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Ketamine poured onto glass and left to dry.
For general information on this drug, including medical usage, see ketamine.

Ketamine is a prescription anesthetic that is federally regulated (e.g., U.S. Schedule III, U.K. Class B) that functions as a dissociative anesthetic, and so has seen use as a recreational drug. Originating in the United States in the 1970s, the recreational use of ketamine has since spread to Europe, Canada, Asia, and Australia. Attempts are made to use the drug at sub-anesthetic doses; contexts for use include both private settings and at club venues (raves and parties), where it initially gained popularity. Despite its emergence as a club drug, users may eventually relegate their use to more private settings.[1]

Ketamine interacts with a variety of other drugs, most pronounced with alcohol, opioids (potentiation), and barbiturates, and with drugs that increase blood pressure (e.g., stimulants, SNRI antidepressants, and especially MAOIs). The latter may have an additive effect on the user's blood pressure, causing tachycardia, palpitations and potentially serious arrhythmias.[not verified in body] Ketamine use as a recreational drug has been implicated in a small but greatly exaggerated number of annual deaths, the majority of which are youth or young adults,[2][3] which have, taken together, led to increasing stringency of its regulation worldwide.[4][5][6]

As a consequence of its drug interactions and adverse effects, including the ability to cause confusion and amnesia, and adverse reactions that occur during emergence from anaesthesia,[7] some cases are known from the media that involved irresponsibly high dosages and accidents in people who were not prepared for the experience and/or took other drugs at the same time, despite ketamine being a physically very safe substance in comparison to other psychoactives like opioids or even alcohol. But ketamine can leave users vulnerable to date rape (i.e., because of the associated confusion and amnesia).[8][9][10]

Due to the complexity of its chemical synthesis, ketamine supplies for recreation use must be diverted from licit medical sources, though there have been reports of industrial-scale illicit ketamine manufacture in China and India.[11]

History

Recreational use of ketamine was documented in the early 1970s in underground literature (e.g. The Fabulous Furry Freak Brothers[12]). It was used in psychiatric and other academic research through the 1970s, culminating in 1978 with the publishing of psychonaut John Lilly's The Scientist, and Marcia Moore and Howard Alltounian's Journeys into the Bright World, which documented the unusual phenomenology of ketamine intoxication.[13] The incidence of non-medical ketamine use increased through the end of the century, especially in the context of raves and other parties.[14][15][16][17][18] Its emergence as a club drug differs from other club drugs (e.g., MDMA), however, due to its anesthetic properties (e.g., slurred speech, immobilization) at higher doses;[18] in addition, reports of ketamine being sold as "ecstasy" are common.[19]

The use of ketamine as part of a "post-clubbing experience" has also been documented.[20] Ketamine's rise in the dance culture was most rapid in Hong Kong by the end of the 1990s.[18]

Epidemiology

North America

United States

According to the ongoing Monitoring the Future study conducted by University of Michigan, prevalence rates of recreational ketamine use among American secondary school student (grades 8, 10, and 12) have varied between 0.8–2.5% since 1999, with recent rates at the lower end of this range.[21] The 2006 National Survey on Drug Use and Health (NSDUH) reports a rate of 0.1% for persons ages 12 or older with the highest rate (0.2%) in those ages 18–25.[22] Further, 203,000 people are estimated to have used ketamine in 2006, and an estimated 2.3 million people used ketamine at least once in their life.[22] A total of 529 emergency department visits in 2009 were ketamine-related.[23]

Europe

Cases of illicit ketamine use in club venues have been observed in the Czech Republic, France, Italy, Hungary, and the United Kingdom.[24] Additional reports of use and dependence have been reported in Poland[25] and Portugal.[26]

Australia

Australia's 2010 National Drug Strategy Household Survey report shows a prevalence of recent ketamine use of 0.3% in 2004 and 0.2% in 2007 and 2010 in persons aged 14 or older.[27] In a recent survey of random roadside oral fluid testing in Victoria, Australia, 1.5% of drivers tested positive for ketamine use.[28]

Asia

China

The small village of Boshe in eastern Guangdong was confirmed as a main production centre when it was raided in 2013.[29]

Hong Kong

Established by the Hong Kong Narcotics Division of the Security Bureau, the Central Registry of Drug Abuse (CRDA) maintains a database of all the illicit drug users who have come into contact with law enforcement, treatment, health care, and social organizations. The compiled data are confidential under the The Dangerous Drugs Ordinance of Hong Kong, and statistics are made freely available online on a quarterly basis.[30][31] Statistics from the CRDA show that the number of ketamine users (all ages) in Hong Kong has increased from 1605 (9.8% of total drug users) in 2000 to 5212 (37.6%) in 2009.[32] Increasing trends of ketamine use among illicit drug users under the age of 21 were also reported, rising from 36.9% of young drug users in 2000 to 84.3% in 2009.[32]

Taiwan

A survey conducted among school-attending Taiwanese adolescents reported prevalence rates of 0.15% in 2004, 0.18% in 2005, and 0.15% in 2006 in middle-school (grades 7 and 9) students; in Taiwanese high-school (grades 10 and 12) students, prevalence was 1.13% in 2004, 0.66% in 2005, and 0.44% in 2006.[33] From the same survey, a large portion (42.8%) of those who reported ecstasy use also reported ketamine use.[33] Ketamine was the second most used illicit drug (behind ecstasy) in absconding Taiwanese adolescents as reported by a multi-city street outreach survey.[34] In a study comparing the reporting rates between web questionnaires and paper-and-pencil questionnaires, ketamine use was reported a higher rate in the web version.[35] Urine sampling at a club in Taipei, Taiwan showed high rates of ketamine use at 47.0%; this prevalence was compared with that of detainees suspected of recreational drug use in the general public, of which 2.0% of the samples tested positive for ketamine use.[36]

Illicit sale

Main article: Ketamine § Legal_status
500 mg ketamine hydrochloride
Ketamine dried and scraped

Ketamine sold illicitly comes either from diverted legitimate supplies and semi-legitimate suppliers, or from theft of legitimate suppliers.

In 2003, the U.S. Drug Enforcement Administration conducted Operation TKO, a probe into the quality of ketamine being imported from Mexico.[37] 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 seized in the United States is of Mexican origin. As of 2011, it was mostly shipped from places like India as cheap as $5/gram.[37] The World Health Organization Expert Committee on Drug Dependence, in its thirty-third report (2003),[38] recommended research into its recreational use due to growing concerns about its rising popularity in Europe, Asia, and North America.

In the 1993 book E for Ecstasy[39] (about the uses of the street drug Ecstasy in the UK), the writer, activist, and Ecstasy advocate Nicholas Saunders highlighted test results showing that certain consignments of the drug also contained ketamine. Consignments of Ecstasy known as "Strawberry" contained what Saunders described as a "potentially dangerous combination of ketamine, ephedrine, and selegiline", as did a consignment of "Sitting Duck" Ecstasy tablets.[40]

Liquid preparations of the drug are also becoming increasing common; users then apply a solution of the drug to cigarettes and allow them to dry, resulting in a prepared dose of the drug.[citation needed]

Effects

Mortality

Ketamine's use as a recreational drug has contributed to more than 90 fatalities—the majority among young adults—in England and Wales in the years of 2005-2013, including accidental poisonings, drownings, and traffic accidents.[3] This has led to its increasingly stringent regulation (e.g., upgrading ketamine from a Class C to a Class B banned substance in the U.K.).[2]

Drug interactions

Ketamine may increase the effects of other sedatives, including, but not limited to: alcohols,[41] benzodiazepines,[42] opioids,[43] and barbiturates.[44] Other drugs which increase blood pressure may interact with ketamine, having an additive effect on blood pressure; such agents include stimulants, SNRI antidepressants, and MAOIs.[citation needed] Increase blood pressure and heart rate, palpitations, and arrhythmias may be potential effects.[citation needed]

Adverse reactions

Ketamine is generally safe even for those critically ill, when administered by trained medical professionals. The dosages used recreationally are somewhat lower than a fully anaesthetic dosage, making the substance physically relatively safe in comparison to other psychoactive drugs.[45] Still, even in these cases, there are known side effects that include one or more of the following:[46]

In addition there are dermatologic adverse reactions (ARs; transient erythema, transient morbilliform rash), gastrointestinal ARs (anorexia, nausea, increased salivation, vomiting), neuromuscular and skeletal ARs (Increased skeletal muscle tone, i.e., tonic-clonic movements),[48] ocular ARs (double vision, increased intraocular pressure, nystagmus), respiratory ARs (airway obstruction, apnea, increased bronchial secretions, respiratory depression, laryngospasm), as well as local pain or exanthema (e.g., at injection sites) and possible anaphylaxis and dependence.

In 10-20% of patients at anesthetic doses, adverse reactions are experienced that occur during emergence from anesthesia, reactions that can manifest as seriously as hallucinations and delirium.[49] These reactions may be less common in some patients subpopulations, and when administered intramuscularly, and can occur up to 24 hours postoperatively; the chance of this occurring can be reduced by minimizing stimulation to the patient during recovery and pretreating with a benzodiazepine, alongside a lower dose of ketamine.[49] Patients who experience severe reactions may require treatment with a small dose of a short- or ultrashort-acting barbiturate.[46]

Non-lethal manifestations

See also: K-hole

Ketamine produces effects similar to phencyclidine (PCP) and dextromethorphan (DXM).[citation needed] Unlike these other well-known dissociatives, ketamine is very short-acting, its hallucinatory effects lasting tens of minutes when inhaled (insufflated) or injected, and hours when ingested.[50] With ketamine, intensities of hallucinations are dose-dependent.[51] Like other dissociative anaesthetics, hallucinations caused by ketamine are fundamentally different from those caused by serotonergic psychedelic (classic) hallucinogens.[citation needed]

The specific dissociative state produced by ketamine is characterised by a sense of detachment from one's physical body and the external world that is known as depersonalization and derealization.[52][non-primary source needed][better source needed] At sufficiently high doses, users may experience what is called the "K-hole", a state of extreme dissociation with phenomenology of schizophrenia (e.g., visual and auditory hallucinations).[53]

John C. Lilly,[54] Marcia Moore[55] and D. M. Turner[56] (amongst others) have written extensively about their own entheogenic use of and psychonautic experiences with ketamine.[57] Both Moore and Turner died prematurely (due to hypothermia and drowning respectively) during presumed unsupervised ketamine use.[58]

Detection of use

Ketamine may be quantitated in blood or plasma to confirm a diagnosis of poisoning in hospitalized patients, provide evidence in an impaired driving arrest or to assist in a medicolegal death investigation. Blood or plasma ketamine concentrations are usually in a range of 0.5–5.0 mg/L in persons receiving the drug therapeutically (during general anesthesia), 1–2 mg/L in those arrested for impaired driving and 3–20 mg/L in victims of acute fatal overdosage. Urine is often the preferred specimen for routine drug use monitoring purposes. The presence of norketamine, a pharmacologically-active metabolite, is useful for confirmation of ketamine ingestion.[59][60][61]

Overdose management

As the recreational dosages used are always below the fully anaesthetic threshold and thus lower than those medically administered, the term 'overdose' needs to be seen a bit differentiated from other drugs. While with continued use, people may build up some degree of tolerance, leading to the use of higher dosages than medically advised, it is technically somewhat difficult to overdose on ketamine. An even higher dosage will just lead to full anaesthesia, amnesia, but no physical danger from the drug itself as long as the environment isn't dangerous. The user will become catatonic when fully dissociated, not experiencing any pain but also unable to move his/her body.

There is no known effective antidote used to treat ketamine overdose, and treatment generally focuses on the maintenance of respiratory and circulatory function until the patient is capable of breathing under their own power and all cardiac abnormalities have subsided.[62] Unlike many other anaesthetics, ketamine has a minimal effect on respiratory drive and tidal volume; while pulse oximetry is always essential it rarely drops enough to require mechanical ventilation or supplemental oxygen, except in the most massive of overdoses and in cases of mixed-drug-overdose.

Verbal reassurance and a calming environment (i.e. dim lights, calming music, and the presence of supportive individuals in the room) should be provided when possible to calm the patient and/or prophylacticly to prevent agitation. Occasionally it may become necessary to restrain highly agitated patients during recovery should they become violent, experience panic attacks, or otherwise present a threat to themselves or others.

Even after all vital signs have normalized and the patient appears functional it is advised to require the patient to be driven home as residual impairment of motor skills may persist for up to a day after apparent resolution.

Dependence

Radar plot showing relative physical harm, social harm, and dependence of ketamine[63]

Ketamine's potential for dependence has been established in various operant conditioning paradigms, including conditioned place preference and self-administration; further, rats demonstrate locomotor sensitization following repeated exposure to ketamine.[64] Increased subjective feelings of 'high' have been observed in healthy human volunteers exposed to ketamine.[64] Additionally, the rapid onset of effects following smoking, insufflation, and/or intramuscular injection is thought to increase the drug's recreational use potential. The short duration of effects promotes bingeing, tolerance can develop, and withdrawal symptoms, including anxiety, shaking, and palpitations, may be present in some daily users following cessation of use.[64]

Due to its primary NMDA-antagonist effect, sudden withdrawal in severely addicted users will result in overexcitability, manifesting as increased sensitivity to stress, anxiety and pain. There are speculations about possible excitotoxicity resulting from the rebound surge in glutamate, but this has not yet been proven or disproven in humans and it doesn't seem to be a huge concern in healthy adults. Unlike GABAergic sedatives however, overexcitation secondary to ketamine withdrawal is not life-threatening as long as no underlying seizure disorders are present and even very tolerant users will likely suffer, at worst, only minor neurological sequela following the abrupt discontinuation of the drug. Some titration or the administration of anti-excitatory agents like memantine could be of benefit.

Ketamine can cause a variety of urinary tract problems that are more likely to occur with heavier and/or higher dosed use, especially in those not watching for a healthy lifestyle, according to a UK study.[65][66]

Slang terms

Production for recreational use has been traced to 1967, when it was referred to as "mean green" and "rockmesc".[67] Recreational names for ketamine include "K",[68][69] "Kitty", "Kallie Ziltz", "Kartáč", "Ket",[70] "Special K",[69] "K2",[68] "Vitamin K",[69][70] "Super K",[69] "Jet" (Texas),[69][71] "Super acid",[69] "Mauve",[69] "Special LA coke",[69] "Purple",[69] "Cat Valium",[71] "Knod-off", "Skittles", "Blind Squid",[72] "Keller",[72] "Kelly's Day",[72] "New ecstasy",[73] "Psychedelic heroin",[73] "bump",[74] "honey oil",[74] "Majestic".[75] A mixture of ketamine with cocaine is called "Calvin Klein" or "CK1".[76] In Hong Kong, where illicit use of the drug is popular, ketamine is colloquially referred to as "kai-jai".[18]

References

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