Kratom
Encyclopedia
Kratom Mitragyna speciosa, is a medicinal leaf harvested from a large tree in the Rubiaceae
family native to Southeast Asia
in the Indochina
and Malesia
floristic regions. The plant has been traditionally used for its medicinal properties.
It was first formally documented by the Dutch colonial
botanist Pieter Korthals
. The genus was given its Mitragyna name 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 Corynanthe, Cinchona
and Uncaria
genera
and shares some similar biochemistry.
The flowers are yellow and grow in clusters. This genus is characterized by a globular flowering head, bearing up to 120 florets each. During the flower bud stage, the developing florets are surrounded and completely covered by numerous overlapping bracteoles.
Kratom leaves are constantly being shed and being replaced, but there is some quasi-seasonal leaf shedding due to environmental conditions. During the dry season of the year leaf fall is more abundant, and new growth is more plentiful during the rainy season.
When grown outside their natural tropical habitat, leaf fall occurs with colder temperatures, around 4 degrees Celsius. The kratom tree grows best in wet, humid, fertile soil, with medium to full sun exposure, and an area protected from strong winds. There are two different strains of Kratom: White Vein and Red Vein Kratom. Though frequently located in the same areas, some places have an excess of white vein trees while others have an excess of red vein trees. For example, Borneo has more red vein Kratom and Sumatra has more white vein Kratom. Though used interchangeably by many, the two strains have different alkaloid makeups and can produce different effects.
s including mitragynine
(once thought to be the primary active constituent), mitraphylline
, and 7-hydroxymitragynine
(which is currently the most likely candidate for the primary active chemical in the plant). Although 7-hydroxymitragynine and mitragynine are structurally related to yohimbine
and other tryptamines, their pharmacology is quite different, acting primarily as mu
-opioid receptor
agonists. Other active chemicals in kratom include raubasine (best known from Rauwolfia serpentina
) and some yohimbe alkaloids such as corynantheidine.
Kratom's primary pharmacology is mediated by the alkaloids 7-hydroxymitragynine
and mitragynine
. While these molecules share structural similarities to the psychedelics, there is no psychedelic activity or similarities in effects to such substances. Instead these alkaloids primarily interact with the opioid receptors. Accordingly, kratom is known to prevent or delay withdrawal symptoms in an opiate dependent individual, and it is often used to mitigate cravings thereafter. It can also be used for other medicinal purposes.
Kratom has been traditionally used in regions such as Malaysia, Thailand, and Indonesia, but was discovered by Western civilization during the 19th century. Besides Kratom, in Southeast Asia and the Pacific Islands it also goes by the names krathom, ithang, biak biak, ketum, kakuam, and in southern regions, thom. In these areas kratom has a history of use by laborers and in folk medicine for opium dependence and diarrhea.
Of the two main active constituents, mitragynine has been studied more thoroughly than 7-hydroxymitragynine. At lower doses, Mitragynine exhibits a yohimbine-like binding to alpha-adrenergic receptors, as well as some binding to the delta opioid receptors. As doses increase, binding to delta receptors increases, and in yet higher doses, crossover to mu receptors occurs.
7-hydroxymitragynine was only recently understood to be the main active ingredient. Limited animal research suggests it is a potent opiate agonist, but with a ceiling effect that limits the potential for respiratory depression and euphoria. No fatal overdose of kratom is known to have occurred.
One study of Thai users reported that kratom has subtle calming effects in low doses, changing over to mild stimulation in higher doses. Other anecdotal sources say that it may be a mild, caffeine-like stimulant in lower doses, but decreases the effect in higher doses, which is consistent with mitragynine's receptor binding profile. However, recent publications indicate that different alkaloids may be at work to achieve mild stimulation versus sedation: whereas higher concentrations of mitragynine are attributed to act as a anti-stimulant, 7-hydroxymitragynine appears to be a significant alkaloid for reducing stress associated with opiod craving. Effects come on within five to ten minutes after use, and last for several hours, depending on individual physiognomy.The feeling has been described as subtly active, while the mind is described as calm.
Side effects, although rare, may include dry mouth, increased or decreased urination, loss of appetite, and nausea or vomiting. Possible side effects from long term use include anorexia and weight loss, insomnia, and dependence. Comprehensive scientific and clinical studies have yet to be conducted to establish the potential health risks associated with consistent long term consumption of kratom.
Kratom has recently become more known and used in Europe
and North America
where it has been prized for its applications to many conditions and ailments, primarily pain, depression, anxiety, and opiate withdrawal.
Although chemically similar, ibogaine and mitragynine work by different pathways, and have different applications in treatment of drug dependence. While ibogaine is intended as a treatment for opiate craving, mitragynine is used to gradually wean the user off opiates. The fact that mitragynine's mu crossover is increased by the presence of opiate drugs may be exploitable in the treatment of drug dependence, because it directs binding to where it is needed, automatically regulating the attachment ratio and modulating it towards the delta receptors over a short time. Within a few days, or months, a person dependent on opiates would stop use of opiates, and the cravings and withdrawal will be moderated by the binding of mitragynine to the delta receptors. Mitragynine could also perhaps be used as a substitution or maintenance drug to manage dependence. In Southern Thailand, many heroin users have been using kratom to break their dependence and to manage craving symptoms.
In 1999, Pennapa Sapcharoen, director of the National Institute of Thai Traditional Medicine in Bangkok said that kratom could be prescribed both for opiate dependence and to patients suffering from depression, but stressed that further research is needed. Chulalongkorn University chemists have isolated mitragynine which researchers can obtain for study.
In 1897 Ridley reported the leaves and bark of Mitragyna speciosa as a cure for the opium habit and this was quoted by Hooper (1907) In 1907 Holmes had referred to the leaves and possibly, the leaves of M. parvifolia as well, as an opium substitute. Certainly the leaves of M. speciosa have been chewed for many years under the local name 'kratom' by the native population of Thailand as a stimulant though the practice is now forbidden. As a consequence the leaves of M. javanica are frequently used as a substitute but are not considered to be as effective. The natives will also distinguish between different kratoms, for example, those with red and those with green midribs (Tantivatana, 1965).
Mitragynine was the only constituent isolated from Mitragyna speciosa it was assumed to be the physiologically active constituent having morphine-like properties, Grewel (1932) reported to be a protozoal poison but in 1933 Raymond-Hamet and Millat undertook a more critical examination and reported it to have markedly depressant properties. This was substantiated in 1934 by Masson. More recently Macko, Weisbach and Douglas (1972) reported that mitragynine possesses pain threshold elevating and antitussive properties but no addictive properties.
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Rubiaceae
The Rubiaceae is a family of flowering plants, variously called the coffee family, madder family, or bedstraw family. The group contains many commonly known plants, including the economically important coffee , quinine , and gambier , and the horticulturally valuable madder , west indian jasmine ,...
family native to Southeast Asia
Southeast Asia
Southeast Asia, South-East Asia, South East Asia or Southeastern Asia is a subregion of Asia, consisting of the countries that are geographically south of China, east of India, west of New Guinea and north of Australia. The region lies on the intersection of geological plates, with heavy seismic...
in the Indochina
Indochina
The Indochinese peninsula, is a region in Southeast Asia. It lies roughly southwest of China, and east of India. The name has its origins in the French, Indochine, as a combination of the names of "China" and "India", and was adopted when French colonizers in Vietnam began expanding their territory...
and Malesia
Malesia
Malesia is a biogeographical region straddling the boundaries of the Indomalaya ecozone and Australasia ecozone, and also a phytogeographical floristic region in the Paleotropical Kingdom.-Floristic province:...
floristic regions. The plant has been traditionally used for its medicinal properties.
It was first formally documented by the Dutch colonial
Dutch Empire
The Dutch Empire consisted of the overseas territories controlled by the Dutch Republic and later, the modern Netherlands from the 17th to the 20th century. The Dutch followed Portugal and Spain in establishing an overseas colonial empire, but based on military conquest of already-existing...
botanist Pieter Korthals
Pieter Willem Korthals
Pieter Willem Korthals was a Dutch botanist. Korthals was the official botanist with the Dutch East India Service from 1831 to 1836....
. The genus was given its Mitragyna name 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 Corynanthe, Cinchona
Cinchona
Cinchona or Quina is a genus of about 38 species in the family Rubiaceae, native to tropical South America. They are large shrubs or small trees growing 5–15 metres in height with evergreen foliage. The leaves are opposite, rounded to lanceolate and 10–40 cm long. The flowers are white, pink...
and Uncaria
Uncaria
Uncaria is a genus of flowering plants in the family Rubiaceae. It has about 40 species. Their distribution is pantropical, with most species native to tropical Asia, three from Africa and the Mediterranean and two from the neotropics. They are known colloquially as Gambier, Cat's Claw or Uña de...
genera
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...
and shares some similar biochemistry.
Description
Mitragyna speciosa, kratom trees, usually grow to a height of 12–30 ft (3.7–9.1 m) tall and 15 ft (4.6 m) wide, although under the right conditions, certain species can reach up to 40 ft (12.2 m)–100 ft (30.5 m) in height. The stem is erect and branching. The leaves of the kratom tree are a dark green colour and can grow to over 7 inches (177.8 mm) long and 4 inches (101.6 mm) wide., ovate-acuminate in shape, and opposite in growth pattern.The flowers are yellow and grow in clusters. This genus is characterized by a globular flowering head, bearing up to 120 florets each. During the flower bud stage, the developing florets are surrounded and completely covered by numerous overlapping bracteoles.
Kratom leaves are constantly being shed and being replaced, but there is some quasi-seasonal leaf shedding due to environmental conditions. During the dry season of the year leaf fall is more abundant, and new growth is more plentiful during the rainy season.
When grown outside their natural tropical habitat, leaf fall occurs with colder temperatures, around 4 degrees Celsius. The kratom tree grows best in wet, humid, fertile soil, with medium to full sun exposure, and an area protected from strong winds. There are two different strains of Kratom: White Vein and Red Vein Kratom. Though frequently located in the same areas, some places have an excess of white vein trees while others have an excess of red vein trees. For example, Borneo has more red vein Kratom and Sumatra has more white vein Kratom. Though used interchangeably by many, the two strains have different alkaloid makeups and can produce different effects.
Alkaloids
Kratom contains many alkaloidAlkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
s including mitragynine
Mitragynine
Mitragynine, an indole alkaloid, is the most abundant active alkaloid in the plant Mitragyna speciosa, commonly known as Kratom.-Pharmacology:...
(once thought to be the primary active constituent), mitraphylline
Mitraphylline
Mitraphylline, an oxindole derivative, is an active alkaloid in the leaves of the trees Mitragyna Speciosa, commonly known as Kratom. As a non-narcotic constituent, it also occurs to a significant amount in the bark of Uncaria tomentosa, Cat’s Claw, along with a number of isomeric alkaloids...
, and 7-hydroxymitragynine
7-Hydroxymitragynine
7-Hydroxymitragynine , an indole, is an active alkaloid in the plant Mitragyna speciosa, commonly known as Kratom. It has opioid agonistic activity. "The potency, calculated using pD values, was 30- and 17-fold higher than that of mitragynine and morphine, respectively...
(which is currently the most likely candidate for the primary active chemical in the plant). Although 7-hydroxymitragynine and mitragynine are structurally related to yohimbine
Yohimbine
Yohimbine is an alkaloid with stimulant and aphrodisiac effects found naturally in Pausinystalia yohimbe . It is also found naturally in Rauwolfia serpentina , Alchornea floribunda , along with several other active alkaloids...
and other tryptamines, their pharmacology is quite different, acting primarily as mu
Mu Opioid receptor
The μ-opioid receptors are a class of opioid receptors with high affinity for enkephalins and beta-endorphin but low affinity for dynorphins. They are also referred to as μ opioid peptide receptors. The prototypical μ receptor agonist is the opium alkaloid morphine; μ refers to morphine...
-opioid receptor
Opioid receptor
Opioid receptors are a group of G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostatin receptors...
agonists. Other active chemicals in kratom include raubasine (best known from Rauwolfia serpentina
Rauwolfia serpentina
Rauvolfia serpentina, or 'snakeroot' or 'sarpagandha' is a species of flowering plant in the family Apocynaceae.-Medicinal uses:It is one of the 50 fundamental herbs used in traditional Chinese medicine, where it has the name shégēn mù or yìndù shémù .Rauwolfia serpentina contains a number of...
) and some yohimbe alkaloids such as corynantheidine.
Effects
7-Hydroxymitragynine
7-Hydroxymitragynine , an indole, is an active alkaloid in the plant Mitragyna speciosa, commonly known as Kratom. It has opioid agonistic activity. "The potency, calculated using pD values, was 30- and 17-fold higher than that of mitragynine and morphine, respectively...
and mitragynine
Mitragynine
Mitragynine, an indole alkaloid, is the most abundant active alkaloid in the plant Mitragyna speciosa, commonly known as Kratom.-Pharmacology:...
. While these molecules share structural similarities to the psychedelics, there is no psychedelic activity or similarities in effects to such substances. Instead these alkaloids primarily interact with the opioid receptors. Accordingly, kratom is known to prevent or delay withdrawal symptoms in an opiate dependent individual, and it is often used to mitigate cravings thereafter. It can also be used for other medicinal purposes.
Kratom has been traditionally used in regions such as Malaysia, Thailand, and Indonesia, but was discovered by Western civilization during the 19th century. Besides Kratom, in Southeast Asia and the Pacific Islands it also goes by the names krathom, ithang, biak biak, ketum, kakuam, and in southern regions, thom. In these areas kratom has a history of use by laborers and in folk medicine for opium dependence and diarrhea.
Of the two main active constituents, mitragynine has been studied more thoroughly than 7-hydroxymitragynine. At lower doses, Mitragynine exhibits a yohimbine-like binding to alpha-adrenergic receptors, as well as some binding to the delta opioid receptors. As doses increase, binding to delta receptors increases, and in yet higher doses, crossover to mu receptors occurs.
7-hydroxymitragynine was only recently understood to be the main active ingredient. Limited animal research suggests it is a potent opiate agonist, but with a ceiling effect that limits the potential for respiratory depression and euphoria. No fatal overdose of kratom is known to have occurred.
One study of Thai users reported that kratom has subtle calming effects in low doses, changing over to mild stimulation in higher doses. Other anecdotal sources say that it may be a mild, caffeine-like stimulant in lower doses, but decreases the effect in higher doses, which is consistent with mitragynine's receptor binding profile. However, recent publications indicate that different alkaloids may be at work to achieve mild stimulation versus sedation: whereas higher concentrations of mitragynine are attributed to act as a anti-stimulant, 7-hydroxymitragynine appears to be a significant alkaloid for reducing stress associated with opiod craving. Effects come on within five to ten minutes after use, and last for several hours, depending on individual physiognomy.The feeling has been described as subtly active, while the mind is described as calm.
Side effects, although rare, may include dry mouth, increased or decreased urination, loss of appetite, and nausea or vomiting. Possible side effects from long term use include anorexia and weight loss, insomnia, and dependence. Comprehensive scientific and clinical studies have yet to be conducted to establish the potential health risks associated with consistent long term consumption of kratom.
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
and North America
North America
North America is a continent wholly within the Northern Hemisphere and almost wholly within the Western Hemisphere. It is also considered a northern subcontinent of the Americas...
where it has been prized for its applications to many conditions and ailments, primarily pain, depression, anxiety, and opiate withdrawal.
Opiate dependence
Inspired by traditional use, H. Ridley reported In 1897 that the leaves of Mitragyna speciosa were a cure for opium dependence. In more recent times, mitragynine has been used in New Zealand for methadone dependence detox. Kratom was smoked whenever the patient experienced withdrawal symptoms, over a 6 week treatment period. Patients reported a visualization effect taking place at night in the form of vivid hypnagogic dreams. While working on plans for ibogaine experiments in the USA, Cures Not Wars activist Dana Beal suggested that mitragynine could be used as an active placebo for comparison in the study. Acting Deputy Director of the NIDA Charles Grudzinskas rejected the proposal, however, saying that even less was known about mitragynine than ibogaine.Although chemically similar, ibogaine and mitragynine work by different pathways, and have different applications in treatment of drug dependence. While ibogaine is intended as a treatment for opiate craving, mitragynine is used to gradually wean the user off opiates. The fact that mitragynine's mu crossover is increased by the presence of opiate drugs may be exploitable in the treatment of drug dependence, because it directs binding to where it is needed, automatically regulating the attachment ratio and modulating it towards the delta receptors over a short time. Within a few days, or months, a person dependent on opiates would stop use of opiates, and the cravings and withdrawal will be moderated by the binding of mitragynine to the delta receptors. Mitragynine could also perhaps be used as a substitution or maintenance drug to manage dependence. In Southern Thailand, many heroin users have been using kratom to break their dependence and to manage craving symptoms.
In 1999, Pennapa Sapcharoen, director of the National Institute of Thai Traditional Medicine in Bangkok said that kratom could be prescribed both for opiate dependence and to patients suffering from depression, but stressed that further research is needed. Chulalongkorn University chemists have isolated mitragynine which researchers can obtain for study.
In 1897 Ridley reported the leaves and bark of Mitragyna speciosa as a cure for the opium habit and this was quoted by Hooper (1907) In 1907 Holmes had referred to the leaves and possibly, the leaves of M. parvifolia as well, as an opium substitute. Certainly the leaves of M. speciosa have been chewed for many years under the local name 'kratom' by the native population of Thailand as a stimulant though the practice is now forbidden. As a consequence the leaves of M. javanica are frequently used as a substitute but are not considered to be as effective. The natives will also distinguish between different kratoms, for example, those with red and those with green midribs (Tantivatana, 1965).
Mitragynine was the only constituent isolated from Mitragyna speciosa it was assumed to be the physiologically active constituent having morphine-like properties, Grewel (1932) reported to be a protozoal poison but in 1933 Raymond-Hamet and Millat undertook a more critical examination and reported it to have markedly depressant properties. This was substantiated in 1934 by Masson. More recently Macko, Weisbach and Douglas (1972) reported that mitragynine possesses pain threshold elevating and antitussive properties but no addictive properties.
Legal status
Kratom is a controlled substance in Thailand, Bhutan, Australia, Finland, Denmark, Poland, Latvia, Lithuania and Sweden (Mitragynin) as of September, 1, 2011. Malaysia and Myanmar (Burma). In Malaysia, kratom is scheduled under the Poisons Act.Thailand
The Thai government passed the Kratom Act 2486 which went into effect on August 3, 1943. This law makes planting the tree illegal and requires existing trees to be cut down. This law was not found effective, since the tree is indigenous to the country. Today, kratom is scheduled in category 5 of the Narcotics Acts (1979), in the same category as cannabis and magic mushrooms (the least punitive category). A related species, Mitragyna javanica, is often used as a substitute to get around the law, but it is not considered as effective. The dominant alkaloid in this species is mitragynine, which has not yet been pharmacologically tested.Canada
Although kratom has not been approved by Health Canada for human consumption, it currently does not fall under the purview of the Controlled Drugs and Substances Act thus, remaining largely unregulated.Other References
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Further reading
- K. M. Babu, Ch. R. McCurdy, E.W. Boyer: Opioid receptors and legal highs: Salvia divi-norum and Kratom, Clinical Toxicology * 46, 146-152
- E.W. Boyer, K. M. Babu, G. E. Macalino, W. Compton, Self-Treatment of Opioid With-drawal with a Dietary Supplement, Kratom, The American Journal on Addictions, 16: 352-356, 2007
- E.W. Boyer, K. M. Babu, J. E. Adkins, Ch. R. McCurdy, J. H. Halpern, Self-treatment of opioid withdrawal using kratom (Mitragynia speciosa korth), Addiction, 103 *. 1048-1050, 2008
- K. S. Grewal, Observations on the pharmacology of mitragynine, J Pharmacology and Experimental Therapeutics 1932, 46:251-71 und K. S. Grewal, The Effect of Mitragynine on Man, British Journal of Medical Psychology 1932, 12: 41-58
- http://www.usdoj.gov/dea/programs/forensicsci/microgram/mg0306/mg0306.pdf
- S. Suwanlert, A study of kratom eaters in Thailand, UNODC – Bulletin on Narcotics Vol. 27*: 21-27, 1975
- Jansen, Prast Psychoactive properties of mitragynine (kratom), Journal of Psychoactive Drugs 1988, 20*-457
- Hiromitsu Takayama: Chemistry and Pharmacology of Analgetic Indole Alkaloids from the Rubiaceous Plant, Mitrgyna speciosa; Review; Chem. Pharm. Bull. 52* 916-928 *
- Suchitra Thongpradichote, et al.: Identification of opioid receptor subtypes in antino-ciceptive actions of supraspinally-administered mitragynine in mice; Life Sciences, Vol. 62, No. 16, Seite 1371-1378, 1998
- UNITED NATIONS OFFICE ON DRUGS AND CRIME, Vienna, BULLETIN ON NARCOTICS, Volume LVII, Nos. 1 and 2, 2005, S. 249-256, UNITED NATIONS New York, 2007
- Aekajit Chaiyawong: “Drugs Situation and the Drugs Information System in Thailand”, Global Workshop on Drug Information Systems: Activities, Methods and Future Oppor-tunities, Wien, 3.-5. Dezember 2001, unterstützt durch das “United Nations International Drug Control Programme under the Global Assessment Programme on Drug Abuse” (GAP). United Nations, New York, 2002, Weitere Informationen sind auf der GAP Inter-netseite www.undcp.org zu finden.