Ketamine

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Summary sheet: Ketamine
Ketamine
Ketamine.svg
Chemical Nomenclature
Common names Ketamine, K, Ket, "Special K", Ketaset, "Vet/Horse/Dog tranquilizer", Ketanest
Substitutive name Ketamine
Systematic name (RS)-2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone
Class Membership
Psychoactive class Dissociative
Chemical class Arylcyclohexylamine
Routes of Administration

WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.



Oral
Dosage
Threshold Common Heavy
50 - 50 - 100 - 300 - 450 mg
Light Strong
Threshold 50 mg
Light 50 - 100 mg
Common 100 - 300 mg
Strong 300 - 450 mg
Heavy 450 mg+
Duration
Onset 5 - 20 minutes
Peak 45 - 90 minutes
After effects 4 - 8 hours



Insufflated
Dosage
Threshold Common Heavy
10 - 10 - 30 - 75 - 150 mg
Light Strong
Threshold 10 mg
Light 10 - 30 mg
Common 30 - 75 mg
Strong 75 - 150 mg
Heavy 150 mg+
Duration
Total 45 - 75 minutes
Onset 2 - 5 minutes
Come up 5 - 10 minutes
Peak 20 - 30 minutes
Offset 20 - 30 minutes
After effects 2 - 12 hours






DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.

Ketamine (also known as ket, K, special K, kitty, horse/dog/vet tranquilizer, among others) is a dissociative substance of the arylcyclohexylamine class. Ketamine is an NMDA antagonist that is structurally related to phencyclidine (PCP) and methoxetamine (MXE). Notable effects include sedation, hallucinations, anesthesia, and out-of-body states, referred to as "dissociative anesthesia".[1]

Ketamine was developed in 1963 by Parke-Davis Laboratories as part of an effort to find a replacement for phencyclidine (PCP). It became available by prescription in 1969 under the name Ketalar.[2]

Ketamine is widely used in human and veterinary medicine, primarily for the induction and maintenance of general anesthesia for surgical procedures.[citation needed] Other applications of ketamine include sedation and anesthesia in emergency medicine and in the treatment of bronchospasm.[3] It is on the World Health Organization’s “Essential Drugs List”, a list of the safest and most effective drugs needed in a modern health system.[4]

History and culture

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As such, it may contain incomplete or wrong information. You can help by expanding it.

Ketamine began as a veterinary anaesthetic when it was patented in Belgium in 1963. After being patented by Parke-Davis for human and animal use in 1966, ketamine became available by prescription in 1969 in the form of ketamine hydrochloride, under the name of Ketalar. It was officially approved for human consumption by the United States Food and Drug Administration in 1970 and, because of its sympathomimetic properties and its wide margin of safety, was administered as a field anaesthetic to soldiers during the Vietnam war.[2]

Chemistry

Ketamine, or (RS)-2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone, is a member of the arylcyclohexylamine chemical class. Arylcyclohexylamines are named for their structures which include a cyclohexane ring bound to an aromatic ring along with an amine group. Ketamine is comprised of a phenyl ring with a chlorine substituent at R2 bonded to a cyclohexane ring substituted with an -Oxo group (cyclohexanone). An amino methyl chain (-N-CH3) is bound to the same location (R1) of the cyclohexanone ring.

Ketamine is a chiral molecule and is typically produced as a racemate.[citation needed] Enantiopure versions such as esketamine (S-ketamine) and arketamine (R-ketamine) are sometimes used in both licit and illicit contexts.[citation needed]

Pharmacology

Further information: NMDA receptor antagonist

Ketamine acts as a non-competitive NMDA receptor antagonist.[1] NMDA receptors allow for electrical signals to pass between neurons in the brain and spinal column; for the signals to pass, the receptor must be open. Dissociatives close the NMDA receptors by blocking them. This disconnection of neurons leads to loss of feeling, difficulty moving, and eventually the notorious state known as the “K-hole”.

At high, fully anesthetic level doses, ketamine has also been found to bind to μ-opioid receptors type 2 in cultured human neuroblastoma cells without agonist activity[5] and to sigma receptors in rats.[6] Also, ketamine interacts with muscarinic receptors, descending monoaminergic pain pathways and voltage-gated calcium channels.[7] At subanesthetic and fully anesthetic doses, ketamine has been found to block serotonin depletion in the brain by inhibiting 5-HT receptors rather than through monoamine oxidase inhibition.[8]

Subjective effects

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. These effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances of inducing a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.

Physical effects
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Visual effects
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Experience reports

Anecdotal reports which describe the effects of this compound within our experience index include:

Additional experience reports can be found here:

Medical uses

Novel antidepressant

It has been demonstrated that ketamine, even if taken in small doses, is effective for patients suffering from chronic depression and bipolar disorder. Studies have shown[9][10] that the effect of the drug is immediate or within 2 hours and consistent in relieving a patient’s depressive and/or suicidal symptoms, lasting up to 3 days after a single dose. In comparison, common antidepressants, such as Prozac, are entirely ineffective for 40% of the population and can take weeks to show effects. This gives ketamine the potential to become an indispensable tool in the treatment of depression and bipolar disorder, which is currently being held back by institutionalized drug prohibition.

Ketamine is a racemate that comprises the R-(−)-ketamine enantiomer (arketamine) and the S-(+)-ketamine enantiomer (esketamine). Esketamine inhibits the reuptake of the dopamine transporter about 8-fold more potently than does arketamine, and so is about 8 times more potent as a dopamine reuptake inhibitor.[11] Arketamine appears to be more effective as a rapid-acting antidepressant than esketamine.[12]

A study conducted in mice found that ketamine's antidepressant activity is not caused by ketamine inhibiting NMDAR, but rather by sustained activation of a different glutamate receptor, the AMPA receptor, by a metabolite, (2R,6R)-hydroxynorketamine; as of 2017 it was unknown if this was happening in humans.[13][14] Arketamine is a AMPA receptor agonist.[15]

Psychedelic therapy

Ketamine psychedelic therapy (KPT) is used for preparation for death (thanatological, Death-Rebirth Psychotherapy)[16]

Toxicity and harm potential

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This toxicity and harm potential section is a stub.

As such, it may contain incomplete or even dangerously wrong information. You can help by expanding or correcting it.
We also recommend that you conduct independent research and use harm reduction practices when using this substance.

This radar plot shows relative physical harm, social harm, and dependence of ketamine.[17]

Fatal ketamine overdoses are particularly rare, but not unheard of. However, the exact toxic dosage is unknown.

The first large-scale, longitudinal study of ketamine users found that frequent ketamine users (at least 4 days/week, averaging 20 days/month) had increased depression and impaired memory by several measures, including verbal, short-term memory and visual memory. However, infrequent (1–4 days/month, averaging 3.25 days/month) ketamine users and former ketamine users were not found to differ from controls in memory, attention and psychological well-being tests. This suggests the infrequent use of ketamine does not cause cognitive deficits and that any deficits that might occur may be reversible when ketamine use is discontinued. However, abstinent, frequent, and infrequent users all scored higher than controls on a test of delusional symptoms.[18]

Short-term exposure of cultures of GABAergic neurons to ketamine at high concentrations led to a significant loss of differentiated cells in one study, and non-cell death-inducing concentrations of ketamine (10 μg/ml) may still initiate long-term alterations of the dendritic arbor in differentiated neurons. The same study also demonstrated chronic (>24 h) administration of ketamine at concentrations as low as 0.01 μg/ml can interfere with the maintenance of dendritic arbor architecture. These results raise the possibility that chronic exposure to low, subanesthetic concentrations of ketamine, while not affecting cell survival, could still impair neuronal morphology and thus might lead to dysfunctions of neural networks.[19] [20]

More recent studies of ketamine-induced neurotoxicity have focused on primates in an attempt to use a more accurate model than rodents. One such study administered daily ketamine doses consistent with typical recreational doses (1 mg/kg IV) to adolescent cynomolgus monkeys for varying periods of time. Decreased locomotor activity and indicators of increased cell death in the prefrontal cortex were detected in monkeys given daily injections for six months, but not those given daily injections for one month.[21]

Studies have shown that the serotonin systems affected by such serotonergic drugs are linked to the NMDA/glutamate systems.[22] Tests on rats indicate that 5-HT agonists like LSD and psilocybin can prevent neurotoxicity due to NMDA receptor antagonists.[23]

Urinary tract effects

According to a recent systematic review, 110 documented reports of irritative urinary tract symptoms from ketamine dependence exist.[24] Urinary tract symptoms have been collectively referred to as "ketamine-induced ulcerative cystitis" or "ketamine-induced vesicopathy" and they include urge incontinence, decreased bladder compliance, decreased bladder volume and painful haematuria (blood in urine).

The time of onset of lower urinary tract symptoms varies depending, in part, on the severity and chronicity of ketamine use; however, it is unclear whether the severity and chronicity of ketamine use corresponds linearly to the presentation of these symptoms. All reported cases where the user consumed greater than 5 grams per day reported symptoms of the lower urinary tract.[25]

Tolerance and addiction potential

As with other NMDA receptor antagonists, the chronic use of ketamine can be considered moderately addictive with a high potential for abuse and is capable of causing psychological dependence among certain users. When addiction has developed, cravings and withdrawal effects may occur if a person suddenly stops their usage.

Tolerance to many of the effects of ketamine develops with prolonged and repeated use. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about 3 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to be back at baseline (in the absence of further consumption). Ketamine presents cross-tolerance with all dissociatives, meaning that after the consumption of ketamine all dissociatives will have a reduced effect.

It is strongly advised to use harm reduction practices when using this substance.

Dangerous interactions

Although many psychoactive substances are safe to use on their own, they can become dangerous or even life-threatening when taken with other substances. The list below contains some potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses but still increase the possibility of injury of death. Independent research should always be conducted to ensure that a combination of two or more substances is safe before consumption.

  • Stimulants - Both stimulants and dissociatives carry the risk of adverse psychological reactions like anxiety, mania, delusions and psychosis and these risks are exacerbated when the two substances are combined.
  • Depressants - Because both depress the respiratory system, this combination can result in an increased risk of suddenly falling unconscious, vomiting and choking to death from the resulting suffocation. If nausea or vomiting occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.

Legal status

  • Australia: Ketamine is a Schedule IV drug.[citation needed]
  • Austria: Ketamine is legal for medical and veterinary use and illegal when sold or possessed without a prescription under the NPSG (Neue-Psychoaktive-Substanzen-Gesetz Österreich).
  • Belgium: It is legal for medical and veterinary use and illegal when sold or possessed without a prescription.[citation needed]
  • Brazil: The drug is legal for veterinary use and illegal when sold or possessed for human use.[citation needed]
  • Canada: Ketamine is a Schedule I drug.[26]
  • China: Ketamine is a Schedule II drug.[citation needed]
  • Czech Republic: It is legal for medical and veterinary use and illegal when sold or possessed without a prescription.[citation needed]
  • Denmark: It is legal for medical and veterinary use and illegal when sold or possessed without a prescription.[citation needed]
  • France: Ketamine is a Schedule IV drug.[citation needed]
  • Germany: It is legal for medical and veterinary use and illegal when sold or possessed without a prescription.[citation needed]
  • Hong Kong: Ketamine is a Schedule I drug.[citation needed]
  • Malaysia: The possession and sale is illegal.[citation needed]
  • Mexico: Ketamine is a Category 3 drug.[citation needed]
  • New Zealand: Ketamine is a Class C drug.[citation needed]
  • Norway: Ketamine is a Class A drug.[citation needed]
  • Singapore: Ketamine is a Class A drug.[citation needed]
  • Slovakia: Ketamine is a Schedule II drug.[citation needed]
  • South Korea: The possession and sale is illegal.[citation needed]
  • Sweden: Ketamine is a Schedule IV drug.[citation needed]
  • Taiwan: Ketamine is a Schedule III drug.[citation needed]
  • United Kingdom: Ketamine is a Class B drug.[27]
  • United States.: Ketamine is a Schedule III drug.[citation needed]

See also

External links

Media

Literature

  • Durieux, M., & Kohrs, R.T. (1998). Ketamine: teaching an old drug new tricks. Anesthesia and A nalgesia, 87 5, 1186-93. PMID: 9806706
  • Mion, G. (2017). History of anaesthesia: The ketamine story–past, present and future. European Journal of Anaesthesiology (EJA), 34(9), 571-575. https://doi.org/10.1097/EJA.0000000000000638
  • Krystal, J. H., Karper, L. P., Seibyl, J. P., Freeman, G. K., Delaney, R., Bremner, J. D., . . . Charney, D. S. (1994). Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans: Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Archives of General Psychiatry, 51(3), 199-214. http://dx.doi.org/10.1001/archpsyc.1994.03950030035004
  • Morris, H., & Wallach, J. (2014). From PCP to MXE: A comprehensive review of the non-medical use of dissociative drugs. Drug Testing and Analysis, 6(7–8), 614–632. https://doi.org/10.1002/dta.1620

References

  1. 1.0 1.1 Bergman, S. A. (1999). "Ketamine: Review of its pharmacology and its use in pediatric anesthesia" - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2148883
  2. 2.0 2.1 Mion, G. (2017). History of anaesthesia: The ketamine story–past, present and future. European Journal of Anaesthesiology (EJA), 34(9), 571-575. https://doi.org/10.1097/EJA.0000000000000638
  3. Peck, T. E.; Hill, S. A.; Williams, M. (2008). Pharmacology for anesthesia and intensive care (3rd edition). Cambridge: Cambridge University Press. p. 111
  4. WHO Model List of Essential Medicines | http://whqlibdoc.who.int/hq/2011/a95053_eng.pdf
  5. Interaction of ketamine with μ2 opioid receptors in SH-SY5Y human neuroblastoma cells | http://link.springer.com/article/10.1007%2Fs005400050035
  6. putative sigma1 receptor antagonist NE-100 attenuates the discriminative stimulus effects of ketamine in rats | http://onlinelibrary.wiley.com/doi/10.1080/13556210020077091/abstract
  7. Pharmaceutical Society of Australia. "2.1.1 IV general anaesthetics". Australian Medicines Handbook. 2011. Australian Medicines Handbook Pty Ltd. p. 13.
  8. Ketamine inhibits serotonin uptake in vivo. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/6460944
  9. Ketamine Improves Bipolar Depression Within Minutes - http://www.medicaldaily.com/articles/10085/20120530/ketamin-bipolar-disorder-depression.htm
  10. Could A Club Drug Offer 'Almost Immediate' Relief From Depression? - http://www.npr.org/blogs/health/2012/01/30/145992588/could-a-club-drug-offer-almost-immediate-relief-from-depression
  11. Nishimura, M., & Sato, K. (1999). Ketamine stereoselectively inhibits rat dopamine transporter. Neuroscience Letters, 274(2), 131-134. PMID: 10553955. https://doi.org/10.1016/s0304-3940(99)00688-6
  12. Zhang JC, Li SX, Hashimoto K (2014). "R (-)-ketamine shows greater potency and longer-lasting antidepressant effects than S (+)-ketamine". Pharmacol. Biochem. Behav. 116: 137–41. doi:10.1016/j.pbb.2013.11.033. PMID 24316345. 
  13. Tyler, M. W., Yourish, H. B., Ionescu, D. F., & Haggarty, S. J. (2017). Classics in Chemical Neuroscience: Ketamine. ACS Chemical Neuroscience. https://doi.org/10.1021/acschemneuro.7b00074
  14. Zanos, P., Moaddel, R., Morris, P. J., Georgiou, P., Fischell, J., Elmer, G. I., ... & Dossou, K. S. (2016). NMDAR inhibition-independent antidepressant actions of ketamine metabolites. Nature, 533(7604), 481-486. https://doi.org/10.1038/nature17998
  15. Yang, C., Zhou, W., Li, X., Yang, J., Szewczyk, B., Pałucha-Poniewiera, A., ... & Nowak, G. (2012). A bright future of researching AMPA receptor agonists for depression treatment. Expert opinion on investigational drugs. https://doi.org/10.1517/13543784.2012.667399
  16. http://www.erowid.org/chemicals/ketamine/ketamine_journal5.shtml
  17. Development of a rational scale to assess the harm of drugs of potential misuse (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0140673607604644
  18. "Addiction Users Study: Consequences of chronic ketamine self-administration upon neurocognitive function and psychological well-being: a 1-year longitudinal study - http://onlinelibrary.wiley.com/doi/10.1111/j.1360-0443.2009.02761.x/abstract
  19. Low concentrations of ketamine initiate dendritic atrophy of differentiated GABAergic neurons in culture (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0300483X07001138
  20. Neuroprotective NMDA antagonists: the controversy over their potential for adverse effects on cortical neuronal morphology (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/7976530
  21. Chronic ketamine exposure induces permanent impairment of brain functions in adolescent cynomolgus monkeys | http://onlinelibrary.wiley.com/doi/10.1111/adb.12004/abstract
  22. author=Arvanov V, Liang X, Russo A, Wang R |title=LSD and DOB: interaction with 5-HT2A receptors to inhibit NMDA receptor-mediated transmission in the rat prefrontal cortex | http://onlinelibrary.wiley.com/doi/10.1046/j.1460-9568.1999.00726.x/abstract
  23. Farber N, Hanslick J, Kirby C, McWilliams L, Olney J | Serotonergic agents that activate 5HT2A receptors prevent NMDA antagonist neurotoxicity | http://www.nature.com/npp/journal/v18/n1/full/1395108a.html
  24. Ketamine-induced vesicopathy: a literature review | http://onlinelibrary.wiley.com/doi/10.1111/j.1742-1241.2010.02502.x/abstract
  25. Ketamine use: a review | http://onlinelibrary.wiley.com/doi/10.1111/j.1360-0443.2011.03576.x/abstract
  26. Controlled Drugs and Substances Act of Canada
  27. Drugs penalties, GOV.UK, 3 September 2016. Retrieved on 25 November 2017.