Drugs & Medication

Ketamine
Systematic (IUPAC) name
2-(2-chlorophenyl)-2-methylamino-cyclohexan-1-one
Identifiers
CAS number	6740-88-1
ATC code	N01AX03 N01AX14
PubChem	3821
DrugBank	APRD00493
Chemical data
Formula	C13H16NClO
Mol. weight	237.725 g/mol
Pharmacokinetic data
Half life	2.5-3 hours.
Excretion	renal (>90%)
Therapeutic considerations
Pregnancy cat.	B
Legal status	Schedule I(CA) Class C(UK) Schedule III(US)
Routes	IV, IM, Insufflated, oral, topical

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, memantine and phencyclidine (PCP). As with many other pharmaceuticals, ketamine is used extramedically as a recreational drug.

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.

Contents 1 History 2 Medical use 2.1 Experimental Antidepressant Use 2.2 Treatment of addiction 3 Neuropharmacology 4 Recreational use 4.1 Illicit sale 4.2 Methods of use 4.3 Psychological effects 5 Ketamine in the media 6 Street Slang 7 References 8 See also 9 External links

History

Ketamine was first synthesized in 1962 in an attempt 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 curtailed because of exaggerated concern about its potential to cause emergence phenomena including out of body experiences in clinical practice. However, it is still used widely in veterinary medicine, or as a battlefield anesthetic 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.[1] In Canada, as of August 31, 2005, ketamine is classified as a Schedule III narcotic.

Medical use

Indicated for: Pain relief, surgical anaesthesia Recreational uses: Dissociative psychedelic

Contraindications: Alcohol Other sedatives Stimulants

Side effects: Severe: Impairs all senses, especially: Sight Balance Sense of time Cardiovascular: Partial depressant Gastrointestinal: Nausea Musculoskeletal: Relaxant Neurological: Analgesia Respiratory: Partial depressant/stimulant

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 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 vivid hallucinations, "going into other worlds" or "seeing God" while anaesthetized, and these unwanted psychological side-effects have reduced the use of ketamine in human medicine.

Experimental Antidepressant Use

The National Institute of Health News reports that a study of 17 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. ^[1] The improvement lasted up to one week after the single dose. ^[2] 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. ^[3] Those findings of Zarate et al corroborate earlier findings by Berman et all. ^[4]

Treatment of addiction

The Russian doctor Evgeny Krupitsky (who is 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 [5]. 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 ^[6].

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). The S form also seems to be better at inducing the drowsiness than the R form.[2]

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.

Recreational use

Illicit sale

Ketamine sold illicitly comes from diverted legitimate supplies or theft, primarily 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 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.[3]

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, also known as "taking bumps"), 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.

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.

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 surroundings. At first, a user may not remember his or her own name, or even know that they are human, or what that means. Movement is extremely difficult, and a user may not be aware that they have a body at all.

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 televison 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*cked in the Ass 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 do a line and i'll do a line honey" followed by "You snort K and I'll snort K honey".
• Both these South Park episodes have been sampled by STITCH for trax on the BAD SEKTA record label.
• PHUQ released a cdep for BAD SEKTA titled "K Musick [volume one]". His next release is titled "When You Gave Me That Powder You Changed My Life".
• 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 is based on the singer's supposed experienced with the drug.
• 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.
• 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 Macauly 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 when she and Theodore went out to have coffee she refers that his cup was full of 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).

Street Slang

• K
• Ket
• D-rod
• Special K
• Vitamin K
• Lady K
• Spangle
• Big K
• Horsey P
• See more on Erowid.org's Ketamine vault

References

See also

• Psychedelics, dissociatives and deliriants
• PCP
• Nitrous oxide
• Dextromethorphan
• Psychoactive drug

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