Mitragyna speciosa

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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]

Though not an opiate itself, kratom is thought to behave similarly to a μ-opioid receptor agonist like morphine.[4] It is not deemed to have any legitimate medical uses.[5] Some people use it for managing chronic pain as well as recreationally.[6] Effects last for between two and five hours.[5] Kratom use is not detected by typical drug screening tests, but its metabolites can be detected by more specialized testing.[7][8] Its efficacy and safety are not well-studied.[4]

Minor side effects may include itchiness, vomiting, and constipation.[5] More severe side effects may include a decreased effort to breathe, seizure, addiction, psychosis, or death.[5][9][10] Naloxone may be used to treat an overdose that results in a decreased effort to breathe.[5]

Taxonomy and etymology[edit]

Mitragyna speciosa was first formally described by the Dutch colonial botanist Pieter Korthals in 1839.[11] and in a 1897 publication by George Haviland.[12] 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.

Description[edit]

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.[13] 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.[14]

Uses[edit]

The United States Drug Enforcement Administration state "There is no legitimate medical use for kratom".[13] 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[edit]

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.[4]

Traditional use[edit]

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.[15] 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.[16][17] A fresh leaf weighs on average 2 grams, which may contain as much as 79 mg of mitragynine,[18] 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.

Safety[edit]

In recent years Kratom has become the subject of increasing concern because of the rising number of hospital visits and deaths among its users.[9]

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][19] 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.[18]

Withdrawal is generally short-lived and mild, and it may be effectively treated with dihydrocodeine and lofexidine.[20] 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.[21][22][23] 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.[23]

Detection in body fluids[edit]

Blood concentrations are expected to be in a range of 10–50 μg/L in persons using the drug recreationally.[23][24]

Pharmacology[edit]

The pharmacological effects of kratom on humans are not well studied. Its metabolic half-life, protein binding, and elimination characteristics are all unknown.[4] Kratom behaves as a μ-opioid receptor agonist, similar to opiates like morphine, although its effects differ significantly from those of opiates.[4]

Chemistry[edit]

There are more than 40 compounds in M. speciosa leaves,[6] including many alkaloids such as mitragynine, mitraphylline, 7-hydroxymitragynine and mitragynine pseudoindoxyl.[25][26][27] Other active chemicals in M. speciosa include raubasine (best known from Rauvolfia serpentina) and Pausinystalia johimbe alkaloids such as corynantheidine.[28][29]

Mitragyna speciosa also contains at least one alkaloid (rhynchophylline) that is a calcium channel blocker, and reduces NMDA-induced current.[30][31] 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.[4] 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%.[32] 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.[33]

Regulation[edit]

Thailand[edit]

Prohibition[edit]

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.[34][35] 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.[36] 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][17]

Proposed decriminalization[edit]

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.[17]

Malaysia[edit]

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.[37] 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.[38]

United States[edit]

There is no FDA-approved medical use for kratom. The U.S. Drug Enforcement Administration has issued a "Drugs of Abuse Resource Guide", which states "Kratom is not controlled under the Federal Controlled Substances Act; however, there may be some State regulations or prohibitions against the possession and use of kratom. Alabama, for example, outlawed the use and possession of kratom in May 2016, and all stores in Alabama were ordered to immediately remove all kratom products from their shelves.[39] In addition, DEA has listed kratom as a "Drug and Chemical of Concern" and "Drug of Abuse".[40] In 2014 and 2016 enforcement actions on the basis that kratom poses a risk to public health and has potential for abuse, is unapproved as a new drug and is a misbranded drug under the Federal Food, Drug, and Cosmetic Act, the Food and Drug Administration (FDA) seized kratom products in California and Illinois.[41][42][43]

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 there is no evidence that Kratom does not pose an unnecessary risk of illness or injury, further 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."[44]

See also[edit]

References[edit]

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  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 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. 
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  12. ^ 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)
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  14. ^ Philippine Department of Agriculture – Bureau of Plant Industry: Eintrag Mambog)
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  19. ^ 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. 
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  28. ^ 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. 
  29. ^ "Chemistry of Kratom -Mitragyna speciosa". Microblog - Kratom Emporium. 
  30. ^ "Kratom Mitragyna speciosa" (PDF). Microgram Bulletin – Department of Justice. XXXIX (3): 30. March 2006. 
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  32. ^ 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. 
  33. ^ 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. 
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  37. ^ "Amend the Act leaves the density of the Dangerous Drugs Act". 13 December 2012. Retrieved 18 April 2014. 
  38. ^ Pengasih wants abuse of kratom leaves penalised under Dangerous Drugs Act. The Malaysian Insider. October 28, 2012.
  39. ^ Hoeger R (13 May 2016). "Mobile Police Department confiscates $30,000 worth of Kratom". Fox10 TV.com. Fox News, Mobile, AL. Retrieved 17 May 2016. 
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  41. ^ "U.S. Marshals seize botanical substance kratom from southern California facility". U.S. Food and Drug Administration. 25 September 2014. Retrieved 5 August 2016. 
  42. ^ "US Marshals seize dietary supplements containing kratom". U.S. Food and Drug Administration. 6 January 2016. Retrieved 5 August 2016. 
  43. ^ "Kratom seized in California by US Marshals Service". U.S. Food and Drug Administration. 4 August 2016. Retrieved 5 August 2016. 
  44. ^ "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[edit]