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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 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.

Kratom prefers wet, humusy soils in a protected position. Being a heavy feeder, it requires very rich, fertile soil. It is drought sensitive, and if grown out of its native habitat, sensitive to frost. Propagation is by very fresh seed or cuttings. There is a low strike rate, due to an endogenous fungus which attacks xylem tissue.
Over 25 alkaloids have been isolated from kratom. The most abundant alkaloids consist of three indoles and two oxindoles. The three indoles are mitragynine, paynanthine, and speciogynine - the first two of which appear to be unique to this species. The two oxindoles are mitraphylline and speciofoline. Other alkaloids present include other indoles, and oxindoles such as ajmalicine, corynanthedine, mitraversine, rhychophylline, and stipulatine.

Mitragynine is the dominant alkaloid in the plant. It was first isolated in 1907 by D. Hooper, a process repeated in 1921 by E. Field who gave the alkaloid its name. Its structure was first fully determined in 1964 by D. Zacharias, R. Rosenstein and E. Jeffrey. It is structurally related to both the yohimbe alkaloids and voacangine. It is more distantly related to other tryptamine-based psychedelic drugs such as psilocybin or LSD. Chemically, mitragynine is 9-methoxy-corynantheidine. It has the molecular formula C23H30N2O4 and a molecular weight of 398.5. Physically the freebase is a white, amorphous powder with a melting point of 102-106 degrees and a boiling point of 230-240 degrees. It is soluble in alcohol, chloroform and acetic acid. The hydrochloride salt has a melting point of 243 degrees.

The alkaloid content of the leaves of Mitragyna speciosa is about 0.5%, about half of which is mitragynine. An average leaf weighs about 1.7 grams fresh or 0.43 grams dried. Twenty leaves contain approximately 17mg of mitragynine. All leaves appear to contain mitragynine, speciogynine, paynanthine, and small quantities of speciociliatine. Oxindole alkaloids usually occur only in small or trace ammounts.

Alkaloid content varies from place to place and at different times. Within each location, there is a quantitative variation in alkaloid content from month to month. While indole content seems to be fairly stable, oxindole content shows tremendous variation.

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. Use dates far enough back that its beginning can't be determined. 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 tread diarrhea. A small minority of users use kratom to prolong sexual intercourse.

Users distinguish different types of kratom, two main kinds being distinguished by the color of veins in the leaf - red or green/white. The green-veined variety is supposed to have a stronger effect. One study which surveyed Thai kratom users found that most users preferred a mixture of both, followed by red-veined alone and then white-veined alone. Growers in Australia report that both red and white veining occurs at different times in different plants which were all cloned from the same mother plant. They have not yet undertaken comparisons between the two.

Nearly all kratom use is by chewing fresh leaves. Other ways it is taken include grinding up and eating fresh, dried, or reconstituted dried leaves. Some villagers use the leaves in cooking. When preparing fresh leaf, the vein is extracted and sometimes salt is added to try and prevent constipation. Consumption of the leaf is usually followed by drinking something hot, such as warm water or coffee. Leaves can also be smoked, made into a tea, or a crude resin extraction can be made. This resin extract is made by preparing a water extract of the leaves, boiling it down, and then shaping it into small balls which are rolled in a material such as flour, then stored until use. This is apparently a quite popular method of consumption.

Users of kratom tend to be peasants, laborers, and farmers who use the plant to overcome the burdens of their hard work and meager existences. Female users are apparently quite rare. Age of usage onset seems to be higher than for other drugs. Some studies have found no addiction problems in villagers using kratom, while others apparently have. It seems likely that if used in doses high enough for mu receptor crossover (discussed below), addiction is a strong possibility. Heavy users may chew kratom between 3 and 10 times a day. While new users may only need a few leaves to obtain the desired effects, some users find with time they need to increase doses to 10-30 leaves or even more per day.

In some parts of the country, it was said that parents would choose to give their daughters in marriage to men who used kratom rather than men who used marijuana. The belief is that kratom users are hard working, while marijuana users are lazy. This belief is also maintained by many of the users themselves, who report beginning use because of a desire to work more efficiently, and who say using the drug gives them a strong desire to do work.

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.

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. One study found 5 people who had psychotic conditions which may or may not have been revealed by very heavy kratom use. As discussed earlier, 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.

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.

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 conclusion, there seems to be much more research done into this plant and its active constituents. Although kratom has been used since time immemorial by Thai natives, Western science hasn't paid it that much attention. What research does exist contains some apparent conflicts. Knowledge even of the plant's existence outside of Thailand has been limited to ethnobotanists and a handful of pharmacology researchers. Availability of live plants and dried leaves has been practically non-existent until very recently.
There is much to learn.

Credits
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Oxford University Press. "Dictionary of Organic Compounds": Volume 4, 4th edition, 1965.
Rifat, Claude. "Mitragynine": http://www.lycaeum.org/drugs/SSRI/mitragy.html
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Shaman Australis. Personal email from owner: shaman@shaman-australis.com
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