Botany
Kratom refers to the plant Mitragyna speciosa Korth., a tree indigenous to
Thailand, Malaysia, Indonesia and Papua New Guinea. In Thailand, kratom 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 (coffee family),
is found in tropical and sub-tropical regions of Asia and Africa. Botanically
and chemically, kratom is closely related to yohimbe. Other relatives include
cat's claw, with which it shares several active chemicals, coffee and cinchona
(the source of quinine). Asian species of Mitragyna are often found in
rainforests, while the African species (which are sometimes still classed in a
separate genus, Hallea) are often found in swamps. In the past, plants in this
genus have been classified under the genera Nauclea, Sarcocephalus, Stephegyne
and Uncaria. Most species are arborescent, some reaching heights of almost 100
feet. The genus was given its name by Pieter Willem Korthals, official botanist
with the Dutch East India Service from 1831 to 1836, because the flower stigmas
in the first species he examined resembled the shape of a bishop's miter. 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 throughout the areas they
grow, for example the West African species M. inermis and M. stipulosa are
effective traditional remedies against malaria, the former having also been
shown by modern science to fight leukemia. Another species, M. africanus, is
used in Nigeria to treat mental illness. The African species M. ciliata (aka M.
ledermanni, M. stipulosa, Hallea ciliata, Hallea ledermanni or Hallea stipulosa)
is used traditionally to treat inflammation, hypertension, headache, rheumatism,
gonorrhea and broncho-pulmonary diseases.
Grove of kratom in Thailand
Mitragyna speciosa itself reaches heights of 50 feet with a branch spread of
over 15 feet. The stem is erect and branching. Flowers are yellow and grow in
ball-shaped clusters, as previously mentioned. Leaves are a dark glossy green in
color, smooth, ovate-acuminate in shape, and opposite in growth pattern. Leaves
can grow over 7 inches long and 4 inches wide. 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° Celsius.
Kratom prefers wet, humusy soils in a protected position, often growing in
swampy areas. Anecdotal reports from growers in Australia indicate that it
prefers partial shade and does not like strong winds, although others report
good results growing it in full sun. 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. In addition to propagation by cuttings, kratom has been cloned by tissue
culture. The first plant grown in this way was planted in February 2002 by
Christian Rätsch and Claudia Müller-Ebeling at Wandjina Gardens (http://www.wandjina.net.au/)
in Australia. Thais believe that seed grown kratom plants are not reliable and
that half of the plants grown from seed of a good kratom tree will be worthless
as a drug plant. Whether this is true or folklore has not been scientifically
investigated, but the same observation was reported by Ben of the Botanical
Preservation Corps.
Kratom flower
In recent years, kratom has been successfully cultivated outside of Thailand
from seeds and then frequently cloned. Most plants available outside of Asia are
clones, as seeds have only a short period of viability. There are several clone
strains worth mentioning. The best known clone is the Robert Rifat Clone. This
plant was originally grown in research funded by Shaman Australis from seed
collected from a research institution in Thailand by the Swiss scientist Claude
Rifat. The parent plant has been used in several research studies, and
presumably is the Chulalongkorn University tree used in the Chiba University
research. The Rifat Clone has a reputation for being especially strong, and is
the most widely available clone outside of Asia. Another clone to come out of
Shaman Australis' research was the Craig's Clone. This plant was grown from Thai
seed collected by Craig White in 1999 from trees which local residents said were
their preferred kratom plants. Craig's Clone was never developed into a
commercial strain out of deference to Rob Montgomery and the Botanical
Preservation Corps, among others, who were developing plants in the USA from the
same batch of seeds. Tissue cultures of the plant were put into storage medium,
but after 5 years the last of these became unrecoverable and this clone is now
lost. However, as previously stated, other researchers in the US were able to
grow plants from the same seed collection, which reportedly included
approximately 100 seeds which were distributed to a variety of botanists and
collectors. Among these are KRW 1 through 4 grown by Rick Warren, which were
used in biochemical analysis work by Daniel Siebert. A plant was also grown from
a cutting sent by Craig White to Jim Bauml of the Los Angeles Arboretum.
Finally, there is the Bumblebee Clone, which was grown by a Spiritplants member
named Bumble from seeds of Vietnamese origin.
Kratom seeds
Although not scientifically studied yet, there is anecdotal evidence that
indicates kratom grown in climates which are cooler than their native habitat
tend to produce weak leaves. In warmer subtropical climates, there seems to be
some seasonal variability, with more potent leaves growing from late summer
through autumn and weak leaves in winter and spring. Greenhouse grown plants are
reportedly also not very potent. Whether this indicates a relationship between
temperature and alkaloid production or is even consistently true has not been
thoroughly researched, but it seems likely this is the case.
A related species, Mitragyna javanica, is reportedly used as a substitute to get
around the Thai laws banning kratom, but it is not considered as effective. The
dominant alkaloid in this species is mitrajavine, which has not yet been
pharmacologically tested.
Chemistry
7-Hydroxymitragynine
Mitragynine
Over 25 alkaloids have been isolated from kratom, most of which are yohimbe-type
indoles and oxindoles. 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, akuammigine, corynanthedine,
mitraversine, rhynchophylline, speciociliatine (also unique to kratom) and
stipulatine. Working with Malay plants, Houghton and Said found new types of
indole alkaloids (mitragynaline, corynantheidaline, mitragynalinic acid, and
corynantheidalinic acid), in very young leaves. Those alkaloids were reported as
having an unusual skeleton, having a carbon function at the C14 position
(compared with previously known monoterpenoid indoles), but Takayama et al.
later revised the structure of mitragynaline and corynantheidaline, showing that
there was no substitution on the 14 position.
Mitragynine is the most abundant alkaloid in the plant, and for this reason was
long assumed to be the major chemical responsible for the effects of kratom. It
was first isolated in 1907 by David Hooper, a process repeated in 1921 by E. J.
Field, who gave the alkaloid its name. Its structure was first fully determined
in 1964 by D. Zacharias, R. Rosenstein and E. Jeffrey. It was not until 1995
that H. Takayama et al. at Chiba University were able to synthetically produce
mitragynine. It is structurally related to both the yohimbe alkaloids and
voacangine. It is more distantly related to tryptamine-based psychedelic drugs
such as psilocybin, ibogaine or LSD. Chemically, mitragynine is
9-methoxy-corynantheidine. It has the molecular formula C23H30N2O4 and a
molecular weight of 398.49. Physically the freebase is a white, amorphous powder
with a melting point of 102-106°C and a boiling point (bp5) of 230-240°C. It is
soluble in alcohol, chloroform and acetic acid. The hydrochloride salt has a
melting point of 243°C. It appears that it may be a fairly stable compound, as a
mitragynine ethane disulphonate reference sample tested after fourteen years by
TLC produced results not substantially different from fresh mitragynine picrate.
Alkaloid content varies from place to place and at different times, leading
Shellard et al. in the 1970s to conclude that there may be different
geographical variants within the species. Within each location, there is a
quantitative variation in alkaloid content from month to month as well. The
alkaloid content of the leaves of Mitragyna speciosa has been reported as 0.5%
to 1.5% in dried leaf. An average leaf weighs about 1.7 grams fresh or 0.43
grams dried.
The Pharmacognosy Research Laboratories at Chelsea College collected thirty
samples of kratom from Malaysia, Thailand, and Papua New Guinea between 1961 and
1970. All contained mitragynine, but beyond that there was considerable
variation. The most common profile in Thai plants was mitragynine, speciogynine,
speciociliatine, paynantheine, traces of ajmalicine, traces of (C9)
methoxy-oxindoles, and traces of other indoles. This same profile was found in
both red and green petioled plants. Other Thai plants contained different
profiles, some with many more alkaloids. Of the Malay specimens, one contained
mitragynine, speciofoline, and other indoles and oxindoles. The other contained
mitragynine, ajmalicine, speciogynine, speciociliatine, paynantheine, traces of
indoles, and (C9) methoxy-oxindoles. The Papua New Guinea specimen contained
mitragynine, speciogynine, speciociliatine, paynantheine, specionoxeine, and
isospecionoxeine.
Takayama et al. found that Thai and Malay kratom had in common the alkaloids
mitragynine, speciogynine, speciociliatine, paynantheine and
7-hydroxymitragynine. In both samples, mitragynine was the most abundant
alkaloid, but in the Thai kratom it made up 66% of the total alkaloid, while it
made up only 12% of the alkaloids from the Malay sample. The Malay sample had
mitragynaline and pinoresinol as major components, as well as mitralactonal,
mitrasulgynine and 3,4,5,6-tetradehydromitragynine.
Beginning in the late 1990s, a group of researchers based out of Chiba
University in Japan and Chulalongkorn University in Thailand began researching
natural and synthetic analogues of mitragynine in search of new drugs with
potential medicinal use. These studies have led to discoveries which have turned
much of what was believed about kratom on its head. Results of a
structure-activity relationship study published in 2002 helped to clarify the
essential structural moieties in the Corynanthe type indole alkaloids required
for opioid agonistic activity. Two oxidative derivatives of mitragynine,
mitragynine pseudoindoxyl and 7-hydroxymitragynine, have been of particular
interest.
Mitragynine pseudoindoxyl was first created in 1974 when a team of researchers
led by Zarembo used the fungus Helminthosporum sp. to biotransform mitragynine
and reported it to have 10 times the anti-nociceptive activity of mitragynine. A
study conducted by the Japanese and Thai researchers previously mentioned has
been found it to be a more potent analgesic than morphine by weight, and to act
by way of mu and delta opioid receptors. Nevertheless, in a mouse tail-flick
test, it demonstrated only weak anti-nociceptive activity compared to morphine.
More important is the research on 7-hydroxymitragynine (or mitragynine
hydroxyindolenine), which is a naturally occurring minor alkaloid (around 2% of
total alkaloids) first mentioned in a paper published in 1994. In a series of
papers beginning in 2001, it has also been shown to be highly selective for mu
receptors and is more potent by weight than morphine. Eventually, it occurred to
the researchers that given the low potency of mitragynine, even though it is the
most abundant alkaloid in the plant it can not account for the effects of kratom.
Bioassays indicated that mitragynine was a much weaker anti-nociceptive than
kratom extracts. Starting with crude extracts of kratom and moving then to five
isolated alkaloids, it was found that 7-hydroxymitragynine is the most likely
candidate for the chief agent of kratom's activity. It is thirty to forty-six
times more potent than mitragynine and seventeen times more potent than morphine
by weight. Antagonism by naloxone was used to confirm opioid-like activity of
this alkaloid. Given that nearly all the chemical studies of kratom have been
done on the assumption that mitragynine was the most important alkaloid, and
that nearly all pharmacological research prior to the late 1990s was done on
mitragynine or crude plant material, this discovery likely means that much of
what we believe about kratom will need to be revised.
Traditional Use
Kratom vendor in Malaysia
Traditional use in Thailand dates back far enough that its beginning can't be
determined. Kratom was first mentioned to in Western literature by Low in 1836,
who wrote that people in Malaysia would use it as a substitute when opium was
unavailable or unaffordable. In 1895, E. M. Holmes identified kratom as
Mitragyna speciosa, and again referred to its use as an opium substitute. In
1907, L. Wray described methods of use such as smoking, chewing, and tea. Hoping
that the active chemical could be discovered and analyzed for medical use, Wray
also sent leaf samples of kratom and its relative Mitragyna parvifolia to the
University of Edinburgh, and it was from these leaves that Field isolated
mitragynine (and from M. parvifolia, mitraversine).
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. In 1930, I. H.
Burkill wrote that kratom was also used as a poultice for wounds and as a cure
for fevers.
Thai and Malay users distinguish different types of kratom, two main kinds being
distinguished by the color of veins in the leaf - red or green (sometimes called
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. Researchers from collected both red
and green veined samples in November 1962. Both were listed as having the same
alkaloids, but the paper published by E. J. Shellard did not list
concentrations, nor was there any mention of what is now believed to be the most
important alkaloid, 7-hydroxymitragynine.
Nearly all kratom use in Thailand 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 and as a stimulant
to help endure long days working in the fields. Female users are apparently
quite rare, perhaps because of the association of kratom with labor in cultures
where women tend to have more domestic roles. 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 have. Based on the pharmacology of kratom,
it seems addiction is a strong possibility with long term use. 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 Thailand, 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.
Making air ketum
Although mostly associated with Thailand (many earlier texts even indicate that
kratom use is limited to that country), kratom is also used in Malaysia, where
it is known as ketum. It is commonly sold at roadside booths in the form of a
tea called air ketum ("kratom water") which usually sold for 1 ringgit per cup
when legal and 2 ringgit since banned. A kilogram of leaf averaged 10 ringgit
when legal, and has gone up to around 16 ringgit since banned. The Malay version
of kratom tea is made by boiling leaves in water for two hours. This is often
cooled by placing the boiling pot into a bucket of cold water, giving the drink
a chill haze which is considered by some visually appealing, although it is
likely that the process of chilling serves the more practical purpose of keeping
the hot liquid from melting the plastic cups and bags the drink is sold in.
According to Dr. Ahmad Mahmud, deputy director of enforcement at the
Pharmaceuticals Services Division of Malaysia's Health Ministry, children as
young as 13 have been buying air ketum from village stalls. "From what we gather
from the sellers, the students are buying them before school and during their
breaks," he said, adding, "Some codeine addicts are also drinking it to get
high." These statements were made to a reporter from the Singaporean New Paper
newspaper for an anti-drug article, so that context should be considered before
assuming there is an actual epidemic of childhood kratom addiction in Malaysia.
The same article quotes Azwira Hassan, a kratom vendor from Kedah, as saying he
boiled 20 kilograms of leaf per day and sold 250 to 300 air ketum drinks from
that. Mr. Azwira also commented that some users felt thirsty after drinking it,
and therefore would drink more kratom.
Kratom is used in Malaysia in similar ways as in Thailand, including chewing,
teas, and smoking. An article entitled "How Ketum Is Abused," which was
published in a Malay newspaper in 2005, mentioned several unusual methods of
use, stating, "Another not so palatable-sounding process is mixing it with dried
cow dung and tobacco, rolling it into a cigarette and smoking it. The leaves can
also be mixed with dried coconut, ginger, onions, nutmeg and lime and rolled
with daun kaduk (wild pepper leaf) and chewed like daun sirih (beetle nut
leaves)." The betel-like preparation is quite plausible, but whether people in
Malaysia are actually smoking cow feces or this is an attempt at propaganda is
an issue for the reader contemplate for themselves. In addition to use as a
psychoactive drug, traditional Malay healers also use the plant for de-worming,
to improve blood circulation, as an energizing tonic, as a cough suppressant and
to treat symptoms of diabetes. A 1994 study by the Health Ministry indicated
that many people had used it to get off of morphine or heroin (although
continuing to use kratom). It has also been grown as an ornamental tree.
While kratom grows naturally throughout Southeast Asia, there is little evidence
of its use in other places where it grows. Myanmar has made it illegal, which
presumably indicates at least some use there, but little is known of its role in
Burmese culture. There is reportedly no tradition of kratom use in Indonesia.
Its status in other countries such as Papua New Guinea, Vietnam, Laos or
Cambodia is unknown.
Pharmacology
While the main alkaloids in kratom are structurally related to psychedelics,
their activity is radically different. The dominant effects seem to be similar
to opioid drugs, and include analgesia and cough suppression. Unlike opioids,
the cough suppression effect of mitragynine does not come packaged with emesis
and dyspnoea (difficulty breathing). Respiratory depression is also much less
than with codeine. In a 1988 paper by Jansen and Prast it was reported that
mitragynine was not antagonized by nalorphine, leading to confusion as to
whether kratom did or did not act in a manner similar to opioids. However,
kratom suppresses opiate withdrawal and its effects are reversed by opiate
antagonists such as naloxone, cyprodime, naltrindole, naloxonazine and
nor-binaltorphimine, showing that opioid receptor activity is clearly a major
element of kratom's effects. Interestingly, while naloxone antagonizes the
analgesic effects of kratom in the tail-flick test, it does not reverse
analgesia in the hot plate test. Kratom alkaloids are very effective pain
killers, and work well when taken orally. These effects are roughly comparable
in strength, but not necessarily in quality, to codeine. These opiate-like
effects appear to be mediated mostly by delta and mu opioid receptors, and this
activity is selective for supraspinal opioid receptors (in mice, at least).
12 grams of cold water extracted kratom resin, approximately 7X
According to the Micromedex Poisindex database, a 50mg of pure mitragynine
produces motor excitement, giddiness, rombergism (a swaying of the body or
falling when standing with the feet close together and the eyes closed; the
result of loss of joint position sense), and tremors of the face, extremities
and tongue. On the other hand, E. Macko noticed no evidence of toxicity such as
tremors or convulsions at doses as high as 920mg/kg in dogs. In cats, Macko
found that high doses had stimulating effects unlike unlike those from opiates.
There was increased exploratory behavior, without the "fear and rage complex"
opiates produce.
Mitragynine also exhibits a yohimbine-like binding to alpha-adrenergic
receptors. Stimulation of postsynaptic alpha-2-adrenoceptors, blockade of 5-HT2A
receptors, or both, are involved in mitragynine's suppression of 5-HT2A mediated
head-twitch response in mice. It has been speculated that mitragynine's activity
at 5-HT2A receptors may suppress the activity of psychedelic drugs, which are
agonists at these receptor sites.
Other effects of mitragynine are a reduction in smooth muscle tone, local
anesthesia, and central nervous system depression. Acute side effects may
include dry mouth, increased urination, loss of appetite, and constipation
coupled with small, blackish stools. As with morphine, mitragynine decreases
2-deoxy-D-glucose-stimulated gastric acid secretion. This may have an anorexic
effect and may be involved in the weight loss reported by some Thai users.
Unlike opiates, mitragynine does not appear to cause nausea or vomiting in
normal doses. Heavy use can result in a prolonged sleep, although many people
find it stimulating and find sleep difficult.
One study has found that mitragynine has anti-malarial activity (Gombak A
strain, IC50 below 16 m g/ml). This same study investigated mitragynine's safety
by testing for cytotoxicity against Madin-Darby bovine kidney (MDBK) cells and
human erythrocytes. No toxicity to uninfected erythrocytes was detected at
concentrations of up to 50mg/ml or in the MDBK cells at up to 64mg/ml.
The alkaloid thought to be the primary active drug in kratom,
7-hydroxymitragynine, interacts with all three major opioid sites, delta, kappa,
and mu, but bound preferentially to mu receptors with pKi values of 8.01 ±0.03.
The relative affinities of 7-hydroxymitragynine for delta, kappa and mu
receptors were 5.6% and 4.6%, and 89.8% respectively. Most research that has
been done on kratom has focused on mitragynine or the whole plant, and since it
has only recently been discovered that 7-hydroxymitragynine is the primary drug,
there is still relatively little information on its activity and what
differences it may have from mitragynine.
Of the other alkaloids in kratom which have been tested, corynantheidine shows
no opioid agonistic activity, but shows a concentration-dependent antagonism of
morphine inhibited twitch contraction in guinea pig ileum (intestinal tissue).
It also does not affect either the atropine or verapamil inhibited twitch
contraction. It selectively binds to mu-opioid receptors, so it appears that it
is a competitive mu opioid antagonist. Another alkaloid,
9-hydroxycorynantheidine, also binds selectively to mu receptors, but it does
inhibit twitch contraction, although with a maximum percentage lower than
mitragynine. It is believed to be a partial agonist at mu receptors. Comparing
the activity of mitragynine, corynantheidine, and 9-hydroxycorynantheidine, it
appears that the C9 position is critical in determining the activity of this
group of alkaloids. Mitragynine with a methoxy substituent is a full agonist,
9-hydroxycorynantheidine has a hydroxy substituent and is a partial agonist,
while coryntantheidine has a hydrogen atom and is an antagonist. Another
alkaloid in kratom, speciociliatine, shows a 13-fold decrease in opioid activity
relative to mitragynine, and inhibits guinea pig ileum twitch contraction in a
naloxone-insensitive manner. The alkaloids speciogynine and paynantheine also
inhibit twitch contraction in a naloxone-insensitive manner, as well as
inhibiting contraction induced by direct stimulation of muscarinic receptors on
ileal smooth muscle.
Kratom also contains several Uncaria alkaloids which are also found in the South
American medicinal plant cat's claw. The most dominant one in kratom is
mitraphylline, which has shown activity as a vasodilator and lowers blood
pressure. It is also a myorelaxant (muscle relaxer). One study has shown that it
increases memory retention performance in animals treated with amnesic drugs. It
also acts as a diuretic. While there is some question as to whether or not it
shares the ability of several other Uncaria alkaloids to enhance the activity of
phagocytes, it is proven that the stereoisomer isomitraphylline, which is also
present in kratom, does have this property. Isomitraphylline also has shown
cytotoxic activity against some strains of cancerous cells (HL-60 and U-937
leukemia). Isopteropodine, an Uncaria alkaloid present in kratom, has been shown
to be the most effective immunostimulant of this group of alkaloids.
Rhynchophylline also lowers blood pressure by blocking the voltage-dependent
calcium and potassium channels, dilating peripheral blood vessels, and lowering
heart rate. It also has antiarrhythmic properties, lowers cholesterol and
prevents blood clots by inhibiting platelet aggregation and thrombosis. It also
has anti-inflammatory and anti-pyretic properties. Speciophylline (also known as
uncarine-D) has shown cytotoxic activity against leukemic cells like
isomitraphylline, slightly less effectively against HL-60 and more effective
against U-937. Rotundifoline is another Uncaria alkaloid found in kratom, but
its activities, if any, are not yet clearly understood. Corynoxine A and
corynoxine B reduce locomotor activity in mice, which appears to be due to
mediating activity in the dopaminergic system. Corynoxeine (not to be confused
with corynoxine A and B) is an oxindole, and has verapamil-like calcium channel
antagonist.
The alkaloid ajmalicine (also called raubasine), which is also found in Indian
snakeroot (Rauvolfia serpentina) and Madagascar periwinkle (Catharanthus
roseus), has multiple pharmacological activities. It inhibits platelet
aggregation by means of an inhibitory action on the release reaction of the
platelets. It increases oxygen availability in the brain, which has led to its
use in cognitive disorders in the elderly and in stroke ischemia, especially in
a drug combination with almitrine marketed as Duxil. It has sedative and
anticonvulsive properties due to agonist activity at the [3H]flunitrazepam
benzodiazepine receptor. It also acts as an antiadrenergic by blocking
alpha-1-adrenergic receptors, which makes ajmalicine lower blood pressure and
act as a diuretic by relaxing smooth muscle. Another indole which kratom shares
with Madagascar periwinkle is tetrahydroalstonine, which has been shown to lower
blood sugar levels and acts as a blocker at the alpha-2-adrenergic receptors.
One final chemical worth mentioning is (-)-epicatechin. This polyphenol, the
cis-isomer of catechin, is closely related to the well-known EGCG. This chemical
is also found in green tea, cranberry juice and dark chocolate, and has a wide
array of beneficial activities. It reduces free radicals in the blood, thereby
reducing cancer risks, and is a powerful antioxidant which helps prevent fat
cells from oxidizing and clogging arteries. It helps treat urinary tract
infections by impairing bacteria's ability to stick to the cell walls of the
urinary tract. Epicatechin is used by many diabetics due to a variety of
beneficial properties. It mimics insulin and protects erythrocytes in a similar
manner. It also inhibits alpha-amylase, preventing the digestion of starch into
absorbable glucose. It also keeps blood sugar levels lower by inhibiting
intestinal glucose absorption. Epicatechin also has demonstrated ability to
inhibit growth of pathogenic bacteria such as E. coli and staph. It also has
anti-viral properties and inhibits the ability of virii to enter and infect
cells.
Many of these secondary chemicals in kratom are present in small quantities,
and their role in the overall pharmacology of kratom are not yet fully
understood. It seems likely that kratom is much more than a simple narcotic.
Research into the pharmacology of this plant and its chemicals is still in its
early stages.
The pharmacology of kratom and mitragynine was first explored by K. S. Grewal at
the University of Cambridge in 1932. He observed that mitragynine seemed to act
as a stimulant in both animal tissues and a group of five male volunteers.
Grewal noted the use of kratom by laborers and falsely concluded that
mitragynine acted like cocaine. This led to a mistaken notion that circulated
for some time that kratom acted like a mixture of opium and cocaine. This was
also stated by Norakanphadung Prayun in the "Thai Narcotic Book" published 1966.
Grewal also reported claims that addicts were thin, had distended stomachs,
unhealthy complexions, dark lips and dry skin.
So far, few in depth study of kratom's use and abuse have been conducted. The
first and best known was the 1975 study by Dr. Sangun Suwanlert of thirty long
term users in Thailand. These subjects 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. Suwanalert's subjects reported effects come on within five to ten
minutes after use, and last for several hours. The feeling was been described as
happy, strong, and active, with a strong desire to do work. The mind was
described as calm.
Some ethnographic studies in Thailand have reported 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 those described as addicts, 30% report limited sexual desire and the
need to use a combination of kratom and alcohol to become sexually stimulated.
Suwanalert's study found 5 people who had psychotic conditions which may or may
not have been revealed by very heavy kratom use.
A second study was conducted by the Malaysian Ministry of Health in 1994.
This study surveyed 54 people who had been using kratom for 1 to 20 years.
Nearly all (94.3%) had been former users of opioids or marijuana who switched to
kratom. Users reported withdrawal when trying to stop kratom, but pointed out
that the withdrawal was much less severe than with opioids. Medical tests showed
the users to all be healthy and that biochemical tests showed no significant
differences from the normal references ranges.
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. The first formal report of a case of addiction was
reported in 1957 by L. C. Thuan. The man had withdrawal symptoms when trying to
go without kratom, but otherwise was physically and mentally "quite normal,"
remaining in good health, maintaining a normal weight, and never increasing his
use level. A. Marcan likewise reports that kratom use in Malaysia was very
common, but did not have a bad reputation and that addicts did not show any
change in their character or physical health.
The Swiss biologist Claude Rifat experimented with a low dose of three smoked
leaves. He found the results unimpressive: "What I observed, subjectively, more
or less reminds the effects of the serotonin re-uptake blockers, such as
zimelidine or fluvoxamine. Mitragynine, mainly, blocks motivations and induce
indifference, together with a strong sense of laziness! Everything becomes
boring to do." Given the usual dose ranges reported by kratom users, it seems
probable that this dose was insufficient to produce anything more than placebo
or threshold activity.
With the increased availability of kratom outside of Asia, it has become
possible to collect much new data on the effects. This is interesting because
many of these new users are from Western cultures and therefore it is now
possible to gather data free from traditional cultural beliefs and without going
through the filter of ethnobotanical research papers. There is now a wide body
of first hand reports from people who have used kratom, and it is now possible
to use this data to get a clearer understanding of the effects of this plant and
to resolve some of the inconsistencies and errors in earlier research conducted
only in kratom's indigenous environment. For the most part, however, effects
reported by non-native users are in line with earlier reports. Most use is oral,
in the form of teas or swallowed extracts. Doses reported depend on the quality
of kratom used (which seems to have considerable variability) and tolerance of
the user, but range from 5 or less grams to 20 grams. Effects reported are often
compared to opioids, although there are subjective differences. Effects come on
within 10 to 20 minutes and continue to build for up to an hour after
consumption. The primary effects generally seem to last for 3 to 6 hours,
although some users report lingering stimulant or sedative effects for a few
hours more.
Regarding side effects, very few are reported in normal doses, with the
exception of occasional insomnia or constipation (which is considerably less
pronounced than with opioids). In unusually high doses, or when novice users
take doses which would be considered moderate to high in experienced users, some
unpleasant side effects do occur. Most common is nausea, occasionally with
vomiting. A sensation of heat or sweating is sometimes reported. Dizziness,
vertigo, and nystagmus can occur. There is at least one report of some sort of
hallucinogenic or deliriant activity with a very high dose (nearly double what
an experienced user might take, taken by a first time user).
Medical Applications
Small kratom plant in Indonesia
Several possible uses for kratom, its alkaloids, and synthetic derivatives are
worthy of investigation.
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 reportedly been used in New Zealand for methadone addiction
detox. This treatment in New Zealand is mentioned first in The Ibogaine Story,
but no other references to this treatment are available, and it seems likely it
never existed. According to the story, 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. In the Australian National Drugs and
Poisons Schedule Committee's meeting notes on kratom, after mentioning that the
NDPSC received a comment regarding the New Zealand story, there is a note
reading, "A member advised there are no listings for either mitragynine or
Kratom being used in a clinical study or as a registered product in New
Zealand." The concluding paragraph of Jansen and Prast's 1988 article in the
Journal of Ethnopharmacology states: "kratom may have a special role as a
replacement for methadone in addiction treatment programs." Jansen and Prast
were based out of the University of Auckland in New Zealand, so a likely
explanations is that Beal simply misinterpreted the article.
Although chemically similar, ibogaine and the kratom alkaloids 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, kratom
alkaloids may be used to gradually wean the user off narcotics. Kratom or its
derivatives 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 either case,
kratom serves in a manner similar to methadone or buprenorphine, as a substitute
narcotic. The advantages of kratom are that it is legal in most countries and
that anecdotal evidence indicates that it is both safer and easier to withdraw
from. Whether or not this is actually true needs to be confirmed by controlled
scientific research. In the mean time, people seeking to use kratom in a
self-administered treatment for narcotics addiction need to be aware that kratom
is potentially addictive itself, and that if used irresponsibly, certainly will
not provide a pathway to a drug-free life. Kratom certainly has potential in
addiction therapy as a slow detox or long term maintenance drug, but unlike
ibogaine, is not seen as offering a cure.
One potential advantage of kratom over currently used opioids is the array of
secondary chemicals such as ajmalicine, epicatechin and the Uncaria alkaloids.
These chemicals have a variety of medicinal properties, including antioxidant
activity, cardiovascular benefits, and ability to fight off various viral and
bacterial infections and to act as immune stimulants. This gives kratom
advantages over opioid narcotics in several applications. If used as a
replacement for codeine as a cough suppressant, the immune enhancing properties
would offer potential benefits in helping fight off whatever infection is
causing the coughs. Used as a mild pain killer in people recovering from
injuries or surgeries, the immune enhancing properties could also help reduce
the chance of infections in the site of the injury or operation. Used as a
replacement for methadone or buprenorphine, the various health benefits of the
secondary kratom chemicals could help the addict recover from the poor health
that is often seen in long term drug abusers. While more research is required to
find out how effective these minor drugs in kratom are, it is certain that
opioid narcotics do not have these properties at all. The potential advantages
certainly merit further investigation of kratom as an alternative to opioids. It
would also be worthwhile to research the possibility of extracting the
non-narcotic chemicals from kratom and developing them into medicines.
In the early 1970s, the pharmaceutical company Smith, Kline and French
Laboratories researched mitragynine, including pre-clinical trials in humans. In
a personal letter to Karl Jansen in 1986, R. Raffauf indicated that this
research was discontinued because of unacceptable acute side effects of some
kind. Meeting notes from the mitragynine scheduling hearings in Australia note:
"It has been speculated that a possible reason for this is the different
pharmacological profiles of pure mitragynine and the unprocessed leaf, the
latter containing several other alkaloids that may modify the effects of the
pure drug." After being contacted by the Committee, GlaxoSmithKline (the modern
incarnation of the company), said they did not object to scheduling in
Australia, presumably indicating a lack of any further interest in developing
medicines from kratom.
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, and that any potential use of kratom in treating
addicts needs to be part of a holistic approach, saying, "We have to pay
attention not only to the medicine itself but also to the application process."
She said the current laws against kratom make investigation of kratom as a
medicine difficult, but Viroj Sumyai, director of the Thai Food and Drug
Administration's narcotics control division has denied that the law banned the
use of kratom in research, adding that Chulalongkorn University chemists have
isolated mitragynine which researchers can obtain for study. Material from
Chulalongkorn University has been used in the extensive research based out of
Chiba University in Japan. Samlee Chaidee, of Chulalongkorn University's
pharmacy department, said the herb was a part of country life before the state
stepped in, and that studies have shown villagers using it did not have problems
with addiction. All parties have stressed the need for further research.
In Malaysia in 2005, Dr. Mustafa Ali Mohd, Associate Professor at the Universiti
Malaya, Pharmacology Department, announced his desire to study the effects of
kratom use, pointing out that the only in depth study of kratom users has been
Suwanalert's research on thirty Thai users in 1975. Unfortunately, since
Malaysia made it illegal, the police have been cutting down trees. While Mohd
and other scientists have been publicly upset over this campaign, Deputy
Internal Security Minister Datuk Noh Omar was quoted saying that unless the
scientists can find people to guard every tree to prevent youth from using the
leaves to get high, the police should be allowed to chop them down. ACP Nooryah
Md Anwar of the Royal Malaysian Police’s Narcotic Department at Bukit Aman has
countered that planting kratom is not illegal under the Section 30 (3) of the
Poisons Act, and that the police do not have the authority to cut down trees.
Nooryah said, “If it is a drug, it is a drug. We would like to have it listed
under the Dangerous Drugs Act as that gives us more power and governs even the
planting of the tree. We have observed that the dosage and frequency of use have
gone up.” Dr. Mohd believes that kratom has medicinal applications such as use
in weaning addicts off opioids. Professor Datuk Ikram Said of Univeristi
Kebangsaan Malaysia believes kratom alkaloids can also be turned into useful
medical pain killers, anti-inflammatories, cough medicines, and treatments for
diarrhea. Since the plant is indigenous to Malaysia, these scientists believe
development of kratom-derived drugs could save the country millions of ringgit
in imported drug costs. A national committee to investigate kratom has been
formed in Malaysia.
First Hand Reports
Freshly picked kratom leaf with green ("white") petiole
Most reports from kratom users are positive.
A person calling themselves Lightwarden wrote a summary of their experiences
with kratom. Doses under 10 grams were compared to a mild caffeine type
stimulant. With doses in the 10-15 gram range, "the wonders of this miracle
plant are revealed." Lightwarden says the initial effects start in around about
ten minutes after drinking the tea, and describes it by saying, "The buzz is
characterized by waves of pleasure running through my limbs, particularly in my
extremities. After about a half an hour to 45 minutes, the buzz strengthens
considerably." The description continues, "It is very euphoric, and makes my
body feel wonderful. It also seems to reduce pain by a lot, or at least make me
care less about it. I should mention that smoking cannabis, especially out of a
bong or other high-powered water pipe, is nearly a must for me, as it synergizes
extremely well. The full effects last for about two hours, and then the pleasant
after-effects, which for me are mostly just like a reduced version of the full
effects, last for another couple of hours generally." The writer has experience
with opioids and reports kratom has fewer side effects. The author goes on to
mention some other miscellaneous observations, for example, "although some
people have stated that they enjoy a little alcohol with their kratom, I find
that to be a bad combination personally, as both times I have tried I ended up
with less euphoria, more dizziness, and a minor headache." The writer also
mentions a friend who had an oxycodone and hydrocodone addiction who was using
kratom to get off the opioids.
Kratom leaf with red petiole
A writer going by the name sepulfreak indicates that using the Rifat strain, low
doses of 1.5-2 grams produce stimulation and mild perceptual changes and
euphoria. At 4 grams, more narcotic type effects become dominant. With doses of
6-6.5 grams, the writer indicates medicinal potential, indicating, "I have
actually used it for back pain before, and it worked better than any reasonable
dose of a pharmaceutical Opiate/Opioid I've used." Contrasting kratom to
opioids, sepulfreak says, "With other Opiates/Opioids, I feel like I'm always
trying to hide something or use them as some sort of escape, but this seems to
actually help me through things. I get some empathy and heart opening happiness
that causes me to talk about personal issues. Unlike other Opiates/Opioids, I
don't feel like it was for nothing the next day. There is somewhat of an Opiate
hangover, though I don't crave and feel the detox. I feel satisfied." Having
tried it at a higher dose, 9 grams, some effects not associated with opioids
were manifested. "My vision was extremely distorted, and there was actually a
mild hallucinogenic effect. The trees seemed to sway a bit, and my sense of
vision was enhanced. Colors seemed brighter, and the euphoria was beyond
powerful. I was really warm, and I just layed in the autumn leaves in the middle
of a beautiful hollow in the woods. There were lots of large Red and White Oak
trees around the area too. I felt a strong connection with nature. I felt unity
and admiration of God's creation." The writer points out that there was some
mild, opioid-like nausea at the higher doses though. In conclusion, the author
says kratom "is a good pain reliever, it motivates the mind and body for work
and study, and gives me a profound sense of well being."
Many people did not get quite so positive experiences, yet did not have negative
experiences either. These people find kratom uninteresting or only slightly
positive or negative.
Writing under the name sile na gig, one user tried kratom twice, feeling mildly
positive effects, but also some nausea the second time. In conclusion, "Frankly,
it's more trouble than just rolling a spliff and getting stoned. I'd rather find
something as user-friendly as pot without the risk of it being detected in a
urine test."
Cactushead found the experience moderately enjoyable, but overrated, saying,
"For the money, it’s probably not worth it though. Honestly, I can’t believe
that this is illegal in some parts of the world. The effects are noticeable, but
certainly not anything that would impair a person, or become addictive." In
conclusion, "I have mixed feelings about Kratom. The positive side is that at
the peak of the experience, this really is a good opiate substitute (without
many of the negative aspects of opiates.) However, the peak lasted only about a
half hour; so between the mild nausea and the expensive price, I’d say that this
isn’t something I’ll purchase again. It certainly has the feel of an opiate,
although there is something missing. I didn’t find Kratom to be as euphoric as
traditional opiates, but I think it is also much less likely to be addictive.
While it was worth a try, I would not consider buying it again unless I could
find a cheaper source."
Red veined kratom
Virtually all of the negative reports involving kratom involve either large
doses, multi-drug combinations, or addictive use.
One report by an inexperienced user going by the name Jesper likens a 15 gram
dose to an "instant hangover" characterized by nausea, dizziness, nystagmus, and
a sensation of heat. Jesper concluded, "I think I’ll stick with the illegal
drugs for a while since they seem to be much safer and reliable than any legal
ones."
One user, using the pseudonym f, reported taking a dose of 23 grams of kratom on
the first try. This resulted in rapid heartbeat, severe nausea, a sensation that
everything was rapidly moving around and through his or her person, and some
sort of hallucinogenic activity. The report says, "I had to close my eyes, and
began to hallucinate somewhat. The hallucinogenic aspect to this was not like
other psychedelics. I had powerful visual impressions in a way, and they were
vivid, but I didn't exactly see them. It was more that I had the feeling that I
was seeing them and experiencing them, very hard to explain. But the scenarios I
was perceiving were getting stranger and much faster. Finally the nausea was
just way too much, and I sprinted to the bathroom projectile vomiting. This was
now probably 90 minutes into the experience. I was in the bathroom for 1-2
hours, vomiting and heaving, unable/willing to move. The body feeling was
related to the feeling of an anxiety attack or the onset of a bad trip, although
I didn't literally feel anxious. Mentally. It was just a blur. Impressions like
above just blasted through my mind constantly, so quickly I only had the
sensation of the rate of change of the hallucinations and not of any one
hallucination. Again this is very hard to explain."
An anonymous user reported experiencing withdrawal after using kratom
continually for nearly a year. For most of that time, use was in low doses, one
to three times per week, and no physical addiction was noticed. After increasing
use to near daily for a few months and noticing tolerance, the user decided to
abstain. The resulting withdrawal was described thusly: "Just the second full
day of no kratom I became very irritable. I tried to keep myself busy to no
avail. I remained irritable and very restless until the fourth full day. Due to
my feelings of restlessness, I slept only several hours per night in the second
through fourth nights. The fifth full day I noticed I could relax, and that
night I slept like a baby. I can't explain the feeling of pure anxiety I
experienced as my body went through (real!) withdrawals. I noticed achy muscles
and mild depression as well." In spite of this, the user says, "Kratom is an
awesome drug. I believe it's very safe if used occasionally."
A user going by the names Patient and UK Patient switched from using high doses
of opioids (fentanyl, morphine, oxycodone, and hydrocodone) to using kratom,
mistakenly believing that simply switching to kratom was a way to cure the
addiction. Describing the withdrawal from this multiple drug addiction, UK
Patient writes, "The first few days are almost identical to serious hydrocodone
withdrawal. But it is days 4-14 that catch me off guard. Fatigue sets in.
Followed by 2-3 days 'lost' to relative detachment from my surroundings. Then I
am welcomed back by a CRIPPLING depression." No timeline is given for how long
the kratom was used, nor for how long or how many times Patient was addicted to
opioids before switching to kratom.
Writing under the name K-ally, a user describes discovering kratom after years
of occasional narcotic use culminating in a year of daily oxycodone use,
writing, "back in December after getting over a three week withdrawal from heavy
oxycodone (100mg to get me high) and methadone (50mg to keep me nice and level),
I discovered Kratom. I learned that it was no ordinary legal high, and this
stuff was actually like an opiate. I start taking it 2-3 times a day and my
tolerance skyrockets; at first I only required 3 grams of leaf, now I was using
up to 10 grams here in March. Kratom was being used on top of occasional
oxycodone, which my tolerance was quite high for, so there is without question
cross-tolerance between Kratom and opioids." This person goes on to say, "I
started having side effects from my use, like depression. I figured it was time
to quit, for real, and I was really scared. Withdrawal has given me days of hell
on earth, pure torture of the mind and soul. A week earlier I had stopped my use
for almost two days, in a failed attempt to quit. The withdrawal set in in about
20 hours and was absolutely hell, so I eagerly ate more Kratom." Deciding not to
continue the cycle, the user writes, "I go through the horrible process again,
my final time, like I always said. This time I scattered my remaining Kratom
through the garbage can. Pure anxiety hits me after a day, along with stomach
problems, twitching, and horrible insomnia." On the second day of withdrawal,
this person decided to take an intramuscular injection of 110mg ketamine.
Interestingly, this user reported having a profound experience with the
ketamine, and upon waking the next morning felt no more withdrawal symptoms. The
report was written over a week after the ketamine experience, at which time the
user had neither used more kratom or opioids nor experienced a return of any
withdrawal symptoms.
A somewhat contrasting report comes from a user named Duncan, who was not using
kratom to come off opioids. He writes, "I personally used a high dose of Kratom
EVERY day for about 1 1/2 years. It got to point where I began to no longer
appreciate the plant and I decided to stop. There were actually NO cravings at
all after that to continue using it although there were definitely withdrawal
symptoms. I found it difficult to sleep at night, had bad diarrhea and was quite
depressed for about 10 to 14 days. All the above symptoms gradually wore off and
everything got back to normal again. I abstained for about 4 months and am now
using kratom only twice a week without any negative effects." He adds, "I would
say it is definitely EASY to quit but if used for a long period of time it is
better to slowly stop using it over a period of time rather than suddenly thus
reducing the negative symptoms."
Law
Kratom remains legal in most of the world. There are a few exceptions, however.
Unfortunately, it is likely that more countries will eventually ban kratom or
its active chemicals.
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. Thailand has the death
penalty for high level drug trafficking offenses, a fact which has spawned a
myth in the United States that kratom possession is punishable by death. In
practice, distributors are jailed for up to two years and fined up to 20,000
baht, and consumers can be jailed up to a month or fined up to 1000 baht. As
with prohibition laws elsewhere in the world, this has succeeded only at
increasing black market prices. In 2001, the Thai Narcotics Control Board issued
a report indicating that kratom was the second most widely abused illegal drug
in the country, after marijuana. 1270 kilograms were seized by Thai authorities
in 2001, and it was estimated that two million Thais had used the drug.
Myanmar (formerly Burma) declared Mitragyna speciosa a controlled narcotic drug
under Section 30 (b) of the Narcotic Drugs and Psychotropic Substances Law in a
Ministry of Health notice dated Yangon, the 6th Waxing Day Tabodwe, 1354 ME (28
January 1993).
Mitragynine was made illegal in Malaysia in 2003, and kratom leaves in August
2004. In June, 2004, a four day operation by Malay authorities resulted in the
arrest of 15 people and the seizure of over 800 liters of prepared tea and 245
kilograms of kratom leaves in the states of Terengganu, Pahang and Kelantan.
Other operations were conducted in 2003 and 2004, and presumably are ongoing. In
November 2004, Parliamentary Secretary to the Natural Resources and Environment
Ministry Sazmi Miah and others spoke out against an incident where 43 policemen
along with local villagers chopped down a 30 meter tall 60 year old kratom tree
in Kampung Badariang (near Gerik). Home Affairs Minister Datuk Azmi Khalid said
the police should have carried out a study first before cutting it, and focus
instead on the more serious problem of synthetic drug abuse. Many feel that
cutting down kratom trees harms the biodiversity of the region. The local deputy
district police chief, Ismail Deraksa, defended the action by saying the sixty
year old tree was cut down to prevent the emergence of a new addiction in the
youth. Slightly more than 1000 kilograms of the leaves and under 236,000 liters
of the drink have been seized since kratom was made illegal. As of April 2005,
there have been 99 cases involving kratom, 29 people have been charged, but no
one has been jailed. Penalties in Malaysia include fines of up to 10,000 ringgit
or jail terms up to four years or both.
The most recent country to ban kratom was Australia. The National Drugs and
Poisons Schedule Committee held several meetings between February 2003 and
February 2004 to consider including mitragynine and Mitragyna speciosa into
Schedule 9 of the Standard for the Uniform Scheduling of Drugs and Poisons. The
NDPSC 39th Meeting in October 2003 agreed to schedule mitragynine, and 40th
Meeting in February 2004 agreed to add kratom to Schedule 9 as well, pending
review of public comments. Although several comments were received arguing that
kratom was relatively harmless and had potential therapeutic value, the
Committee pointed out the widespread sale and promotion of kratom on the
internet was reason to believe it was a potential problem drug. Regarding
potential medical uses, the NDPSC meeting minutes state, "A Member noted that
based on the available data there was little evidence to show that M. speciosa
was widely used for therapeutic purposes other than as a substitute for other
addictive opiates and one other traditional use as an antidiarrhoeal. Although
the pharmacology of M. speciosa suggested that analgesic effects were likely
given the findings of studies quoted in several papers [e.g. Journal of
Psychoactive Drugs (Vol 20[4], Oct-Dec 1988], there was little data to suggest
that Kratom was used traditionally as a pain reliever. On this basis, the
Committee noted that despite post-meeting comments about the usefulness of M.
speciosa for treating migraines, there was little evidence available to support
a legitimate therapeutic need for the plant and members also noted that a number
of other alternatives including complementary medicines were already available.
A Member observed that information on Internet websites referred mainly to the
use of Kratom for producing psychoactive effects and in contrast, there was
paucity of information about its therapeutic use." The NDPSC then confirmed the
decision to schedule kratom, and the amended SUSDP law went into effect 1
January 2005. Furthermore, a New Zealander on the Committee suggested that
Australia should officially recommend to New Zealand that it also schedule
kratom.
Mellow Gold
"Mellow Gold" fake kratom leaf material
"Mellow Gold" fake kratom seeds
Beginning in late 2002, Bruno Phillips of Ebotashop, a botanical vendor located
in France, began marketing a product which was alleged to be kratom imported
from Myanmar (where kratom is illegal). This product was sold to other vendors
as well as through Ebotashop. Many exotic botanical retailers around the world
carried it, Shaman Australis estimates that 100 kilograms or more in total may
have been sold to vendors at prices from $200 to $600 per kilogram. Some
retailers produced extracts of this alleged kratom, either as a "full-spectrum
alkaloid free-base" or as an extract made using vinegar which was called
"mitragynine acetate" - or even more incorrectly, "kratom acetate." One vendor
who had purchased this plant material, Daniel Siebert, began to notice that the
leaves did not match published botanical descriptions of kratom. Notably, the
leaves had some hairs. Daniel Siebert did a TLC analysis, and Mark Brady of MJB
Botanicals did an HPLC analysis, and neither test indicated the presence of
mitragynine. The TLC analysis did not produce any visible indole spots with
Ehrlich's reagent. However, the HPLC results had two peaks with retention times
similar to yohimbine, leading Brady to speculate that it could contain similar
alkaloids. The alkaloid content of the dried leaf was approximately 4%, although
the alkaloids remain unidentified. Some companies kept selling the product after
this discovery, but renamed it to "Mellow Gold." Many people who have tried it
report psychoactivity of some kind, while others have reported no activity. No
harmful effects have been reported. Seeds from the same source were also
available, and sold through various resellers as well. Based on examination of
the leaves and seeds, some have theorized that this material could be Mitragyna
parvifolia, but this is only a guess. Whether the psychoactivity reported for
"Mellow Gold" is real or placebo is also uncertain.
Personal Observations
Kratom is a fascinating plant with great potential. I first became interested in
it after reading some passing references to this psychoactive tree from Thailand
in books such as Jonathan Ott's "Pharmacotheon" and "Plants of the Gods" by
Schultes and Hofmann in the late 1990s. This grabbed my interest, as I was born
and spent much of my childhood in Thailand and had grown up surrounded by Thai
culture. I had never heard of kratom however. There was very little information
available on kratom at that time, so it lingered in the back of my mind until
1999, when a very small quantity of dried leaf became available and was briefly
sold by a mail-order specialty botanicals supplier after an intrepid individual
brought 10-15 kilograms of leaf and some seeds home from Thailand. I purchased
10 grams for $25 sometime in 2000. There was no practical information available
other than the catalog listing which said kratom could be used "for producing a
distinctive sedation coupled with a paradoxical physical exhilaration" along
with a mental state described as "putting one's pieces together" when feeling
scattered or fatigued. the which suggested doses of around a gram could be
chewed, smoked, or made into tea for effects that were both stimulating and
relaxing. This was in line with the little information I'd run across in books,
which mentioned that it was usually chewed or smoked. I tried smoking and
chewing it several times, with no results. Finally when I was down to 5 grams, I
decided to try tea. This finally produced results - not very strong, but
certainly enjoyable. I tried to order more, but there had only been a small
supply and it was already sold out.
I was able to obtain a small sample of kratom from an associate a few months
later, and it became possible to find real kratom commercially again beginning
in 2003. Likewise, scientific information became easier to obtain, and realizing
that my "Kratom: What Is It?" paper was bursting with errors, I decided to begin
researching kratom for a new paper. As often happens, life and other projects
delayed this project for some time, and I didn't begin seriously researching or
experimenting with kratom much until the summer of 2004. For the past few months
I have researched kratom in depth, and have come to have a deep appreciation for
the plant. I also have found it to be a useful and enjoyable plant, and it is a
valuable element of my herbal medicine cabinet.
On paper, reading about the pharmacology, it can seem as if kratom is virtually
interchangeable with opioids. The reality is somewhat different. Certainly there
are many similarities, as would be expected of a plant with at least two opioid
receptor agonist chemicals. I have had fairly extensive experience with opioids
including codeine, oxycodone, buprenorphine, opium poppies and others, and I
consider myself well versed in their effects and the differences between them.
Kratom has a substantially different feel from opioid narcotics, both in the
short and long term. Serious pharmacological research into kratom has only
barely begun, and it seems likely that as more is learned about it, science will
be able to quantify these differences. Perhaps 7-hydroxymitragynine and
mitragynine are active at more receptors than currently thought, or perhaps
there are as yet undiscovered active chemicals in the plant which modify the
activity of the whole. Or perhaps the properties of the kratom alkaloid
molecules are such that even just binding to the opioid receptors, they produce
activity which is not the same as opioids.
Whatever the reason, there are notable differences. In a superficial sense, the
high produced by kratom feels somewhat like that of opioids. There is a warm,
tingly sensation which will certainly feel familiar to people experienced with
opioids. Kratom is useful as a pain killer and a cough suppressant, and I have
used it for both purposes with results just as good as with opioids. While
kratom is used to treat diarrhea in Thailand and Malaysia, I personally have
found that it has very little constipating effect compared to opioids.
Fortunately, I have not had the opportunity to try it as a diarrhea remedy, but
based on the near lack of constipation I've gotten from it, I'm skeptical that
it will work nearly as well as opioids. A major difference between kratom and
opioids is the stimulating property of kratom. There are some opioids, mostly
thebaine derivatives such as hydrocodone or oxycodone, which are stimulant in
the sense that they can cause insomnia. Kratom produces more of a real
stimulation, giving a focused energy which lasts for several hours and is well
suited to engaging in productive and creative work, exercize, or for social
situations. I am particularly fond of going on long nature hikes after a cup of
kratom tea. This is in stark contrast to opioids, which tend to promote more
sedentary activities (or lack thereof). While kratom is relaxing, it does not
seem to act like as much of a CNS depressant as opioids do. I have never nodded
off or even slid into daydreams with kratom like with opioids. The mind feels
active and alert - tranquilized perhaps, but not sedated. There also is no real
noticeable come down from kratom. The effects gradually and smoothly transition
back to baseline consciousness, and I have never experienced a hangover or crash
of any sort.
In the long term, kratom does not seem to have nearly the reinforcing lure to
compulsive use that opioids have. However, I'm sure that for some people, it
will, and that anybody who overuses it has the potential to develop a physical
and/or psychological dependence. Even with periods of frequent use, kratom does
not seem to produce the effects I have experienced from opioids, such as
constipation, lack of motivation, reduced sex drive, or general feelings of
reduced health. In fact, when I use it, I generally feel energetic and healthy,
and the pharmacology of many of its chemical components does provide evidence
that occasional moderate use of kratom is not only safe but potentially
beneficial.
I have mostly experimented with kratom as a tea. With most material I have
sampled, 5 grams will make a tea with noticeable effects, and 15 grams will
produce the strongest effects which I still find enjoyable. With some of the
more potent material I have tried, 10 grams can be rather strong, but in my
experience the stronger strains which are sold as "super" or "premium" kratom
are not really worth the money. While these varieties often cost four or five
times more, I have found them to only be around 50% stronger than the standard
material I've used. I have found smoking kratom to be a complete waste, although
an associate told me that smoking 3 grams of leaf did produce some effects. I
haven't had much luck with chewing it, but I haven't really explored that route
much. It works well as a tea, and since oral consumption is generally the safest
way to use any drug, I probably wouldn't recommend any other methods for using
it.
Conclusion
The sort of unethical marketing that gets drugs banned: "It's a lot nicer than
being stoned"
Another example of greed trumping wisdom
In conclusion, there needs to be much more research done into this plant and its
active constituents, especially in light of the recent discovery that
mitragynine is not the chemical primarily responsible for kratom's activity.
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 and errors. Knowledge even of the plant's existence
outside of Southeast Asia has been limited to ethnobotanists and a handful of
pharmacology researchers until the last few years, and availability of live
plants and dried leaves has been practically non-existent until very recently.
Beginning in 2004, I began seeing kratom sold in tacky, exploitive ways by
people seeking to make money off it. This pattern has sadly repeated itself more
times than I care to remember. An interesting drug is made available by traders
and vendors with integrity and ethics, and sold discretely. Then, some greedy
bastard discovers it and sets up a sleazy website and begins aggressively
marketing it with no regard for the consequences. Sooner or later, people begin
doing stupid things because of a lack of adequate education. The drug comes to
the attention of the media or authorities, and eventually is made illegal. It
saddens me greatly that people are willing to push kratom in such unethical
ways, encouraging reckless use by hyping up how fun it is, promoting it as
similar to or better than opium or marijuana, not making the attempt to educate
their customers and urge moderation, and advertising in ways so aggressively
that it seems inevitable that it will eventually come to the attention of the
wrong people.
Kratom is a special plant with both recreational and medicinal value which is
only beginning to be understood. There is much to learn, and hopefully humanity
will have the opportunity to learn what this plant has to offer before it too
falls victim to the drug war juggernaut.
Credits
Anonymous. "Withdrawal Symptoms":
http://www.erowid.org/experiences/exp.php?ID=36275
ASEAN and China Cooperative Operations in Response to Dangerous Drugs.
"Counterdrug Press Summary 25 November - 1 December 2004":
http://www.accordplan.net/Dec-1.htm
Atthakor P. "Role Seen For Traditional Herbal
Stimulant" (http://www.murple.net/yachay/archives/kratom/kratom-bkpost.html):
Bangkok Post, 27 November 1999
Botanical Preservation Corps (http://www.botanicalpreservationcorps.com/).
Product catalog: 2000 (1999? 2001?)
Botanical Preservation Corps (http://www.botanicalpreservationcorps.com/).
Personal email from Ben: 6 May 2005, orders@botanicalpreservationcorps.com
Cactushead. "Good, But Not Worth the Price":
http://www.erowid.org/experiences/exp.php?ID=38869
Carbonin PU, Greco A, Pisanti P, Gemma A, Cattelin F. "Efficacy of
almitrine-raubasine in cognitive disorders of aging: a double-blind,
placebo-controlled, clinical and psychometric study": Clin Neuropharmacol.
1990;13 Suppl 3:S92-9
Charveron M, Assie MB, Stenger A, Briley M. "Benzodiazepine agonist-type
activity of raubasine, a rauwolfia serpentina alkaloid": Eur J Pharmacol. 1984
Nov 13;106(2):313-7
Darklight. Personal email: 6 May 2005
De Rienzo P, Beal D, The Statten Island Project. "The Ibogaine
Story" (http://www.cures-not-wars.org/ibogaine/iboga.html)
f. "Careful on Dosage": http://www.erowid.org/experiences/exp.php?ID=40466
Falkiewicz B, Łukasiak, J. "Vilcacora [Uncaria tomentosa (Willd.) DC. and
Uncaria guianensis (Aublet)
Gmell. (http://www.murple.net/yachay/archives/uncaria/uncaria-review.pdf) a
review of published scientific literature"]: Case Rep Clin Pract Rev, 2001;
2(4): 305-316
Hanna, Jon. "Bogus Kratom Market
Exposed" (http://www.murple.net/yachay/archives/kratom/bogus-kratom-er.pdf):
Entheogen Review, Spring 2003; XII(1):26-28, Errata
Horie S, Koyama F, Takayama H, Ishikawa H, Aimi N, Ponglux D, Matsumoto K,
Murayama T. "Indole alkaloids of a Thai medicinal herb, Mitragyna speciosa, that
has opioid agonistic effect in guinea-pig
ileum" (http://www.murple.net/yachay/archives/kratom/7-hydroxymitraginine-primary-active.pdf):
Planta Med., March 2005; 71(3):231-6
IAmShaman (http://www.iamshaman.com/). Photos of kratom flower and grove.
http://iamshaman.com/kratom/
Idid S Z, Saad L B, Yaacob H, Shahimi M M. "Evaluation Of Analgesia Induced By
Mitragynine, Morphine And Paracetamol On
Mice" (http://www.murple.net/yachay/archives/kratom/mitragynine-morphine-apap.pdf):
ASEAN Review of Biodiversity and Environmental Conservation, Nov-Dec 1999
Institute For Medical Research (Malaysia). "Kratom: Possible Cure for Drug
Addiction" (http://www.murple.net/yachay/archives/kratom/addiction.txt):
http://www.imr.gov.my/webpage%20HMRC/foc04(1).html
Jansen K, Prast C. "Ethnopharmacology of Kratom and the Mitragyna
Alkaloids" (http://www.murple.net/yachay/archives/kratom/jansen-1): Journal of
Ethnopharmacology, 1998; 23:115-119
Jesper. "Instant Hangover Tea":
http://www.erowid.org/experiences/exp.php?ID=30154
K-ally. "Me, My Brain, Ketamine, and a Miracle":
http://www.erowid.org/experiences/exp.php?ID=41759
Kemper, KJ. "Cat's Claw (Uncaria tomentosa)":
http://www.mcphs.edu/herbal/catsclaw/catsclaw.PDF, 29 July 1999
Lightwarden. "One of My Favorites":
http://www.erowid.org/experiences/exp.php?ID=40361
Matsumoto K, Horie S, Ishikawa H, Takayama H, Aimi N, Ponglux D, Watanabe K.
"Antinociceptive effect of 7-hydroxymitragynine in mice: Discovery of an orally
active opioid analgesic from the Thai medicinal herb Mitragyna
speciosa" (http://www.murple.net/yachay/archives/kratom/7-hydroxymitragynine-discovery.pdf):
Life Sci, 2004; 74(17):2143-55
Matsumoto K, Mizowaki M, Takayama H, Sakai S, Aimi N, Watanabe H. "Suppressive
effect of mitragynine on the 5-methoxy-N,N-dimethyltryptamine-induced
head-twitch response in
mice" (http://www.murple.net/yachay/archives/kratom/mitragynine-5meodmt-twitch.pdf):
Pharmacol Biochem Behav, 1997; 57(1-2):319-23
Merck & Co., Inc. "The Merck Index": 12th edition, 1996.
Mohamed AF, Matsumoto K, Tabata K, Takayama H, Kitajima M, Watanabe H. "Effects
of Uncaria tomentosa total alkaloid and its components on experimental amnesia
in mice: elucidation using the passive avoidance test": J Pharm Pharmacol. 2000
Dec;52(12):1553-61
National Drugs and Poisons Schedule Committee (Australia): "Edited Minutes of
Meeting 37 - February
2003" (http://www.murple.net/yachay/archives/kratom/ndpsc-37.pdf): February
2003; 108-110
National Drugs and Poisons Schedule Committee (Australia): "Edited Minutes of
Meeting 38 - June
2003" (http://www.murple.net/yachay/archives/kratom/ndpsc-38.pdf): June 2003;
96-98
National Drugs and Poisons Schedule Committee (Australia): "Edited Minutes of
Meeting 39 - October
2003" (http://www.murple.net/yachay/archives/kratom/ndpsc-39.pdf): October 2003;
80-82
National Drugs and Poisons Schedule Committee (Australia): "Edited Minutes of
Meeting 40 - February
2004" (http://www.murple.net/yachay/archives/kratom/ndpsc-40.pdf): February
2004; 103-105
Neuman J, de Engel AM, Neuman MP. "Pilot study of the effect of raubasine on
platelet biological activity": Arzneimittelforschung. 1986 Sep;36(9):1394-8
New Straits Times (author unspecified). "Daun ketom has similar effect to
morphine, study shows": New Straits Times, 16 June 2003
Oxford University Press. "Dictionary of Organic Compounds": Volume 4, 4th
edition, 1965
Patient. "Great for Easing RX Withdrawal":
http://www.erowid.org/experiences/exp.php?ID=38806
Psychoactive Herbs (http://www.psychoactiveherbs.com). Personal email from
Duncan, 24 April 2004: duncan@psychoactiveherbs.com
Psychoactive Herbs (http://www.psychoactiveherbs.com). Personal email from
Duncan, 30 April 2004: duncan@psychoactiveherbs.com
Razak DA. "Kratom versus Tobacco: Get the priority right about the dangers of
these plants" (http://www.murple.net/yachay/archives/kratom/nst-7jun2004): New
Straits Times, 7 June 2004
Razak DA. "Poison Control: 'Ketum' Ban Smacks Of Double
Standards" (http://www.murple.net/yachay/archives/kratom/nst-4sep2004): New
Straits Times, 4 September 2004
Rifat, Claude. "Mitragynine": http://www.lycaeum.org/drugs/SSRI/mitragy.html
Roquebert J, Demichel P. "Inhibition of the alpha 1 and alpha
2-adrenoceptor-mediated pressor response in pithed rats by raubasine,
tetrahydroalstonine and akuammigine": Eur J Pharmacol. 1984 Oct 30;106(1):203-5
sepulfreak. "A New Favorite": http://www.erowid.org/experiences/exp.php?ID=38490
Shaman Australis (http://www.shaman-australis.com.au/). "Fake Kratom Herb,
Kratom acetate, Mitragynine acetate":
http://www.shaman-australis.com/Website/MitragynaspeciosaFake.htm, May 2003
Shaman Australis (http://www.shaman-australis.com.au/). Mitragyna speciosa
catalog page: http://www.shaman-australis.com/Website/subcat82.htm
Shaman Australis (http://www.shaman-australis.com.au/). Personal email from
owner: shaman@shaman-australis.com
Shellard E J. "The alkaloids of Mitragyna with special reference to those of
Mitragyna speciosa,
Korth" (http://www.murple.net/yachay/archives/kratom/mitragyna-alkaloids-unodc/):
Bulletin On Narcotics, 1974 issue 2
sile na gig. "Not Bad, But Nothing to Shout About":
http://www.erowid.org/experiences/exp.php?ID=41343
Stuppner H, Sturm S, Geisen G, Zillian U, Konwalinka G. "A Differential
Sensitivity of Oxindole Alkaloids to Normal and Leukemic Cell
Lines" (http://www.murple.net/yachay/archives/uncaria/oxindoles-leukemia.pdf):
Planta Med. 59, Supplement Issue 1993:A583
Suwanlert M D Sangun. "A study of kratom eaters in
Thailand" (http://inti.murple.net/yachay/archives/kratom/kratom-eaters-unodc/):
Bulletin on Narcotics, 1975 issue 3
Takayama H. [http://www.murple.net/yachay/archives/kratom/kratom-alkaloids.pdf
"Chemistry and Pharmacology of Analgesic Indole Alkaloids from the Rubiaceous
Plant, Mitragyna speciosa": Chem. Pharm. Bull. 52(8) 916--928 (2004)
Takayama H, Aimi N, Sakai S. "Chemical studies on the analgesic indole alkaloids
from the traditional medicine (Mitragyna speciosa) used for opium substitute":
Yakugaku Zasshi, 2000; 120(10):959-67
Takayama H, Ishikawa H, Kitajima M, Aimi N. "Formation of an Unusual Dimeric
Compound by Lead Tetraacetate Oxidation of a Corynanthe-Type Indole Alkaloid,
Mitragynine" (http://www.murple.net/yachay/archives/kratom/dimeric-derivative.pdf):
Chem. Pharm. Bull. 50(7) 960--963 (2002)
Takayama H, Ishikawa H, Kurihara M, Kitajima M, Aimi N, Ponglux D, Koyama F,
Matsumoto K, Moriyama T, Yamamoto LT, Watanabe K, Murayama T, Horie S. "Studies
on the synthesis and opioid agonistic activities of mitragynine-related indole
alkaloids: discovery of opioid agonists structurally different from other opioid
ligands" (http://www.murple.net/yachay/archives/kratom/mitragynine-analogues.pdf):
J Med Chem, 2002; 45(9):1949-56
Takayama H, Ishikawa H, Kurihara M, Kitajima M, Aimi N, Ponglux D, Koyama F,
Matsumoto K, Moriyama T, Yamamoto LT, Watanabe K, Murayama T, Horie S. "Studies
on the synthesis and opioid agonistic activities of mitragynine-related indole
alkaloids: discovery of opioid agonists structurally different from other opioid
ligands (Supporting
Information)" (http://www.murple.net/yachay/archives/kratom/mitragynine-analogues-suppinfo.pdf):
J Med Chem, 2002 (American Chemical Society); Takayama jm010476e Supporting
Info:1-24
Thongpradichote S, Matsumoto K, Tohda M, Takayama H, Aimi N, Sakai S, Watanabe
H. "Identification of opioid receptor subtypes in antinociceptive actions of
supraspinally-administered mitragynine in
mice" (http://www.murple.net/yachay/archives/kratom/mitragynine-receptors.pdf):
Life Sci 1998;62(16):1371-8
Tsuchiya S, Miyashita S, Yamamoto M, Horie S, Sakai S, Aimi N, Takayama H,
Watanabe K. "Effect of mitragynine, derived from Thai folk medicine, on gastric
acid secretion through opioid receptor in anesthetized
rats" (http://www.murple.net/yachay/archives/kratom/mitragynine-gastric.pdf):
Eur J Pharmacol, 2002; 443(1-3):185-8
UK Patient. "Withdrawal is Horrendous":
http://www.erowid.org/experiences/exp.php?ID=41322
Wong, Jocelyn. "Don't drink
this..." (http://www.murple.net/yachay/archives/kratom/ketum.html): The Electric
New Paper, 23 July 2004
World of Molecules. "The Epicatechin Molecule":
http://www.worldofmolecules.com/antioxidants/epicatechin.htm
Yamada R. "Re: Is Mitragynine anti-addictive?": Usenet post
199702031505.KAA21187@interport.net
Yamamoto LT, Horie S, Takayama H, Aimi N, Sakai S, Yano S, Shan J, Pang PK,
Ponglux D, Watanabe K. "Opioid receptor agonistic characteristics of mitragynine
pseudoindoxyl in comparison with mitragynine derived from Thai medicinal plant
Mitragyna
speciosa" (http://www.murple.net/yachay/archives/kratom/mitragynine-pseudoindoxyl.pdf):
Gen Pharmacol, 1999; 33(1):73-81
Yoga, SS. "Drug In
Demand" (http://inti.murple.net/yachay/archives/kratom/the_star-in_demand.html):
The Star Online (http://http://thestar.com.my/), 4 April 2005
Yoga, SS. "How Ketum Is
Abused" (http://inti.murple.net/yachay/archives/kratom/the_star-ketum_abused.html):
The Star Online (http://http://thestar.com.my/), 4 April 2005
Zarembo J E, Douglas B, Valenta J, Weisbach, J A, 1974. "Metabolites of
mitragynine": J Pharm Sci 63, 14071414
Zongxian L, Cheng LH, Kun LY. "Effects of Tea Polyphenols and Their Derivatives
on Fecal Microbial Flora":
http://staff.science.nus.edu.sg/~scilooe/srp_2003/sci_paper/microb/research_paper/li_zongxian.pdf
Specific to Mitragyna speciosa
(Kratom):
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