Ketamine

Ketamine is a general dissociative anesthetic for human and veterinary use. Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist, and, like other drugs of this class such as tiletamine, memantine, and phencyclidine (PCP), induces a state referred to as "dissociative anaesthesia." As with other pharmaceuticals of this type, ketamine is used extramedically as a recreational drug.

Ketamine has a wide range of effects in humans, including analgesia, anesthesia, hallucination, arterial hypertension, and bronchodilation. It is primarily used for the induction and maintenance of general anesthesia, usually in combination with some sedative drug. Other uses include sedation in intensive care, analgesia (particularly in emergency medicine), and treatment of bronchospasm. It is also a popular anesthetic in veterinary medicine.

Ketamine is a chiral compound. Most pharmaceutical preparations of ketamine are racemic, however reportedly some brands have (mostly undocumented) differences in enantiomeric proportions. The more active enantiomer, S-Ketamine, is also available for medical use under the brand name Ketanest S.

History
Ketamine was first reported in 1962 as part of an effort to find a safer anaesthetic alternative to Phencyclidine (PCP), which was more likely to cause hallucinations and seizures. The drug was first given to American soldiers during the Vietnam War, but today in the developed world its use on humans has been dramatically reduced because of concern about its potential to cause emergence phenomena because of the drug's possible psychotomimetic effects. However, it is still used widely in veterinary medicine, or as a battlefield anaesthetic in developing nations.

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. In Canada ketamine is classified as a Schedule I narcotic. In Hong Kong, as of year 2000, Ketamine is regulated under Schedule 1 of Hong Kong Chapter 134 Dangerous Drugs Ordinance. It can only be used legally by health professionals, for university research purposes, or with a physician's prescription.

Medical use


In medical settings, Ketamine is usually injected intramuscularly, but it is also effective when injected intravenously, insufflated, smoked, or taken orally.

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, depression suppression, 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/h) as a local anesthetic, 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, and so is most effective when used alongside a low-dose opioid; while it does have analgesic effects by itself, the higher doses required can cause disorientating side effects. The combination of ketamine with an opiate or opioid is however particularly useful for pain caused by cancer.

The effect of Ketamine on the respiratory and circulatory systems is different from that of other anaesthetics. When used at anaesthetic doses, it will usually 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 vivid hallucinations, "going into other worlds" or "seeing God" while anesthetized, and these unwanted psychological side-effects have reduced the use of ketamine in human medicine. They can, however, usually be avoided by concomitant application of a sedative such as a benzodiazepine.

Experimental Antidepressant Use
The National Institute of Health News reports that a study of 18 patients led by Dr Carlos Zarate Jr. of the National Institute of Mental Health found that ketamine significantly improved treatment-resistant major depression within hours of injection. The improvement lasted up to one week after the single dose. The patients in the study were previously treatment resistant, having tried an average of six other treatments that failed. The importance of these findings was articulated by NIMH director Dr Thomas Insel: "To my knowledge, this is the first report of any medication or other treatment that results in such a pronounced, rapid, prolonged response with a single dose. These were very treatment-resistant patients." The researchers apparently attribute the effect to ketamine being an NMDA receptor antagonist. The study appears in the Archives of General Psychiatry. Those findings of Zarate et al corroborate earlier findings by Berman et al.

Treatment of addiction
The Russian doctor Evgeny Krupitsky (Clinical Director of Research for the Saint Petersburg Regional Center for Research in Addiction and Psychopharmacology) has gained encouraging results by using ketamine as part of a treatment for alcohol addiction which combines psychedelic and aversive techniques. This method involved psychotherapy, controlled ketamine use and group therapy, and resulted in 60 of the 86 alcoholic males selected for the study remaining fully abstinent. He has also treated heroin addicts and reached the conclusion that ketamine reduces the craving for heroin without any adverse reaction.

Neuropharmacology
Ketamine, like Phencyclidine, is primarily a non-competitive antagonist of the NMDA receptor, which opens in response to binding of the neurotransmitter glutamate. This NMDA receptor mediates the analgesic (reduction of pain) effects of ketamine at low doses. Evidence for this is reinforced by the fact that naloxone, 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. Thus, loss of consciousness that occurs at high doses may be partially due to binding at the opioid mu and sigma receptors.

Ketamine is racemic, and its R and S stereoisomers have different binding affinities: (S)-Ketamine has about four times greater affinity for the PCP site of the NDMA receptor than does (R)-Ketamine (in guinea pig brain). (S)-ketamine seems to induce drowsiness more strongly than the (R) enantiomer; it is probable that (R)-ketamine is the stronger sigma agonist and so this enantiomer is likely to be responsible for the lowering of the seizure threshold that can occur with ketamine. Since (S)-ketamine has greater analgesic effects and less hallucinogenic side effects than (R)-ketamine, the pure (S) enantiomer is sometimes preferred to the racemic mix for use in medical procedures, especially when lower doses are used for minor surgical procedures where the patient remains conscious during the operation.

The effects seem to take place 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 inhibit the filtering function of the brain and may mirror the sensory overload associated with schizophrenia and near death experiences.

The local anesthetic effects are likely from the blocking action of ketamine on sodium channels. Its in vitro blocking potency of sodium channels in the resting state is similar to that of lidocaine

Illicit sale
{| bgcolor="#ffffff" border="1" cellpadding="3" cellspacing="0" align="right" width="167px" style="border-collapse: collapse; clear: right; margin: 0 0 0 0.5em" Ketamine sold illicitly comes from diverted legitimate supplies or theft, primarily from veterinary clinics. In the US near its border with Mexico, the drug is most commonly acquired in Mexico, where it can be bought over the counter in veterinary clinics, and smuggled across the border.

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, Laboratorios Tokkyo, 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.

The World health Orginisation (WHO) Expert Committee on Drug Dependence in its thirty third report (2003). recomended research into its recreational use/abuse due to growing concerns about its rising popularity in Europe, Asia and North America.

Methods of use
Ketamine is sold in either powdered or liquid form. In powdered form, its appearance is similar to that of pharmaceutical grade cocaine and can be insufflated (snorted), injected, or placed in beverages. It is also possible to smoke the drug in a joint or pipe, usually mixed with marijuana and tobacco. The smoke has a distinctive bitter taste but the effects of the high hit much faster than when insufflated or ingested. 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. 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). These factors make intravenous self-injection dangerous.

Some drug users' first contact with ketamine is accidental, 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 its powerful dissociative effects, but this has never been documented.

Psychological effects
Unlike true psychedelics, ketamine is powerfully reinforcing to many users and compulsive use is frequently reported. Both ketamine pioneer John Lilly and pseudonymous author D.M. Turner reported prolonged periods of "ketamine dependency", and the latter drowned in a bathtub while on ketamine.

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. Some users claim that a trip due to ketamine use 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.

Like the other dissociative anaesthetics DXM and PCP, hallucinations caused by ketamine are fundamentally different from those caused by tryptamines and phenethylamines. At low doses hallucinations are only seen when one is in a dark room with one's eyes closed, while at medium to high doses the effects are far more intense and obvious. These effects include changes in the perception of distances and durations as well as a slowing of the visual system's ability 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. At high doses sounds can be out of sync with the users visual field.

Ketamine puts users 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, users 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 their individual identities or the outside world. Users may feel as though their perceptions are 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 surroundings. At first, users may not remember their own names, or even know that they are human, or what that means. Movement is extremely difficult, and a user may not be aware that he or she has a body at all.

Danger
Like other NMDA Receptor Antagonists, it is postulated that ketamine can cause a certain kind of brain damage called Olney's Lesions. Studies conducted on rats have shown that high doses of the NMDA receptor antagonist MK-801 caused vacuoles to form in certain regions of test rats' brains that developed into irreversible lesions, and experts say that it is possible that similar brain damage can occur in humans.

Ketamine in the media

 * In the seventh episode of the first season of the American television series The Dead Zone, titled "Enemy Mind", the lead character, psychic Johnny Smith, accidentally inhales Ketamine in aerosol state, and the drug wreaks havoc with his "dead zone", the primary brain center for his psychic visions.
 * In the last episode of the second season of the American television series House, titled "No Reason", the lead character, Dr. Gregory House, is administered Ketamine to try to relieve the terrible leg pain he has been suffering throughout the course of the series. At the beginning of the third season, it seems that the Ketamine treatment has worked, though by the end of the second episode his pain has returned and he has started using a walking cane and Vicodin again.
 * In the sixth episode of the second season of I'm Alan Partridge, entitled "Alan Wide Shut", Alan Partridge attends a radio interview on a program called Prayer Wave to promote his autobiography and has a surreal, barbed conversation with a woman called Kate Fitzgerald who is also promoting her autobiography. They discuss her ketamine use and move on to talk about Alan's addiction to chocolate, specifically Toblerone.
 * In the South Park episode Stupid Spoiled Whore Video Playset (referring to Paris Hilton), the girls say they are going to a party to do ketamine and then make fun of Wendy for knowing what ketamine is, saying they have no idea but are going to do it anyway. It is also referred to in the episode You Got F'd in the A where Stan and Chef go to recruit a duck in their dance team. The owner plays two songs for the duck to dance to which contains the line "You snort K and I'll snort K honey".
 * Phuq released a cdep for BAD SEKTA titled "K Musick [volume one]". Phuq has also produced many songs featuring titles or samples relating to Ketamine, e.g. "Ketamine Love", "Another K-Hole", "Ketafuk" and "Ketaminhahaha".
 * Ketamine is featured also in the episode 44 of the HBO TV-series Six Feet Under, where Russell, one of the students in Claire's art school, reports his experiences after a lengthy trip.
 * The band Placebo has a song titled "Special K", the content of which compares the singer's experience with love to that of the effects of ketamine.
 * Ricardo Villalobos, a popular electronic musician affiliated with the microhouse movement, began a unique form of microhouse which eventually came to be called ketamine house.
 * Underground hip hop artist Cage Kennylz has a track on his album Hell's Winter, "The Subtle Art of the Breakup Song", featuring a narrative under the influence of ketamine.
 * The band Carfax Abbey has a song entitled Ketamine.
 * Chemical Brothers have a song titled "Lost in the K-Hole" on their Dig Your Own Hole album.
 * The Californian punk band NOFX have a song titled "Kids of the K Hole" on their 1997 album So Long and Thanks for All the Shoes
 * CocoRosie, the indie/psych-folk sister duet, has a song called 'K-Hole' on their 2005 album Noah's Ark on Touch and Go Records.
 * The indie rock group Silver Jews have a song titled 'K-Hole' on their 2005 album Tanglewood Numbers.
 * The indie pop group The Clientele have songs titled 'Since K Got Over Me' and 'K' on their 2005 album Strange Geometry.
 * In the movie Cecil B. DeMented, the drug addict character, Lyle, runs in place and shouts "Help! Cherish! I'm stuck in a K-Hole and I can't get out!".
 * In the movie Party Monster, starring Macaulay Culkin and Seth Green, ketamine was a large part of the main protagonists' downfall.
 * In the movie Children of Men, when Julian is talking about how Theodore spiked a cop's coffee with ketamine.
 * Rock singer Marilyn Manson claims that the experience that resulted from his accidental use of Ketamine (which he mistook for cocaine) inspired the appropriately titled song, 'Disassociative' (from his Mechanical Animals album). Also on a television interview on the Howard Stern show he was asked when was the last time he got high to which he replied "just recently, Ketamine". There were teenage fans there asking him if he wanted to go smoke pot with them after the show.
 * The group Pet Shop Boys have an instrumental track called "K-Hole" in the musical they wrote called "Closer Than Heaven" and the lyrics for the song "Vampires" (from the album "Nightlife") were inspired by seeing a friend do ketamine in a nightclub.
 * In the book Neuromancer by William Gibson, protagonist Case delivers a "brick" of Ketamine to a buyer.
 * In Ring of Honor, there was once a stable called "Special K" which was a play on Ketamine. All the members had gimmicks of rich boys who were ravers and were on drugs.
 * The thrash metal band Municipal Waste has a song titled "Accelerated Vision" about a bad Ketamine trip.
 * In "Don't Try This At Home Presents: Steve-O Out On Bail" Steve-O snorts ketamine in Cancun, Mexico. Afterwords he states "This is legal in Mexico" and "I'm going to make Special K popular again!"
 * In the book 'the edge of battle' by Dale brown the Mexican president is murdered by being forcibly overdosed.
 * In the book 'Untouchable' by 'Chris Ryan' a group of drug dealers in Scotland are making and dealing ketamine for the Russian mafia but stop when the Russian Mafia state their clients want more than quick highs. It is shown in tablet form in the book.
 * New-Rave artist Ali Love's 2006 song entitled 'K-hole' documents a night spent on the drug.
 * Mitch Dorge, drummer for the Crash Test Dummies, has a piece called Ketamine on his solo album As Trees Walking.

Common Street Slang
The Greater Dallas Council on Alcohol and Drug Abuse (GDCADA) lists the following common slang terms for ketamine:


 * Blind Squid
 * Breakfast Cereal
 * Cat Valium
 * Date Rape Drug
 * Green
 * K
 * Keller
 * Keller’s Day
 * Ket
 * Ketaject
 * Ketalar
 * Kit Kat
 * New Ecstasy
 * Psychedelic Heroin
 * Purple
 * Special-K
 * Special LA Coke
 * Super Acid
 * Super-C
 * Super-K
 * Vitamin K
 * Vit K