Kratom

Kratom
File:Kratomtree.jpg
Scientific classification
Kingdom:	Plantae
Division:	Magnoliophyta
Order:	Gentianales
Family:	Rubiaceae
Genus:	Mitragyna
Species:	M. speciosa
Binomial name
Mitragyna speciosa Korth.

Kratom (Mitragyna speciosa) is a medicinal leaf harvested from a large tree in the Rubiaceae family native to Southeast Asia. It was first formally documented by the Dutch colonial botanist Pieter Korthals. It is botanically related to the Corynanthe, Cinchona and Uncaria genera and shares some similar biochemistry. It is in the same family as coffee and the psychoactive plant Psychotria viridis. Other species in the Mitragyna genus are used medicinally in Africa, and also used for their wood.

Kratom has been traditionally used for its psychoactive properties in Thailand and Malaysia, although it is now illegal in these countries. In Southeast Asia the fresh leaves are commonly chewed, often continuously, by workers or manual laborers seeking a numbing, stimulating effect. Less commonly, the leaves are decocted or extracted into water and then evaporated into a tar that can be swallowed. Kratom is not often smoked due to the active alkaloids being destroyed by the heat.

Kratom contains many alkaloids including mitragynine (once thought to be the primary active), mitraphylline, and 7-hydroxymitragynine (which is currently the most likely candidate for the primary active chemical in the plant). Although 7-hydroxymitraygynie 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.

Effects

File:Kratom Pills.jpg

Kratom capsules

File:Kratom.jpg

Dried kratom leaf

Kratom's primary pharmacology is mediated by the alkaloids 7-hydroxymitragynine and mitragynine, which share molecular similarities to the alkaloids yohimbine and ibogaine but which act on the brain primarily on opiate receptors. The subjective effects of kratom use are similar to the effects of opiate receptor agonists such as codeine or hydrocodone, and will prevent withdrawal symptoms in an opiate addicted person. Kratom's psychoactive effects typically fade after a few hours. Kratom is traditionally only used in Thailand, although some use in Malaysia has been reported. Besides kratom (or krathom), it also goes by the names ithang, kakuam, and in southern regions, thom. In addition to being used as a narcotic drug in its own right, it is often used as a substitute for opium when opium is unavailable, or to moderate opium addiction. In folk medicine, it is often used to treat diarrhea. A small minority of users use kratom to prolong sexual intercourse.

"While the main alkaloids in kratom are structurally related to psychedelics, there appears to be no psychedelic activity. The dominant effects seem to be similar to opiate drugs, and include analgesia and cough suppression. These effects are roughly comparable in strength to codeine. Mitragynine suppresses opiate withdrawal, but its effects are not reversed by the opiate antagonist nalorphine. These opiate-like effects appear to be mediated mostly by delta and mu opioid receptors. In lower dosages, 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. Interestingly, mu crossover is increased by the presence of opiate drugs. While delta receptor selective opiate drugs have little abuse potential, it seems that they could be used as a primer which would allow mitragynine to more effectively bind to the mu receptor, which mediates the euphoric high produced by narcotics such as morphine.

Other effects of mitragynine are a reduction in smooth muscle tone, local anesthesia, and central nervous system depression. Acute side effects include dry mouth, increased urination, loss of appetite, and constipation coupled with small, blackish stools. Unlike opiates, mitragynine does not appear to cause nausea or vomiting. Heavy use can result in a prolonged sleep.

Side effects from long term use 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 kratom and alcohol to become sexually stimulated. As discussed earlier, addiction seems to be a possibility if high doses are used.

While one study of Thai users reported that it is sedative in low doses changing over to stimulation in higher doses, this seems to be incorrect. Most other sources say that it is a stimulant in lower doses, becoming sedative in higher doses, which is consistent with mitragynine's receptor binding profile. Effects come on within five to ten minutes after use, and last for several hours. The feeling has been described as happy, strong, and active, with a strong desire to do work. The mind is described as calm. The Swiss biologist Claude Rifat experimented with a low dose of three smoked leaves and reported the effects reminded him somewhat of SSRIs, in that it blocked motivation, induced indifference, made doing everything boring, and brought on a strong laziness. It seems likely that these two almost opposite results may be influenced by cultural expectations."

Withdrawal

As with most other opiate receptor agonists, kratom is addictive and withdrawal symptoms may occur after prolonged regular use. At this time, no scientific research has been done on kratom addiction or withdrawal in humans. However, anecdotal reports indicate that this withdrawal is often less severe than from opioids while heavy users may experience a more significant withdrawal syndrome comparable to that from opioids. Withdrawal symptoms can include depression, fatigue, restlessness and insomnia.

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.

Withdrawal from Kratom may range from light to severe. Severe withdrawal from Kratom is not often reported, but suddenly discontinuing use may cause a range of withdrawal symptoms because of the variety of alkaloids and their active strengths.

Cure for Opiate Addiction

Inspired by traditional use, H. Ridley reported In 1897 that the leaves of Mitragyna speciosa were a cure for opium addiction. In more recent times, mitragynine has been used in New Zealand for methadone addiction 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 narcotic addiction. While ibogaine is intended as a one time treatment to cure addiction, mitragynine used to gradual wean the user off narcotics. The fact that mitragynine's mu crossover is increased by the presence of opiate drugs may be exploitable in the treatment of narcotics addiction, 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, the addict would stop use of the narcotic they are addicted to, 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 maintenance drug for addicts not wishing to quit but trying to moderate an out of hand addiction.

In 1999, Pennapa Sapcharoen, director of the National Institute of Thai Traditional Medicine in Bangkok said that kratom could be prescribed both to opiate addicts 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.

Physiology

The most potent leaves generally come from older trees, most of which grow on mildly acidic jungle type soils. Alkaloid content is a function of age, genetics, soil, location, and season. Alkaloid production is highest in late summer and early fall.

Plant description

Kratom trees usually grow to a height of 12–15 ft tall and 15 ft (4.6 m) wide, although under the right conditions, certain species can reach to 40 ft (12 m)–100 ft (30 m) in height tall.

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. The flowers are yellow and grow in clusters.

The kratom tree grows best in wet, humid, fertile soil, with medium to full sun exposure, and an area protected from strong winds.

Kratom refers to the plant Mitragyna speciosa Korth, a tree indigenous to Thailand. It is mostly grown in the central and southern regions of the country, and only rarely in the north. The Mitragyna genus, part of the family Rubiaceae, is found in tropical and sub-tropical regions of Asia and Africa. Asian Mitragynas are often found in rainforests, while the African species (which are sometimes still classed in a separate genus, Hallea) are often found in swamps. Most species are arborescent, some reaching heights of almost 100 feet. The genus was given its name by Korthals because the stigmas in the first species he examined resembled the shape of a bishop's mitre. 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. Mitragyna species are used medicinally as well as for their fine timber through the areas they grow.

Mitragyna speciosa or Kratom itself reaches heights of 50 feet with a spread of over 15 feet. The stem is erect and branching. Flowers are yellow. Leaves are evergreen, and are a dark glossy green in color, ovate-acuminate in shape, and opposite in growth pattern. Kratom is evergreen rather than deciduous, and 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.

Legal status

Kratom is a controlled substance in Thailand, Bhutan, Australia, Finland, Denmark, Poland, Lithuania, Malaysia and Myanmar (Burma).

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 classed in the same enforcement group as cocaine and heroin by Thai law, and has the same penalties. One ounce of extract is punishable by death. As with prohibition laws elsewhere in the world, this has succeeded only at increasing black market prices. 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 mitrajavine, which has not yet been pharmacologically tested.

See also

• Mitragynine
• 7-hydroxymitragynine
• Mitraphylline

References

Notes

• 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
• http://www.deadiversion.usdoj.gov/drugs_concern/index.html
• 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.

External links

• Video Of A Rifat Kratom Tree
• Mitragyna Speciosa Rifatde:Kratom

th:กระท่อม (พืช)