View source for Kratom

{{Taxobox
| color = lightgreen
| name = Kratom
| image = Kratomtree.jpg
| image_width = 245px
| regnum = [[Plant]]ae
| divisio = [[Flowering plant|Magnoliophyta]]
| classis = [[Magnoliopsida]]
| ordo = [[Gentianales]]
| familia = [[Rubiaceae]]
| genus = ''[[Mitragyna]]''
| species = '''''M. speciosa'''''
| binomial = ''Mitragyna speciosa''
| binomial_authority = [[Korth.]]
}}

'''Kratom''' (''Mitragyna speciosa'') is a medicinal leaf harvested from a large tree native to [[Southeast Asia]] in the Rubiaceae, first documented by [[Dutch Empire|Dutch colonial]] botanist [[Pieter Willem Korthals|Korthals]]. It is botanically related to the [[Corynanthe]], [[Cinchona]] and [[Uncaria]] [[genus|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.

It is a well established [[psychoactive drug]] in its native region and there is some use elsewhere in the world.  In Southeast Asia the fresh leaves are usually chewed, often continuously, by workers or manual laborers seeking a numbing, stimulating effect.  Elsewhere, the leaves are often made into a tea or extracted into water and then evaporated into a tar that can be swallowed.  Kratom is not often smoked, although this method does provide some effect.

Kratom contains many [[alkaloid]]s 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 structurally related to [[yohimbine]] and other [[tryptamines]], its pharmacology is quite different, acting primarily as a mu-opioid receptor agonist. It also shares some adrenergic receptor activity similar to that of yohimbine. Kratom also contains alkaloids found in [[uncaria tomentosa|uña de gato]], which are thought to play a beneficial role on the immune system and lower blood pressure, as well as [[epicatechin]], a powerful antioxidant also found in dark [[chocolate]] and closely related to the [[EGCG]] that gives green [[tea]] its beneficial effects. Other active chemicals in kratom include [[raubasine]] (best known from ''[[Rauwolfia serpentina]]'') and some [[yohimbe]] alkaloids such as [[corynantheidine]].

Kratom has many potential medicinal uses, for example as a low grade analgesic comparable to codeine or propoxyphene, as a cheaper and potentially much safer alternative to [[methadone]], and as a source of other chemicals with a wide range of beneficial activities which could be isolated from the psychoactive constituents.

==Effects==

[[Image:deakratom.jpg|thumb|right|Dried kratom leaf]]
Kratom's pharmacology shares some elements of the activity of other substances including [[opiates]] and [[yohimbine]].  The comparison to opiates is valid at doses high enough to produce these effects.  Kratom has the ability to alleviate withdrawal in people dependent on opiates owing to the mu receptor agonism of [[mitragynine]] and 7-hydroxymitragynine.  Kratom may cause constipation at these doses.  It produces [[analgesia]] similar to weaker opiates such as codeine. Kratom also has a [[yohimbe]]-like stimulant activity, and uncaria-like immunostimulant activity. Kratom's effects are reported to be relatively short-lived, typically fading after a few hours. Some experience nausea after drinking kratom tea; this may in large part be due to the extremely bitter taste which can be remedied with a teaspoon of hot chocolate or cocoa per mug.

==Addiction and Habituation==

Kratom use is potentially habit-forming, and people who abuse it continuously may experience withdrawals upon cessation.  Ethnological researchers conducting a survey of long-time kratom users in Southeast Asia reported a belief that users may develop dark patches of skin discoloration on their cheeks, however there seems no actual documentation of this occurring. No long term human studies have been done, so any assessment of l
ong term consequences of kratom must be extrapolated from animal studies and the few reports from anthropologists.

The potential addictiveness of kratom's primary active component, [[7-hydroxymitragynine]] has been demonstrated in a study by Matsumoto et al. <ref> Matsumoto et al. ''Life Sciences 78'', 2-7. 2004 </ref>  In an animal model, this study demonstrated tolerance, cross-tolerance with morphine, and naloxone-precipitated withdrawal from [[7-hydroxymitragynine]].  The withdrawal symptoms were nearly identical to those from morphine, indicating that the drug might produce dependence in humans similar to other opiates. Anecdotal evidence (see next paragraph) would seem to lend credence to this theory; however, no human research has been done and many of those people reporting addiction are using kratom either as a home remedy for opiate addiction or in conjunction with an ongoing opiate dependence, which makes scientifically definitive claims impossible at this time.

Anecdotal evidence of kratom helping with opiate withdrawal is widespread on the Internet, most often found in various chat forums that are either dedicated to kratom or recreational drug use/abuse in general [http://www.kratomforum.com]. However some people claim that the kratom withdrawal syndrome resembles that of opiates, only milder and shorter-lasting.  Some people have mentioned mild depression following cessation of physical symptoms, and have noted that this makes quitting kratom use very difficult. The physical withdrawal symptoms most often noted are fatigue and agitation. Other opiate-like withdrawal symptoms have been mentioned (e.g. sweating, chills, diarrhea) but are apparently much milder and less common than those caused by withdrawal from opiates, if in fact they appear at all. Physical symptoms of kratom withdrawal seem to last up to four or five days, then cease completely.  Other than the aforementioned depression, protracted withdrawal episodes are rarely mentioned. Kratom appears to be a much safer treatment for opiate withdrawals than the currently prescribed [[Methadone]].

==Minor Alkaloids==

It is interesting to note that whole ''Mitragyna speciosa'' leaf also contains a partial mu-opioid agonist ([[9-hydroxycorynantheidine]]), and a mu-opioid antagonist ([[corynantheidine]]). <ref> Takayama et al.  Journal of Medicinal Chemistry 45, 1949-1956. 2002. </ref>  The combination of a full agonist (such as [[7-hydroxymitragynine]] and [[Mitragynine]]) with an antagonist or partial agonist may be compared to the use of partial opioid-agonists to interrupt opiate addiction.  [[Buprenorphine]] is one such example of a partial agonist/antagonist that is FDA approved to treat addiction.  It may be that ingesting whole kratom does not have the same addictive potential as 7-OHM alone.  

Furthermore, kratom contains at least one alkaloid ([[rhynchophylline]]) that is a calcium channel blocker, and reduces NMDA-induced current.  There is considerable research as to the role of NMDA receptor activity in the formation of dependence, and the symptoms of withdrawal.  In 2005, Inturrisi demonstrated that co-administration of d-methadone (the isomer that lacks opioid activity, but is an NMDA antagonist) in small doses with morphine prevented the development of morphine tolerance in rats. <ref> Inturrisi, CE.  Minerva Anestesiology 71, 435-437.  2005. </ref> The presence of rhynchophylline in kratom should be investigated in order to determine its potential to modify the development of dependence.

==Legal Status==
Kratom is a controlled substance in Thailand, Australia, Malaysia, and Myanmar (Burma). A handful of people in Malaysia and possibly other countries are lobbying their governments to allow medical research into kratom as a potential prescription substance. However as of January 2007, Malaysia is moving to make kratom more illegal rather than less, and plans to reclassify it under the dangerous drugs law rather than the less severe poisonous substances laws.

The U.S. [[Drug Enforcement Administration]] has become aware of kratom in 
recent months, and has added it to their list of [http://www.deadiversion.usdoj.gov/drugs_concern/index.html "Drugs and Chemicals of Concern."]  This list does not appear to indicate anything other than that the DEA has noticed the existence of a substance and [http://www.deadiversion.usdoj.gov/drugs_concern/kratom.htm has come to believe] it may be a problem of some sort.  Of course, the presence of a substance on this list is probably a good indication that it will be scheduled as a controlled substance in the U.S. at some future date (if it isn't already).

== See Also ==
*[[Mitragynine]]
*[[7-hydroxymitragynine]]
*[[Mitraphylline]]

== External links ==
* [http://www.murple.net/yachay/index.php/Kratom Kratom paper by Murple]
* [http://www.erowid.org/plants/kratom/kratom.shtml Erowid Kratom Vault]
* [http://www.sagewisdom.org/kratomguide.html Kratom Users Guide]
* [http://www.entheology.org Entheology.org] Articles, research, and knowledgebase for entheogens and teaching plants

[[Category:Psychoactive drugs]]