Mitragyna speciosa

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

Kratom (Thai: กระท่อม), 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.^{[clarification needed]} The plant has been traditionally used for its medicinal properties.^{[clarification needed]} 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.

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 m)–100 ft (30 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 (180 mm) long and 4 inches (100 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. ^{[citation needed]}

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.

Alkaloids

Kratom contains many alkaloids 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).^[1] 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.^[2]

Uses

Kratom's primary pharmacology is primarily 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.^[1] 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.

Combating 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.^[3]

Safety

In its natural form, kratom appears to be relatively safe. While dependence to its opioid effects is known to occur with frequent use, serious respiratory depression and life-threatening adverse events are almost unheard of. Highly concentrated extracts of the alkaloids may be more hazardous than the unprocessed leaf, however, and kratom may potentially cause additive effects if mixed with sedatives such as alcohol. As with any substance that is ingested, adulteration or contamination is also a risk. In Europe branded kratom illegally laced with undisclosed synthetic opioid agonists such as O-desmethyltramadol have been reported. One brand that contained a mix of several different substances rather than natural kratom was linked to the deaths of nine people in Sweden during 2010-2011. ^[4]^[5]^[6]^[7]^[8]^[9]

Regulations

Kratom is a controlled substance in Thailand, Malaysia, Myanmar, Bhutan, New Zealand, Australia, Finland, Denmark, Poland, Latvia, Lithuania and Sweden (Mitragynin)as of writing.^[10] ^[11] ^[12]

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.

References

^ ^a ^b Chittrakarn 2010, p. 344., "Over 25 alkaloids have been isolated from kratom leaves with mitragynine being the most dominant (Chittrakarn et al., 2005)... 7-Hydroxymitragynine has a more potent analgesic activity than that of morphine (Matsumoto et al., 2004)."
^ Takayama et al. 2002
^ Macko E, Weisbach JA, Douglas B. Some observations on the pharmacology of mitragynine. ARCHIVE OF INTERNATIONAL PHARMACODYNAMICS AND THERAPEUTICS. 1972; 198(1):145-61. PMID 20411370
^ Nelsen JL, Lapoint J, Hodgman MJ, Aldous KM. Seizure and coma following Kratom (Mitragynina speciosa Korth) exposure. Journal of Medical Toxicology. 2010 Dec;6(4):424-6. PMID 20411370
^ Arndt T, Claussen U, Güssregen B, Schröfel S, Stürzer B, Werle A, Wolf G. Kratom alkaloids and O-desmethyltramadol in urine of a "Krypton" herbal mixture consumer. Forensic Science International. 2011 May 20;208(1-3):47-52. PMID 21112167
^ Bäckstrom BG, Classon G, Löwenhielm P, Thelander G. Krypton--new, deadly Internet drug. Since October 2009 have nine young persons died in Sweden. (Swedish). Lakartidningen. 2010 Dec 15-21;107(50):3196-7. PMID 21294331
^ Kronstrand R, Roman M, Thelander G, Eriksson A. Unintentional fatal intoxications with mitragynine and O-desmethyltramadol from the herbal blend Krypton. Journal of Analytical Toxicology. 2011 May;35(4):242-7. PMID 21513619
^ Kapp FG, Maurer HH, Auwärter V, Winkelmann M, Hermanns-Clausen M. Intrahepatic cholestasis following abuse of powdered kratom (Mitragyna speciosa). Journal of Medicinal Toxicology. 2011 Sep;7(3):227-31. PMID 21528385
^ Adkins JE, Boyer EW, McCurdy CR. Mitragyna speciosa, a psychoactive tree from Southeast Asia with opioid activity. Current Topics in Medicinal Chemistry. 2011;11(9):1165-75. PMID 21050173
^ http://www.lakemedelsverket.se/Alla-nyheter/NYHETER-2011/8-nya-amnen-narkotikaklassade/
^ http://www3.lrs.lt/pls/inter3/dokpaieska.showdoc_l?p_id=328773
^ http://www.likumi.lv/doc.php?mode=DOC&id=50539

Citations

Chittrakarn S, Keawpradub N, Sawangjaroen K, Kansenalak S, Janchawee B (2010). "The neuromuscular blockade produced by pure alkaloid, mitragynine and methanol extract of kratom leaves (Mitragyna speciosa Korth.)". J Ethnopharmacol. 129 (3): 344–9. doi:10.1016/j.jep.2010.03.035. PMID 20371282. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

Adkins JE, Boyer EW, McCurdy CR (2010). "Mitragyna speciosa, a Psychoactive Tree from Southeast Asia with Opioid Activity". Curr Top Med Chem. 11 (9): 1165–75. PMID 21050173. {{cite journal}}: |access-date= requires |url= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

Takayama H, Ishikawa H, Kurihara M, Kitajima M, Aimi N, Ponglux D; et al. (2002). "Studies on the synthesis and opioid agonistic activities of mitragynine-related indole alkaloids: discovery of opioid agonists structurally different from other opioid ligands". J Med Chem. 45 (9): 1949–56. doi:10.1021/jm010576e. PMID 11960505. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)