Page semi-protected

Mitragyna speciosa

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Mitragyna speciosa
Mitragyna speciosa111.JPG
Scientific classification
Kingdom: Plantae
(unranked): Angiosperms
(unranked): Eudicots
(unranked): Asterids
Order: Gentianales
Family: Rubiaceae
Subfamily: Cinchonoideae
Tribe: Naucleeae
Genus: Mitragyna
Species: M. speciosa
Binomial name
Mitragyna speciosa
(Korth.) Havil.
Synonyms[1]
  • Nauclea korthalsii Steud. nom. inval.
  • Nauclea luzoniensis Blanco
  • Nauclea speciosa (Korth.) Miq.
  • Stephegyne speciosa Korth.

Mitragyna speciosa, also known as ketum or kratom,[2] is a tropical deciduous and evergreen tree in the coffee family (Rubiaceae) native to Southeast Asia in the Indochina and Malaysia phytochoria (botanical regions). M. speciosa is indigenous to Thailand where it has been used in traditional medicine.[3]

Little research has been done on the health effects and it has no approved medical uses.[4][5] Some people use it for managing chronic pain, opioid withdrawal, or recreationally.[6][4] Effects last for between two and five hours.[4] Kratom use is not detected by typical drug screening tests, but its metabolites can be detected by more specialized testing.[7][8]

Minor side effects may include itchiness, vomiting, and constipation.[4] More severe side effects may include a decreased effort to breathe, seizure, addiction, and psychosis.[4] Other side effects include high heart rate and blood pressure, liver toxicity, and trouble sleeping.[9][10] Naloxone may be used to treat an overdose that results in a reduced effort to breathe.[4] In the United States between 2014 and 2016, 15 deaths have been associated with kratom use.[9] Though not an opiate itself, kratom is thought to behave similarly to an opiate like morphine.[5]

Description

Young M. speciosa tree

Mitragyna speciosa trees usually grow to a height of 12–30 ft (3.7–9.1 m) tall and 15 ft (4.6 m) wide, although some species can reach 40–70 ft (12–21 m) in height.[11] Mitragyna speciosa can be either evergreen or deciduous depending on the climate and environment in which it is grown. The stem is erect and branching. The leaves of the kratom tree are a dark green colour and can grow to over 7 inches (180 mm) long and 4 inches (100 mm) wide, are ovate-acuminate in shape, and opposite in growth pattern. The flowers are yellow and round and tend to grow in clusters at the end of the branches. The leaves of M. speciosa are elliptic and are smaller at the end of the branchlets and are pointed at the tip. The leaves have a round and heart-shape at the base with the petioles between 2–4 centimetres (0.79–1.57 in) long. The flowers are crowded in a round terminal inflorescences that are three to five centimeters long. The calyx-tube is short and cup-shaped, with round lobes. The corolla-tube is 5 millimetres (0.20 in) long with 3 millimetres (0.12 in) long lobes and smooth and revolute in between.[12]

Uses

The United States Drug Enforcement Administration states, "There is no legitimate medical use for kratom".[11] Kratom has become popular as a recreational drug and has been promoted with claims that it can improve mood, relieve pain and help with opiate addiction.[9]

Opioid withdrawal

Data on how often it is used are lacking as it is not detected by typical drug screening tests.[6] Kratom metabolites can be detected by specialized mass spectrometry tests.[8] Rates of kratom use appears to be increasing among those who have been self-managing chronic pain with opioids purchased without a prescription and are cycling (but not quitting) their use.[6] As of 2011, there have been no formal trials to study the efficacy or safety of kratom to treat opioid addiction.[5]

Traditional use

Kratom leaves

Kratom has been traditionally chewed, in raw leaf form, by people in Thailand and especially in the southern peninsula.[3] Kratom is often used by workers in laborious or monotonous professions to stave off exhaustion as well as a mood enhancer and/or painkiller. Kratom is also used in neighboring countries in Southeast Asia where it grows naturally.[3] Kratom has been used in Thailand as a form of traditional medicine as an antidiarrhoeal, as a treatment for opioid use disorder, and for premature ejaculation during sexual intercourse.[13] As traditionally used, kratom is not seen as a drug and there is often no stigma associated with kratom use or discrimination against kratom users.[3] In Southern Thailand, kratom has been a part of traditional culture and is common in cultural performances and agriculture.[14][15] A fresh leaf weighs on average 2 grams, which may contain as much as 79 mg of mitragynine,[16] with the average number of leaves consumed daily between 10 and 60 leaves. In some areas of Southern Thailand, kratom is often referred to by the street name P̄hī "Goblin". Kratom leaves may also be brewed as a tisane.

Side effects

Kratom has become a subject of concern in many countries because of the rising number of hospital visits and reports of deaths associated with its users.[17] According to the DEA, 15 deaths in the United States between 2014 and 2016 were caused by kratom.[9]

In July, 2016, the Centers for Disease Control (CDC) issued a report stating that between 2010 and 2015 US Poison Centers received 660 reports of exposure to kratom. Medical outcomes associated with kratom exposure were reported as minor (minimal signs or symptoms, which resolved rapidly with no residual disability) for 162 (24.5%) exposures, moderate (non-life threatening, with no residual disability, but requiring some form of treatment) for 275 (41.7%) exposures, and major (life-threatening signs or symptoms, with some residual disability) for 49 (7.4%) exposures.[10] One death was reported in a person who was exposed to the medications paroxetine (an antidepressant) and lamotrigine (an anticonvulsant and mood stabilizer) in addition to kratom. For 173 (26.2%) exposure calls, no effects were reported, or poison center staff members were unable to follow up again regarding effects.[10]

The US Drug Enforcement Administration reported that kratom causes tachycardia, nausea, drowsiness, and high blood pressure.[9] Health risks occurring in kratom abusers include hepatotoxicity, psychosis, weight loss, insomnia, vomiting and death.[9]

Other side effects associated with chronic kratom use include loss of appetite and weight loss, delayed ejaculation, constipation, and darkening of the skin color of the face and bowel obstruction.[6][18] Chronic users have also reported withdrawal symptoms including irritability, runny nose and diarrhea.[8] One other study on chronic Malaysian users of kratom (more than 6 months, estimated 276 mg of mitragynine daily) showed severe symptoms of muscle spasms and pain, sleeping difficulty, fever, decreased appetite and psychological withdrawal.[16]

Withdrawal is generally short-lived and mild, and it may be effectively treated with dihydrocodeine and lofexidine.[19] Three case reports document deaths involving kratom. Other drugs were used in all cases, and Kratom was not found to be the cause in each case.[20][21][22] Several deaths in Sweden did occur from the use of a product that was at first believed to consist solely of kratom, called "Krypton Kratom", which was later found to contain O-Desmethyltramadol, the active metabolite of the prescription drug tramadol.[22]

Detection in body fluids

Blood concentrations are expected to be in a range of 10–50 μg/L in persons using the drug recreationally.[22][23]

Pharmacology

The pharmacological effects of kratom on humans are not well studied. Its metabolic half-life, protein binding, and elimination characteristics are all unknown.[5] Kratom behaves as a μ-opioid receptor agonist, similar to opiates like morphine, although its effects differ significantly from those of opiates.[5]

Chemistry

There are more than 40 compounds in M. speciosa leaves,[6] including many alkaloids such as mitragynine, mitraphylline, 7-hydroxymitragynine and mitragynine pseudoindoxyl.[24][25][26] Other active chemicals in M. speciosa include raubasine (best known from Rauvolfia serpentina) and Pausinystalia johimbe alkaloids such as corynantheidine.[27][28]

Mitragyna speciosa also contains at least one alkaloid (rhynchophylline) that is a calcium channel blocker, and reduces NMDA-induced current.[29][30] The amount of mitragynine within the leaves depends highly on many factors; one major factor is the location of the tree. When trees are grown in Southeast Asia, the levels tend to be higher, but when grown elsewhere (even in greenhouses), the levels tend to be low or non-existent.[5] One analysis of products marketed as kratom leaf found, using liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS), mitragynine at levels of 1–6% and 7-hydroxymitragynine at levels of 0.01–0.04%.[31] The chemical structure of mitragynines incorporate the nucleus of the tryptamine, and these may be responsible for the molecules observed in the serotonin and adrenergic systems. In mitragynine, the phenolic methyl ether is considered to be stronger in analgesic paradigms according to some studies. Moreover, the pharmacokinetics of M. speciosa in humans has not been well known.[32]

Taxonomy and etymology

Mitragyna speciosa was first formally described by the Dutch colonial botanist Pieter Korthals in 1839.[33] and in a 1897 publication by George Haviland.[34] The genus was named Mitragyna by Korthals because the stigmas in the first species he examined resembled the shape of a bishop's mitre. It is botanically related to the genera Corynanthe and Uncaria.

Regulation

Thailand

Prohibition

Possession of kratom leaves is illegal in Thailand.[3] The Thai government passed the Kratom Act 2486, effective August 3, 1943, which made planting the tree illegal and required existing trees to be cut down. This law was not found effective, since the tree is indigenous to the country. A large aspect of Thai culture supports kratom; indeed, kratom leaves have been used for medicinal purposes by nomadic tribes throughout history.[35][36] However, despite this fact the Thai government had initiated a program of destroying kratom trees by burning forests or chopping large sections of kratom forests down. Eradication campaigns often destroy not only the trees but also other trees and wildlife in these areas, which are often untouched rainforests with sensitive ecosystems.[37] A general consensus exists in southern Thailand among leaders, public health officials, academics and policymakers that kratom use causes few health risks and may reduce dependence on imported morphine.[3][15]

Proposed decriminalization

In 2010, the Thai Office of the Narcotics Control Board proposed decriminalizing kratom and affirmed its use as an integral part of Thai culture.[3] The ONCB concluded that decades of non-problematic use, and an absence of health and social harm, make prohibiting the leaf unnecessary and counterproductive. According to the ONCB's report, kratom was in fact banned for economic reasons, not for health or social concerns. The Transnational Institute stated:

In Thailand, kratom was first scheduled for control in 1943 under the Kratom Act. At the time, the government was levying taxes from users and shops involved in the opium trade. Because of the increasing opium costs, many users were switching to kratom to manage their withdrawal symptoms. However, the launch of the Greater East Asia War in 1942 and declining revenues from the opium trade pushed the Thai government into action to curb and suppress competition in the opium market by making kratom illegal.[3]

As of October, 2013, the justice ministry of Thailand suggested removal of kratom from the narcotic drug list relating to Category 5 of the Narcotic Drug Law of 1979, though still recommended regulating kratom in other ways due to its effects on the nervous system. This recommendation will be made to the Ministry of Public Health, which can move forward with the removal from the list or not.[15]

Malaysia

The use of kratom leaves, known locally as 'ketum', is prohibited in Malaysia under Section 30 (3) Poisons Act 1952 and the user may be penalized with a maximum compound of MYR 10,000 (USD 3,150) or up to 4 years imprisonment.[38] Certain parties have urged the government to penalize the use of kratom under the Dangerous Drugs Act instead of the Poisons Act, which will carry heavier penalties.[39]

United States

On 30 August 2016, the Drug Enforcement Administration (DEA) announced its intention to place the active materials in the kratom plant into Schedule I of the Controlled Substances Act as a warning about an imminent hazard to public safety.[9]

According to the DEA press release, "Kratom is abused for its ability to produce opioid-like effects and is often marketed as a legal alternative to controlled substances. Law enforcement nationwide has seized more kratom in the first half of 2016 than any previous year and easily accounts for millions of dosages intended for the recreational market, according to DEA findings. In addition, kratom has a high potential for abuse, has no currently accepted medical use in treatment in the United States, and has a lack of accepted safety for use under medical supervision. These three factors constitute a Schedule I controlled substance according to the Controlled Substances Act passed by Congress in 1970."[9] DEA reported 15 kratom-related deaths between 2014 and 2016.[9]

On June 9, 2015, FDA announced an import alert for kratom, issuing guidance that shipments are to be seized without physical examination from several vendors listed due to concerns that kratom poses a risk of illness or injury, stating that "[C]onsumption of kratom can lead to a number of health impacts, including respiratory depression, nervousness, agitation, aggression, sleeplessness, hallucinations, delusions, tremors, loss of libido, constipation, skin hyperpigmentation, nausea, vomiting, and severe withdrawal signs and symptoms."[40]

See also

References

  1. ^ Mitragyna speciosa (Korth.) Havil. is an accepted name . Theplantlist.org. Retrieved 2013-12-26.
  2. ^ Mitragyna speciosa information from NPGS/GRIN. Ars-grin.gov. Retrieved 2013-12-26.
  3. ^ a b c d e f g h Tanguay, Pascal; Drug Policy Consortium, International (April 2011). "Kratom in Thailand: Decriminalization and Community Control?". Series on Legislative reform of Drug Policies. 13. doi:10.2139/ssrn.1908849. Retrieved 2013-03-07. 
  4. ^ a b c d e f Rech, MA; Donahey, E; Cappiello Dziedzic, JM; Oh, L; Greenhalgh, E (February 2015). "New drugs of abuse.". Pharmacotherapy. 35 (2): 189–97. doi:10.1002/phar.1522. PMID 25471045. 
  5. ^ a b c d e f Ward J, Rosenbaum C, Hernon C, McCurdy CR, Boyer EW; Rosenbaum; Hernon; McCurdy; Boyer (December 2011). "Herbal medicines for the management of opioid addiction: safe and effective alternatives to conventional pharmacotherapy?". CNS Drugs. 25 (12): 999–1007. doi:10.2165/11596830-000000000-00000. PMID 22133323. 
  6. ^ a b c d e Adkins, Jessica E.; Edward W. Boyer; Christopher R. McCurdy (2011-05-01). "Mitragyna speciosa, a psychoactive tree from Southeast Asia with opioid activity". Current Topics in Medicinal Chemistry. 11 (9): 1165–1175. doi:10.2174/156802611795371305. PMID 21050173. 
  7. ^ Le D, Goggin MM, Janis GC; Goggin; Janis (2012). "Analysis of mitragynine and metabolites in human urine for detecting the use of the psychoactive plant kratom". Journal of Analytical Toxicology. 36 (9): 616–25. doi:10.1093/jat/bks073. PMID 23024321. 
  8. ^ a b c Rosenbaum CD, Carreiro SP, Babu KM; Carreiro; Babu (2012). "Here today, gone tomorrow…and back again? A review of herbal marijuana alternatives (K2, Spice), synthetic cathinones (bath salts), kratom, Salvia divinorum, methoxetamine, and piperazines". Journal of Medical Toxicology. 8 (1): 15–32. doi:10.1007/s13181-011-0202-2. PMC 3550220free to read. PMID 22271566. 
  9. ^ a b c d e f g h i "DEA Announces Intent to Schedule Kratom: SE Asian drug is imminent hazard to public safety". US Drug Enforcement Administration. 30 August 2016. Retrieved 31 August 2016. 
  10. ^ a b c Anwar, Mehruba; Law, Royal; Schier, Josh (2016-01-01). "Notes from the Field: Kratom (Mitragyna speciosa) Exposures Reported to Poison Centers — United States, 2010–2015". MMWR. Morbidity and Mortality Weekly Report. 65 (29): 748–749. doi:10.15585/mmwr.mm6529a4. ISSN 0149-2195. PMID 27466822. 
  11. ^ a b "KRATOM (Mitragyna speciosa korth)" (PDF). U.S. Drug Enforcement Administration. January 2013. Archived from the original (PDF) on 11 June 2016. 
  12. ^ Philippine Department of Agriculture – Bureau of Plant Industry: Eintrag Mambog)
  13. ^ Jansen, Karl L.R.; Prast, Colin J. (1988). "Ethnopharmacology of kratom and the Mitragyna alkaloids". Journal of Ethnopharmacology. 23 (1): 115–9. doi:10.1016/0378-8741(88)90121-3. PMID 3419199. 
  14. ^ Asnangkornchai, S; Siriwong, A (2005). "Kratom Plant in Thai society; culture, behavior". Health Science Laws. 
  15. ^ a b c Jeerapong Prasertpolkrung (29 August 2013). "Kratom may be taken off narcotics list". The Nation (Bangkok, Thailand). Retrieved 6 May 2016. 
  16. ^ a b Singh D, Müller CP, Vicknasingam BK (2014). "Kratom (Mitragyna speciosa) dependence, withdrawal symptoms and craving in regular users". Drug Alcohol Depend. 139: 132–7. doi:10.1016/j.drugalcdep.2014.03.017. PMID 24698080. 
  17. ^ Warner ML, Kaufman NC, Grundmann O (2016). "The pharmacology and toxicology of kratom: from traditional herb to drug of abuse". Int. J. Legal Med. (Review). 130 (1): 127–38. doi:10.1007/s00414-015-1279-y. PMID 26511390. 
  18. ^ Hassan, Zurina; Muzaimi, Mustapha; Navaratnam, Visweswaran; Yusoff, Nurul H.M.; Suhaimi, Farah W.; Vadivelu, Rajakumar; Vicknasingam, Balasingam K.; Amato, Davide; von Hörsten, Stephan; Ismail, Nurul I.W.; Jayabalan, Nanthini; Hazim, Ammar I.; Mansor, Sharif M.; Müller, Christian P. (2013). "From Kratom to mitragynine and its derivatives: Physiological and behavioural effects related to use, abuse, and addiction". Neuroscience & Biobehavioral Reviews. 37 (2): 138–51. doi:10.1016/j.neubiorev.2012.11.012. PMID 23206666. 
  19. ^ McWhirter L, Morris S; Morris (2010). "A case report of inpatient detoxification after kratom (Mitragyna speciosa) dependence". European Addiction Research. 16 (4): 229–31. doi:10.1159/000320288. PMID 20798544. 
  20. ^ Neerman, Michael F.; Frost, Randall E.; Deking, Janine (2013). "A Drug Fatality Involving Kratom". Journal of Forensic Sciences. 58: S278–9. doi:10.1111/1556-4029.12009. PMID 23082895. 
  21. ^ Holler, J. M.; Vorce, S. P.; McDonough-Bender, P. C.; Magluilo, J.; Solomon, C. J.; Levine, B. (2011). "A Drug Toxicity Death Involving Propylhexedrine and Mitragynine". Journal of Analytical Toxicology. 35 (1): 54–9. doi:10.1093/anatox/35.1.54. PMID 21219704. 
  22. ^ a b c Kronstrand, R.; Roman, M.; Thelander, G.; Eriksson, A. (2011). "Unintentional Fatal Intoxications with Mitragynine and O-Desmethyltramadol from the Herbal Blend Krypton". Journal of Analytical Toxicology. 35 (4): 242–7. doi:10.1093/anatox/35.4.242. PMID 21513619. 
  23. ^ Baselt RC (2014). Disposition of toxic drugs and chemicals in man. Seal Beach, Calif.: Biomedical Publications. p. 1382. ISBN 978-0-9626523-9-4. 
  24. ^ Suhaimi FW, Yusoff NH, Hassan R, Mansor SM, Navaratnam V, Müller CP, Hassan Z (2016). "Neurobiology of Kratom and its main alkaloid mitragynine". Brain Res Bull. Mar 25. doi:10.1016/j.brainresbull.2016.03.015. PMID 27018165. 
  25. ^ Chittrakarn, S; Keawpradub, N; Sawangjaroen, K; Kansenalak, S; Janchawee, B (2010). "The neuromuscular blockade produced by pure alkaloid, mitragynine and methanol extract of kratom leaves (Mitragyna speciosa Korth.)". Journal of Ethnopharmacology. 129 (3): 344–349. doi:10.1016/j.jep.2010.03.035. PMID 20371282. 
  26. ^ Prozialeck, WC; Jivan, JK; Andurkar, SV (2012). "Pharmacology of kratom: an emerging botanical agent with stimulant, analgesic, and opioid-like effects". The Journal of the American Osteopathic Association. 112 (12): 792–799. PMID 23212430. 
  27. ^ Takayama, Hiromitsu; Ishikawa, Hayato; Kurihara, Mika; Kitajima, Mariko; Aimi, Norio; Ponglux, Dhavadee; Koyama, Fumi; Matsumoto, Kenjiro; Moriyama, Tomoyuki; Yamamoto, Leonard T.; Watanabe, Kazuo; Murayama, Toshihiko; Horie, Syunji (2002). "Studies on the Synthesis and Opioid Agonistic Activities of Mitragynine-Related Indole Alkaloids: Discovery of Opioid Agonists Structurally Different from Other Opioid Ligands". Journal of Medicinal Chemistry. 45 (9): 1949–56. doi:10.1021/jm010576e. PMID 11960505. 
  28. ^ "Chemistry of Kratom -Mitragyna speciosa". Microblog - Kratom Emporium. 
  29. ^ "Kratom Mitragyna speciosa" (PDF). Microgram Bulletin – Department of Justice. XXXIX (3): 30. March 2006. 
  30. ^ Hendrickson, James B.; Sims, James J. (1963). "Mitragyna alkaloids: The structure of stipulatine". Tetrahedron Letters. 4 (14): 929–935. doi:10.1016/S0040-4039(01)90746-4. 
  31. ^ Kikura-Hanajiri, Ruri; Kawamura, Maiko; Maruyama, Takuro; Kitajima, Mariko; Takayama, Hiromitsu; Goda, Yukihiro (2009). "Simultaneous analysis of mitragynine, 7-hydroxymitragynine, and other alkaloids in the psychotropic plant 'kratom' (Mitragyna speciosa) by LC-ESI-MS". Forensic Toxicology. 27 (2): 67–74. doi:10.1007/s11419-009-0070-5. 
  32. ^ Ward, Jeanine; Rosenbaum, Christopher; Hernon, Christina; McCurdy, Christopher R.; Boyer, Edward W. (2011). "Herbal Medicines for the Management of Opioid Addiction". CNS Drugs. 25 (12): 999–1007. doi:10.2165/11596830-000000000-00000. PMID 22133323. 
  33. ^ Pieter Willem Korthals, "Observasions de Nauclais Indicis"; Bonnea; 1839; p. 20.
  34. ^ George Darby Haviland, "A Revision of the Tribe Naucleeae (Nat. Ord. Rubiaceae)"; Journal of Linnean Society; p. 65-69; Linnean Society of London, Feb. 4 1897. A Revision of the Tribe Naucleeae (Nat. Ord. Rubicae)
  35. ^ Suwanwela, C. (1983). "Thailand: Traditional and urban patterns of opium use". Drug Use and Misuse: cultural perspectives: 50–57. 
  36. ^ "A Culture Born on Kratom: Thailand's Prohibition Symposium". Kratomystic. Retrieved 4 June 2015. 
  37. ^ Cheurprakobkit, Sutham (2000). "The drug situation in Thailand: the role of government and the police". Drug and Alcohol Review. 19 (1): 17–26. doi:10.1080/09595230096101. 
  38. ^ "Amend the Act leaves the density of the Dangerous Drugs Act". 13 December 2012. Retrieved 18 April 2014. 
  39. ^ Pengasih wants abuse of kratom leaves penalised under Dangerous Drugs Act. The Malaysian Insider. October 28, 2012.
  40. ^ "Import Alert 54-15; Detention without physical examination of dietary supplements and bulk dietary ingredients that are or contain Mitragyna speciosa or kratom". U.S. Food and Drug Administration. 28 February 2014. Retrieved 18 April 2014. 

External links

Wikimedia Commons has media related to Mitragyna speciosa.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Mitragyna_speciosa&oldid=737274609"