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Biak

Plant Part Used

Leaves

Active Constituents

indoles, mitragynaline, orynantheidaline, mitragynalinic acid, corynantheidalinic, mitragynaline, speciogynine, speciociliatine, paynantheine, 7alpha-hydroxy-7H-mitragynine, isocorynoxeine, and mitralactonine were isolated. In addition, a porphine derivative, phaeophorbide. (-)-9-methoxymitralactonine, 3-dehydromitragynine and (-)-Epicatechin. (1) , (2) , (3) ,

Introduction

M. speciosa Korth is a tree growing to about 50 feet tall with a spread of over 15 feet and usually is found in the northern part of the Malaysian peninsula. The leaves are simple, large (3 to 20 cm x 2 to 12 cm), decussate and stipulate. The stipules are lanceolate and conspicuous. The blade is coriaceous, elliptic, ovate or obovate, slightly hairy beneath with inconspicuous tertiary nerves, with a pointed apex and round base with several conspicuous secondary nerves. Petiole is slender. Flowers are yellow in a solitary sphere-like shape and have a small head. Each head may bear up to 120 florets. During the flower bud stage, the developing florets are surrounded and completely covered by numerous overlapping bracteoles. The stems are erect and branch out. The tree prefers wet, humusy soils in a protected position. It needs very rich, fertile soil. Propagation is done by very fresh seed or cuttings.

The plants are widely used in folk medicine for self-medication of a variety of conditions and ailments including splenomegaly, worm infestation, provide analgesic effects, and promote wound healing. It is also abused due to its claimed hallucinogenic effects or used in treatment of opium addiction.

Dosage Info

Dosage Range

The leaves of M. speciosa Korth are commonly chewed or a preparation is smoked much like the use of opium to obtain its hallucinogenic effects. The leaves were picked and put out to dry under the sun until they became crisp, then powdered by rubbing between the hands and later stoned to get finer powder. The dose may be set down at 136 grains or 21/2 drams apothecary weight, swallowed either in a cup of cold water or infused with hot water and drunk like tea. Some may boil the dried leaves and this infusion is poured off and evaporated to syrup. It is then mixed with hot water and drunk, or put on the tongue and washed down with water. The dose is 1 hun or 5.85 grains troy. The syrup may also be rolled between the fingers into a pellet that fits the bore of a brass tube attached to one end of a bamboo pipe. The pellet is then heated over a flame and the smoke produced is inhaled via the open end of the pipe. About 20-30 pellets may be smoked in succession. It has also been reported to

Most Common Dosage

The leaves of M. speciosa Korth are commonly chewed or a preparation is smoked much like the use of opium to obtain its hallucinogenic effects. The leaves were picked and put out to dry under the sun until they became crisp, then powdered by rubbing between the hands and later stoned to get finer powder. The dose may be set down at 136 grains or 21/2 drams apothecary weight, swallowed either in a cup of cold water or infused with hot water and drunk like tea. Some may boil the dried leaves and this infusion is poured off and evaporated to syrup. It is then mixed with hot water and drunk, or put on the tongue and washed down with water. The dose is 1 hun or 5.85 grains troy. The syrup may also be rolled between the fingers into a pellet that fits the bore of a brass tube attached to one end of a bamboo pipe. The pellet is then heated over a flame and the smoke produced is inhaled via the open end of the pipe. About 20-30 pellets may be smoked in succession. It has also been reported to

Standardization

Mitragynine is the dominant alkaloid of the plant. The alkaloid content of the leaves of M. speciosa is about 0.5%, and about half is mitragynine. An average leaf weighs about 1.7 gm fresh or 0.43 gm dried. Twenty leaves contain about 17 mg of mitragynine

Toxicities & Precautions

Introduction

Safety in young children, patients with severe liver or kidney disease has not been established.

Side Effects

M. speciosa Korth has not been clinically studied in humans. However, there are reports of acute side effects including dry mouth, increased urination, loss of appetite, and constipation. It does not appear to cause nausea or vomiting. Heavy use can be associated with prolonged sleep. Chronic side effects include anorexia and weight loss, insomnia, and a darkening of the skin, particularly on the cheeks, giving an appearance similar to a hepatic face. Among addicts, 30% report limited sexual desire and the need to use a combination of M. speciosa and alcohol to become sexually stimulated. One study found 5 people who had psychotic conditions which may or may not have been revealed by very heavy M. speciosa use. Addiction seems to be a possibility if high doses are used. Some withdrawal symptoms reported by addicts include hostility, aggression, wet nose, inability to work, flow of tears, muscle and bone aches, and jerky limb movement.

Pregnancy/ Breast Feeding

Women who are pregnant, or who intend to become pregnant and breast-feeding mothers should inform their health care provider if they are using M. speciosa Korth or any medicinal botanicals.

Age Limitations

Safety in young children has not been established.

Pharmacology

Analgesia
Effect of mitragynine, an indole alkaloid isolated from M. speciosa on electrically stimulated contraction was studied in the guinea-pig ileum. Mitragynine (1 mM - 3 mM) inhibited the ileum contraction elicited by electrical stimulation, and its pD2 value was 6.91 ± 0.04 (n = 5). Morphine (1 nM - 1 mM) also inhibited the electrically stimulated contraction in a dose-dependent manner (pD2 7.68 ± 0.11; N = 5). Mitragynine was 10 fold less potent than morphine. Mitragynine (3–10 mM) did not show any effects on the smooth muscle contraction induced by acetylcholine or histamine. Naloxone (10–300 nM) reversed the inhibitory effect of mitragynine on electrically stimulated contraction. Furthermore, naloxone showed a shift of the dose-response curve of mitragynine to the right. There was no significant difference in the affinity of naloxone (i.e. pA2) in the presence of mitragynine or morphine. Mitragynine (3–10 mM) inhibited the naloxone-precipitated withdrawal contraction following a brief (5 min) exposure of the ileum to morphine. Tetrodotoxin (1 mM) and atropine (1 mM) inhibited the withdrawal contraction. The results suggest that mitragynine inhibits the electrically stimulated contraction of guinea-pig ileum through the opioid receptor. (4) Mitragynine pseudoindoxyl, whose analgesic activity may be more potent than that of morphine, were clarified in in-vitro experiments. The essential structural features in mitragynine for revealing the analgesic activity were elucidated by pharmacological evaluation of the natural and synthetic mitragynine derivatives. (5) Results from a local study demonstrated that the extract of M. speciosa Korth exerted a transient dose dependent analgesic effect. In the tail-flick method, the extract (125 mg/kg) produced a reaction time of 11.2 - 2.5 seconds vs. that of morphine (7.5 mg/kg), 13.5 - 2.5 seconds. The extract did not produce a significant increase in reaction time using the hot-plate method. Naloxone, an opioid antagonist, has been shown to block the analgesic effects of M. speciosa Korth in rats via the tai-flick method but not the hot-plate method.

The opioid receptor subtypes involved in the antinociceptive action of mitragynine was determined by studying the effects of selective antagonists for various opioid receptors on antinociception caused by the intracerebroventricular (i.c.v.) injection of mitragynine in the tail-pinch and hot-plate tests in mice. The co-administration of a selective m-opioid antagonist, cyprodime (1–10 mg, i.c.v.) and the pretreatment with a selective m1-opioid antagonist naloxonazine (1–3 mg, i.c.v.) significantly antagonized the antinociceptive activities of mitragynine (10 mg, i.c.v.) and morphine (3 mg, i.c.v.) in the tail-pinch and hot-plate tests. Naltrindole (1–5 ng, i.c.v.), a selective gamma-opioid antagonist, also blocked the effects of mitragynine (10 mg, i.c.v.) without affecting morphine (3 mg, i.c.v.) antinociception. Nor-binaltorphimine, a selective k-opioid antagonist, significantly attenuated mitragynine (10 mg, i.c.v.) antinociception in the tail-pinch test but not in the hot-plate test at the dose (1 mg, i.c.v.) that antagonized the antinociceptive effects of the selective k-opioid agonist U50,488H in both tests, while it had no effect on morphine antinociception in either tests. These results suggest that antinociception caused by i.c.v. mitragynine is dominantly mediated by m- and d-opioid receptor subtypes, and that the selectivity of mitragynine for the supraspinal opioid receptor subtypes differs from that of mitragynine in mice.

Opium addiction
Leaves of M. speciosa have been chewed or prepared in different ways, or smoked to obtain hallucinogenic effects. Although the main alkaloids in M. speciosa are structurally related to psychedelics, there appears to be no psychedelic activity. However, no data is available regarding its pharmacological action for this purpose. (6)

Miscellaneous activity
The fresh leaves of M. speciosa are also pounded and applied directly to wounds. The poultice of the leaves is applied to the upper part of the abdomen to expel worms in children. (7)

Reported Uses

Reported uses included: analgesia, opium addiction, wound healing, and worm infestation.

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  1) Botanical Info

  2) Safety

References

  1. Houghton PJ, Latiff A, Ikram M, Said Saunders MKR. Alkaloids from Mitragyna speciosa. Phytochemistry. 1991;30(1):347-350.
  2. Takayama H, Ishikawa H, Kurihara M, et al. Structure revision of mitragynaline, an indole alkaloid in Mitragyna speciosa. Tetrahedron Letters. 2001;42(9):1741-1743.
  3. Shellard EJ. The alkaloids of Mitragyna with special reference to those of Mitragyna speciosa, Korth. Bulletin On Narcotics. 1974;26(2):41-55.
  4. Thongpradichote S, Matsumoto K, Tohda M, et al. Identification of opioid receptor subtypes in antinociceptive actions of supraspinally-admintstered mitragynine in mice. Life Sciences. 1998;62(16):1371-1378.
  5. Foong TG, Syed Zahir I, Shahimi MM. Kesan Mitragyna Speciosa ke atas rasa sakit, kontraksi ileum tikus belanda dan kebolehannya menyebabkan dependens fizikal. Seventh Annual Scientific Meeting of MASPET. Kuala Lumpur. 1987.
  6. Shellard EJ. The alkaloids of Mitragyna with special reference to those of Mitragyna speciosa, Korth. Bulletin On Narcotics. 1974;26(2):41-55.
  7. 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 Sciences. 1997;60(12):933-942.

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