Khat drug profile

Source: Wikimedia Commons.

Khat (also known as qat or chat) comprises the leaves and fresh shoots of Catha
edulis Forsk, a flowering evergreen shrub cultivated in East Africa and the SouthWest Arabian Peninsula. Khat leaves are typically wrapped as a bundle in banana
leaves. The principal active components in khat are cathinone and cathine
(norpseudoephedrine) (see also Drug profile on synthetic cathinones). Chewing khat
releases these substances into the saliva; they are rapidly absorbed and eliminated.
Both cathinone and cathine are closely related to amphetamine, and the
pharmacological effects of cathinone are qualitatively similar to those
of amphetamine, although it is less potent. Only fresh leaves are chewed, because
cathinone soon degrades into old or dry plant material. Analysis relies on the
characteristic appearance of khat and the presence of cathinone and/or cathine.
Khat is not under International control, but is scheduled by some Member States.
Cathinone and cathine are listed in the 1971 United Nations Convention on
Psychotropic Substances under Schedules I and III respectively.

Chemistry
Molecular structure: Cathinone

Molecular formula: C9H11NO

Molecular weight: 149.19 g/mol
Molecular structure: Cathine

Molecular formula: C9H13NO

Molecular weight: 151.21 g/mol
The principal active component in khat is S-cathinone, otherwise known as (-)-2aminopropiophenone or, more formally, S-(-)-2-amino-1-phenyl-1-propanone.
Cathinone is labile and is transformed within a few days of harvesting to
a dimer (3,6-dimethyl-2,5-diphenylpyrazine). It is for this reason that khat needs to
be consumed while still fresh. Cathine (1S, 2S-norpseudoephedrine), a further
psychoactive substance, arises from the metabolism of cathinone in the mature
plant. Apart from common plant products such as tannins, terpenes, flavonoids and
sterols, a number of other substances occur in khat including smaller amounts of 1R,
2S-norephedrine and a large number of cathedulins (polyhydroxylated
sesquiterpenes). Both cathinone and cathine are close chemical relatives of the
phenethylamines. Thus cathinone is the -keto analogue of amphetamine. A large
number of synthetic cathinone derivatives have been produced, some of which have
found use as active pharmaceutical agents.
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Physical form
Khat is usually supplied as a bundle of leaves and fresh shoots wrapped in banana
leaves. It is reported to have a sharp taste and an aromatic odour. Alcoholic extracts
(tinctures) of khat have occasionally been reported, especially in herbal high sales
outlets and at music festivals.
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Pharmacology
Both cathinone and cathine are central nervous system (CNS) stimulants, but have a
lower potency than amphetamine. Khat consumption leads to effects that are
qualitatively similar to those of amphetamine, i.e. increased blood pressure, a state
of euphoria and elation with feelings of increased alertness and arousal. This may be
followed by depression, irritability, anorexia and difficulty in sleeping. Frequent use of
high doses may evoke psychotic reactions. Gastrointestinal effects include
constipation and urine retention. The role of other constituents of the khat plant is
less well understood. The euphoric effects of khat start after about one hour of
chewing. Peak plasma levels of cathinone are obtained 1.5 to 3.5 hours after the
onset of chewing. The mean plasma level may reach 100 ng/ml after chewing 60 g
fresh khat for one hour. Cathinone is barely detectable in blood after eight

hours. First-pass metabolism of cathinone in the liver leads to the formation of

norephedrine. Only 2 % of cathinone is excreted unchanged in the urine. The
elimination half-life of cathinone is 1.5 +/ 0.8 hours and that of cathine 5.2 +/ 3.4
hours. Specific associations have been proposed between khat consumption and
myocardial infarction, liver failure and oral cancer, but in many cases confounding
effects could not be eliminated.
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Origin
Khat comprises the leaves and fresh shoots of Catha edulis Forsk, a flowering
evergreen shrub cultivated in East Africa and the Arabian Peninsula. It is usually
imported into Europe via air freight.
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Mode of use
Although khat can be ingested as an infusion or smoked, by far the most common
route of administration is to chew the plant. Fresh vegetable material (stems, leaves
and flower buds) is chewed and the juice of the masticated material is swallowed,
while the residues are spat out. Typically, an individual consumes 100200 g of khat
leaves (one bundle) in a session, and its effects last for several hours. Infusions from
dried leaves are also consumed. With the exception of tobacco, the concomitant use
of other drugs, including alcohol, by khat users is uncommon.
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Other names
Khat is also known as qat, chat, miraa, murungu and Arabian or Abyssinian tea.
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Analysis
Although a bundle of khat appears reasonably characteristic, botanical and
microscopic features are of limited use in confirming identity. It is usual for laboratory
analysis to confirm the presence of cathinone and/or cathine.
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Typical purities
Fresh khat contains around 0.1 % cathinone and smaller amounts of cathine.
Although khat comprises an inhomogeneous plant preparation, it is not normally
adulterated with other material.
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Control status
Khat has been reviewed by the WHO Expert Committee on Drug Dependence
(ECDD) on a number of occasions, the most recent assessment being made at the
34th meeting of ECDD in 2006. However, Catha edulis remains outside international

control, although cathinone and cathine have been listed in the 1971 UN Convention
under Schedules I and III respectively since the early 1980s. Khat is controlled in a
number of European countries including Belgium, Denmark, Germany, Greece,
France, Ireland, Italy, Latvia, Lithuania, Poland, Slovenia, Finland, Sweden, Norway,
and Switzerland.
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Prevalence
Khat chewing is a traditional practice in Yemen and certain East African countries.
Nevertheless, khat use is sporadically reported in Europe as a substance of choice
among immigrants from Somalia, Ethiopia, Kenya and Yemen. There are a few
published studies of khat use by immigrant communities in European countries.
However, these have mostly been conducted in the UK, and it is unclear to what
extent their findings can be assumed to reflect patterns of use elsewhere in Europe.
Such reports are subject to sampling bias due to the way in which interviewees are
recruited. Nonetheless, the studies available do point to significant levels of use
within some migrant communities. For example, a study found that in 2005, among
the Somalis interviewed, 34 % had used khat in the month prior to the interview
although less than 4 % reported using the drug on a daily basis. Studies generally
report more use of the plant among males, generally in group settings. There may be
a tendency to under-report khat use among women, which is a more stigmatised
behaviour and more likely to occur at home or alone. Most studies have suggested
that khat users are unlikely to use other psychoactive substances, which
distinguishes them from most other groups of recreational drug users in Europe,
where polysubstance patterns of use are increasingly the norm. Use of khat among
Somali communities has also been reported in Denmark (around 1 350 users) and
Sweden (2 0003 000 users).
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Street price
In the United Kingdom, a bundle of khat sells for around EUR 5, but the price is
higher in countries where it is controlled. Possibly due to the lability of cathinone,
khat leaves seem not to be commonly sold over the Internet, whereas Internet sales
of khat seeds have been observed.
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Medical use
Khat is used as a traditional medicine by some indigenous people of East Africa, but
neither khat nor its isolated active ingredients have been widely recognised for their
therapeutic use.
In Germany, preparations of cathine containing up to 5 % as solution (maximum
dose 1 600 mg per packaging unit) without any other narcotic substances or per unit
dose up to 40 mg cathine, calculated as base, are exempted from special
prescription and may be prescribed by normal medical prescription. In the UK, khat
is licensed as a medicinal product under the Medicines Act 1968, but to date it has
not been imported as a medicinal product.

Salvia divinorum drug profile

Photo: Wikimedia Commons

The psychoactive plant Salvia divinorum, or the diviners sage, is a rare member of
the mint family (Lamiaceae; formerly Labiatae), characterised in the mid-twentieth
century. The plant is endemic to a limited area of the highlands of the Mexican
Oaxaca state, where the Mazatec Indians ingest its fresh leaves or leaf preparations
for divinatory rituals, healing ceremonies and medical purposes. Since the late
1990s, the use of the plant as a legal herbal hallucinogen has been increasing,
partly due to its availability. Smoking the dried and crushed leaves provides shortlived but intense hallucinations. The effective dose of salvinorin A, the active
ingredient of the plant, is comparable to that of the synthetic
hallucinogens LSD or DOB. The toxicity of Salvia divinorum is currently poorly
understood.

Chemistry
The chemical identification of the psychoactive principle of Salvia divinorum was
completed simultaneously by Ortega and Valds in the early 1980s. The main

ingredient responsible for the psychoactive effect of the plant is

a neoclerodane diterpene called salvinorin A. The IUPAC systematic name is
(2S,4aR,6aR,7R,9S,10aS,10bR)-9-(acetyloxy)-2-(3-furanyl)dodecahydro-6a,10bdimethyl-4,10-dioxo-2H-naphtho[2,1-c]pyran-7-carboxylic acid methyl ester
(CAS number: 83729-01-5). Unlike classical natural or synthetic
hallucinogens, salvinorin A does not contain a nitrogen atom it is not an alkaloid.
The dried leaves, leaf extracts and pure salvinorin A are stable at ambient
temperature in the absence of light or air, although there is no systematic study on
this. Salvinorin A is unstable in basic solutions and is soluble in conventional
organic solvents, including acetone, acetonitrile, chloroform, dimethyl sulfoxide and
methanol, but is essentially insoluble in hexane and water.
Molecular structure of salvinorum A

Molecular formula: C23H28O8

Molecular weight: 432.47 g/mol
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Physical form
Salvia divinorum is a 0.5 to 1.5 metre high perennial shrublike herb. It can be easily
recognised from its square-shaped and hollow stem and opposite pairs of ovate-

lanceolate, jagged-edged leaves, which are usually velvety or hairy. The

characteristic flower of the plant has a white corolla surrounded by a violet blue
calyx. Salvia divinorum hardly ever sets seeds, and even when produced, they are
rarely viable. The propagation of the plant is thus exclusively vegetative and most of
the Salvia divinorum plants now cultivated worldwide are clones of a few early
Oaxaca collections.
Dried and crushed leaves fortified with extracts from other leaves are dark green,
brownish or even blackish green, due to concentrated pigments.
Pure salvinorin A forms colourless crystals with a melting point of 242244 oC.
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Pharmacology
Salvinorin A has a unique mode of action and pharmacology. The potent and
selective full agonist activity at -opioid receptor (KOR) subtypes is primarily
responsible for the hallucinogenic effect of the drug. Whereas, classical
hallucinogens such as psilocybin, LSD or DOB, all alkaloidal in nature, interact with
specific serotonin receptor subtypes. Salvinorin A shows no significant binding to
over 50 other (psycho)pharmacologically important receptors, transporter proteins
and ion channels.
In humans, salvinorin A induces short-lived, profound hallucinations. Inhalation of
doses equivalent to 200500 micrograms of salvinorin A leads to loss of control
over physical movements (incapacitation); uncontrollable laughter; vivid, colourful
and often bizarre, dream- or film-like hallucinations. Temporal boundaries among
past, present and future disappear and the user is transported to alternative time and
places (spatiotemporal dislocation) with perceptions of being in several locations
simultaneously. The trip, especially at higher doses, can be frightening and can
cause serious psychotic disturbances. It has been reported that this can last for
hours after the hallucinations have disappeared. Common after-effects include
tiredness, dizziness and amnesia. Emergency reports have described lasting
psychosis in vulnerable individuals.
Although preliminary experiments by Mowry et al. (2003) indicated that salvinorin
A has relatively low toxicity to rodents, no other study has examined the acute or
chronic physiological toxic effect of Salvia divinorum leaves or of the various
extracts.
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Origin
Because Salvia divinorum seeds are difficult to obtain, the plant is propagated from
cuttings. Seedlings as well as dried leaves are readily available either from Internet
suppliers or specialised shops in countries where no regulatory restrictions exist.
Home cultivation of plants is possible and instructions describing optimal growing
conditions, the use of fertilisers and pest control chemicals are available on the
Internet in several languages.
Salvinorin A is found in the resin secreted by special, hairy epidermal cells
(trichomes), which are especially abundant on the leaves. Preparations of one leaf

fortified by extracts of 4 to 49 other leaves (the respective products then labelled as

5X to 50X extracts) are also available online and in specialised shops. However, the
actual salvinorin A concentration of Salvia divinorum products is generally
unknown. Pure, crystalline salvinorin A does not appear to be offered on markets
(neither online or in smartshops) but illustrated procedures for its isolation are
available on the Internet.
Chemical total syntheses of salvinorin A have recently been completed but they are
too complex to be used for the production of the substance.
To date, salvinorin A has not been found in any other Salvia species analysed.
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Mode of use
Traditionally, the Mazatec Indians roll the fresh leaves of the plant into a cigar-like
quid, which is then sucked or chewed while retaining the juice in the mouth to
increase absorption of the active ingredient.
Alternatively, the fresh foliage is crushed by hand or ground on a milling stone which
can be used for making a drinkable infusion. At least six fresh leaves are needed to
achieve noticeable effects, which manifest after about 10 minutes and lasts for 45
minutes or longer.
For recreational use, the most common way of administration is smoking the crushed
dried leaves from a pipe or water bong, providing short-lasting (1520 minute)
hallucinations within a minute. Typically, 0.250.75 gram leaf material is smoked.
Chewing the bitter leaves as a quid gives a longer lasting effect and the typical
dosages to produce mild to medium effects are 1030 grams of fresh leaves or 25
grams of dried leaves.
Sublingual application of aqueous ethanol tinctures made from leaves results in an
onset taking 510 minutes and lasting up to 2 hours.
Drinking tea made by steeping the leaves in hot water is relatively ineffective
because salvinorin A is readily degraded in the gastrointestinal tract. Vaporisation of
the dried leaves or extracts without burning requires special devices and rather high
temperatures (>200 oC) and is not a typical method of use.
Health risks of inhaling the vapours of pure salvinorin A are high because the
inhaled amount cannot be controlled. This can lead to an overdose, in the form of
psychotic disturbances.
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Other names
In Mexico, the plant is called in Spanish hojas de la pastora or ska Mara pastora.
Common names in English are: Diviners Sage, Lady Salvia, Magic Mint, Purple
Sticky, Sally D, Sage of the Seers or simply and most widely Salvia. Names in other
European languages include: French sauge des devins, sauge divinatoire;
German Wahrsagersalbei.

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Analysis
The salvinorin A content of botanical samples can be analysed by thin layer
chromatography or high performance liquid chromatography with UV detection. The
detection and quantitation of salvinorin A in blood, urine and saliva at nanogram/ml
level requires more sensitive methods such as gas chromatography or high
performance liquid chromatography, both coupled with a mass spectrometer.
The mass spectrum obtained by electron ionisation of salvinorin A shows
significant fragments at m/z 94, 55, 121, 107, 273, 166, 220, 252, 234, 359, 318, 404
and 432 (in decreasing abundance).
The UV spectrum of the methanolic solution of salvinorin A shows a maximum at
211 nm. The characteristic absorption bands in the infra-red spectrum of salvinorin
A in KBr pellet are at 3 220, 1 745, 1 735, 1 240, and 875 cm -1. For the unequivocal
identification of powdered plant material, DNA fingerprinting methods can be used.
Salvinorin A and the other diterpenoids of the plant are not detected by
conventional drug screening methods.
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Typical potency
The chemical composition of Salvia divinorum leaves depends on the developmental
stage of the plant and/or type of preparation. Systematic studies of plants obtained
from various collections show that the salvinorin A concentration of mature plants
ranges from 0.893.7 mg/g dried leaves (corresponding to an average of 0.245 %).
Results of recent analyses of Salvia divinorum, five product samples obtained via the
Internet or from head shops in the US indicated wide variations in salvinorin
A concentrations. In dried leaves (nominal 1X enrichment, where the X refers to
the number of times the extract is stronger than the leaf) the concentration of the
psychoactive ingredient was 0.408 mg/g, while in the 5X (two samples), 10X and
20X enriched extracts, the salvinorin A concentrations were 0.126/1.137, 0.951 and
0.461 mg/g, respectively. This suggests that labelling did not correspond to actual
content.
The study of the samples also revealed that some contained Vitamin E and caffeine
as adulterants.
A recent analysis of samples sold in Japan showed salvinorin A concentrations in
the range of 3.25.0 mg/g for the dried leaves, and, 4.138.9 mg/g for the 2X to 25X
enriched preparations.
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Control status
Neither Salvia divinorum nor salvinorin A are listed in any of the Schedules of the
United Nations Drug Conventions.
However, in recent years both Salvia divinorum and its active principle salvinorin
A have become controlled under drugs legislation in Belgium, Denmark, Italy, Latvia,

Lithuania, Romania and Sweden, in Australia and Japan as well as in a number of

states of the US.
Croatia, Germany, Poland and Spain only regulate the plant. In Estonia, Finland and
Norway, Salvia divinorum falls under medicines legislation. Lastly, in Canada it is
illegal to sell Salvia without authorisation under the Natural Health Products
Regulation.
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Prevalence
There is limited information on the extent of use of Salvia divinorum and its
preparations in European countries.
In Romania, a 2008 survey amongst Bucharest-based young people aged 15 to 34
who attend recreational settings, showed that 0.3 % had tried Salvia divinorum at
least once in their life.
In an online survey of UK club-goers carried-out late 2009, 3.2 % of respondents
admit to a last month consumption of Salvia divinorum, making it the fifteenth most
commonly used drug with this frequency. Lifetime prevalence reaches 29.2 %. These
findings cannot, however, be considered as representative of the wider population of
club-goers, due to the methodological limitations of online surveys.
In the US, the annual National Survey on Drug Use and Health conducted in 2006
indicates that the last 12 month use of Salvia divinorum was 0.3 % among persons
aged 12 or older; overall, about 1.8 million persons admit to using the drug in their
lifetime.
According to the more recent Monitoring the Future report of the National Institute
on Drug Abuse, last year prevalence of Salvia divinorum in 2009 was 6.0 % among
high school seniors (this percentage is higher than the previous year prevalence for
ecstasy). It appears that the use is restricted and experimental, rather than as a
social or party drug.
According to a 2006 study conducted by Khey et al. among students in a US college
(average age 19.8 years), the lifetime, last year and last month prevalences were
6.7, 3.0 and 0.5 % respectively, with half of the sample expressing no desire to use
the drug again: this suggests that Salvia divinorum use may have a low continuation
rate.
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Price
Prices vary between countries and depend on the type and amount of product
concerned. In early 2011, an EMCDDA snapshot of online shops found that the
European market prices for Salvia divinorum dried leaves ranged from EUR 0.27 (1
kilogram package) to EUR 1.5 per gram (one-gram package).
A 2011 EMCDDA snapshot also showed that Salvia 5X extracts are sold in small
amounts such as gram for around EUR 1112. Salvia 40X costs around EUR 30
for gram.
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Medical use
There is no approved medicinal use for Salvia divinorum or salvinorin A. However,
there is intensive research to explore the therapeutic potential of structurally related
KOR agonists or antagonists.
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Kratom (Mitragyna speciosa) drug profile

This photo has been kindly provided by Dr Istvn Ujvry.

Mitragyna speciosa Korth. (of the Rubiaceae family) is a 4 to 16 metre high tropical
tree indigenous to South East Asia, the Philippines and New Guinea but now
cultivated elsewhere. In Thailand, the tree and leaf-preparations from it are called
kratom. Traditionally, fresh or dried kratom leaves are chewed or made into tea; they
are seldom smoked. At a low dose, kratom has stimulant effects and is used to
combat fatigue during long working hours. At high dosages, however, it can have
sedative-narcotic effects. It is also used in traditional medicine and as an opium
substitute. The phytochemicals isolated from various parts of the tree include over 40
structurally related alkaloids as well as several flavonoids, terpenoid saponins,
polyphenols, and various glycosides. The main psychoactive components in the
leaves are mitragynine and 7-hydroxymitragynine, both found only in Mitragyna
speciosa.

Chemistry
Molecular structure: Mitragynine

Molecular formula: C23H30N2O4

Molecular weight: 398.50 g/mol
Mitragynine is the most abundant alkaloid in the leaves. It was first isolated in 1921
and its chemical structure was fully elucidated in 1964. The systematic (Chemical
Abstract) name is (E,2S,3S,12bS)-3-ethyl-1,2,3,4,6,7,12,12b-octahydro-8-methoxy-(methoxymethylene)-indolo[2,3-a]quinolizine-2-acetic acid methyl ester
(CAS Registry Number: 4098-40-2). Other names: (E)-16,17-didehydro-9,17dimethoxy-17,18-seco-20-yohimban-16-carboxylic acid methyl ester, 9methoxycorynantheidine, and SK&F 12711.
Mitragynine is insoluble in water but soluble in conventional organic solvents,
including acetone, acetic acid, alcohols, chloroform and diethyl ether providing
fluorescent solutions. Mitragynine distils at 230240 C at 5 mmHg. It forms white,
amorphous crystals that melt at 102106 C. The melting point of mitragynine
hydrochloric acid salt is 243C; the picrate melts at 223224 C and the acetate at
142 C.
Molecular structure: 7-hydroxymitragynine

Molecular formula: C23H30N2O5

Molecular weight: 414.50 g/mol
7-Hydroxymitragynine is present only in very small amounts in kratom leaves and
was identified in 1993. Its systematic (Chemical Abstract) name is
(E,2S,3S,7aS,12bS)-3-ethyl-1,2,3,4,6,7,7a,12b-octahydro-7a-hydroxy-8-methoxy-(methoxymethylene)-indolo[2,3-a]quinolizine-2-acetic acid methyl ester
(CAS Registry Number: 174418-82-7).
The chemical total syntheses reported for several kratom alkaloids are too complex
to be used for economic production of any these compounds. However, mitragynine
can serve as a chemical precursor to the more potent 7-hydroxymitragynine.

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Physical form
The leaves of the tree Mitragyna speciosa are oval or ovate-lanceolate and dark
green in colour and can grow to 180 mm long and 100 mm wide. The veins of the
leaves are either greenish-white or red the former is reputed to be more potent.
The average weight of a fresh and a dried leaf is about 1.7 and 0.43 g respectively.
The yellow and globular flowers of the tree bear up to 120 florets. The fruit is a
capsule containing numerous small flat seeds.
Kratom products are usually supplied as crushed or powdered dried leaves that are
light to dark green in colour. Powdery, greenish or beige-brown kratom preparations
fortified with extracts from other leaves are also available. Stable, paste-like extracts
and dark brown kratom resin can be made by partially or fully boiling down the water
from aqueous kratom leaf suspensions. Tinctures and capsules, filled with powdered
kratom, are also available.
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Pharmacology
Kratom preparations contain several phytochemicals in varying ratios rendering their
proper pharmacological evaluation difficult. Human clinical studies are scarce.
In general, the effects of kratom in humans are dose-dependent: small doses
produce cocaine-like stimulation while larger dosages cause morphine-like
sedative-narcotic effects.
After taking a few grams of dried leaves, the invigorating effects and euphoria are felt
within 10 minutes and last for one to one and a half hours. Kratom users report
increased work capacity, alertness, sociability and sometimes heightened sexual
desire. The pupils are usually normal or very slightly contracted; blushing may be
noted. In one of the few human clinical experiments, a 50 mg oral dose of
mitragynine produced motor excitement, followed by giddiness, loss of motor
coordination (positive Rombergs test), and tremors of the extremities and face. For
regular kratom users, loss of weight, tiredness, constipation, and hyperpigmentation
of the cheek may be notable side effects. The pharmacological mechanism
responsible for stimulant activity is unclear.
Kratom taken in large, sedating doses corresponding to 1025 g of dried leaves may
initially produce sweating, dizziness, nausea and dysphoria but these effects are
shortly superseded with calmness, euphoria and a dreamlike state that last for up to
six hours. Contracted pupils (miosis) are noted.
Mitragynine and 7-hydroxymitragynine, the two alkaloids mainly responsible for the
effects of kratom, are selective and full agonists of the -subtype opioid receptor
(MOR). The receptor agonist effect of kratom alkaloids is antagonised by the opioid
receptor antagonist naloxone. In addition, 5-HT2a and postsynaptic 2-adrenergic
receptors, as well as neuronal Ca2+ channels are also involved in the unique
pharmacological and behavioural activity of mitragynine.

In animal studies, the antinociceptive and cough-suppressant effects of mitragynine

were comparable to those of codeine. In mice, 7-hydroxymitragynine was several
times more potent analgesic than morphine even upon oral administration.
Kratom is slightly toxic to animals. Mice chronically treated with 7hydroxymitragynine developed tolerance, cross-tolerance to morphine and
withdrawal signs that could be precipitated by naloxone administration.
Regular kratom use may produce dependence. The withdrawal symptoms in humans
are relatively mild and typically diminish within a week. Craving, weakness and
lethargy, anxiety, restlessness, rhinorrhea, myalgia, nausea, sweating, muscle pain,
jerky movements of the limbs, tremor as well as sleep disturbances and hallucination
may occur. Treatment, if needed, may include dihydrocodeine-lofexidine
combination, non-steroidal antiinflammatory agents, antidepressants and/or
anxiolytics.
The metabolism of mitragynine in humans occurs via hydrolysis of the side-chain
ester, O-demethylation of the methoxy groups, oxidative and/or reductive
transformations, and the formation of glucuronide and sulfate conjugates. In a man
who fatally overdosed propylhexedrine and kratom, the postmortem mitragynine
concentrations ranged from 0.01 mg/kg to 1.20 mg/l.
The consumption of kratom concomitantly with other drugs can provoke serious side
effects. In fact, adverse drug interactions involving kratom tea taken with
carisoprodol, modafinil, propylhexedrine or Datura stramonium have been reported.
A fatal case in the United States involved a blend of kratom, fentanyl,
diphenhydramine, caffeine and morphine sold as a herbal drug.
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Origin
Dried kratom leaves sold in head/smart/herbal shops and over the Internet are
thought to originate from Mitragyna speciosa cultivated in South East Asia, most
likely in Indonesia (Bali kratom) where the plant is not controlled.
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Mode of use
Traditionally, the fresh or dried leaves of kratom are chewed or brewed into tea.
When making tea, lemon juice is often added to facilitate the extraction of
plant alkaloids; before drinking, sugar or honey may be added to mask the bitter
taste of the brew. The dried leaves are occasionally smoked.
To experience vigour and euphoria, traditional kratom eaters chew one to three
fresh leaves at a time. The veins are usually removed from the leaves before eating
and sometimes salt is added to prevent constipation. Only the masticated material
is swallowed. Consumption is followed by drinking warm water or coffee, tea or palm
sugar syrup. Regular and addicted users chew 3 to 10 times a day. When kratom is
not available, the leaves of Mitragyna javanica (other name Mitragyna parvifolia) are
used as substitute.
In southern Thailand, in recent years homemade ice-cold cocktails, called 4x100,
have become popular for their alleged alcohol-mimicking effect among young Muslim

people. The cocktails are made from kratom leaves, a caffeine-containing soft drink,
and codeine- or diphenhydramine-containing cough syrup as the three basic
ingredients to which ice cubes, an anxiolytic, an antidepressant or an analgesic drug
is added.
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Other names
The genus was given its Mitragyna name by the Dutch botanist Korthals because the
leaves and the stigmas of the flowers of the plant resemble the shape of a bishops
mitre. Other names of the plant are krathom, kakuam, ithang or thom (Thailand),
biak-biak or ketum (Malaysia), and mambog (Philippines).
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Analysis
The alkaloid composition of botanical and forensic samples can be analysed by
regular chromatographic and spectroscopic methods. Phylogenetic characterisation
of kratom samples by specific DNA nucleotide sequences can complement the
phytochemical analyses.
Kratom alkaloids can be separated by thin layer chromatography on silica gel plates
with detection by UV (254 nm). Upon spraying with either modified Ehrlichs reagent
or ferric chloride-perchloric acid reagent, mitragynine gives purple or grey-to-brown
spots, respectively.
The UV spectrum of the methanol solution of mitragynine shows a maximum at 225
nm with shoulders at 247, 285 and 293 nm. The characteristic absorption bands in
the IR spectrum of mitragynine are at 3 365, 1 690 and 1 640 cm -1. Significant
fragments in the electron impact ionisation mass spectrum (m/z): 398(M+), 383, 366,
269, 214, 200 and 186.
The UV spectrum of the ethanol solution of 7-hydroxymitragynine shows a
maximum at 220 nm with shoulders at 245 and 305 nm. The characteristic
absorption bands in the IR spectrum of 7-hydroxymitragynine in CHCl3 are at 3
590, 2 850, 2 820, 2 750, 1 700, 1 645, 1 630, 1 600, 1 490, 1 465 and 1 440 cm -1.
Significant fragments in the electron impact ionisation mass spectrum (m/z):
414(M+), 397, 383 and 367.
The parent alkaloids and their metabolites can be quantified in the urine at >100
ng/ml by GC-MS, at >25 ng/ml by HPLC-UV, and at >0.02 ng/ml for HPLC-MS. For
example, the concentration of mitragynine in a forensic urine sample of a regular
kratom user was 167 ng/ml (HPLC-MS). In a poisoning case, the blood serum
concentration of mitragynine two weeks after cessation of regular oral ingestions of
large doses (1421 grams daily) of dried kratom leaves was 0.020 ng/ml (HPLCMS).
No conventional immunological drug screening test is known that will detect
kratom alkaloids.
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Typical potency

The chemical composition of kratom in commercial products is unspecified and

depends on several factors, such as the particular variety and age of the plant, the
environment, and the time of harvest. The total alkaloid concentration in dried leaves
ranges from 0.51.5 %. In Thai varieties, mitragynine is the most abundant
component (up to 66 % of total alkaloids) while 7-hydroxymitragynine is a minor
constituent (up to 2 % of total alkaloid content). In Malaysian kratom varieties,
mitragynine is present at lower concentration (12 % of total alkaloids). The typical
mitragynine and 7-hydroxymitragynine concentrations in dried leaf or powdered
kratom products available in Japan were 1221 mg/g and 0.110.39 mg/g,
respectively; kratom resins contained 35.662.6 mg/g of mitragynine and 0.120.37
mg/g of 7-hydroxymitragynine.
According to GC-MS analysis of freshly made Malaysian ketum drinks, prepared by
extended boiling of fresh leaves in water, one 250 ml glass of ketum contained
22.525 mg mitragynine. About three such drinks a day are said to be sufficient to
diminish opiate withdrawal symptoms.
In the early 2000s, some obscure products labelled kratom acetate or mitragynine
acetate did not actually contain mitragynine. In recent years, products sold in
Germany and Sweden under the name Krypton as enhanced kratom preparations
turned out to contain caffeine and synthetic O-desmethyltramadol
(ODT) as adulterants. ODT is a bioactive metabolite of the synthetic opioid
analgesic tramadol and was apparently added to the herbal preparations to mimic
the sedative-narcotic effects of kratom.
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Control status
Neither Mitragyna speciosa nor mitragynine or other alkaloids from the plant are
listed in any of the Schedules of the United Nations Drug Conventions. Mitragyna
speciosa and/or mitragynine and/or 7-hydroxymitragynine are currently (September
2011) controlled in a number of EU Member States such as Denmark, Latvia,
Lithuania, Poland, Romania and Sweden.
Other countries that control kratom under their narcotic law are Australia, Malaysia,
Myanmar and Thailand. New Zealand controls Mitragyna
speciosa and mitragynine under its Medicines Amendment Regulations. In the USA,
kratom is not controlled though considered as a drug of concern.
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Prevalence
Kratom appeared on the global drug market only recently, thus there is no
information on the extent of its use outside South East Asia.
In Thailand, the National Household Surveys provide information on drug use
prevalence in that country. The 2007 Survey (26 633 respondents aged 1265 years)
indicated that the lifetime, past year and past 30 days prevalences for kratom were
2.32 %, 0.81 % and 0.57 %, respectively. These figures, with the exception of lifetime
use, were significantly higher than those for cannabis making kratom the most widely
used illicit drug in the country. Also in Thailand, lifetime, past year and past 30-days
prevalence studies among 13- to 16-year-old high-school students (n = 8 70812

148) in 2002, 2003 and 2004 showed an increase in the lifetime use of kratom (from
3.97 % to 9.43 %) and cannabis (from 4.44 % to 6.75 %), while a slight decrease
was noted for the use of amphetamines (2.79 % to 2.32 %). Past year and past 30days prevalence use data followed similar trends.
A recent roadside survey involving 1 635 motor vehicle drivers in Thailand revealed
the use of kratom by 0.9 % of the drivers, a prevalence close to that of cannabis (1.1
%) but much lower than that of amphetamines (1.8 %).Internet surveys conducted by
the EMCDDA in 2008 indicated that kratom was one of the most widely offered legal
highs in 44 % of the investigated 27 European online shops along with Salvia
divinorum (74 %), Hawaiian Baby Woodrose seeds (48 %), Spice smoking mixtures
(37 %), and stimulant-containing capsules (59 %). A more extensive EMCDDA
Internet survey in July 2011 showed that kratom was the most widely offered product
with 128 out of 631 (or 20 %) of online retailers shipping it to the EU. An Internet
snapshot carried out in the UK in April 2009 showed that among the 346 unique
products offered by 39 shops kratom (n = 30) was second only to Salvia
divinorum (n = 44).
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Price
Prices vary between countries and depend on the type and amount of the product
purchased. According to the EMCDDA Internet surveys conducted in 2008, the
prices of Kratom 15X extracts ranged from EUR 2.1 to 10.3 per gram in the
sampled European countries. In 2011, a follow-up EMCDDA snapshot of 314 online
shops found that prices ranged from EUR 6 to 15 per 10 gram of dried kratom and
EUR 7 to 8 per gram of Kratom 15X extract.
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Medical use
Six Asian and four African Mitragyna species are known to be used in traditional
medicine but the stimulant/sedative-narcotic/psychoactive effects are characteristic
only for Mitragyna speciosa. In South East Asia, kratom is used as an antidiarrheal, a
cough suppressant, an antidiabetic, an intestinal deworming agent and wound
poultice as well as to wean addicts off heroin. Outside Asia, anecdotal use of kratom
preparations for the self-treatment of chronic pain and opioid withdrawal symptoms
and as a replacement for opioid analgesics have been reported. There is, however,
no approved use of kratom or its alkaloids in modern medicine. It has been
suggested that the therapeutic potential of kratom or its purified ingredients for the
treatment of pain, depression and drug withdrawal symptoms should be explored.
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