Ketamine

File:(RS)-Ketamine-Structural Formulae V2.svg

Ketamine

Ketamine
File:Ketamine2DCSD.svg
INN
Drug class	NMDA receptor antagonist; general anesthetic; dissociative hallucinogen; analgesic; antidepressant
Routes of administration	Any<ref>, Ketamine as an adjuvant to opioids for cancer pain, The Cochrane Database of Systematic Reviews, Vol. 6(Issue: 9), pp. CD003351, DOI: 10.1002/14651858.CD003351.pub3, PMID: 28657160, PMC: 6481583, Full text, Accessed on: 10 September 2018.</ref><ref>, Perioperative Ketamine Administration for Thoracotomy Pain, Pain Physician, Vol. 20(Issue: 3), pp. 173–184, PMID: 28339431,</ref><ref name="MathewZarate2016">, Ketamine for Treatment-Resistant Depression: The First Decade of Progress. online version, Springer, ISBN 978-3-319-42925-0, Pages: 8–10, 14–22,</ref><ref name="MD"> Ketamine Hydrochloride: Martindale: The Complete Drug Reference(link). MedicinesComplete. Pharmaceutical Press. 9 January 2017. London, UK. Accessed 24 August 2017. </ref>
Pregnancy category
Bioavailability	* Intravenous: 100%<ref name="MathewZarate2016" /> Intramuscular: 93%<ref name="MathewZarate2016" /> Epidural: 77%<ref name="Kintz2014">, Toxicological Aspects of Drug-Facilitated Crimes. online version, Elsevier Science, ISBN 978-0-12-416969-2, Pages: 87–,</ref> Intranasal: 45–50%<ref name="MathewZarate2016" /><ref name="pmid23521979">, Ketamine: use in anesthesia, CNS Neurosci Ther, Vol. 19(Issue: 6), pp. 381–9, DOI: 10.1111/cns.12072, PMID: 23521979, PMC: 6493613,</ref> Sublingual: 24–30%<ref name="MathewZarate2016" /><ref name="Hashimoto2019">, Rapid-acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective, Psychiatry and Clinical Neurosciences, Vol. 73(Issue: 10), pp. 613–627, DOI: 10.1111/pcn.12902, PMID: 31215725, PMC: 6851782,</ref> Rectal: 25–30%<ref name="pmid23521979"/> By mouth: 16–20%<ref name="MathewZarate2016" /><ref name="pmid23521979"/>
Metabolism	Liver, intestine (oral): Major: CYP3A4, CYP2B6<ref name="MathewZarate2016" /><ref>, Contribution of CYP3A4, CYP2B6, and CYP2C9 isoforms to N-demethylation of ketamine in human liver microsomes, Drug Metabolism and Disposition, Vol. 30(Issue: 7), pp. 853–8, DOI: 10.1124/dmd.30.7.853, PMID: 12065445,</ref> Intramuscular: 1–5 min Subcutaneous: 15–30 min Insufflation: 5–10 min By mouth: 15–30 min
Elimination half-life	* Ketamine: 2.5–3 hours Norketamine: 12 hours
Excretion	* Urine: 91% Feces: 3%
Legal status	In general Rx-only
CAS Number	6740-88-1
PubChem	3821
DrugBank	DB01221
ChemSpider	3689
KEGG	D08098

Ketamine is a dissociative anesthetic. It is a type of drug a doctor might give to put someone to sleep for an operation. Ketamine can also be used as a painkiller and a bronchodilator (which makes it easier for air to get into your lungs).<ref>,

 Pharmacology for anaesthesia and intensive care (3rd edition), 
  
 Cambridge:Cambridge University Press, 
 2008, 
  
  
 ISBN 978-0-521-70463-2,</ref>

Sometimes it can lead to a special type of hallucination which makes you feel detached from yourself and the things around you<ref>Bergman, S. A.,

 Ketamine: review of its pharmacology and its use in pediatric anesthesia, 
 Anesthesia Progress, 
 1999,
 Vol. 46(Issue: 1),
 pp. 10–20,
 
 PMID: 10551055,
 PMC: 2148883,</ref> which is why some people use it as a recreational drug. As it can have severe side effects, it is usually not available as an over-the-counter drug.

Medical use

In medicine, ketamine is normally injected into a vein or muscle.<ref name="lankenau">Lankenau SE, Sanders B, Bloom JJ, et al.,

 First injection of ketamine among young injection drug users (IDUs) in three U.S. cities, 
 Drug and Alcohol Dependence, 
 
 Vol. 87(Issue: 2–3),
 pp. 183–93,
 DOI: 10.1016/j.drugalcdep.2006.08.015,
 PMID: 16979848,
 PMC: 1852477,</ref>

Ketamine is not the first anaesthetic a doctor would think of using in most situations because of the hallucinations it causes. On the other hand, while most anaesthetics suppress your breathing, resulting in the need for a machine to help you breathe, ketamine does not.<ref name="heshmati">Heshmati F, Zeinali MB, Noroozinia H, Abbacivash R, Mahoori A,

 Use of ketamine in severe status asthmaticus in intensive care unit, 
 Iranian Journal of Allergy, Asthma, and Immunology, 
 
 Vol. 2(Issue: 4),
 pp. 175–80,
 
 PMID: 17301376,</ref>

This can make it a useful anaesthetic when you don't have any equipment available, for example, in a war zone. ^{(December 2013)}

Side effects

Short term

Short term side effects happen in about 40% of people and include:<ref name ="Quibell">Quibell R, Prommer EE, Mihalyo M, et al.,

 "Ketamine*", 
 Journal of Pain and Symptom Management, 
 
 Vol. 41(Issue: 3),
 pp. 640-649,
 DOI: 10.1016/j.jpainsymman.2011.01.001,
 PMID: 21419322,</ref>

• Dizziness
• Double vision
• Euphoria
• Blurred vision
• Finding it hard to express emotions, not being very emotionally reactive
• High blood pressure
• Fast heart beat
• Feeling sick and vomiting
• Having trouble understanding or producing speech
• Nightmares
• Illusions
• Hallucinations
• Changed body image
• Impaired memory and attention.

Long term

In the medical setting, ketamine is only given a few times so most long term effects mentioned below are found in recreational ketamine users and animal models.<ref name=morgan11>Morgan, Celia J. A.,

 Ketamine use: a review, 
 Addiction, 
 
 Vol. 107(Issue: 1),
 pp. 27–38,
 DOI: 10.1111/j.1360-0443.2011.03576.x,
 PMID: 21777321,</ref>

Urinary tract effects

There are 110 reports of people with problems in their urinary tract due to using ketamine.<ref name=middela>Middela, S.,

 Ketamine-induced vesicopathy: a literature review, 
 International Journal of Clinical Practice, 
 
 Vol. 65(Issue: 1),
 pp. 27–30,
 DOI: 10.1111/j.1742-1241.2010.02502.x,
 PMID: 21155941,</ref>

Symptoms include:

• Urgently needing to urinate.
• Finding it painful to urinate and having blood in your urine.
• Not being able to hold as much urine in your bladder
• These urinary tract problems are most common in people who have abused ketamine daily for a long time.<ref name =morgan11 />

Neurological effects

People who abuse ketamine a lot (more than 4 times a week) have been found to have impaired memory and increased depression when compared to people who don't abuse ketamine. Those who use ketamine less frequently (1-4 times per week) and those who had stopped taking ketamine showed no difference in the aforementioned parameters. This suggests that these problems with memory and mood do not affect infrequent users and might be reversible once ketamine use is stopped.<ref name="Addiction Users Study">,

 Consequences of chronic ketamine self-administration upon neurocognitive function and psychological wellbeing: a 1-year longitudinal study, 
 Addiction, 
 2009,
 Vol. 105(Issue: 1),
 pp. 121–33,
 DOI: 10.1111/j.1360-0443.2009.02761.x,
 PMID: 19919593,</ref>

One study has recently been done using monkeys as a model to see if ketamine is toxic to the brain.<ref name="Cynomolgus monkey neurotoxiciy">Sun, Lin,

 Chronic ketamine exposure induces permanent impairment of brain functions in adolescent cynomolgus monkeys, 
 Addiction Biology, 
 
 
 
 DOI: 10.1111/adb.12004,
 PMID: 23145560,
 
 
 Full text,</ref>

The study found that injecting the monkeys every day for 6 months with ketamine caused more cells to die in the front of their brain and also caused a decrease in activity in the areas of the brain which control movement.

Mechanism of action

Ketamine is an NMDA antagonist in the CNS. By inhibiting NMDA receptors in inhibitory neurons in the brain, it causes increased CNS activity and sympathomimetic effects. As a result, there is not only an anaesthetic effect, but also activation of the CNS unlike other anaesthetics. This is beneficial in surgical settings because it maintains blood pressure, airway reflexes, bronchioles remain dilated, and airways patent. Making this a particularly useful drug in shock and surgery patients because of blood pressure maintained with ketamine use, unlike typical anaesthetics which cause decreased BP and respiratory suppression.

Research

Treating addiction

One study by Evgeny Krupitsky has found that using ketamine along with psychotherapy and group therapy was a lot more effective at treating alcohol addiction than the traditional treatment.<ref>

The Combination of Psychedelic and Aversive Approaches in Alcoholism Treatment - Eleusis(link). {{{website}}}.

</ref> The same scientist found that ketamine might also be useful for treating heroin addiction. Patients who had been treated for their addiction with multiple sessions of ketamine fared much better than those who had only had one session of ketamine, with abstinence rates of 50% and 22.2% respectively.<ref>http://www.eleusis.us/resource-center/references/ketamine-psychotherapy-heroin.pdf</ref>

As an antidepressant

Some small studies have been done which found that a single dose of ketamine was able to improve treatment-resistant depression after just a few hours, with the effects lasting for one week.<ref>NIH. "Experimental Medication Kicks Depression in Hours Instead of Weeks" NIH News, 7 August 2006</ref><ref>Khamsi, R. "Ketamine relieves depression within hours" New Scientist, 8 August 2006.</ref> The rapid antidepressant effects of ketamine may prove to be a useful alternative compared to current antidepressants, which can take several weeks to have their effects.<ref name=pmid8788498>Eison AS, Mullins UL,

 Regulation of central 5-HT2A receptors: a review of in vivo studies, 
 Behavioural Brain Research, 
 1996,
 Vol. 73(Issue: 1–2),
 pp. 177–81,
 DOI: 10.1016/0166-4328(96)00092-7,
 PMID: 8788498,</ref>

Complex regional pain syndrome

CRPS is a disease that causes severe pain and swelling, getting worse over time.<ref>

Complex Regional Pain Syndrome (CRPS)(link). {{{website}}}. Marks & Harrison.

</ref> Some researchers have been investigating the use of ketamine to treat this condition. In some cases, low-dose ketamine infusions have shown promising results in reducing pain levels, even in patients who have not responded to other treatments.<ref>Schwartzman RJ, Alexander GM, Grothusen JR, Paylor T, Reichenberger E, Perreault M,

 Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: a double-blind placebo controlled study, 
 Pain, 
 2009,
 Vol. 147(Issue: 1–3),
 pp. 107–15,
 DOI: 10.1016/j.pain.2009.08.015,
 PMID: 19836135,</ref>

Post-traumatic stress disorder (PTSD)

Ketamine has been studied for its potential use in treating post-traumatic stress disorder (PTSD). Some early studies suggest that ketamine may be effective in rapidly reducing the severity of PTSD symptoms, and its effects may last for several weeks following a single treatment.<ref>Feder A, Parides MK, Murrough JW, et al.,

 Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder: A Randomized Clinical Trial, 
 JAMA Psychiatry, 
 2014,
 Vol. 71(Issue: 6),
 pp. 681–688,
 DOI: 10.1001/jamapsychiatry.2014.62,
 PMID: 24740528,</ref> More research is needed to determine the safety and efficacy of ketamine for treating PTSD in the long term.

Recreational use

Ketamine is sometimes used recreationally, typically at sub-anesthetic doses. Users often report feelings of dissociation, hallucinations, and a sense of detachment from their body or reality. This experience is sometimes referred to as entering the "K-hole."<ref> Max Daly. What Is a K-Hole and What Does It Feel Like?(link). {{{website}}}. VICE.

</ref> However, frequent or high-dose recreational use can lead to a variety of negative health consequences, including bladder damage, cognitive impairment, and addiction.<ref>Morgan CJ, Curran HV,

 Acute and chronic effects of ketamine upon human memory: a review, 
 Psychopharmacology, 
 2006,
 Vol. 188(Issue: 4),
 pp. 408–24,
 DOI: 10.1007/s00213-006-0572-3,
 PMID: 17019667,</ref>

Risks and side effects

Ketamine can cause various side effects, including nausea, vomiting, dizziness, nystagmus (involuntary eye movements), and increased heart rate and blood pressure. High doses or frequent use of ketamine can lead to more severe side effects, such as bladder damage, cognitive impairment, and addiction.<ref>Morgan CJ, Curran HV,

 Acute and chronic effects of ketamine upon human memory: a review, 
 Psychopharmacology, 
 2006,
 Vol. 188(Issue: 4),
 pp. 408–24,
 DOI: 10.1007/s00213-006-0572-3,
 PMID: 17019667,</ref>

Long-term use of ketamine can lead to a condition called ketamine cystitis, which is characterized by severe inflammation of the bladder, causing symptoms such as frequent and painful urination, blood in the urine, and incontinence.<ref>Chu PS, Ma WK, Wong SC, et al.,

 The destruction of the lower urinary tract by ketamine abuse: a new syndrome?, 
 BJU International, 
 2008,
 Vol. 102(Issue: 11),
 pp. 1616-1622,
 DOI: 10.1111/j.1464-410X.2008.07917.x,
 PMID: 19021601,</ref> Additionally, chronic ketamine use has been associated with cognitive deficits, including impairments in memory, attention, and executive function.<ref>Morgan CJ, Curran HV, 
 Acute and chronic effects of ketamine upon human memory: a review, 
 Psychopharmacology, 
 2006,
 Vol. 188(Issue: 4),
 pp. 408–24,
 DOI: 10.1007/s00213-006-0572-3,
 PMID: 17019667,</ref>

Ketamine can also have psychological side effects, such as feelings of anxiety, agitation, and paranoia. These effects may be more pronounced in individuals with a history of mental health disorders. There is also a risk of developing a psychological dependence on ketamine, especially with frequent use.<ref>Muetzelfeldt L, Kamboj SK, Rees H, Taylor J, Morgan CJ, Curran HV,

 Journey through the K-hole: phenomenological aspects of ketamine use, 
 Drug and Alcohol Dependence, 
 2008,
 Vol. 95(Issue: 1-2),
 pp. 219–29,
 DOI: 10.1016/j.drugalcdep.2008.01.024,
 PMID: 18355990,</ref>

It is essential to use ketamine under the supervision of a healthcare professional to minimize the risk of side effects and complications. When used medically, ketamine is typically administered in a controlled setting, with appropriate monitoring and management of potential side effects.

References

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Pharmacodynamics

Medical uses

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Recreational uses