What is Kratom?

Mitragyna speciosa (kratom) is a tree from the family Rubiaceae (same as coffee) which grows

in Southeast Asia. It is one of 10 species of Mitragyna which grow in tropical and sub-tropical

regions of Africa and Asia. It is used by natives in Thailand and Malaysia as a tonic to combat

fatigue and enhance tolerance to hard work under the scorching sun (Grewal 1932, Takayama

2004, Shellard 1978). It has also been used as a wound poultice and a cure for fever (Burkill

1930). In 1975, a study of 30 Thai kratom users appeared (Suwanlert 1975). Of the mostly older,

married men who had used kratom for 5 years or longer, ninety percent chewed the fresh leaf or

took it as a powder after drying and crushing. The leaves were typically chewed three to ten

times a day with stimulant effects beginning 5 - 10 minutes later. The subjects reported that they

used kratom to "calm the mind" and to help increase their work output. Side effects were listed

as dry mouth, frequent urination, constipation, and weight loss. Kratom use was said to be a

largely a ritualistic, rural phenomenon, with villages accepting only male users who worked to

support their families but not female users.

Until recently, kratom use in the Western world has been largely unknown. With the advent of

the internet; however, kratom is now available at the click of a mouse (Boyer 2008). While

kratom is legal in most of the world except for Australia, Malaysia, Thailand, and Myanmar, the

United States Food and Drug Administration (FDA) does not recognize kratom as a food or drug

product (personal communication). For this reason it is typically sold as incense online.

Although sold "not for human consumption", it is clear from discussion on various internet

forums that the vast majority of kratom users in the United States ingest the herb as a powder or

brew tea from the crushed leaves. Because kratom is not regulated by the FDA, the only quality

control in place is provided by manufacturers and vendors. Many users have expressed concern

about pesticides or other contaminants that may be present in kratom (Kratomforum 2008). Since

many use kratom in lieu of various legal and illegal substances including opiate drugs and

alcohol, the consensus among users is that it is better to risk contaminants in kratom than to go

back to much more addictive and potentially harmful substances. It would be nice to see the

FDA finally admit that kratom has medicinal potential; however, this may be unlikely to happen.

Kratom is an opioid agonist which exhibits interesting pharmacology. It has strong analgesic

(pain relieving) properties, and is often used in place of powerful prescription opiates (Boyer

2008). In small amounts, kratom has a stimulating effect with increased energy, sociability, and a

general sense of well being. This is best described as having the stimulation of a cup of coffee

with the increased sociability and mood lift of a beer or two (without the intoxication). At larger

doses, kratom causes unpleasant effects including nausea and sedation. Because this nausea

typically causes emesis, it is very difficult to overdose on kratom. There have been no known

cases of hospitalization due to kratom. Kratom users tend to take minimal amounts to achieve the

desired effect and avoid nausea experience with higher doses, and the addage "less is more" is a

common mantra (Kratomforum 2008).

The primary alkaloid contained in the leaves of mature kratom trees was first isolated by Hooper

(1907) and again by Field (1921) who named it mitragynine. Although mitragynine, which is

only found in Mitragyna speciosa, is the dominant alkaloid (Table 1) of mature kratom trees, the

leaves of younger trees have a different chemical makeup with speciogynine, mitraphylline,

rhynchophylline, and isorhynchophylline being dominant and mitragynine present in only trace

amounts (Shellard 1974, Shellard 1978). There is also variation between batches of leaf obtained

from different geographical locations; however, mitragynine remains the dominant alkaloid in

mature specimens together with speciogynine and paynantheine. The total alkaloid content of

kratom leaves varies from 0.5% to 1.5% (Iamshaman 2008). Most of the alkaloids in kratom are

yohimbe and Uncaria type indoles and oxindoles.

Table 1. Alkaloid profile of kratom

Mitragynine 66%

analgesic, antitussive,

antidiarrheal, adrenergic,

antimalarial

Paynantheine 9% smooth muscle relaxer

Speciogynine 7% smooth muscle relaxer

7-hydroxymitragynine 2% analgesic, antitussive,

antidiarrheal

Speciociliatine 1% weak opioid agonist

Speciofoline < 1% analgesic, antitussive

Isospeciofoline < 1%

Mitraphylline < 1% immunostimulant, anti-leukemic

Isomitraphylline < 1% immunostimulant

Speciophylline < 1% anti-leukemic

Mitrafoline < 1%

Isomitrafoline < 1%

Rhynchophylline < 1%

vasodilator, antihypertensive,

calcium channel blocker,

antiaggregant, anti-

inflammatory, antipyretic, anti-

arrhythmic, antithelmintic

Isorhynchophylline < 1% immunostimulant

Ajmalicine < 1%

cerebrocirculant, antiaggregant,

anti-adrenergic, sedative,

anticonvulsant, smooth muscle

relaxer

Corynantheidine < 1% opioid agonist

Corynoxeine < 1% calcium channel blocker

Corynoxine < 1% anti-locomotive

Corynoxine B < 1% anti-locomotive

Mitragynine oxindole B < 1%

Ciliaphylline < 1% analgesic, antitussive

Mitraciliatine < 1%

It was oringinally thought that mitragynine, being the primary alkaloid in kratom, was

responsible for the activity of the herb. However, recent studies indicate that 7-

hydroxymitragynine has a much higher activity at opioid receptors compared to mitragynine and

is probably responsible for most of the analgesic activity of kratom (Matsumoto 2004,

Matsumoto 2006). Mitragynine has been found to be much less active as a pain reliever when

administered subcutaneously rather than orally suggesting that it is likely metabolized into 7-

hydroxymitragynine or another more active compound in vivo (Macko 1972). Given it's high

concentration, it is probable that mitragynine also contributes significant activity to the herb.

Since the more stimulating varieties of kratom have a high concentration of mitragynine relative

to other varieties, it may be that mitragynine is responsible for much of the stimulant effect.

There is also evidence of this in the published literature (Grewal 1932). The two remaining

primary alkaloids, paynantheine and speciogynine, act as smooth muscle relaxers. Kratom also

contains lower concentrations of alkaloids similar to those found in Uncaria tomentosa (Cat's

Claw) which have been found to stimulate the immune system, reduce hypertension and lower

blood pressure . Other constituents contribute anti-inflammatory, antioxidant, and anti-cancer

activities.

A resurgence of interest in kratom in the 1960s was spurred by a search for non-opiate

analgesics. Mitragynine is comparable to codeine as an analgesic and cough suppressant;

however, unlike codeine, it did noes cause significant respiratory depression. The opiate-like

addiction syndrome is much less severe, and minimal effect on gastric motility and blood

pressure are noted at analgesic levels (Macko 1972, Boyer 2008). Kratom alkaloids are

chemically unrelated to any known analgesic, and appear to be significantly less toxic. No

evidence of toxicity (tremors and convulsions) was observed after large doses (920 mg/kg) in the

mouse (Macko 1972). In cats, large doses had stimulating effects quantitatively different from

opiates with increased exploratory behavior and without the "fear and rage" complex associated

with opiates. Pre-clinical trials in humans conducted by Smith, Kline and French Laboratories,

revealed unacceptable side effects including nausea and vomiting (Raffauf 1986). Kratom is,

however, well tolerated by a large number of Thai on a chronic basis. Although recent work has

focused on development of analgesic compounds related to mitragynine (Takayama 2002,

Kitajima 2006, United States Patent 1967), further investigation may do well to concentrate upon

the whole leaves rather than on pure mitragynine or other isolated compounds.

While there are a number of non-opiate analgesics, kratom may have a special role as a

replacement for synthetic opiates in addiction treatment programs. Because of kratom's opioid

agonist activity, it is able to greatly reduce the severity of withdrawal symptions for addicts

weaning off of opiate drugs (Takayama 2004, Boyer 2008). While methadone is currently used

for this purpose, it is a powerful drug with the potential to cause additional problems for the

addict. Methadone is typically given out in portions meant to last for weeks which can be

tempting for the recovering addict. Being an opioid agonist, kratom is also potentially addictive.

It is not, however, an opiate and the potential for causing addiction is much lower than for opiate

drugs. Furthermore, although the symptoms of withdrawal experienced with kratom are

qualitatively similar to those of opiates, but are quantitatively much less severe (Boyer 2008).

Thuan (1957) was first to report a case of kratom addiction in the medical literature. A chronic

user was identified who had marked withdrawal syndrome on attempted cessation. Despite his

addiction, the user had never increased his use, did not lose weight, and remained in good health.

He was reported to be mentally and physically "quite normal". Thuan quotes Marcan (1929,

1934) as stating that the kratom habit does not have a bad reputation like opium smoking, nor

does it cause a deterioration of physical condition or emotional character of the addict.

Given this information, we can conclude that kratom should be considered an herbal supplement

with tremendous medicinal potential. Kratom is especially useful for the addict interested in

beating a drug or alcohol habit. It may also have potential in treatment of social anxiety disorder.

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