives
• Arylcyclohexylamines
• MXE
• PCP

External links

• Ketamine (Wikipedia)
• Ketamine (Erowid)
• Ketamine (Bluelight)
• Ketamine (TripSit)
• Ketamine experiences (Erowid)