Mitragyna speciosa

Synonyms

Nauclea speciosa Miq.; Stephegyne speciosa Korth [1]

Vernacular Names:

Malaysia: Kutum; Ketum; bia biak
Thailand:  Kataun, Krataum, Taum, Kratom, Ithang, Kakuan
Philippines:  Mambog (Tagalog) [1]

General Information

Description

Mitragyna speciosa is a tall tree of the Rubiaceae family. It can grow up to 20 m high and with a girth of 1 m. The leaves are large measuring up to 15 cm long and 6 cm wide. They are membranous, oblong-ovate subacuminate, with base broad and rounded. It is generally glabrous but the elevated nerves beneath may be puberulous. The petioles measures 1 cm long. The stipules are lanceolate and pubescent. The heads consisting of 3 where one is very shortly peduncled between two on the ends of long branches measuring 4 cm long and 2.5 cm through in flower, deep yellow. The corolla measures 0.75 cm long. The fruit-head measures 1 cm through. [1]

Plant Part Used

Leaves [3][4]

Chemical Constituents

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[9]

Traditional Used:

The leaves of M. speciosa has 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. [2] In both Malaysia and Thailand a decoction of the leaves is used to treat opium addiction by giving a gradual dilution of the decoction. [3] Today, it has been abused by the younger generation to provide them with a cheaper alternative to heroin. 

Pounded leaves of M. speciosa is applied over wounds to both relieve pain and promote healing. [4] It is used as a poultice to induce expulsion of worms in children and also to treat enlarged spleen. 

Pre-Clinical 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. mtragynine 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 lead 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. [5][6][7][8][9][10][11][12][13][14][15][16] 

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. [17]

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. [18] 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. [19] 

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. [20] 

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. [21] 

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. [22]

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. [23] 

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. [24]

Toxicities

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. [25] 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. [26] 

Clinical Data

Clinical Trials

No documentation

Adverse Effects in Human:

No documentation

Used in Certain Conditions

Pregnancy / Breastfeeding

No documentation

Age Limitations

Neonates / Adolescents

No documentation

Geriatrics

No documentation

Chronic Disease Conditions

No documentation

Interactions

Interactions with drugs

No documentation

Interactions with Other Herbs / Herbal Constituents

No documentation

Contraindications

Contraindications

No documentation

Case Reports

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. [27] 

Read More

  1) Botanical Info

  2) Malaysian Herbal Plants

References

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  2. S. Raymond. The Book of Aphrodisiacs. Ontario: Methuen Publications; 1980.63
  3. J. Timothy. CRC ethnobotany desk reference. Boca Raton: CRC Press; 1999.538
  4. I.H. Burkill. A. Dictionary of Economic Products of the Malay Peninsula. Kuala Lumpur: Ministry of Agriculture and Cooperatives; 1966.1507
  5. M. Tohda, S. Thongpraditchote, K. Matsumoto, Y. Murakami, S. Sakai, N. Aimi, Takayama H, Tongroach P, Watanabe H. Effects of mitragynine on cAMP formation mediated by delta-opiate receptors in NG108-15 cells. Biol Pharm Bull. Apr1997;20(4):338-340
  6. K. Matsumoto, M. Mizowaki, H. Takayama, S. Sakai, N. Aimi, H. Watanabe. Suppressive effect of mitragynine on the 5-methoxy-N,N-dimethyltryptamine-induced head-twitch response in mice. Pharmacol Biochem Behav. May-Jun1997;57(1-2):319-323
  7. S. Thongpradichote, K. Matsumoto, M. Tohda, H. Takayama, N. Aimi, S. Sakai, H. Watanabe. Identification of opioid receptor subtypes in antinociceptive actions of supraspinally-administered mitragynine in mice. Life Sci. 1998;62(16):1371-1378
  8. L.T. Yamamoto, S. Horie, H. Takayama, N. Aimi, S. Sakai, S. Yano, J. Shan, P.K. Pang, D. Ponglux, K. Watanabe. Opioid receptor agonistic characteristics of mitragynine pseudoindoxyl in comparison with mitragynine derived from Thai medicinal plant Mitragyna speciosa. Gen Pharmacol. Jul 1999;33(1):73-81
  9. H. Takayama, N. Aimi, S. Sakai. Chemical studies on the analgesic indole alkaloids from the traditional medicine (Mitragyna speciosa) used for opium substitute. Yakugaku Zasshi. Oct2000;120(10):959-967
  10. K. Matsumoto, S. Horie, H. Ishikawa, H. Takayama, N. Aimi, D. Ponglux, K. Watanabe. Antinociceptive effect of 7-hydroxymitragynine in mice: Discovery of an orally active opioid analgesic from the Thai medicinal herb Mitragyna speciosa. Life Sci. 12Mar2004;74(17):2143-2155
  11. S. Horie, F. Koyama, H. Takayama, H. Ishikawa, N. Aimi, D. Ponglux, K. Matsumoto, T. Murayama. Indole alkaloids of a Thai medicinal herb, Mitragyna speciosa, that has opioid agonistic effect in guinea-pig ileum. Planta Med. Mar2005;71(3):231-236
  12. K. Matsumoto, L.T. Yamamoto, K. Watanabe, S. Yano, J. Shan, P.K. Pang, D. Ponglux, H. Takayama, S. Horie. Inhibitory effect of mitragynine, an analgesic alkaloid from Thai herbal medicine, on neurogenic contraction of the vas deferens. Life Sci. 26Nov2005;78(2):187-194
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  14. K. Matsumoto, Y. Hatori, T. Murayama, K. Tashima, S. Wongseripipatana, K. Misawa, M. Kitajima, H. Takayama, S. Horie. 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. 7Nov2006;549(1-3):63-70
  15. E. Kumarnsit, U. Vongvatcharanon, N. Keawpradub, P. Intasaro. Fos-like immunoreactivity in rat dorsal raphe nuclei induced by alkaloid extract of Mitragyna speciosa. Neurosci Lett. 12Apr2007 ;416(2):128-132
  16. K.M. Babu, C.R. McCurdy, E.W. Boyer. Opioid receptors and legal highs: Salvia divinorum and Kratom. Clin Toxicol (Phila). Feb2008;46(2):146-152
  17. S. Parthasarathy, J. Bin Azizi, S. Ramanathan, S. Ismail, S. Sasidharan, M.I. Said, S.M. Mansor. Evaluation of antioxidant and antibacterial activities of aqueous, methanolic and alkaloid extracts from Mitragyna speciosa (Rubiaceae family) leaves. Molecules. 9Oct2009;14(10):3964-3974
  18. K. Watanabe, S. Yano, S. Horie, L.T. Yamamoto. 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
  19. S. Chittrakarn, K. Sawangjaroen, S. Prasettho, B. Janchawee, N. Keawpradub. Inhibitory effects of kratom leaf extract (Mitragyna speciosa Korth.) on the rat gastrointestinal tract. J Ethnopharmacol. 28 Feb2008;116(1):173-178
  20. J. Purintrapiban, N. Keawpradub, S. Kansenalak, S. Chittrakarn, B. Janchawee, K. Sawangjaroen. Study on glucose transport in muscle cells by extracts from Mitragyna speciosa (Korth) and mitragynine. Nat Prod Res. 10Oct2008:1-9
  21. S. Tsuchiya, S. Miyashita, M. Yamamoto, S. Horie, S. Sakai, N. Aimi, H. Takayama, K. Watanabe. Effect of mitragynine, derived from Thai folk medicine, on gastric acid secretion through opioid receptor in anesthetized rats. Eur J Pharmacol. 17May2002;443(1-3):185-188
  22. J. Azizi, S. Ismail, M.N. Mordi, S. Ramanathan, M.I. Said, S.M. Mansor. In vitro and in vivo effects of three different Mitragyna speciosa korth leaf extracts on phase II drug metabolizing enzymes--glutathione transferases (GSTs). Molecules. 20Jan2010;15(1):432-441
  23. E. Kumarnsit, N. Keawpradub, W. Nuankaew. Acute and long-term effects of alkaloid extract of Mitragyna speciosa on food and water intake and body weight in rats. Fitoterapia. Jul2006;77(5):339-345
  24. E. Kumarnsit, N. Keawpradub, W. Nuankaew. Effect of Mitragyna speciosa aqueous extract on ethanol withdrawal symptoms in mice. Fitoterapia. Apr2007;78(3):182-185
  25. B. Jerrold, Leikin, B. Robin. McFee Handbook of nuclear, biological, and chemical agent exposures. Boca Raton:CRC Press; 2007.329
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  27. E.W. Boyer, K.M. Babu, J.E. Adkins, C.R. McCurdy, J.H. Halpern. Self-treatment of opioid withdrawal using kratom (Mitragynia speciosa korth). Addiction. Jun2008;103(6):1048-1050.