Ketamine
| File:Ketamine-2D-skeletal.png | |
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| Routes of administration | IV, IM, Insufflated, oral, topical |
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| Pharmacokinetic data | |
| Bioavailability | 93% IM, 17% oral |
| Metabolism | liver |
| Elimination half-life | 2.5-3 hours. |
| Excretion | renal (>90%), urine |
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| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.027.095 |
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| Formula | C13H16ClNO |
| Molar mass | 237.725 g/mol |
- For the collaborative acoustic project, see Katamine.
Ketamine is a general dissociative anaesthetic for human and veterinary use. Its hydrochloride salt is sold as Ketanest®, Ketaset®, and Ketalar®. Pharmacologically it is very similar to other dissociative anesthetics such as tiletamine and phencyclidine (PCP).
Ketamine is a chiral compound, with two distinct enantiomers. Most pharmaceutical ketamine preparations are racemic, however reportedly some brands have (mostly undocumented) differences in enantiomeric proportions.
History
Ketamine was first synthesized in 1962 in an attempt to find a safer anaesthetic alternative to PCP, which was more likely to cause hallucinations and seizures. The drug was first used on American soldiers during the Vietnam War, but is often avoided now because it can cause potentially unpleasant out-of-body experiences. It is still used widely in veterinary medicine, and for select human applications.
Ketamine's side effects eventually made it a popular psychedelic in 1965. The drug was used in psychiatric and other academic research through the 1970s, culminating in 1978 with the publishing of John Lilly's The Scientist, a book documenting the author's ketamine, LSD, and isolation tank experiments. The incidence of recreational ketamine use increased through the end of the century, especially in the context of raves and other parties. The increase in illicit use prompted ketamine's placement in Schedule III of the United States Controlled Substance Act in August 1999. In the United Kingdom, it became outlawed and labelled a Class C drug on January 1, 2006.[1] In Canada, as of August 31, 2005, ketamine is classified as a Schedule I narcotic.
Medical use
Indicated for:
Recreational uses: |
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Severe: Impairs all senses, especially:
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Since it suppresses breathing much less than most other available anaesthetics, ketamine is still used in human medicine as a first-choice anaesthetic for victims with unknown medical history (e.g. from traffic accidents), in podiatry and other minor surgery, and occasionally for the treatment of migraine. There is ongoing research in France, Russia, and the U.S. into the drug's usefulness in pain therapy and for the treatment of alcoholism and heroin addiction.
In veterinary medicine, ketamine is often used for its anaesthetic and analgesic effects on cats, dogs, rabbits, rats, and other small animals. Veterinarians often use ketamine with sedative drugs to produce balanced anaesthesia and analgesia, and as a constant rate infusion to help prevent pain wind-up. Ketamine is used to manage pain among horses and other large animals, though it has less effect on bovines.
Ketamine may be used in small doses (0.1–0.5 mg/kg/hr) as an analgesic, particularly for the treatment of pain associated with movement and neuropathic pain. It has the added benefit of counter-acting spinal sensitization or wind-up phenomena experienced with chronic pain. At these doses, the psychotropic side effects are less apparent and well managed with benzodiazepines. Ketamine is a co-analgesic, requiring a concomitant low-dose opioid to be effective.
The effect of Ketamine as a depressant on the respiratory and circulatory systems is less than that of other anaesthetics. When used at anaesthetic doses, it will sometimes stimulate rather than depress the circulatory system. It is sometimes possible to perform ketamine anaesthesia without protective measures to the airways. Ketamine is also a potent analgesic and can be used in sub-anaesthetic doses to relieve acute pain; however, its psychotropic properties must be taken into account. Patients have reported going into other worlds or seeing God while anaesthetized, and these unwanted psychological side-effects have marginalized the use of ketamine in human medicine.
Experimental Antidepressant Use
According to a National Institute of Mental Health press release on 7 August 2006, a study of 17 patients led by Dr Carlos Zarate Jr. of the NIMH showed that ketamine significantly improved treatment-resistant major depression within two hours of injection. The improvement lasted up to one week after the single dose.[2] The patients in the study were previously treatment resistant,[3] having tried an average of six other treatments that failed. The importance of these findings was articulated by NIMH director Dr Thomas Insel: "This is the first report of any medication or other treatment that results in such a pronounced, rapid, prolonged response." The researchers apparently attribute the effect to ketamine being an NMDA receptor agonist. The study appears is the Archives of General Psychiatry.[4]
Neuropharmacology
Ketamine, like Phencyclidine, is primarily a non-competitive glutamate NMDA receptor antagonist. At low doses, the analgesia (loss of pain) effects of ketamine are mediated by antagonism on the NMDA receptors. Evidence for this is reinforced by the fact that naloxene, an opioid antagonist, does not reverse the analgesia. Studies also seem to indicate that ketamine is 'use dependent' meaning it only initiates its blocking action once a glutamate binds to the NMDA receptor.
At high fully anesthetic level doses, ketamine has also been found to bind to opioid mu receptors and sigma receptors. This indicates that loss of conciousness at high doses is at least partially due to binding at the opioid mu and sigma recepters.
Ketamine is racemic, and its R and S stereoisomer have different binding affinities. (S)-Ketamine has about four times greater affinity for the PCP site of the NDMA receptor than (R)-Ketamine (in guinea pig brain). The S form also seems to be better at inducing the drowsiness than the R form.[5]
The effects seem to occur mainly in the hippocampal formation and in the prefrontal cortex. This evidence along with the NMDA receptor's connection with the memory formation process explains ketamine's profound effects on memory and thought. These effects inhibits the filtering function of the brain and may mirror the sensory overload associated with schizophrenia and near death experiences.
Recreational use
When used recreationally, ketamine can be known as K, Ket, Special K, Vitamin K (not to be confused with the true vitamin K), Smack K, Kit-Kat, Keller, Barry Keddle, HOSS, The Hoos, Hossalar, kurdamin, Wonk, Regreta and tranq.
Ketamine produces effects similar to PCP and DXM. Like other dissociative anesthetics in low- to upper-middle dosages, its hallucinogenic effects are only seen against a background lacking sensory stimulation, such as darkness. Users tout its trip is as good or better than that of PCP or LSD because its overt hallucinatory effects are short-acting, lasting an hour or less in most cases. Effects on the senses, judgment, and coordination, however, can last for 18 to 24 hours. Standing up and moving may be more dangerous than lying still in one place.
Ketamine sold illicitly comes from diverted legitimate supplies or theft, primarily veterinary clinics, in either powdered or liquid form. Along the US-Mexico border it is most commonly acquired in Mexico, where it can be bought over the counter in veterinary clinics, and smuggled across the border. In powdered form its appearance is similar to that of pharmaceutical grade cocaine and can be insufflated (snorted, also known as "taking bumps") or placed in beverages. Oral use usually requires more material, but results in a longer trip. The liquid can be heated to drive off the solvent (usually saline), leaving powder, or it can be injected. In therapeutic and psychedelic use, the liquid is typically injected intramuscularly. Intravenous injection is uncommon (recreationally), though possible. It is essentially identical in effect to intramuscular injection, but leads to a much quicker onset — usually within 10 to 15 seconds of dosing. Additionally, intravenous injection tends to lead to a more sudden and marked respiratory depression, especially if the solution is injected at too high of a potency (too fast). This combination makes intravenous self-injection dangerous.
Like the other dissociative anaesthetics DXM and PCP, hallucinations caused by ketamine are fundamentally different to those caused by tryptamines and phenethylamines. At low doses a user must be in a dark room or have one's eyes closed in order to see any hallucinations, while at medium to high doses the effects are far more intense and obvious, including changes in the perception of distances and durations as well as the visual system being slow to update what the user is seeing. There are reports of high-dosage users being able to see their surroundings in two sharp images, as if the brain is unable to merge the images each eye is sending. Speech often sounds unintelligible and auditory hallucinations may occur.
Ketamine puts the user in a dissociated state, meaning that they are less connected to both a sense of self and the reality around them. If a large enough amount is taken the user may go into or through a "K-hole", a state of wildly dissociated experience in which other worlds or dimensions that are difficult to describe with language are said to be perceived, all the while being completely unaware of one's individual identity or the outside world. A user may feel as though his or her perception is located so deep inside the mind that the real world seems distant (hence the use of a "hole" to describe the experience). Some users may not remember this part of the experience after regaining consciousness, in the same way that a person may forget a dream. The "re-integration" process is slow, and the user gradually becomes aware of things around them. At first they may not remember their own name, or even know that they are human, or what that means. Movement is extremely difficult, and users may not be aware that they have a body at all. It may be possible to use this state therapeutically, taking advantage of the dissociation and removing associations from the user's brain.
Some drug users' first contact with ketamine is accidental, often from a pill sold as something else (commonly ecstasy). Ketamine is also commonly combined with other drugs to enhance their effects. There have been claims that ketamine has been used as a date rape drug because of the powerful dissociative effects.
In 2003, Operation TKO was a probe conducted by the U.S. Drug Enforcement Agency (DEA). As a result of operation TKO, U.S. and Mexican authorities shut down the Mexico City company, Laboratories Ttokkyo, which was the biggest producer of ketamine in Mexico. According to the DEA, over 80% of ketamine found in the U.S. is of Mexican origin.[6]
See also
External links
- Erowid.org's Ketamine vault
- Erowid.org's John C. Lilly Vault
- TRIPproject.ca: Ketamine, harm reduction initiative
- The Guardian: Ketamine (29/12/05)
- Eleusis References on the uses of ketamine as an entheogen for treating alcoholism, the use of ketamine in psychiatry, and for treating drug addiction
- Radical Relief Use of ketamine as an agent to "reboot" the brain of a patient in chemically induced coma to greatly diminish chronic pain.
- Club drug finds use as antidepressant - Psychedelic ketamine hits the blues surprisingly fast; Nature.com