Mitragyna speciosa (Korth.) Havil.

Last updated: 26 Apr 2016

Scientific Name

Mitragyna speciosa (Korth.) Havil.

Synonyms

Nauclea korthalsii Steud. [Invalid], Nauclea luzoniensis Blanco,           Nauclea speciosa (Korth.) Miq, Stephegyne speciosa Korth. [1]

Vernacular Name

Malaysia Kutum; ketum; bia biak [2]
Thailand Kataun, krataum, taum, kratom, ithang, kakuan [2]
Philippines Mambog (Tagalog) [2]

Geographical Distributions

Mitragyna speciosa is found from Peninsular Malaysia, Sumatra and Borneo to the Philippines and New Guinea. It is cultivated in southern Vietnam, peninsular Thailand and Burma (Myanmar). [3]

Botanical Description

M. speciosa is a tall tree of the Rubiaceae family. M. speciosa is a large tree, which can reach 10-30 m tall. The big bole measures 60-100 cm in diameter. The bark is grey, shallowly sculptured and with blister-like prominent lenticels. [3]

The leaves are opposite, simple, entire, oblong-ovate and measure 8-15 cm x 4-10 cm. The leaf base is broadly rounded, apex abruptly acuminate, smooth or veins beneath covered with soft short hairs, veins 12-15 pairs and stalk is measures (1-)2-5 cm long. The stipules are lance-shaped, measure 2 cm long, with soft hair, 9 veins and with colleters inside at the base. [3]

The inflorescence is terminally on lateral branches, composed of 3(-7) spherical heads, where 1 head is nearly subsessile between the 2 others on long peduncles which are 5 cm long and head 2.5 cm in diameter when flowering, shortened to 1.5 cm when fruiting with receptacle hairy and leafy bracts measuring up to 4 cm long. The petiolate is between flower bracteoles measuring up to 3.5 mm long. The flowers are bisexual, 5-merous, sessile with cup-shaped sepal, measuring up to 2 mm long and 5-lobed. The funnel shaped petals are yellowish-white turning deep yellow which are 5-8 mm long with 5 lobes that are 3 mm long and thickened at apex while margin is revolute. There is a conspicuous ring of hairs inside at the base of its lobes. The stamens are 5 which intersection with lobes while anthers are lance-shaped, heart-shaped and conspicuously protruding from the petal with ovary inferior consists of 2-celled. The style is exerted with 13 mm long while the stigma is rounded and 2 mm long. [3]

The fruit composed of 2 cocci, exocarp thin, splitting from the dorsal suture along its length and 10-ridged. The seeds are numerous and shortly winged on 2 sides while the lower wing shortly bifid or notched. [3]

Cultivation

M. speciosa generally occurs rather sparsely in open savanna and secondary forest, at low altitudes. In Borneo, it is usually encountered in swamp and riverine forests which are periodically flooded, where it is one of the dominant species observed as colonizing vegetation on old ox-bow riverbeds. The plant propagates by seed. [3]

Harvesting

The leaves of M. speciosa are harvested throughout the year. [3]

Postharvest handling

In Peninsular Malaysia, the leaves of M. speciosa are dried in the sun until they are crisp. After that there are several possibilities for further use. The leaves can be powdered between the hands, the coarser parts removed, and the rest stored for later use. A small amount of this powder can be swallowed daily to twice daily in a cup of cold water or drunk as a hot infusion. The dry leaves can also be boiled, and the infusion is boiled down to syrup. This syrup can be kept for a long time. The syrup can be mixed with hot water and drunk or it is put on the tongue and washed down with water. The syrup can also be mixed with finely shredded leaves of the palm Licuala paludosa Griffith, and the resulting sticky pellet is smoked in a bamboo pipe. In southern Thailand, the syrup may also been taken with betel leaf (Piper betle L.). [3]

Estimated cost of production

No documentation

Chemical Constituent

M. speciosa  has been reported to contain mitraphylline, isomitraphylline, rhynchophylline, speciophylline, rotundifoline, specionoxeine, isospecionoxeine, speciofoline, mitragynine, 3-Dehydromitragynine, mitraciliatine, mitraspecine, paynantheine, 3-isopaynantheine, mitrafoline, isomitrafoline, corynantheidine, corynoxeine, corynoxine, 3-isocorynantheine, isospeciofoline, isospecionoxeine, speciociliatine, speciogynine, specionoxeine, epicathechin. [4]

Plant Part Used

Leaves [6][7]

Traditional Use

The leaves of M. speciosa have been used in local traditions as a masticatory either alone or in combination with betle leaves and areca nuts. It is believed that chewing on the leaves would help revitalize the body and provide the user endless energy to carry on working in the fields. Chewing the leaves induces an euphoric effecta which is followed by sexual arousal and this is used as an aphrodisiac. [5] In both Malaysia and Thailand a decoction of the leaves is used to treat opium addiction by giving a gradual dilution of the decoction. [6] Today, it has been abused by the younger generation to provide them with a cheaper alternative to heroin. Pounded leaves of M. speciosa are applied over wounds to both relieve pain and promote healing.  It is used as a poultice to induce expulsion of worms in children and also to treat enlarged spleen. [7]

Preclinical Data

Pharmacology

The potential of indole alkaloids, isolated from the leaves of M. speciosa for use in the treatment of heroin addiction had attracted many researchers throughout the world to do extensive studies on this plant. Today we have understood the mechanism of the two most active principles responsible for the opiod-like actions i.e. mitragynine and 7-hydrpxymitragynine. 

Mitragynine was one of the first 9-methoxy-coryanthe-type monoterpeniod isolated from the young leaves of M. speciosa from Southern Thailand and Northern Malaysia. Its opioid agonist activity had been identifed and the site of action was determined to be the m- and d-opioid receptors in the periphery. Its weak action did not correspond to the strong opioid activity of the leaf extracts. This had led to the isolation of a more potent compound i.e 7-hydroxy-mitragynine. This newly discovered compound seems to show a more potent analgesic activity. This compound was shown to act on the m-opioid receptor in manners similar to morphine i.e. analgesia and inhibition of gastro-intestinal transit time. However, it showed a more potent analgesia than morphine and a less constipating effect. There was an element of tolerance seen in its effects upon prolonged usage. [8-19]

Anti-oxidant and antibacterial activity

Among the uses of the leaves of M. speciosa is in the treatment of wounds as cited above. Investigation on the anti-oxidant and antibacterial activity of the leaves reported that the methanol extracts showed very high anti-oxidant activity and attribute this to the probability of the presence of high amount of phenolic compounds in the extract. On the other hand, the same extracts showed antibacterial activity against Salmonella typhi and Bacillus subtilis. where the alkaloids are the most potent against all tested organism. [20]

Antispasmodic activity

Mitraginine is an alkaloid found in the leaves of M. speciosa which showed analgesic properties. It was found that it also has antispasmodic activity when the compound inhibits electrically stimulated contraction of guinea-pic ileum via the opioid receptor. [21] The methanol extract of the leaves caused a dose dependent protection against castor-oil induced diarrhoea in rats and also inhibited intestinal transit. A single dose of the extract affects the intestinal transit which chronic application did not. The effects were postulated to be via pathways in addition to the action on opioid receptors. [22]

Antidiabetic activity

There had been heresay reports of the effectiveness of M. speciosa leave tea as a remedy for diabtetes mellitus amongst the people of Langkawi. Studies on the effect of leaf extract on glucose transport into muscle cells reported found that the extract did increase the glucose uptake by mucle cells and this it attributed to the increase in GLUT 1 protein content. This concluded that this activity is associated with increases in activities of the key enzymes dependent to insulin-stimulated glucose transport for its acute action, and increases in GLUT-1 content for its long-term effects. [23]

Gastic acid secretion activity

Tsuchiya et al studied the opiod agonistic properties of the indole-alkaliods of M. speciosa Korth on the gastric mucosa i.e. its ability to inhibit gastric acid secretion and found that its activity is centrally mediated. [24] 

Liver enzyme stimulating activity

The effects of M. speciosa leaf extracts on phase II drug metabolizing enzymes – glutathione transferases (GSTs) was carried out by which found that the methanolic extract has the most potent GSTs specific activity inhibition in a dose dependant manner in their in vitro studies using untreated rat liver cytosolic fraction. In the in vivo studies an increase in the GST specific activity was generally observed with the aqueous extracts at 100 mg/kg showed significant results. [25]

Effects on food and water intake and weight gain activity

Acute administration of M. speciosa extract was noted to significantly decreases food and water intake in rats. Upon chronic admintration of the extracts for 60 consecutive days there was a significant supression of weight gain. [26]

Effects on ethanol withdrawal symptoms activity

Studies on the effects of aqueous extract of M. speciosa on ethanol withdrawal symptoms in mice. showed a significant inhibition of the withdrawal induced behaviour. At doses of 100, 300 and 500 mg/kg the extract showed antidepressant activity without effects on the spontaneous motor activity. [27]

Toxicity

M. speciosa contains mitragyne, an indone alkaloid that is similar to psilocybin and is a m- and d-subtype receptor agonist (about 10% of the action of morphine). Upon acute exposure it can cause coma, vertigo, lethergy, tremors, nausea, vomiting, can be a stimulant (at doses of mitragynine >50mg), miosis, constipation, doses >25g of the leaves can be toxic. No specific antidote is known to the modern world thus, supportive care is the mainstay of therapy. [28] To the local community of Thailand and Malaysia coconut water is the universal antidote for overdose. 

Long term addicts presents clinically as follows: thin, darkened skin, constipated with black stools and urinate frequently. They show hostility, aggression, lacrimation, jerky limb movements and aching muscles as withdrawal symptoms. [29]

Clinical Data

Clinical findings

No documentation

Interaction & Depletion

No documentation

Contraindications

No documentation

Case Report

Self-treatment of opioid withdrawal using kratom (M. speciosa ). Report of a case of self managed opioid withdrawal using kratom with modafinil. The patient abruptly ceased injection of hydromorphone. [30]

Dosage

Dosage Range

No documentation

Poisonous Management

No documentation

Line drawing

38

Figure 1: The line drawing of M. speciose. [3]

References

  1. The Plant List. Ver1.1. Mitragyna speciosa (Korth.) Havil. c2013 [updated 2012 Mar 23; cited 2016 Apr 26]. Available from: http://www.theplantlist.org/tpl1.1/record/kew-128805
  2. Ridley HN. The flora of the Malay Peninsula. Volume 2. London: L. Reeve & Co., 1923; p. 6
  3. Chua LSL, Schmelzer GH. Mitragyna speciosa (Korth.) Havil. In: van Valkenburg JLCH, Bunyapraphatsara N, editors. Plant Resources of South-East Asia No. 12(2): Medicinal and poisonous plants 2. Leiden, Netherlands: Backhuys Publisher, 2001; p. 380-382
  4. Takayama H, Aimi N, Sakai S. Chemical studies on the analgesic indole alkaloids from the traditional medicine (Mitragyna speciosa) used for opium substitute. Yakugaku Zasshi. 2000;120(10):959-967
  5. Raymond S. The book of aphrodisiacs. Ontario: Methuen Publications, 1980; p. 63
  6. Timothy J. CRC ethnobotany desk reference. Boca Raton: CRC Press, 1999; p. 538
  7. Burkill IH. A dictionary of economic products of the Malay Peninsula. Volume 2. Kuala Lumpur: Ministry of Agriculture and Cooperatives of Malaysia, 1966; p. 1507
  8. Tohda M, Thongpraditchote S, Matsumoto K, et al. Effects of mitragynine on cAMP formation mediated by delta-opiate receptors in NG108-15 cells. Biol Pharm Bull. 1997;20(4):338-340
  9. Matsumoto K, Mizowaki M, Takayama H, Sakai S, Aimi N, Watanabe H. Suppressive effect of mitragynine on the 5-methoxy-N,N-dimethyltryptamine-induced head-twitch response in mice. Pharmacol Biochem Behav. 1997;57(1-2):319-323
  10. Thongpradichote S, Matsumoto K, Tohda M, et al. Identification of opioid receptor subtypes in antinociceptive actions of supraspinally-administered mitragynine in mice. Life Sci. 1998;62(16):1371-1378
  11. Yamamoto LT, Horie S, Takayama H, et al. Opioid receptor agonistic characteristics of mitragynine pseudoindoxyl in comparison with mitragynine derived from Thai medicinal plant Mitragyna speciosa. Gen Pharmacol. 1999;33(1):73-81
  12. Takayama H, Aimi N, Sakai S. Chemical studies on the analgesic indole alkaloids from the traditional medicine (Mitragyna speciosa) used for opium substitute. Yakugaku Zasshi. 2000;120(10):959-967
  13. Matsumoto K, Horie S, Ishikawa H, et al. Antinociceptive effect of 7-hydroxymitragynine in mice: Discovery of an orally active opioid analgesic from the Thai medicinal herb Mitragyna speciosa. Life Sci. 2004;74(17):2143-2155
  14. Horie S, Koyama F, Takayama H, et al. Murayama. Indole alkaloids of a Thai medicinal herb, Mitragyna speciosa, that has opioid agonistic effect in guinea-pig ileum. Planta Med. 2005;71(3):231-236
  15. Matsumoto K, Yamamoto LT, Watanabe K, et al. Inhibitory effect of mitragynine, an analgesic alkaloid from Thai herbal medicine, on neurogenic contraction of the vas deferens. Life Sci. 2005;78(2):187-194
  16. Matsumoto K, Horie S, Takayama H, et al. Antinociception, tolerance and withdrawal symptoms induced by 7-hydroxymitragynine, an alkaloid from the Thai medicinal herb Mitragyna speciosa. Life Sci. 2005;78(1):2-7
  17. Matsumoto K, Hatori Y, Murayama T, et al. Involvement of mu-opioid receptors in antinociception and inhibition of gastrointestinal transit induced by 7-hydroxymitragynine, isolated from Thai herbal medicine Mitragyna speciosa. Eur J Pharmacol. 2006;549(1-3):63-70
  18. Kumarnsit E, Vongvatcharanon U, Keawpradub N, Intasaro P. Fos-like immunoreactivity in rat dorsal raphe nuclei induced by alkaloid extract of Mitragyna speciosa. Neurosci Lett. 2007;416(2):128-132
  19. Babu KM, McCurdy CR, Boyer EW. Opioid receptors and legal highs: Salvia divinorum and Kratom. Clin Toxicol (Phila). 2008;46(2):146-152
  20. Parthasarathy S1, Bin Azizi J, Ramanathan S, et al. Evaluation of antioxidant and antibacterial activities of aqueous, methanolic and alkaloid extracts from Mitragyna speciosa (Rubiaceae family) leaves. Molecules. 2009;14(10):3964-3974
  21. Watanabe K, Yano S, Horie S, Yamamoto LT. Inhibitory effect of mitragynine, an alkaloid with analgesic effect from Thai medicinal plant Mitragyna speciosa, on electrically stimulated contraction of isolated guinea-pig ileum through the opioid receptor. Life Sci. 1997;60(12):933-942
  22. Chittrakarn S, Sawangjaroen K, Prasettho S, Janchawee B, Keawpradub N. Inhibitory effects of kratom leaf extract (Mitragyna speciosa Korth.) on the rat gastrointestinal tract. J Ethnopharmacol. 2008;116(1):173-178
  23. Purintrapiban J, Keawpradub N, Kansenalak S, Chittrakarn S, Janchawee B, Sawangjaroen K. Study on glucose transport in muscle cells by extracts from Mitragyna speciosa (Korth) and mitragynine. Nat Prod Res. 2011;25(15):1379-1387.
  24. Tsuchiya S, Miyashita S, Yamamoto M, et al. Effect of mitragynine, derived from Thai folk medicine, on gastric acid secretion through opioid receptor in anesthetized rats. Eur J Pharmacol. 2002;443(1-3):185-188
  25. Azizi J, Ismail S, Mordi MN, Ramanathan S, Said MI, Mansor SM. In vitro and in vivo effects of three different Mitragyna speciosa korth leaf extracts on phase II drug metabolizing enzymes--glutathione transferases (GSTs). Molecules. 2010;15(1):432-441
  26. Kumarnsit E, Keawpradub N, Nuankaew W. Acute and long-term effects of alkaloid extract of Mitragyna speciosa on food and water intake and body weight in rats. Fitoterapia. 2006;77(5):339-345
  27. Kumarnsit E, Keawpradub N, Nuankaew W. Effect of Mitragyna speciosa aqueous extract on ethanol withdrawal symptoms in mice. Fitoterapia. 2007;78(3):182-185
  28. Jerrold B, Leikin, Robin B. McFee Handbook of nuclear, biological, and chemical agent exposures. Boca Raton: CRC Press, 2007; p. 329
  29. Irving SR. Encyclopedia of clinical toxicology: A comprehensive guide and reference. New York: Parthenon Publishing Group, 2002; p. 590
  30. Boyer EW, Babu KM, Adkins JE, McCurdy CR, Halpern JH. Self-treatment of opioid withdrawal using kratom (Mitragynia speciosa korth). Addiction. 2008;103(6):1048-1050