Brown Lund Murch Ethnobotanika Mitragyna Speciosa

Author’s Accepted Manuscript
A Botanical, Phytochemical and Ethnomedicinal

Review of the Genus Mitragyna Korth:
Implications for Products Sold as Kratom
Paula N. Brown, Jensen A. Lund, Susan J. Murch
www.elsevier.com/locate/jep
PII: S0378-8741(16)30678-X
DOI: http://dx.doi.org/10.1016/j.jep.2017.03.020
Reference: JEP10769
To appear in: Journal of Ethnopharmacology
Received date: 3 September 2016
Revised date: 14 March 2017
Accepted date: 15 March 2017
Cite this article as: Paula N. Brown, Jensen A. Lund and Susan J. Murch, A
Botanical, Phytochemical and Ethnomedicinal Review of the Genus Mitragyna
Korth: Implications for Products Sold as Kratom, Journal of
Ethnopharmacology, http://dx.doi.org/10.1016/j.jep.2017.03.020
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1
A Botanical, Phytochemical and Ethnomedicinal Review of the Genus Mitragyna

Korth: Implications for Products Sold as Kratom.
Paula N. Brown1,2, Jensen A. Lund1,3, Susan J. Murch3*
1
Natural Health Products and Food Research Group, British Columbia Institute of Technology,
4355 Mathissi Place, Burnaby, British Columbia, Canada, V5G 4S8.
2
Department of Biology, University of British Columbia, 3247 University Way, Kelowna,
British Columbia, Canada, V1V 1V7
3
Department of Chemistry, University of British Columbia, 3247 University Way, Kelowna,
British Columbia, Canada, V1V 1V7
*Corresponding Author. Susan J. Murch, 3247 University Way, Kelowna, British Columbia,
Canada, V1W 2N3. e-mail: susan.murch@ubc.ca
Abstract
Ethnopharmacological Relevance
The genus Mitragyna (Rubiacaeae) has been traditionally used in parts of Africa, Asia and
Oceania. In recent years, there has been increased interest in species of Mitragyna with the
introduction of products to western markets and regulatory uncertainty.
Aim of the Study
This paper reviewed the traditional ethnomedicinal uses of leaves for species belonging to the
genus Mitragyna with reference to the botany and known chemistry in order to highlight areas of
interest for products currently being sold as kratom.
Materials and Methods
A literature search was conducted using Web of Science, Google Scholar, the Royal Museum for
Central Africa, Internet Archive, Hathi Trust, and Biodiversity Heritage Library search engines
in the spring of 2015, fall of 2016 and winter of 2017 to document uses of bark, leaf and root
material.
2
Results
Leaves of M. speciosa (kratom) had the most common documented ethnomedicinal uses as an
opium substitute or remedy for addiction. Other species of Mitragyna were reportedly used for
treating pain, however the mode of preparation was most often cited as topical application.
Other uses of Mitragyna included treatment of fever, skin infections, and as a mild anxiolytic.
Conclusions
Mitragyna species have been used medicinally in various parts of the world and that there is
significant traditional evidence of use. Modern products that include formulations as topical
application of liniments, balms or tinctures may provide effective alternatives for treatment of
certain types of pains. Future research is required to establish safety and toxicology limits,
medicinal chemistry parameters and the potential for different physiological responses among
varying genetic populations to support regulatory requirements for Mitragyna spp.
Keywords: Kratom, Mitragyna, M. speciosa, review, Mitragynine, 7-hydroxymitragynine

3
1.0. Introduction
The genus Mitragyna (Rubiaceae) encompases 10 species which grow in tropical and/or
arid parts of Africa, India, Bangladesh, China, Sri Lanka and southeast Asia (Govaerts et al.,
2015; Lofstrand et al., 2014; Table 1). Though traditionally used as medicine in these parts,
interest for species of Mitragyna has erupted in regions located outside of their native habitat.
Most notably Mitragyna speciosa (Korth.) Havil, commonly refered to as kratom, is now
commercially grown for a wide range of products (Figure 1A). Conducting a Google trends
search for the term “kratom” and revealed that the number of queries has increased steadily since
2004 (Figure 2), with individuals located in the United States, Canada, Austria and Germany
executing the most searches, usually for the purpose of purchasing products containing kratom.
M. speciosa leaf can be purchased in whole, shredded or powder form, encapsulated powder or
extract, resin or as a tincture for a variety of kratom ‘strains’ (i.e. Bali kratom, Indo red vein,
Malaysian kratom, Thai green vein, Thail red vein, etc) (Raffa, 2015). Depending on dosage and
mode of preparation, consumption of kratom (M. speciosa) is believed to have ‘cocaine’ and/or
‘opiate’ like effects with the latter leading individuals to consume products for treatment of pain
or opiate addiction.
Although species of Mitrgayna possess a long history of ethnomedicinal use outside of

North America, the earliest records that have been found to date describing their use in the
United States pertain to kratom (M. speciosa), and is published in the 1999/2000 issues of the
Entheogen Review, “a quarterly publication that served as a clearinghouse for data about the use
of visionary plants and drugs” between 1992 and 2008 (http://www.entheogenreview.com/). The
consumption of kratom in the United States has grown significantly over the last decade with the
availability of products being primarily via internet sales (PinneyAssociates, 2016). These
products are marketed for diverse uses, comparable to modern use in Southeast Asia. They are
used predominately for minor pain relief and to facilitate opioid withdrawal (Babu et al., 2008;
Boyer et al., 2007; Ward et al., 2011). Although there have been no formal epidemiological
studies on usage outside of Southeast Asia, Boyer et al. (2007) reports that a cyber-community
survey indicates many consumers use undefined kratom products for self-treatment of chronic
pain.
4
To complicate matters further, since kratom’s introduction into the United States, there
has been some concern over safety with conflicting evidence as to whether M. speciosa has
potential to be addictive, misused, or lead to adverse reactions including death
(PinneyAssociates, 2016; Suwanlert, 1975; Warner et al., 2016; Yearsley, 2016). On February
28th, 2014, the US Federal Drug Administration (FDA) issued an import alert indicating that the
FDA considers kratom to be a new dietary ingredient under section 413(d) of the Act [21 U.S.C.
350b(d)] because, to the best of the agency's knowledge, there is no information demonstrating
that this substance was marketed as a dietary ingredient in the United States before October 15,
1994. Since this announcement, the FDA has made several high-value seizures of kratom plant
material. On August 30, 2016, the US Drug Enforcement Administration (DEA) announced its
intent to place the active compounds found in kratom, mitragynine and 7-hydroxymitragynine,
into Schedule I of the controlled substances act (US Drug Enforcement Administration, 2016a).
The DEA has since withdrawn this intention pending further discussion and risk analysis (US
Drug Enforcement Administration, 2016b).
In Southeast Asia kratom use is most prevalent in Thailand and Tanguay (2011) reviewed
available epidemiological data, in support of his argument that kratom use should be
decriminalized. Tanguay stated, that regardless of use pattern, "there is a general consensus
among community members and leaders, academics and policymakers, as well as public health
and law enforcement representatives in southern Thailand that kratom use and dependence carry
little, if any, health risks". It is recognized that regular use of kratom, over long periods of time,
may result in physical dependence similar to that developed with regular coffee consumption.
The physical dependence is dose- and time- dependent, and withdrawal symptoms are generally
moderate, short and benign with such physical dependence, in combination with similarity to
effects observed for other addictive substances (e.g. excessive work endurance and alertness, like
amphetamines) has resulted in some Southeast Asian reports that kratom is addictive
(Suwanlert, 1975). However, in some respects, the real world profile of kratom consumption
resembles that of coffee and tea consumption in that it appears primarily motivated by lifestyle
and potential health benefiting reasons, and does not appear to be in the category of compulsive
5
use despite harmful consequences that is often considered a hallmark of addiction

(PinneyAssociates, 2016; Raffa, 2015; Warner et al., 2016).
Due to the uncertaintly surrounding the legality of M. speciosa, other species from this
genus are now being marketed and sold on-line as a ‘legal alternative’ to kratom. In light of the
growing interest in members of Mitragyna, this paper will review traditional ethnomedicinal uses
making reference to the botany, known chemistry, and toxicology of species. It is important to
gain a better understanding of this Genus and to identify potential gaps in knowledge that could
impact the safety of consumers purchasing products being sold as kratom or alternatives to
kratom.
2.0 Methods
A literature search was conducted using Web of Science TM, Google ScholarTM, the Royal
Museum for Central Africa http://www.africamuseum.be/collections/external/prelude, Internet
Archive https://archive.org, Hathi Trust http://www.hathitrust.org/ , and Biodiversity Heritage
Library http://www.biodiversitylibrary.org/ search engines in the spring of 2015, updated in the
late fall of 2016 and winter 2017. Search terms included all known latin binomial names for
members of the genus (Table 1). Results were then mined individually and grouped by theme
(i.e. botany, medicinal use and chemistry). In addition to the above, non-digitized texts were
retrieved using resources provided by the University of British Columbia library. Uses pertaining
to bark, leaf and root material were all recorded, however for the purpose of this paper only
medicinal uses pertaining to leaves will be described in detail.
3.0. Botany
Mitragyna is a genus composed of small (max. height < 15 m tall), medium (max. height
beween 15 m -25 m tall) and large (max. height > 25 m tall) decidudous, semi-deciduous or
evergreen trees (Balasubramanyan et al., 1985; Lemmens et al., 2012; Puff, 2007; Tao and
Taylor, 2011). Ecological requirements and habitat for Mitrgyna varies between species, for
example Mitragyna can be found growing in tropical forests, in close proximity to waterways or
in swamp forests and marshes (Lemmens et al., 2012; Pufff, 2007). Alternatively, others have
been known to thrive in disturbed ares (Puff, 2007) or under more arid conditions (i.e. deserts or
6
savannahs) in which periodic rainfall or flooding occur (Abdullahi et al., 2011; Maydell, 1988;
Panwar and Tarafdar, 2006). The above is not surprising given members of this genus are
distributed across tropical Africa and surrounding areas, eastwards towards the Indian
subcontinent through to China, and downwards through to Southeast Asia and Melanisa (Table
1). All trees produce a compound inflorescense, which consists of ellipsoidly arranged greenish
white to yellow flowers heads. Some flowers purportedely give off a sweet scent and are visited
by various insects including (i.e. bees, butterflies, beetles) in order to disperse their pollen
(Abdullahi et al., 2011; Kato et al., 2008; Maydell, 1988). Plants will reproduce through
dispersal of their seeds by wind, although certain species have been propagated via stem and
sucker cuttings (Lemmens et al., 2012).
3.1. Taxonomy of Mitragyna
Mitragyna belongs to the family Rubiaceae (the fourth largest angiosperm family with
~13,000 species world-wide) (Davis et al., 2009). Members of the Rubiaceae can be classified
further amongst three subfamilies: Cinchonoideae, Ixoroideae, and Rubioideae (Davis et al.,
2009); with the Cinchonoideae being the smallest (~120 genera including Mitragyna) (Manns
and Bremer, 2010). Within the Cinchonoideae, Mitragyna is a member of the tribe Naucleeae
(subtribe Mitragyninae), and recent work suggests that Mitrgayna is monophyletic (Löfstrand et
al., 2014; Razafimandimbison and Bremer, 2002). Presently the genus Mitragyna consists of the
following 10 species: Mitragyna diversifolia (Wall. Ex G.Don) Havil., Mitragyna hirsuta Havil.,
Mitragyna inermis (Willd.) Kuntze., Mitragyna ledermannii (K. Krause) Ridsdale, Mitragyna
parvifolia (Roxb.) Korth. Mitragyna rotundifolia (Roxb.) Kuntze., Mitragyna rubrostipulata (K.
Schum.) Havil., M. speciosa, Mitragyna stipulosa (DC.) Kuntze, and Mitragyna tubulosa (Arn.)
Kuntze (Govaerts et al., 2015; Lofstrand et al., 2014; Table 1). Taxonomic re-arrangement
between subtribes in Naucleeae has led to multiple synonyms and heteronyms for this genus,
thus when reviewing the literature it is important to consider all latin binomial names for
members of this genus (Table 1).
3.2. Identification of the genus Mitragyna
Like other members of the Rubiaceae, Mitragyna can be identified through examination
of leaf (simple opposite and interpetiolar stipules; Figure 1B) and floral morphology (inferior
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ovary, gameopetalous flowers) (Davis et al., 2009; Razafimandimbison and Bremer, 2001). As a
member of the tribe Naucleeae, Mitragyna species will posseses a globular spherical
inflorescence but differ from other members of this tribe most notably by possessing mitriform
stigmas (though some can look clavate in shape). In addition to stigma shape, individuals can be
distinguished using characteristics such as ovule placentation (numerous, basally attached) and
pollen structure (three zonocolporate, H-shaped endoaperatures) (Löfstrand et al., 2014;
Razafimandimbison and Bremer, 2001; Tao and Taylor, 2011).
By examining the distribution of species found in Table 1, Mitragyna can be divided into
two categories: 1) African species (n = 4, M. inermis, M. ledermannii, M. rubrostipulata, M.
stipulosa) or 2) Asian species (n = 6, M. speciosa, M. tubulosa, M. rotundifolia, M. parvifolia,
M. hirsuta, M. diversifolia). Within each group there is great potential for misidentifaction
without having access to flowers and fruits. For example, M. parvifolia can be mistaken for M.
diversifolia (Havilland, 1897; Tao and Taylor, 2011), while M. stipulosa can be misidentified as
M. ledermanii (Lemmens et al., 2012; Nyemb, 2011). Differences between distribution patterns
for Mitragyna species as well as the shape and length of the corolla and clayx are very imprtoant
ensuring the proper identify of species (Baerts and Lehmann, 1989; Nyemb, 2011; Tao and
Taylor, 2011).
3.3 Substituion of species
Several sources report that leaves from M. speciosa are prone to substitution by members
of the same tribe or genus. For example, leaves from Uncaria homomalla (syn: Uncaria
quadrangularis) (Rubiaceae, tribe Naucleeae) and M. diversifolia1 (Ponglux et al., 1977; Shellard
et al., 1967; Tantivatana et al., 1979) have both purportedly been used as a substitute for kratom
(M. speciosa). Similar to the above, analysis of rDNA extracted from kratom products revealed
the occurrence of substitution of M. speciosa for other species belonging to the tribe Naucleeae,
although the exact identities could not be determined (Maruyama et al., 2009). Hanna (2003)
also reports that an unidentified species was mistakenly being sold as M. speciosa, and that once
1
This species was originally described as M. javanica var. microphylla in Shellard et al. 1976. Although this name is
now considered a synonym for M. parvifolia var. microphylla, we have chosen to name this species M. diversifolia
for the following reason: The specimen was collected in Thailand and according to to Puff 2007 “var. microphylla”
has been incorrectly used to identify small-leaved plants of M. diversifolia from Thailand, since M. parvifolia does
not grow in Thailand.
8
the mistake was conveyed to suppliers, the unidentified material continued to be sold by some as
as an alternative to kratom with “kratom-like effects” under the name “Mellow Gold”.
Mitragyna species can display a wealth of phenotypic plasticity in the field, making it
challenging to identify individuals solely through macroscopic examination of vegetative
materials. Asian species of Mitragyna including M. diversifolia, M. hirsuta, M. parvifolia, and
M. rotundifolia are most likely to be used as a substitute for M. speciosa and substantial effort
has been put into characterizing leaf tissues in these species (Balasubramanyan et al., 1985;
Risdale, 1978; Shellard and Shadan, 1964; Shellard and Lees, 1965; Shellard and Wright, 1967;
Tao and Taylor, 2011; Puff, 2007; Walker and Ahmad, 1968, 1970, 1971). In addition to
macroscopic observation, microscopic investigation of leaf tissues can be useful for identifying
Asian species of Mitragyna. For example a study by Lersten and Horner (2011) examined 8
species of Mitragyna and noted diffrences between leaf tissues with respect to the type of
crystals that are present (druse, concretions, crystal sand, secondary crystal) and their location
(i.e. idoblasts, vascular bundle mesophyll). In addition to the genus Mitragyna, members from
the tribe Naucleeae were also examined in this study, with the authors noting that crystal
concretions were unique to M. hirsuta, M. inermis, M. parvifolia, and M. rotundifolia. Similar to
the above, concretions have also been reported by Shellard and Wright (1967), Shellard and Lee
(1965) and Walker and Ahmad (1968, 1970) in M. hirstua, M. diversifolia, M. speciosa and M.
parvifolia but refer to these species as ‘cluster crystals’. While the distribution of crystal
structures may potentially provide a promising approach for authentication of materials to genus
or species level, these studies are based on limited samples, thus larger in depth analysis in order
to determine whether the observerd patters are consistent across all taxa.
4.0. Chemistry of Mitragyna
The chemistry of Mitragyna has been investigated for more than 100 years. The earliest
studies focused on the isolation and identification of the indole alkaloid mitragynine from M.
speciosa leaves (Field, 1921; Hooper, 1907; Shellard, 1974). To this point, 79 individual
alkaloids have been described in plant materials of Mitragyna as well as a spectrum of other
secondary metabolites including flavonoids, polyphenolic compounds, triterpenoids, triterpenoid
9
saponins, monoterpenes, and secoirioids (Gogineni et al., 2015). Based upon our survey of
literature pertaining to Mitragyna phytochemistry and a search of the NAPALERT database for
records of natural products isolated in Mitragyna spp., a total of 57 phytochemicals, 37 of which
are alkaloid compounds, are unique to M. speciosa leaf. Other Mitragyna species are also a rich
source of useful phytochemicals, however many of the alkaloids in these species have only been
studied in non-leaf materials.
There is a wide range of alkaloids described in leaves across the genus Mitragyna (Table
2; Figures 3,4). The most well described species, M. speciosa, contains a number of
pharmacologically active alkaloids in appreciative amounts including mitragynine, 7-hydroxy
mitragynine, mitraphylline, speciociliatine, speciogynine, and paynantheine. Depending on
ecotype, the total proportion of mitragynine in leaf tissue as a fraction of total alkaloids ranges
from 66% in plants of Thai origin (Ponglux et al., 1994) to 12% in plants of Malaysian origin
(Takayama et al., 1998). Mitragynine is the most abundant pharmacologically active constituent
of M. speciosa, however recent studies have shown 7-hydroxymitragynine (or 7α-hydroxy-7H-
mitragynine; Hassan et al., 2013) to be significantly more active. 7-hydroxymitragynine was first
isolated in M. speciosa in 1994 and comprises less than 2% of total alkaloid content in crude leaf
extracts (Ponglux et al., 1994). The vast majority of studies on M. speciosa emphasize these two
alkaloids (Houghton and Said, 1986; Houghton et al., 1991; Kikura-Hanajiri et al., 2009;
Ponglux et al., 1994; Shellard et al., 1978; Takayama et al., 1998; Takayama, 2004).
Proportions of alkaloid compounds can vary dramatically in Mitragyna plants depending

on stage of maturity (Houghton et al., 1991; Shellard et al., 1978), or ecotype (Leon et al., 2009;
Takayama et al., 1998). Commercial products labeled as kratom also show dramatic variation in
phytochemical content (Kikura-Hanajiri et al., 2009; Mudge and Brown, 2016; Parthasarathy et
al., 2013). In addition to the alkaloid-type phytochemicals in the leaves; bark and stem bark
contain a variety of terpenoids not detected in leaf materials from the same plants (Cheng et al.,
2002a, 2002b; Gogineni et al., 2015; Kang and Hao, 2006; Tapondjou et al., 2002; Takayama et
al., 2004). Additional secondary metabolite classes have been isolated in various Mitragyna
species, including flavonoids and polyphenolics (Gogineni et al., 2015; Said et al., 1991),
10
however unlike alkaloids of the genus, these additional chemical classes are not attributed in the
literature to producing kratom’s psychoactive effects.
5.0. Pharmacology and Toxicity of Kratom Leaf and Kratom Leaf Alkaloids
The pharmacology and toxicology of Mitragyna and phytochemicals isolated from

members of this genus is not discussed in detail here but has been extensively reviewed in recent
literature (Adkins et al., 2011; Hassan et al., 2013; Raffa et al., 2013; Warner et al., 2016). At the
time of writing, the vast majority of Mitragyna-related mechanistic pharmacological studies
focus either upon purified kratom alkaloid compounds (Table 3) or extracts from M. speciosa.
5.1. Pharmacology
Much of the analgesic and opiate-like psychoactive effect of kratom has been associated
with two compounds only detected to date in M. speciosa, mitragynine and 7-
hydroxymitragynine. These two alkaloids are μ-opioid receptor agonists and have demonstrated
suppression of thermal and mechanical nociceptive responses (Horie et al., 2005; Matsumoto et
al., 1997, 2004; Thongpradichote et al., 1998; Takayama et al., 2002; Wigdor and Wilcox, 1987;
Wantanabe et al., 1997;) with 7-hydroxymitragynine demonstrating a 13-fold higher opioid
agonist effect over morphine and a 46-fold higher opioid agonist effect over mitragynine
(Matsumoto et al., 2004; Takayama et al., 2002). Furthermore, one study determined that
mitragynine antagonizes both serotonergic and noradrenergic receptor systems, leading to
antinociception of both thermal and mechanical stimuli via an in vivo study of mice (Matsumoto
et al., 1996).
Extracts of M. speciosa demonstrate analgesic/antinoceceptive properties. In one study of
extracts administered to mice, methanolic extracts of M. speciosa leaf (50, 100, 200 mg/kg
doses) and purified alkaloid fractions from M. speciosa leaf (5, 10, 20 mg/kg doses) were
compared for antinociceptive properties in mice. Via heat-induced pain, both extracts
demonstrated antinociceptive properties, however the authors suggest that the methanolic extract
was more potent due to possible additive or potentiative effect by other compounds (Wantana et
al., 2007). In addition to mitragynine’s analgesic properites, one in vitro study determined that
the compound may suppress prostaglandin E-2 production via inhibition of mRNA expression
11
leading to production of COX-2 enzymes, suggesting a possible anti-inflammatory action (Utar

et al., 2011).
An assortment of other pharmacological activities have been attributed to kratom and it’s
alkaloids. Other Mitragyna alkaloids, aside from the widely studied mitragynine and 7-
hydroxymitragynine, such as mitragynine pseudoindoxyl, corynantheidine, speciociliatine
(Takyama et al., 2002), and 9-hydroxycorynantheidine (Matsumoto et al., 2006) all demonstrate
opioid receptor agonist activity. 9-hydroxycorynantheidine demonstrated an agonistic effect
upon μ-opioid receptors in guinea pig ileum in a dose-dependent manner, however weaker than
the effect of mitragynine (Matsumoto et al., 2006). A recent study examined the structure-
activity relationship of mitragynine pseudoindoxyl in a combination of in vitro radioligand
binding assays and in vivo studies of mice. The authors determined that the compound provides
analgesia via a µ-opioid receptor agonism/δ-opioid receptor antagonism pathway with negative
side effects and addictive properties not unlike, but less intense than morphine (Varadi et al.,
2016). Vasodilation, anti-arrythmatic, and anti-hypertensive effects due to calcum channel
blocking and potassium channel modulation via rhynchophylline have been observed in vitro
(Zhou and Zhou, 2010).
A 2010 study of effects of mitragynine (0.0156 mg/mL) and M. speciosa methanolic
extract (0.1-1 mg/mL) on neuromuscular junctions of sacrificed Wistar rats showed both have a
muscle relaxation effect, with the extract more effective than mitragynine alone (Chittrakarn et
al., 2010). The extract contained the same concentration of mitragynine (0.0156 mg/mL) and
authors attribute the additional efficacy to other alkaloids present in the extract (Chittrakarn et
al., 2010). In another study Wistar rats were administered methanolic kratom extract in
treatments ranging from 50-400 mg/kg in order to examine a possible antidiarrheal effect of
kratom, as described in Thai ethnomedicine. The authors determined that the kratom extracts did
have an antidiarrheal effect in a dose-dependent fashion in a castor oil-induced diarrhea model
(Chittrakarn et al., 2007). Both mitragynine and M. speciosa leaf extracts have also been studied
to establish a pharmacological mechanism for ethnomedical use of the plant for treatment of
diabetes. The authors determined leaf extracts, and to a lesser extent, mitragynine, upregulate
glucose transporter protein expression in vitro in a similar fashion to insulin, providing
preliminary evidence for the plant’s role in treatment of diabetes (Purintrapiban et al., 2011).
12
The effect of kratom and kratom alkaloids upon psychological disorders in a

pharmacological context is still poorly understood. To study antidepressant effects of
mitragynine, mice were fed doses ranging from 5-30 mg/kg with psychological changes
oberseved during forced swim tests and tail suspension tests and locomotor changes in an open
field test. The results showed that doses of 10 mg/kg and 30 mg/kg had a significant
antidepressant effect without significant locomotor impairment (Idayu et al., 2011). The
pharmacokinetics of kratom and kratom alkaloids in humans is also not well understood.
Pharmacokinetic data from nine participants of a 2015 study on 10 male chronic kratom users in
Thailand exhibited an oral two-compartment model. After administration of kratom tea,
maximum plasma concentration of mitragynine was achieved in 0.83 ± 0.35 hours with the
terminal half-life found to be 23.24 ± 16.07 hours, and its apparent volume of distribution
determined as 38.04 ± 24.32 L/kg (Trakulsrichai et al., 2015).
In addition to studies of M. Speciosa leaves and kratom alkaloids, there are many
publications focused on the pharmacological activity of related species, other plant parts and
other chemical classes. These include: snake venom inhibition via M. stipulosa quinovic acid
glycosides (Fatima et al., 2002); Anti-inflammatory and analgesic properties of M. ciliata stem
bark extract (Dongmo et al., 2003); vasodilation in rodent models induced by administration of
M. ciliata stem bark extract (Dongmo et al., 2004); and muscle relaxation induced by M. inermis
stem bark extract in Wistar rat ileum tissue (Sy et al., 2004). Further, some mechanistic studies
have been conducted on M. inermis to connect a pharmacological mechanism with the use of M.
inermis leaf for treatment of hepatic illnesses in the ethnomedicine of Mali. The authors
determined that administration of alkaloid extracts from M. inermis leaf significantly increased
bilary flow in Wistar rats without adverse hepatotoxic events (Toure et al., 1996). Another study
of M. inermis determined that hydromethanolic extracts of leaf or roots displayed antimalarial
activity in vitro, but not with aqueous extracts (comparable to traditional preparation in Mali
ethnomedicine) of the plant (Traore-Keita et al., 2000).
5.2. Toxicity
13
Toxicity is not well understood for kratom and kratom alkaloids and toxic and lethal
dosages are not yet fully established (Karinen et al., 2014). There are, however, numerous
regular kratom users in Southeast Asia and a history of kratom consumption across hundreds of
years with relatively very few reports of adverse events associated with its use
(PinneyAssociates, 2016). Case studies exist were a combination of chronic kratom use with
other narcotic drugs resulted in liver damage and even death in humans (Dorman et al., 2015;
Warner et al., 2016). In addition to the presence of multiple other drugs found in the serum,
mitragynine concentrations in these fatalities range anywhere from 0.39 – 1.06 mg/L (Holler et
al., 2011; Karinen et al., 2014; Neerman et al., 2013). Another cause for concern is adulteration
of kratom with other narcotic substances. In Sweden, nine deaths were reported after persons
consumed an herbal blend, “Krypton”, containing O-desmethyltramadol—a active metabolite
associated with repiratory depression leading to death when overdosed. It should be noted that to
date, there are no reports originating in the United States causatively linking kratom overdosing
alone to death (PinneyAssociates, 2016).
In vitro study of mitragynine demonstrated cytotoxicity partially due to metabolic

transformations by CYP 2E1 and 2A6 enzymes—authors caution that users with high CYP2E1
activity, such as heavy alcohol consumers, may be at higher risk of illness associated with
kratom use (Saidin et al., 2015). There is also evidence of a possible interaction of mitragynine
and 7-hydroxymitragynine with P-glycoprotein substrates dugs (Manda et al., 2014). Interactions
of drugs with kratom and kratom alkaloids have also been reported for other plants and
substances (Warner et al., 2016). Another recent study found that mitragynine and related kratom
alkaloids, including paynantheine, speciogynine, and speciociliatine exert cardiotoxicity at low
concentrations in comparison with cytotoxic half-killing doses in various cell lines (0.91-2.47
µM and 10.43-1412.06 µM, respectively) via inhibition of an ion channel associated with the
rapid delayed rectifier potassium current. This inhibition led to action potential duration causing
arrhythmia in cardiac cells (Lu et al., 2014). A recent study examined in vitro cytotoxicity of
kratom leaf extracts, pure mitragynine, and commercial kratom products via evaluation of human
intestinal Caco-2 and neuronal SH-SY5Y cell line models. The authors determined that there is a
concentration-dependent relationship of the kratom extracts, products, and mitragynine with
decreasing cell viability, particularly in neuronal cells. Furthermore, the commercial powders
14
and resin were significantly more cytotoxic than kratom leaf extract or pure mitragynine
(Oliveira et al., 2016).
In vivo studies of M. speciosa and Mitragyna alkaloid toxicity have been performed on
mice (Idayu et al., 2011; Reanmongkol et al., 2007; Sabetghadam et al., 2011) and rats (Kamal et
al., 2012; Kumarnsit et al., 2006; Muhammad et al., 2010; Sabetghadam et al., 2013). LD50 was
established in male Swiss mice by Reanmongkol et al. (2007) via increasing single dosages of
either methanol (LD50 = 4.90 g/kg) or alkaloid (LD50 = 173.20 mg/kg) extracts of M. speciosa
leaf. Sabetghadam et al. (2011) also lethality in male Swiss mice via increasing single dosages of
either mitragynine (LD50 = 477 mg/kg) or alkaloid extracts of M. speciosa leaf (LD50 = 592
mg/kg). A study of neurological effects upon injection of 0, 10, or 30 mg/kg methanolic extracts
of M. speciosa leaf concluded no dose-dependent effect on open field test performance in
Jcl:ICR mice (Idayu et al., 2011).
Aqueous M. speciosa leaf extracts were fed to male and female Sprauge-Dawley rats via
oral gavage at 0, 1, 10, 100 mg/kg; after 14 days no mortality occurred, however hepatic steatosis
was present in all treated rats with centrilobular necrosis in the male 2000 mg/kg-treated group
(Kamal et al., 2012). Another study of daily doesed mitragynine (0, 1, 10, 100 mg/kg) over 28
days via oral gavage also examined pathologies, clinical chemistry or behavioural differences in
male and female Sprauge-Dawley rats. For all doses hematological paramaters were significantly
reduced with increased serum concentrations of liver enzymes (Sabetghadam et al., 2013). At 10
and 100 mg/kg, some liver histopathologies were apparent and at 100 mg/kg, brain
histopathology was apparent (Sabetghadam et al., 2013). One study of Sprauge-Dawley rats fed
varying doses of methanolic extracts of M. speciosa leaf over 14 days showed no mortality or
toxicity symptoms, however all treated rats demonstrated significantly elevated blood pressure.
Furthermore, the highest-dosed group (1000 mg/kg) showed evidence of severe hepatotoxicity
and mild nephrotoxicity upon cytological examination (Harizal et al., 2010).
The effects of ethanolic M. speciosa leaf extracts upon pregnant Sprauge-Dawley rats
determined that defects were only present in oral doses exceeding 1000 mg/kg daily during days
8-13 of pregnancy (Muhammad et al., 2010). A longer-term (60 day) study examined differences
15
in food and water intake after single 0 or 40 mg/kg methanol M. speciosa leaf extract injections
to male Wistar rats and determined that there was a significant reduction in both food and water
intake in the treated group (Kumarnsit et al., 2006).
Overall the toxicity of M. Speciosa and kratom alkaloids appears to be relatively low at
typical dosages however there is little information related to the toxicology of pure kratom
alkaloids and other Mitragyna species. Only one study on M. inermis was found; after rats were
fed a dose up to 3 g/kg/day of hydroethanolic leaf extracts over a 28 day period, no significant
abnormalities or toxicity was observed aside from slight histological variations (Monjanel-
Mouterde et al., 2006). However given the plethora of kratom and kratom alternative products in
the marketplace and traditional practice of the species substitution across the Genus Mitragyna
there is a suprising paucity of toxicological data.
6.0. Ethnomedical Uses of Plant Tissues
Our review of the literature revealed that bark, branches, fruit, flower, leaf, root, stems
and trunks of Mitragyna species are employed together, alone or with other species to treat a
wide range of ailments, with the majority of references pertaining to bark (n=75), leaf (n=66),
and root (n=22) material. Reported uses for a specific plant part were not evenly distributed
across species (Figure 5). Bark, leaf, and root material from M. inermis, M. parvifolia, M.
rotundifolia, M. rubrostipulata and M. stipulosa were all used medicinally, while only leaves
from M. speciosa and bark from M. diversifolia and M. hirsuta had reported uses (Figure 5). No
uses were found for M. tubulosa. Reported uses for bark, leaf and root material were described
for all ethnomedicinal categories (Figure 6), except for drug addiction (4), fatigue, weakness and
wasting (5), opium substitute (9) and other (14) categories (Figure 6). With respect to kratom
use, it is interesting to note that ethnomedicinal uses as an opium substitute or remedy for
addiction were only described for leaves of M. speciosa.
6.1 Fever, Malaria, and African sleeping sickness
Leaf, bark and root material were reportedly used to treat fever, malaria or African
sleeping sickness from 30%, 50%, and 20% of species found within the genus Mitragyna
16
respectively (Figure 6; Tables 4-6). Leaves from M. inermis are boiled on their own, with twigs
from M. inermis, or in conjunction with other plants and comsumed to treat malaria (Ahua et al.,
2007; Asase et al., 2005; Chevalier and Laffitte, 1937; Sangare, 2003; Traore et al., 2013). Stems
and/or leaves from M. inermis can also be boiled with other plants and used as a wash/bath to
treat fever or malaria (Fernandez de la Pradilla, 1981, 1985, 1988; Sangare, 2003; Van Der Steur,
1994). Similarly, a steam-bath or fumigation treatment is made from leaves of M. inermis and
used against malaria (Asase and Yeboah, 2012; Malgras, 1992). Leaves from M. inermis or a
mixture with other plants can be comsumed as a decoction to treat fever (Igoli et al., 2005;
Nordeng et al., 2013). A decoction made from leaves and stem bark of M. inermis is taken
internally to treat African sleeping sickness (Diallo et al., 2006). Though less frequently
reported, leaves from M. ledermannii and M. rubrostipulata are used to treat malaria or fever
(Cihyoka, 1999; Lamidi et al., 2007; Muganga et al., 2010; Muganga, 2012).
6.2. Anti-poison
Leaf, bark and root material were reportedly used as an anti-venom, anti-poison or emetic
for only 10% of species found within the genus Mitragyna (Figure 6; Tables 4-6). Leaves from
several species of Mitragyna have previously been described as toxic or a poison. For example,
healers from the Bamako districts, Mali consider leaves from M. inermis as toxic and capable of
making someone vomit (Maiga et al., 2005) Furthermore, Pammel (1910) and Castellani (1919)
report M. speciosa as a poison in Borneo and Malacca respectively. Interestingly, leaves from M.
rubrostipulata are macerated in water with other plants and taken internally as an anti-poison in
Rwanda (Kayonga and Habiyaremye, 1987), it is possible that leaves may possess emetic
properties which could lead them useful as an anti-poison.
6.3. Dermatological aid
Leaf, bark and root material were reportedly used as dermatological aids from 60%, 20%,
and 20% of species found within the genus Mitragyna respectively (Figure 6; Tables 4-6). A
majority of reported ethnomedicinal uses for these species involved external application of a
specific preparation made from leaves. For example, leaves from M. inermis are made into a
decoction and used either topically, through inhalation, ingestion or bathing in order to treat skin
ailments such as boils (Inngjerdingen et al., 2004; Nadembega et al., 2011; Zerbo et al., 2011).
17
Leaves from M. ledermannii are applied to wounds as a dressing (Pobeguin, 1911), while leaves
and flowers from M. parvifolia are used to treat tumours, cuts and wounds (Chavre, 2011),
sometimes by topically applying a paste that is made from its leaves (Sharma et al., 2014). Latex
collected from leaves of M. rotundifolia is used topically in order to prevent the formation of pus
from tumours and boils (Debnath et al., 2014). Powder or juice made from leaves of M.
rubrostipulata are used to soothe skin ailments or to wash wounds by applying locally (Baerts
and Lehmann, 1989; Durand, 1960). Decoctions and poultices made from leaves of M. speciosa
are used to treat skin ailments (Burkhill and Haniff, 1930; Maneenoon et al., 2015).
6.4 Drug dddiction
Modern use of kratom includes a wealth of anecdotal evidence for treatment of drug addiction,
most commonly addiction to opiods. Interestingly, this use as an opium substitute may have
have been influenced by a historical inaccuracy in the literature that is frequently misquoted.
Articles published by D. Hooper in 1907 incorrectly quote Ridley (1897) by stating that leaves of
M. speciosa are “employed in Perak as a remedy for the opium habitat”. Interestingly, Ridley
(1897) never used the word remedy, instead he claims that “leaves [of M. speciosa are] used as a
substitute for opium in Perak, according to Mr. Wray”. Annoyed by the misquote, Leonard
Wray (Ridley’s informant), published an articlein 1907 to point out this mistake:
“This is quite another matter; “remedy” and “substitute” being words of such widely diverse
meaning. It only shows, once again, how very necessary it is to look up references” (Wray,
1907).
Wray’s efforts did not put an end to assumptions that M. speciosa and other members of the
genus Mitrgayna are remedies for addiction to opium. The following year, E. Merck’s
“Jahresberioltte, Jahkrqang XXI” compendium of drugs and preparations lists M. speciosa as an
anti-opium remedy according to Hooper and Ridley (The Lancet, 1908). Similarly, articles
published in the national druggist refer to both M. speciosa and M. parvifolia as opium remedies
(Hooper, 1907). To the best of our knowledge, a reference directly suggesting the use of M.
speciosa as a treatment for opium cravings could not be found until 1930, in which Burkhill and
Haniff published their notes collected on “Malay Village Medicine” while stating that
consumption of M. speciosa is “a remedy apparently worse than the disease [opium addiction]”.
18
More modern clinical studies are needed to determine whether the reported effects are
pharmacological or placebo.
6.5. Wasting syndrome, poor nutrition or stimulant
Leaf and bark material were reportedly used to treat wasting syndrome (pathological
weight loss), poor nutrition or as a stimulant for 30% and 20% of species found within the genus
Mitragyna respectively (Figure 6; Tables 4-6). A decoction of leaves from M. inermis are used as
a bath or taken internally to treat wasting syndrome or children suffering from bad nutrition
(Kerharo and Adam, 1964, 1974; Van Der Steur, 1994; Thoen and Thiam, 1990). In Indo-China
leaves from M. parvifolia are used as an appetite stimulant (Perry, 1980). In Peninsular Siam and
Bangkok, chewing of leaves from M. speciosa is said to give energy to “those who do arduous
work, as elephant drivers, collectors of jungle produce, boatmen” which enables them “to endure
great fatigue and exposure to torrid heat” (Chemist and Druggist, 1930; Suwanlert, 1975).
6.6. Gastrointestinal aid and parasites
Leaf, bark, and root material were reportedly used as a gastrointestinal aid for 60%, 70%
and 30% of species found within the genus Mitragyna respectively (Figure 6; Tables 4-6).
Leaves from M. inermis are used to treat abdominal pain (Kerharo and Adam, 1964) or to
stimulate the intestine (Potel, 2002). A decoction made from leaves, roots, and trunk bark of M.
inermis is taken internally or bathed in to treat digestive disorders (Zerbo et al., 2011). Leaves
from M. ledermanni and M. rotundifolia are used to treat dysentery, stomach pains, or diarrhoea
(Kerharo and Bouquet, 1950; Mulholland, 1987). Leaves from M. rubrostipulata are powdered
and made into a decoction and taken internally or used as an enema for laxative or purgative
purposes (Baerts and Lehmann, 1989; Durand, 1960; Lejeune, 1940). Leaves can also be
comsumed to treat gastrointestinal complaints such as diarrhea (Alphonse et al., 2010; Polygenis-
bigendako and Letjoly, 1989; Polygenis-Bigndako, 1990). Leaves from M. speciosa can be
boiled and used to treat infections of the intestine, dysentery, or diarrhea (Chirttrakan et al.,
2008; Maneenoon et al., 2015; Mohammad et al., 2012a; Neamsuvan et al., 2012). A poultice
made from leaves of M. speciosa has been applied to the upper abdomen in order to expel worms
from children (Burkhill and Haniff, 1930; Wray, 1907). A decoction made from leaves of M.
stipulosa is taken internally to treat gastritis (Konda et al., 2012).
19
6.7. Liver and kidney aid, jaundice, diabetes
Leaf, bark, and root material were reportedly used as a liver and kidney aid or to treat
jaundice and diabetes for 30%, 20% and 20% of species found within the genus Mitragyna
respectively (Figure 6; Tables 4-6). Leaves from M. inermis are made into a decoction and used
as an antidiabetic or to treat liver disorders (Diallo et al., 2012; Konkon et al., 2008; Nadembega
et al., 2011; Sourabie et al., 2013). In addition to the above, leaves, stem bark, branches and
trunk from M. inermis can be made into a sugared decoction and ingested as a hypoglycaemic
(Adjanohoun et al., 1986). Preparations made from leaves in order to treat jaundice (Kerharo and
Adam, 1964). A decoction of M. rubrostipulata leaves made from water and banana wine or beer
is used to treat liver disease (Kayonga and Habiyaremye, 1987; Mukazayire et al., 2011). In
addition to the above, leaves from M. speciosa are used to treat illness of the kidneys (Milow et
al., 2011).
6.8. Neurological aid
Leaf, bark, and root material were reportedly used as a neurological aid for 20%, 30%
and 20% of species found within the genus Mitragyna respectively (Figure 6; Tables 4-6). A
decoction made from leaves and/or other parts of M. inermis is comsumed or bathed in to treat
neurological disorders such as psychosis (Kerharo and Adam, 1974; Nadembega et al., 2011).
Juice from leaves and branches of M. stipulosa and other plants is placed into one’s eyes and the
nose to treat psychosomatic disorders. Furthermore, a decoction made from this plant mixture
can be used as a steam bath to treat neurological conditions (Konda et al., 2012)
6.9. Pain, inflammation, rheumatism, and swelling
Leaf, bark, and root material were reportedly used to treat pain, inflammation,
rheumatism and swelling for 40%, 50% and 30% of species found within the genus Mitragyna
respectively (Figure 6; Tables 4-6). A decoction made from leaves of M. inermis are ingested or
bathed in to treat muscular and nerve complaints such as arthritic, intercostal, and myalgia pain
(Kerharo and Adam, 1964, 1974; Malgras, 1992). A steam bath made from leaves of M. inermis
can also be used to treat pain (Van Der Steur, 1994), while a decoction made from its leaves can
be applied topically to treat swelling (Adjanohoun et al., 1986) or used as a diuretic (Potel, 1992;
Thoen and Thiam, 1990). A poultice made from leaves of M. parvifolia is applied topically to
20
treat swelling caused by sprains (Singh and Ali, 2012). Leaves of M. parvifolia can also be used
to dress wounds in order to mitigate pain and swelling (Panwar and Tarafdar, 2006) or used to
treat rheumatism (Kshirsagar and Saklani, 2007). Stems and leaves from M. rotundifolia can be
boiled and bathed in to treat broken bones or back pain (Khuankaew et al., 2014). Leaves of M.
rotundifolia are also used to treat muscular pain (Mulholland, 1987), while leaves from M.
rubrostipulata are ingested to treat rheumatism (Alphonse et al., 2010).
6.10. Pregnancy and reproductive aid
Leaf, bark, and root material were reportedly used as a pregnancy and reproductive aid
for 30%, 60% and 40% of species found within the genus Mitragyna respectively (Figure 6;
Tables 4-6). A decoction of leaves from M. inermis is taken internally during childbirth (Ake
Assi, 1981). An infusion made from leaves of M. rubrostipulata and other species is given as an
enema to treat menstrual pain, ease childbirth, or issues involving the placenta (Baerts and
Lehmann, 1989). Leaves from M. rubrostipulata and other species can also be ingested in order
to make childbirth easier or to treat ailments encountered during pregnancy (Kayonga and
Habiyaremye, 1987). Similarly, an enema made from an infusion of M. stipulosa and other plant
species is used to treat dysmenorrhea and uterine bleeding (Konda et al., 2012). Individuals will
also bathe in an infusion made from leaves and other species to prevent abortion or prevent re-
occurrence (Konda et al., 2012).
6.11. Respiratory aid
Leaf, bark, and root material were reportedly used as a respiratory aid for 30%, 10% and
10% of species found within the genus Mitragyna respectively (Figure 6; Tables 4-6). Leaves
from M. ledermanni and M. rubrostipulata are used to treat cough and asthma respectively
(Alphonse et al., 2010; Lamidi et al., 2007). Preparations made from leaves of M. rubrostipulata
are also ingested in order to treat pneumonia or asthma (Kayonga and Habiyaremye, 1987; Van
Puyvelde et al., 1977). Similarly, a preparation made from leaves of M. stipulosa is ingested to
treat pneumonia (Konda et al., 2012).
6.12. Urogenital aid

21
Leaf, bark, and root material were reportedly used as a urogenital aid for 30%, 50% and
10% of species found within the genus Mitragyna respectively (Figure 6; Tables 4-6). A
decoction made from leaves of M. inermis is used consumed or bathed in to treat syphilis
(Kerharo and Adam, 1964, 1974). Leaves and bark from M. ledermanni are used to treat sexually
transmitted diseases (Kerharo and Bouquet, 1950). Similarly, a decoction made from leaves,
bark, branch and trunk of M. stipulosa is mixed with other plants to treat urinary diseases (Baerts
and Lehmann, 1989).
6.14. Other therapeutic activity
An infusion made from leaves of M. inermis is used to treat heart conditions and
hypertension (Nadembega et al., 2011; Potel et al., 2002) Stems and leaves from M. inermis and
M. stipulosa are used to treat leprosy (Adjanohoun et al., 1989; Kerharo and Adam, 1974).
Leaves and flowers of M. rubrostipulata are placed in water and ingested to treat polio (Van
Puyvelde et al., 1977). Leaves from M. speciosa are used to treat broken bones (Anderson,
1993).
7.0. Discussion
Leaves from the genus Mitragyna have traditionally been used internally and externally
to treat a wide spectrum of ailments in many parts of the world. While overlap between species
for reported uses was observed i.e. gastrointestinal aid, fatigue, dermatological aid, etc., only M.
speciosa was reported as a substitute for opium in the literature while also being considered a
remedy for addiction. The medicinal virtues of M. speciosa were noted early on by European
botanists such as Low (1865), Cliffor and Swettenham (1894), Ridley (1897), Holme (1907) and
Wray (1907) who described the use of Biah (kratom) as a substitute or supplement for opium.
Given the widespread use and popularity of opioids at this point in time, it is not surprising that
news of a potential substitute travelled quickly to Europe and other parts of the world. In 1895,
Merck’s market report notes that specimens collected from an opium substitute known as Biah
were sent to the Museum of the Pharmaceutical Society of Great Britain for identification, and
later identified as M. speciosa (Merck & Co., 1895).
22
To the best of our knowledge the first description in English pertaining to the use of M.
speciosa as an anti-opium remedy comes from Burkhill and Haniff (1930) who describe the
remedy as worse then the disease, since then several other studies have described the
ethnomedicinal use of M. speciosa an anti-opium remedy (Ong and Nordiana, 1999;
Vichnasingam et al., 2010). Unfortunately, due to resource and language constraints, we did not
have access to traditional Thai pharmacopoeias to determine whether any source predating
Burhill and Haniff’s (1930) quote for M. speciosa as an anti-opium (although we would expect to
find some). Still, as Leonti and Casu (2013) points out, globalization and economic liberalism
can lead to the introduction of foreign medicines into local pharmacopoeias, and though unlikely,
it is possible that M. speciosa’s use as a remedy for addiction is not deeply rooted in Thai
medicine and evolved during the early 1900s in response to pharmaceutical demand for anit-
opium drugs.
Despite growing interest towards species of Mitragyna as either a susbstitutes for M.

speciosa or ‘legal alternative to Kratom’, we could not find detailed descriptions in the literature
which directly referenced species other then M. speciosa as a substitutes for opium or treatment
for addiction, despite references suggesting that M. diversifolia and U. homomalla are
susbstitutes for Kratom. Still our review did find references that suggest other species of
Mitragyana such as M. inermis, M. parvifolia, M. rotundifolia, and M. rubrostipulata can be
employed like M. speciosa to treat certain types of pain including inflammation, rheumatism, or
muscle/joint pains. Unlike M. speciosa, many of these references describe external uses by
soaking onself in a bath made from leaves or applying a poultice made topically. Though less
common, there is anecdotal evidence available online describing the topical use of extracts made
from M. speciosa to treat muscular or joint pain, thus development of topical products from other
species of Mitragyna may provide a new avenue for development of products which mitigate
pain, while also potentially leading to novel insights with respect to the pharmacology of
Mitragyna species.
As previously mentioned, there is growing evidence to support that products sold as

kratom (M. speciosa) are being substituted with species from the same genus or tribe (Hanna,
2003; Maruyama et al., 2009). In order to authenticate M. speciosa morphological,
23
phytochemical and molecular approaches have been suggested (Kowalczuk et al., 2003). Our
review the litereature found that macro and microscopic characteristics of leaves are likely
insufficient to differentiate leaf samples between species due to phenotypic plasticity.
Furthermore, given the majority of works investigating leaf characteristics are based on a small
number of samples, much larger studies are needed in order to the develop novel screening
approaches for this taxonomically complicated genus. Despite these shortcomings, screening
methods through examination of leaf trichomes, oxalate crystals, and other leaf tissues can serve
as a quick and cost-effective ‘first step’ approach for pseudo-authentication of kratom products
to tribe or genus level (Cornara et al., 2013; Kowalczuk et al., 2011) and should be used in
conjunction with phytochemical and molecular tools.
M. speciosa’s utility in pain relief and treatment of opiate addiction in traditional

ethnomedicine is believed to be due to the presence of mitragynine and 7-hydroxymitragynine in its
leaves and the ability of these phytochemicals to act upon opioid receptors. Although substitution
of M. speciosa with members of the same genus or tribe is well documented, the distribution of
mitragynine and 7-hyrdroxmitragynine amongst other members of this genus as well as their
potential for treating pain has received far less attention. Still, there is some evidence to suggest
that mitragynine is only present in M. speciosa. Kikura-Hanajiri et al. (2009) quantified
mitragynine and 7-hydroxymitragynine in aqueous methanol extracts of M. speciosa and M.
hirsuta leaf by liquid chromatography-electrospray ionization-mass spectrometry and ultraviolet
detection; both compounds were present in M. speciosa but not detected in M. hirsuta. Another
recent study by Sanagi et al. (2013) quantified mitragynine in chloroform methanol extracts of
M. speciosa and M. rotundifola leaf by gas chromatography-mass spectrometry. The authors
were able to detect mitragynine in M. speciosa, but there was no detectable amount of the
compound in M. rotundifolia. Current methods to authenticate M. speciosa in products sold as
kratom have focused on quantification of mitragynine and 7-hydroxmitragynine (Mudge and
Brown, 2016). It is interesting to note that the majority of phytochemical studies on species
other then M. speciosa were done over 25 years ago and it is possible that modern analytical
approaches might be able to detect low levels of these compounds in leaf tissues, which in turn
could generate false positive during testing. These data are important for the regulation and
authentication of kratom in natural products and more research comparing the content of these
compounds across the genus as well as other species known to be susbsituted is warranted.
24
Distinctly different modes of preparation for M. speciosa were also found within the
literature. A cold infusion made from powdered leaf material can be comsumed as a tea (Burkhill
and Haniff, 1930; Suwanlert, 1975; Wray, 1907). Alternatively, one can boil the leaves of M.
speciosa in water, and evaporate the filtrate until a syrupy substance is left which can be smoked
or ingested (Wray, 1907). Leaves can also be chewed in a similar manner to which cocoa leaves
are used as a stimulant (Chemist and Druggist, 1930; Suwanlert, 1975) or smoked (Burkhill,
1935; Grewal, 1932). While no references could be found describing the use of other Mitragyna
species as opium substitutes, M. inermis, M. parvifolia, M. rotundifolia, and M. rubrostipulata
have reportedly been used to treat pain, inflammation, rheumatism, or muscle/joint pains. Unlike
M. speciosa, many of these references describe external use by soaking onself in a bath made
from leaves or applying a poultice made topically. Though less common, there is anecdotal
evidence available online describing the topical use of extracts made from M. speciosa to treat
muscular or joint pain, thus development of topical products may provide a safe alternative for
management of certain types of pain as well as novel insights to the mode of action of Mitragyna
species.
Given taxonomic re-arrangement for members in the genus Mitragyna as well as

substitution of M. speciosa with other species from the same genus and tribe, it is imperative that
individuals approach traditional uses of this genus more hollistically, taking into account that M.
speciosa has formed a complex web of relationships with other species. In light of growing
interest towards the use of M. speciosa (PinneyAssociates, 2016) and the limited information
readiliy available on the historical and traditional use of this species for treatment of addiction,
future ethnopharmocological investigation into this matter is warranted through projects such as
the Thai Medicinal Plant Recipe Database “MANOSROI III”
(http://www.manose.co/en/portfolio-item/work-2/). Establishing the comparative phytochemistry
of kratom across different ecotypes and gaining a better understanding pharmacological/chemical
differences among various Mitragyna spp. will aid in development of authentication and quality
control measures to ensure only safe kratom products enter the market. Future research is
needed to establish accurate methods for authentication of plant material for commercial
products, and to establish the medicinal chemistry, safety, and toxicology parameters that are
needed to support regulatory requirements for species belonging to this genus.
25
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45
Figure 1: Dietary supplements and natural products containing Mitragyna speciosa (kratom). A.
Plants growing in a greenhouse (bar = 12 cm). B. Characteristic features of shoot and leaves of
kratom (bar = 1.5 cm).
Figure 2: Data retrieved from Google trends showing increased interest in Mitragyna speciosa
and kratom (graphed line).
Figure 3: Indole alkaloids found in Mitragyna leaf.
Figure 4: Oxindole alkaloids found in Mitragyna leaf.
Figure 5: Distribution of references by species and plant part.
Figure 6: Distribution of species by ethnomedicinal use and plant part. 1 Anti-pyretic, anti-
malarial, African sleeping sickness; 2 Anti-venom, anti-poison, emetic; 3 Dermatological aid; 4
Drug addiction; 5 Fatigue, weakness, wasting syndrome, stimulant, appetite stimulant, anemia,
sickle cell; 6 Gastrointestinal aid; 7 Liver and kidney aid, jaundice and diabetes; 8 Neurological
aid; 9 Opium substitute; 10 Pain, inflammation, rheumatism, muscle or joint pain, swelling
(diuretic); 11 Pregnancy and reproductive aid; 12 Respiratory aid; 13 Uritogenital aid; 14 other.
Table 1: Botanical Nomenclature for the genus Mitragyna
Species Synonyms Heteronyms Distribution

Nauclea diversifolia Wall.
Mitragyna Ex. G. Don; Stephegyne Mamboga capitata Blanco; Nauclea
Bangladesh to
diversifolia diversifolia (Wall. Ex. G. adina Blanco; Stephegnyne tubulosa
China (Yunnan)
(Wall. Ex Don) Brandis; Stephegyne Fern; Stephegyne parvifolia Vidal;
and Malesia
G.Don) Havil. diversifolia (Wall. Ex G. Mitragyna javanica Koord;
Don) Hook.
Nauclea africana Willd.;

Cephalanthus africanus Rchb.;
Nauclea africana var. luzoniensis
DC.; Mitragyna africana (Willd.)
Mitragyna Paradina hirsuta (Havil.) China (Yunnan)
Korth. ; Stephegyne africana
hirsuta Havil. Pit. to Indo-China
(Willd.) Walp.; Nauclea
platanocarpus Hook.f.;
Platanocarpum africanum (Willd.)
Hook
46
Nauclea africana Willd.;

Cephalanthus africanus Rchb.;
Nauclea africana var. luzoniensis
Uncaria inermis Willd.;
Mitragyna DC.; Mitragyna africana (Willd.)
Nauclea inermis (Willd.) West tropical
inermis (Willd.) Korth. ; Stephegyne africana
Baill; Adina inermis Africa to Sudan
Kuntze. (Willd.) Walp.; Nauclea
(Willd.) Roberty
platanocarpus Hook.f.;
Platanocarpum africanum (Willd.)
Hook
Adina ledermannii K.
Mitragyna
Krause; Hallea ledermannii Mitragyna ciliatea Aubrév. & West and West
ledermannii (K.
(K. Krause) Verdc.; Fleroya Pellegr.; Hallea ciliata (Aubrév. & Central
Krause)
ledermannii (K. Krause) Pellegr) J.F. Leroy Tropical Africa
Ridsdale
Y.F. Deng
Mitragyna Nauclea parvifolia Roxb.; Indian
parvifolia Stephegyne parvifolia subcontinent to
(Roxb.) Korth. (Roxb.) Korth. Myanmar
Darjiling to
Mitragyna Nauclea rotundifolia Roxb.; Nauclea brunonis Wall. Ex G. Don.;
China (S.
rotundifolia Bancalus rotundifolius Mitragyna brunonis (Wall. Ex
Yunnan) and
(Roxb.) Kuntze. (Roxb.) Kuntze G.Don) Craib.
Indo-China
Adina rubrostipulata K.
Mitragyna Schum; Hallea
rubrostipulata rubrostipulata (K. Schum.) Adina rubrostipulata var. discolor
Tropical Africa
(K. Schum.) J.F. Leroy; Fleroya Chiov.
Havil. rubrostipulata (K. Schum)
Y.F. Dengs
Mitragyna Stephegyne speciosa Korth;
Nauclea korthalsii Steud.; Nauclea Pen. Thailand
speciosa (Korth.) Nauclea speciosa (Korth.)
luzoniensis Blanco to New Guinea
Havil. Miq.
Nauclea stipulosa DC.;
Mamboga stipulosa (DC.)
Mitragyna Hiern.; Adina stipulosa Nauclea bracteosa Welw.; Mitragyna
stipulosa (DC.) (DC.) Roberty.; Hallea macrophylla Hiern.; Mitragyna Tropical Africa
Kuntze stipulosa (DC.) J.F. Leroy; chevalieri K. Krause
Fleroya stipulosa (DC.)
Y.F. Deng
Mitragyna India (Kerala,
tubulosa (Arn.) Nauclea tubulosa Arn. Tamil Nadu),
Kuntze Sri Lanka
Table 2: Alkaloids described in leaf materials of Mitragyna

Species Alkaloids described in leaf Reference
47
M. mitrafoline, mitradiversifoline, specionoxeine-N(4)-oxide, 7- Badger et al., 1950; Cao et al., 2013

diversifolia hydroxyisopaynantheine, 3-dehydropaynantheine, 3-isopaynantheine-
N(4)-oxide
M. hirsuta mitraphylline, isomitraphylline , isomitraphylline N-oxide, Kitajima et al., 2007; Phillipson et

rhynchophylline, isorhynchophylline, isopteropodine, isomitraphyllinol, al., 1973b; Shellard et al., 1966,
hirsuteine, mitrajavine 1967b
M. inermis uncarine D (speciophylline), rhynchophylline, isorhynchophylline, Donfack et al., 2012; Fiot et al.,
rotundifoline, isorotundifoline 2005; Shellard and Alam, 1968;
Shellard and Sarpong, 1970;
Takayama et al., 2004b;
M. mitraciliatine, rhynchophylline, rhynchociline, cilaphylline, Beckett et al., 1963

ledermannii rotundifoline, isorotundifoline
M. parvifolia mitraphylline, isomitraphylline, rhynchophylline, isorhynchophylline, Shellard et al., 1968; Shellard and
rotundifoline, isorotundifoline, speciophylline N-oxide, uncarine F, Houghton, 1974; Pandey et al., 2006
uncarine F N-oxide, dihydrocorynantheol, dihydrocorynantheol N-oxide,
akuammigine, akuammigine N-oxide, 3-isoajmalicine, pteropodine,
isopteropodine, uncarine D (speciophylline), 16,17-dihydro-17β-hydroxy
isomitraphylline, 16, 17-dihydro-17β-hydroxy mitraphylline
M. mitraphylline, isomitraphylline, rhynchophylline, isorhynchophylline, Barger et al., 1939; Houghton and

rotundifolia isorhynchophylline N-oxide; rotundifoline Shellard, 1974; Shellard and Alam,
1968
M. mitraphylline, isomitraphylline, rotundifoline, isorotundifoline, Hendrickson et al., 1993; Shellard

rubrostipulat rotundifoline N-oxide, rhynchophylline, isorhynchophylline, and Lala, 1978
a rhynchophylline N-oxide, hirsutine, rotundifoline (stipulatine)
M. speciosa mitragynine, mitraphylline, 7-hydroxymitragynine, paynantheine, Ali et al., 2014; Avula et al., 2015;
mitralactonal, mitragynaline, speciociliatine, speciogynine, Kikura-Hanajiri et al., 2009;
mitrasulgynine, 3,4,5,6-tetradehydromitragynine, mitragynaline, Houghton and Said, 1986; Houghton
mitragynalinic acid, corynantheidinaline, corynantheidinalinc acid, 3- et al., 1991; Lesiak et al., 2014;
dehydromitragynine, mitraciliatine, 7β-hydroxy-7H-mitraciliatine, 9- Limsuwanchote et al., 2014;
methoxymitralactonine, corynoxine, corynoxine B, 3-isopaynantheine, Parthasarathy et al., 2013; Philipp et
ajmalicine, isomitraphylline, isocorynantheidine, mitragynine al., 2010; Ponglux et al., 1994;
pseudoindoxyl, mitragynine oxindole A, mitragynine oxindole B, Shellard et al., 1978a,b; Takayama
ajmalicine (raubasine), rhynchophylline, rhyncocilline, cilaphylline, et al., 1998, 2000; Wang et al., 2014
isospeciofoleine, isospeciofoline, isorotundifoline
M. stipulosa mitraphylline, rhyncophylline, isorhynchophylline, rotundifoline, Beckett et al., 1963; Houghton et al.,
isorotundifoline 1966
M. tubulosa mitraciliatine, rhynchociline, ciliaphylline, rotundifoline, Phillipson et al., 1973a; Shellard and
isorotundifoline, rhynchophylline, isorhyncophylline, mitraphylline,
48
isomitraphylline, ciliaphylline N-oxide Rungsiyakul, 1973;
Table 3: Summary of pharmacological effects for Mitragyna alkaloids

n (per
Study Test/Assay Dosage Animal/Tissue group Major Findings
)
Watanab electrical male albino
1 nM-3 1. Mitragynine was found to act as opioid
e et al. stimulation-induced Guinea pig 4-7
μM agonist on guinea-pig ileum.
1997 contraction ileum
electrical male albino
stimulation-induced 0.3-30 nm Guinea pig 4-7
contraction ileum
radioligand binding 1. Mitragynine and mitragynine pseudoindoxyl
Yamamot male Dunkin-
assay/opioid 10 pm-2 were found to act as opioid agonists through
o et al., Hartley guinea 3-5
receptor binding nM μ-receptors in the ileum and through δ
1999 pigs brain
assay receptors in mouse vas deferens.
electrical
1 nM-10 male ddY mice
stimulation-induced 5
μM vas deferens
contraction
antinociceptive 9-75 1. The essential structural moieties in the
mouse tail flick
assay: analgesic nmol/mou 7-12 corynanthe-type indole alkaloids for
test
activities se inducing the opioid agonistic activity were
electrical male albino clarified.
Takayam 100 pM to
stimulation-induced Guinea pig 5 2. Mitragynine, mitragynine pseudoindoxyl and
et al., 30 μM
contraction ileum 7-hydroxymitragynine were found to act as
2002
radioligand binding opioid agonists with higher potency than
male Dunkin-
assay/opioid morphine.
0.01-2 nM Hartley guinea 3
receptor binding 3. Mitragynine pseudoindoxyl induced an
pigs brain
assay analgesic activity.
Matsumo stimulation-induced 3 μM Guinea-pig 5 1. 9-hydroxycorynantheidine has partial agonist
to et al. contraction ileum properties on A-opioid receptors in the
2006 receptor binding 30-300 male guinea-pig guinea-pig ileum
5
assay nM brain
1. Mitragynine, paynantheine, speciogynine,
speciociliatine were found to act as opioid
Horie et 100 nM to agonists; leaf extract of M. speciosa exihibits
stimulation-induced Guinea pig 5
al., 2005 3 μM opioid agonist effect.
contraction ileum
2. 7-hydroxymitragynine showed the most
potent opioid effect.
Mastumo opioid agonistic male albino 1. Mitragynine was found to act as opioid
0.3-10 μM 4-6
to et al., activities Guinea pig vas agonists on vas deferens.
49
2005 deferens 2. Mitragynine was found to block T- and L-

type Ca2+ channel currents in N1E-115
Ca2+ channel mouse
neuroblastoma cells.
current recording, 3-30 μM neuroblastoma 4-6
cytosolic Ca2+ level cells
20-100
μg/mL
(methanol
1. Mitragynine and M. speciosa extracts were
extract);
found to modulate glucose transport
10-70
Purintrap pathways—upregulating GLUT1 protein
Western blot μg/mL rat L8 myotube
iban et 3 production and increasing activities of key
analysis (alkaloid cell culture
al., 2011 enzymes required for insulin-stimulated
extract);
glucose transport
20-120
μg/mL
(mitragyni
ne)
macrophage cell 1. "Mitragynine suppressed PGE2 production
Utar et COX-1 and COX-2
line RAW 264.7 3 by inhibiting COX-2 expression in LPS-
al., 2011 mRNA expression
treated with LPS stimulated RAW264.7 macrophage cells."
1. Mitragynine, paynantheine, speciogynine,

and speciociliatine supppressed the rapid
stable transgenic delayed rectifier potassium current in the
Lu et al., 0.1-100
patch-clamp assay hERG-HEK293 5 cells.
2014 μM
cells 2. Mitragynine significantly prolonged APD
and induced arrhythmia, without altering the
L-type Ca2+ current.
1. "Mitragynine produced antinociceptive

Carpenter
30-100 male Sprague 17- effects similar to the reference opioid
et al., hotplate test
mg/kg Dawley rats 19 agonists when administered IP and PO
2016
routes."
radioligand binding 1. Mitragynine pseudoindoxyl displays μ-
assay/opioid receptor opioid agonism and δ-opioid antagonism
binding assay 2. Mitragynine pseudoindoxyl does not recruit
Chinese hamster
[35S]GTPγS <10 μM 3 β-arrestin-2
ovary cells
functional assay 3. Mice administered mitragynine
Varadi et
β-arrestin-2 pseudoindoxyl developed analgesic tolerance
al., 2016
recruitment assay slower than morphine. Limited change to
tail flick test; dependence/reward behavior, repiratory
aversion test; 0.01-30 depression, and constipation.
male CD1 mice 5
respiratory mg/kg
depression test
50
Table 4: Summary of Ethnomedicinal Data for Leaves of Mitragyna

Use Affliction
Species Category Treated/Function Prepartion/Administration Reference
not documented Carrière, 1994
Chevalier and
anti- decoction; taken orally
Laffitte, 1937
pyretic,
anti- fever decoction of 3 plants is taken orally Igoli et al., 2005
malarial, decoction taken orally; may combine with leaves of
Igoli et al., 2005
african Stachytarpheta indica and Nauclea latifolia
sleeping wash with decoction, combine with Piliostigma
Igoli et al., 2005
sickness reticulatum
Nordeng et al.,
fever due to malaria drink boiled decoction
2013
decoction Ahua et al., 2006
boil leaves and drink infusion, may combine with Asase and Oteng,
Ocimum canum 2012
boil leaves and drink infusion, may combine with
Asase et al., 2005
Ocimum canum
Ahua et al.,
2007; Maiga et
not documented
al., 2005; Traore
et al., 2013
Diallo et al.,
anti- decoction prepared from fresh or dry leaf
1999
pyretic, infusion and bath, combine with male flowers of Zea Van Der Steur,
anti- malaria mays 1994
malarial, boil leaves of Ocimum canum with that of Mangifera
african indica, M. inermis and whole plants of Indigofera Asase, 2005
M. inermis sleeping indica and drink
sickness boil twigs and leaves of M. inermis with whole plant
of Indigofera pulchra, drink 3 times daily; may
Asase, 2005
combine with whole plant or leaves of Ocimum
canum
decoction combined with of roots or leaves of several
herbs; taken orally for 5 days; decoction of leaves Sangare, 2003
alone administered orally for a week
Nordeng et al.,
boiled decoction, taken orally
2013
trypanosomiasis, Diallo et al.,
decoction/infusion and taken orally
sleeping sickness 2006
anti-
venom/an
Maiga et al.,
ti- posion not documented
2005
poison/e
metic
Adjanohoun et
blisters, edema water decoction; apply to afflicted area by sprinkling
dermatol al., 1986
ogical aid Inngjerdingen et
boils decoction; vapours are inhaled, apply locally
al., 2004
infections decoction taken orally, and/or bath Zerbo et al., 2011
Adjanohoun et
dermatol leprosy not documented
al., 1989
ogical aid
pimples not documented Carrière, 1994
skin disorders decoction taken orally, and/or bath Zerbo et al., 2011
51
fatigue, Thoen and

anaeasthenia, cachexia water decoction
weakness Thiam, 1990
, wasting Kerharo and
asthenia not documented
syndrome Adam, 1974
, Kerharo and
cachexia decoction taken orally, and/or bath
stimulant, Adam, 1974
appetite poor nutrition in taken orally, 1/2 glass in the morning and evening
Kone et al., 2002
stimulant, children with baths
anemia,
general fatigue or after Van Der Steur,
sickle bath in preparation
delivery 1994
cell
Kerharo and
gastrointe diarrhea taken orally
Adam, 1974
stinal aid
digestive disorder decoction taken orally, and/or bath Zerbo et al., 2011
Funke and
Melzig, 2005;
not documented Konkon et al.,
2008; Sourabie et
liver and diabetes al., 2013
kidney Diallo et al.,
decoction
aid, 2012
jaundice Adjanohoun et
water decoction taken orally
and al., 1986
diabetes Thoen and
water decoction
diuretic Thiam, 1990
decoction Potel, 2002
Kerharo and
jaundice oral intake with bath
Adam, 1964
Muazu et al.,
epilepsy not documented
2008
neurologi
mental diseases not documented Malgras, 1992
al aid
water decoction taken orally; may combine with Kerharo and
psychosis
several herbs Adam, 1974
decoction; combine with leaves of Kiggelaria
other Igoli et al., 2005
Africana; administer orally 3x daily
therapeut hypertension
Traore et al.,
ic activity decoction is taken 3x daily
2013
pain, Van Der Steur,
headache steam bath
inflamma 1994
tion,
rheumatis
m,
muscle
pains or arthritis, myalgia decoction and taken orally Malgras, 1992
joint
pain,
swelling
(diuretic)
pregnanc expulsion of the Kerharo and
decoction taken orally during deliveries
y or placenta Adam, 1964
reproduct Ake Assi et al.,
oxytocic, delivery aid water decoction taken orally
ive aid 1981
uritogenit water decoction taken orally; may bathe in the Kerharo and
syphills
al aid decoction; may combine with other plants Adam, 1974
anti- Kerharo and
fever not documented
pyretic, Bouquet, 1950
M. anti-
ledermannii malarial, Lamidi et al.,
paludism not documented
african 2007
sleeping
52
sickness
gastrointe Kerharo and
diarrhea not documented
stinal aid Bouquet, 1950
neurologi Kerharo and
madness not documented
al aid Bouquet, 1950
pregnanc
y or Kerharo and
sexual incapcity not documented
reproduct Bouquet, 1950
ive aid
respirator Lamidi et al.,
cough not documented
y aid 2007
uritogenit Kerharo and
chlamydia not documented
al aid Bouquet, 1950
tumors, cuts, wounds not documented Chavre, 2011
dermatol Panwar and
not documented
ogical aid Tarafdar, 2006
wound/cut healing
Sharma et al.,
apply the paste of leaves locally
2014
pain,
inflamma
tion,
rheumatis
m,
Singh and Ali,
muscle swelling apply the paste of leaves locally
2012
pains or
joint
pain,
swelling
(diuretic)
fatigue,
weakness
M. parvifolia , wasting
syndrome
,
stimulant, appetite stimulant not documented Perry, 1980
appetite
stimulant,
anemia,
sickle
cell
pain,
inflamma
tion,
rheumatis
m,
extract used to massage the rheumastism afftected Kshirsagar and
muscle rheumatism
joints Saklani, 2007
pains or
joint
pain,
swelling
(diuretic)
dermatol Debnath et al.,
prevent pus formation apply the paste of leaves locally
ogical aid 2014
gastrointe Mulholland,
diarrhea, dysentery not documented
stinal aid 1987
M.
other
rotundifolia Khuankaew et
therapeut fracture boiled and used in bath
al., 2014
ic activity
pain, Khuankaew et
lumbago boiled and used in bath
inflamma al., 2014
53
tion,
rheumatis
m,
muscle
Mulholland,
pains or muscular pain not documented
1987
joint
pain,
swelling
(diuretic)
anti-
pyretic,
anti-
extracted in hot water in combination with several
malarial, anti-pyretic, malaria Cihyoka, 1999
other herbs; taken orally 3x daily
african
sleeping
sickness
anti-
venom/an Kayonga and
maceration taken orally or via enema in combination
ti- anti-poison Habiyaremye,
with several other herbs
poison/e 1987
metic
Kayonga and
eczema combined with palm oil Habiyaremye,
dermatol 1987
ogical aid Baerts and
fungal infections powdered and applied locally
Lehmann, 1989
treat wounds juiced and heated; applied locally Durand, 1960
fatigue,
weakness
, wasting
syndrome
,
Baerts and
stimulant, anemia water decoction combined with bark and taken orally
Lehmann, 1989
M. appetite
rubrostipulat stimulant,
a anemia,
sickle
cell
Polygenis-
antiemetic water decoction taken orally
Bigendako, 1990
5-10 leaves rumpled and combined with water; taken
Lejeune, 1940
via enema
Baerts and
Lehmann, 1989;
diarrhea Polygenis-
water decoction taken orally Bigendako, 1990;
gastrointe Polygensis-
stinal aid Bigendako and
Letjoly, 1989
water decoction combined with bark (may include
Baerts and
several other herbs), several herbs and taken orally
Lehmann, 1989
GI pain and/or via enema
Polygenis-
water decoction taken orally
Bigendako, 1990
water decoction combined with leaf and taken orally Baerts and
laxative
and/or via enema Lehmann, 1989
liver and Kayonga and
water decoction combined with leaf of Erythrina
kidney Habiyaremye,
abyssinica taken orally
aid, liver disease 1987
jaundice banana wine and water decoction taken orally, 1 Mukazayire et
and glass daily for, 1 week; may be combined with other al., 2011
54
diabetes herbs
decoct a handful of fresh leaves with, 2 L of water
Mukazyire et al.,
and L l of
2011
banana wine, one glass a day for a week
neurologi water maceration combined with flowers and taken Van Puyvelde et
polio, paralysis
al aid orally al., 1977
other Kayonga and
water decoction combined with leaf of Erythrina
therapeut spleen disease Habiyaremye,
abyssinica taken orally
ic activity 1987
pain, Baerts and
headache powder combined with bark taken orally
inflamma Lehmann, 1989
tion,
rheumatis
m,
muscle
orally administer filtrate of the crushed and fresh Alphonse et al.,
pains or rheumatism
leaves; one spoon, 3x daily for 5 days 2010
joint
pain,
swelling
(diuretic)
Baerts and
dysmenorrhoea water decoction taken via enema
Lehmann, 1989
infusion combined with several herbs and taken via Baerts and
enema Lehmann, 1989
pregnanc oxytocic, delivery aid Kayonga and
maceration taken orally in combination with several
y or Habiyaremye,
other herbs; 3 soup spoons
reproduct 1987
ive aid Kayonga and
pregnancy maceration taken orally in combination with several
Habiyaremye,
complications other herbs
1987
water decoction combined with leaf of cyathula Baerts and
prevent miscarriage
uncinulata taken via enema Lehmann, 1989
Kayonga and
maceration taken orally in combination with several
asthma Habiyaremye,
respirator other herbs
1987
y aid
water maceration combined with Melantthera Van Puyvelde et
pneumonia
scandens flitered and taken orally al., 1977
asthma orally administer macerated fresh leaves; 3x daily for Alphonse et al.,
5 days; may be combined with other herbs 2010
uritogenit Baerts and
uterine bleeding water infusion taken orally and/or via enema
al aid Lehmann, 1989
dermatol Burkhill and
skin disorders poultice or decoction applied locally
ogical aid Haniff, 1930
drug overcome drug Ong and
decoction of the leaves is taken orally
addiction addiction Nordianan, 1999
fatigue,
weakness
, wasting
syndrome
, Chemist and
stimulant, endure hot
stimulant, raw leaf chewed Druggist, 1930;
M. speciosa weather
appetite Suwanlert, 1975
stimulant,
anemia,
sickle
cell
Chittrakarn et al.,
powdered leaf or tea taken orally
2008
gastrointe Mohammad et
diarrhea decoction of the leaves taken orally
stinal aid al., 2012a
boiled Neamsuvan et
55
al., 2012
Burkhill and
expel worms poultice applied to upper abdomen Haniff, 1930;
Wray, 1907
Chittrakarn et al.,
intestinal infection powdered leaf or tea taken orally
2008
liver and
kidney
aid, Milow et al.,
kidney ailment not documented
jaundice 2011
and
diabetes
Burkhill and
not documented
opium Haniff, 1930
opium subsitute
substitute cold infusion tea taken orally or boil to extract syrup
Wray, 1907
and smoke or ingest
anti-
pyretic,
anti-
Kerharo and
malarial, anti-pyretic taken orally in combination with bark, root
Adam, 1974
african
sleeping
sickness
dermatol Kerharo and
leprosy taken orally in combination with bark
ogical aid Adam, 1974
gastrointe Konda ku Mbuta
gastritis decoction taken orally
stinal aid et al., 2012
other broken bones not documented Anderson, 1993
therapeut decoction prepared in combination with bark taken Konda ku Mbuta
ic activity hernia
orally or via enema; 1 glass, 3x daily for 7 days et al., 2012
respirator Konda ku Mbuta
pneumonia decoction taken orally
y aid et al., 2012
Table 5: Summary of Ethnomedicinal Data for Bark of Mitragyna

Affliction
Speci Treated/Funct
es Use Category ion Prepartion/Administration Reference
M.
diver
sifoli
a gastrointestinal aid diarrhea not documented Jebunnessa et al., 2009
febrile
Bouquet and Debray,
stiffness and not documented
1974
asthenia
fever decoction Potel, 2002
M. boil twigs with whole plant of Indigofera
anti-pyretic, anti-malarial,
inerm pulchra; administer orally 3x daily Asase et al., 2005
african sleeping sickness
is steam bath; may combine with Ocimum
canum Asase and Oteng, 2012
Doka and Yagi, 2009;
decoction Nadembega et al., 2011
malaria decoction taken orally, and/or bath Zerbo et al., 2011
56
decoction taken orally Doka et al., 2009

not documented Malgras, 1992
decoction taken orally; 3x daily Togola et al., 2005
trypanosomia
sis, sleeping
sickness decoction taken orally Diallo et al., 2006
Inngjerdingen et al.,
boils decoction applied locally 2004
infections decoction taken orally, and/or bath Zerbo et al., 2011
skin disorders decoction taken orally, and/or bath Zerbo et al., 2011
wounds local application Potel, 2002
antiseptic,
disinfectant
for wounds local application of dry powder Kerharo and Adam, 1974
wounds by
cold steel powder or water decoction taken orally Adjanohoun et al., 1980
dermatological aid wounds local application of dry powder Malgras, 1992
fatigue, weakness, wasting
syndrome, stimulant, appetite lack of
stimulant, anemia, sickle cell appetite not documented Adjanohoun et al., 1989
abdominal
pain wash with decoction, or taken orally Igoli et al., 2005
bilharziosis taken orally Kerharo and Adam, 1974
diarrhea taken orally Kerharo and Adam, 1974
digestive
disorders decoction taken orally, and/or bath Zerbo et al., 2011
dysentery not documented Malgras, 1992
gastrointestin
al diseases taken orally Kerharo and Adam, 1974
internal
parasitism water decoction taken orally Keita, 1999
intestianl
worms water decoction taken orally Keita et al., 1995
intestine
stimulant decoction Potel, 2002
flatulent water maceration taken orally; may be
gastrointestinal aid colic, bloat combined with other herbs Adjanohoun et al., 1980
water decoction taken orally; may be
liver disease combined with other herbs Adjanohoun et al., 1986
decoction taken orally; 3x daily Igoli et al., 2005
water decoction combined with roots of
Stereospermum kunthianum; taken orally
three times daily Igoli et al., 2005
water decoction taken orally Adjanohoun et al., 1986
diabetes decoction Diallo et al., 2012
liver and kidney aid, jaundice
and diabetes diuretic decoction Potel, 2002
maceration of roots and barks of M.
inermis and leaves and bark of Diospyros
mespiliformis; taken orally Muazu and Kaita, 2008
Kerharo and Adam,
1974; Malgras, 1992;
neurological aid epilepsy not documented Muazu and Kaita, 2008
cancer decoction taken orally Ashidi et al., 2010
other therapeutic activity hypertension decoction Potel, 2002
57
decoction taken orally; may be combined

pain, inflammation,
rheumatism with other herbs Adjanohoun et al., 1980
rheumatism, muscle pains or
joint pain, swelling (diuretic) colic maceration Bognounou et al., nd
Bouquet and Debray,
not documented 1974
amenorrhea decoction taken orally Adjanohoun et al., 1989
facilitate Bouquet and Debray,
deliveries not documented 1974
postpartum
pregnancy or reproductive aid aid not documented Kerharo and Adam, 1964
urethral water decoction taken orally and/or via
disease enema; may combine with Acacia seyal Igoli et al., 2005
venereal
disease/infect Royal Botanic Gardens
ion not documented Kew, 1915
vaginal
inflammation, water decoction applied in vagina; may
uritogenital aid vaginitis combine with Acacia seyal Igoli et al., 2005
febrile
stiffness and Bouquet and Debray,
asthenia not documented 1974
Bouquet, 1969; Kerharo
fever not documented and Bouquet, 1950
african sleeping sickness paludism not documented Lamidi et al., 2007
emetic,
vomitive decoction taken orally Bouquet, 1969
anti-venom/anti- food
poison/emetic poisoning decoction taken orally Bouquet, 1969
fatigue, weakness, wasting
syndrome, stimulant, appetite Bouquet and Debray,
stimulant, anemia, sickle cell asthenia not documented 1974
abdominal
pain, stomach ground powder or water decoction taken
aches orally Pobeguin, 1911
Bouquet, 1969; Kerharo
diarrhea not documented and Bouquet, 1950
Bouquet and Debray,
M. gastrointestinal aid nausea not documented 1974
leder
mann neurologial aid madness decoction taken orally Bouquet, 1969
ii Bouquet and Debray,
backache not documented 1974
maceration; combine with seeds of Piper
guineense and Xylopa aethiopica Angone et al., 2009
Van der Veen and
boil barks with pimento and seeds of o- Bodinga-bwa-Bodinga,
pain, inflammation,
nongo, o-a madi ND
rheumatism, muscle pains or
joint pain, swelling (diuretic) chest pain decoction taken orally Bouquet, 1969
Bouquet, 1969; Bouquet
amenorrhea not documented and Debray, 1974
maceration; combine with seeds of Piper
infertility guineense and Xylopa aethiopica Angone et al., 2009
oxytocic, Bouquet and Debray,
delivery aid not documented 1974
Van der Veen and
sterility in Bodinga-bwa-Bodinga,
pregnancy or reproductive aid women maceration, may mix with other barks ND
not documented Lamidi et al., 2007
respiratory aid cough decoction taken orally Bouquet, 1969
58
chlamydia,
sexually
transmitted Kerharo and Bouquet,
uritogenital aid diseases not documented 1950
febrifuge and
antispasmodi
c not documented Khare, 2007
20 mL extract of bark and root
administered orally for one week, twice a
day Dahare and Jain, 2010
Arjariya et al., 2009;
Mathur and Joshi, 2013;
anti-pyretic, anti-malarial, Panwar and Tarafdar,
african sleeping sickness fever not documented 2006
Panwar and Tarafdar,
poisoning not documented 2006
anti-venom/anti- Kshirsagar and Singh,
poison/emetic snake bite infusion taken orally 2001, 2007
burning Panwar and Tarafdar,
sensation not documented 2006
M. edema not documented 2006
parvif dermatological aid leucoderma apply paste locally Sharma et al., 2014
olia colic and
febrifuge not documented Gritto et al., 2015
Ong and Nordianan,
gastrointestinal aid colic pain, 1999; Panwar and
peptic ulcers not documented Tarafdar, 2006
apply paste locally Singh and Ali, 2012
Khare, 2007; Panwar and
pain, inflammation, not documented Tarafdar, 2006
rheumatism, muscle pains or muscular pain apply paste locally Arjariya et al., 2009
joint pain, swelling (diuretic) pain in
abdomen not documented Mathur and Joshi, 2013
pregnancy or reproductive aid aphrodisiac not documented 2006
respiratory aid cough not documented 2006
gyneological Panwar and Tarafdar,
uritogenital aid disoders not documented 2006
M. pain, inflammation,
rotun rheumatism, muscle pains or
difoli joint pain, swelling (diuretic) lumbago boil and used in bath Khuankaew et al., 2014
a other therapeutic activity fractures boil and used in bath Khuankaew et al., 2014
malaria not documented Muganga et al., 2010
water decoction taken orally Lejeune, 1940
anti-pyretic, anti-malarial, extracted by steam bath in combination Banderembako and
african sleeping sickness anti-pyretic with several other herbs; taken orally Ntitangirageza, 1978
intestinal
M. gastrointestinal aid worms not documented Muganga et al., 2010
rubro fatigue, weakness, wasting
stipul syndrome, stimulant, appetite water decoction combined with leaf and Baerts and Lehmann,
ata stimulant, anemia, sickle cell anemia taken orally 1989
juiced and administered via enema Durand, 1960
water decoction (may be combined with Baerts and Lehmann,
diarrhea several herbs); taken orally 1989
Baerts and Lehmann,
gastrointestinal aid GI pain powder taken orally or inhaled 1989
59
water decoction combined with leaf (may

include several other herbs) and taken Baerts and Lehmann,
orally and/or via enema 1989
water decoction combined with leaf and Baerts and Lehmann,
laxative taken orally and/or via enema 1989
water decoction combined with several Baerts and Lehmann,
pain, inflammation, back pain herbs taken via enema 1989
rheumatism, muscle pains or Baerts and Lehmann,
joint pain, swelling (diuretic) headache powder combined with leaf taken orally 1989
urogenital water decoction combined with several Baerts and Lehmann,
infection herbs taken orally 1989
uterine Baerts and Lehmann,
uritogenital aid bleeding water infusion taken orally 1989
Carrière, 1994; Bouquet
and Debray, 1974;
not documented Nsimundele, 1968
taken orally in combination with leaf,
root Kerharo and Adam, 1974
anti-pyretic fumigation Wome, 1985
febrile
anti-pyretic, anti-malarial, stiffness and Bouquet and Debray,
african sleeping sickness asthenia not documented 1974
anti-venom/anti- food prolonged boiling until a dark red liquid
poison/emetic poisioning is obtained Bouquet, 1969
antiseptic decoction taken orally Magassouba et al., 2007
leprosy taken orally in combination with leaf Kerharo and Adam, 1974
leprosy water infusion taken orally Wome, 1985
Bouquet and Debray,
dermatological aid yaws not documented 1974
anemia decoction Ahombo et al., 2012
fatigue, weakness, wasting fatigue water decoction taken orally Adjanohoun et al., 1988
syndrome, stimulant, appetite lack of
stimulant, anemia, sickle cell appetite water decoction taken orally Adjanohoun et al., 1988
M. haemorrhoids hip bath infusion of macerations of
stipul , prolapse several herbs combined Claudie, 1979
osa
agitated in water and taken orally Claudie, 1979
macerated in combination with several
other herbs and taken via enema Claudie, 1979
intestinal
worms water infusion taken orally Wome, 1985
stomach Bouquet and Debray,
gastrointestinal aid aches not documented 1974
liver and kidney aid, jaundice
and diabetes diabetes water decoction taken orally Mandango et al., 1990
Bouquet and Debray,
not documented 1974
Bouquet and Debray,
convulsion not documented 1974
neurologial aid treat madmen water decoction taken orally; 500 mL Bouquet, 1969
dental water decoction combined with bark of
disease/infect Mangifera indica, inhaled vapour via
ion mouth Diafouka, 1997
eyesight Bouquet and Debray,
disorders not documented 1974
decoction prepared in combination with
leaf taken orally or via enema; 1 glass, 3x Konda ku Mbuta et al.,
hernia daily for 7 days 2012
other therapeutic activity hypertension water maceration taken orally over 3 Diafouka, 1997
60
days
vison Bouquet and Debray,
problem not documented 1974
Akendengue and Louis,
cold not documented 1994
Konda ku Mbuta et al.,
colic decoction taken orally or via enema 2012
pain, inflammation, rheumatism used in baths or steam baths Bouquet, 1969
rheumatism, muscle pains or Akendengue and Louis,
joint pain, swelling (diuretic) chest pains not documented 1994
agalactia not documented Betti, 2002
water decoction combined with leaf of
Acanthospermum hispidum taken orally
amenorrhea over 4 days Diafouka, 1997
decoction taken orally, 3 glasses per day Konda ku Mbuta et al.,
dysmenorrhea for 14 days 2012
female
sterility decoction Ahombo et al., 2012
red wine decoction combined with root
of Acridocarpus congolensis and egg
yolk taken orally, twice daily over 30
days Diafouka, 1997
water maceration taken orally at morning
and evening Diafouka, 1997
infertility water decoction taken orally Ake Assi et al., 1981
water decoction combined with root of
prevent Dichrostachys cinera taken orally, 100
miscarriage mL over 3 days Diafouka, 1997
water maceration combined with several
herbs administered via enema Walker, 1953
menstruation water decoction combined with several
pregnancy or reproductive aid complications herbs administered via enema Walker, 1953
water decoction combined with bark of
Syzygium brazzavillense taken orally,
respiratory aid bronchitis 100 mL over 3 days Diafouka, 1997
Bouquet and Debray,
gonorrhea not documented 1974
urinary
antiseptic decoction Ahombo et al., 2012
water decoction taken orally Adjanohoun et al., 1988
urogenital
infection water infusion taken orally Wome, 1985
water maceration taken orally, twice
venereal daily Diafouka, 1997
disease/infect Bouquet and Debray,
uritogenital aid ion not documented 1974
anti-pyretic, anti-malarial, Jain, 1991 (in Dhanapal
african sleeping sickness anti-pyretic not documented et al., 2012)
pain, inflammation,
M. rheumatism, muscle pains or Jain, 1991 (in Dhanapal
parvif joint pain, swelling (diuretic) muscular pain not documented et al., 2012)
olia Jain, 1991 (in Dhanapal
pregnancy or reproductive aid contraceptive not documented et al., 2012)
syphillis Jain, 1991 (in Dhanapal
uritogenital aid treatment not documented et al., 2012)
61
decoction Rao et al., 2012

mouth Brun and Schumacher,
other therapeutic activity freshner not documented 1987
anti-pyretic, anti-malarial, Ssegawa and Kasenene,
african sleeping sickness malaria not documented 2007
pain, inflammation,
M. rheumatoid
rheumatism, muscle pains or decoction Junsonduang et al., 2014
rubro arthritis
joint pain, swelling (diuretic)
stipul
erectile
ata
dysfunction
and Kamatenesi-Mugisha et
pregnancy or reproductive aid impotence pounded and boiled; taken orally al., 2005
Table 6: Summary of Ethnomedicinal Data for Root of Mitragyna

Affliction
Species Use Category Treated/Function Prepartion/Administration Reference
pregnancy or reproductive
M. hirsuta aid galactogogue water decoction taken orally Chuakul et al., 2002
water decoction taken orally;

anti-pyretic, anti-malarial, combined with several additional
african sleeping sickness malaria herbs Sangare, 2003
powder diluted with water and Adjanohoun et al.,

dermatological aid blisters taken orally 1986
Thoen and Thiam,

gastrointestinal aid belly pain decoction with water 1990
liver and kidney aid,
jaundice and diabetes diabetes decoction Diallo et al., 2012
Muazu and Kaita,
not documented 2008
maceration taken orally; combined Muazu and Kaita,
epilepsy with several additional herbs 2008
neurologial aid mental diseases not documented Malgras, 1992
Sonibare and Gbile,
respiratory aid asthma not documented 2008
root powder combined with

macerated Tamarindus indica fruit;
M. inermis uritogenital aid venereal disease combined in water or milk Adam et al., 1972
colic and febrifuge not documented Gritto et al., 2015
malaria not documented Khare et al., 2007
Mathur and Joshi,
2013; Panwar and
not documented Tarafdar, 2006
anti-pyretic, anti-malarial, 21 mL extract of bark and root is Dahare and Jain,
african sleeping sickness fever used 2x daily for 1 week 2010
anti-venom/anti- Panwar and Tarafdar,
poison/emetic poisoning not documented 2006
M. parvifolia anti-venom/anti- snake bite ground and combined with water; Arjariya et al., 2009
62
poison/emetic taken orally

burning sensation not documented 2006
edema not documented 2006
hair lice juiced root Bhardwaj et al., 2011
dermatological aid skin infection powder Bhardwaj et al., 2011
colic pain/peptic Panwar and Tarafdar,
ulcers not documented 2006
Mathur and Joshi,
gastrointestinal aid pain in abdomen not documented 2013
liver and kidney aid, Ong and Nordianan,
jaundice and diabetes diabetes decoction 1999
pain, inflammation,
rheumatism, muscle pains
or joint pain, swelling Panwar and Tarafdar,
(diuretic) muscular pain not documented 2006
gyneological Panwar and Tarafdar,
disoders not documented 2006
pregnancy or Panwar and Tarafdar,
reproductive aid aphrodisiac not documented 2006
respiratory aid cough not documented 2006
african sleeping sickness malaria not documented Muganga et al., 2010
pregnancy or reproductive erectile dysfunction Kamatenesi-Mugisha
aid and impotence pounded and boiled; taken orally et al., 2005
fatigue, weakness,
wasting syndrome,
M. stimulant, appetite maceration taken orally in
rubrostipulat stimulant, anemia, sickle combination with several other Kayonga and
a cell anemia herbs; 3 soup spoons Habiyaremye, 1987
anti-pyretic, anti-malarial, taken orally in combination with Kerharo and Adam,
african sleeping sickness anti-pyretic bark, leaf 1974
anti-parasitic not documented Sofowara, 1982
Royal Botanic
gastrointestinal aid colic boiled in water Gardens Kew, 1915
pregnancy or oxytocic, delivery
M. stipulosa reproductive aid aid water decoction taken orally Ake Assi et al., 1981
pain, inflammation,
rheumatism, muscle pains
M. or joint pain, swelling Junsonduang et al.,
rotundifolia (diuretic) rheumatoid arthritis decoction 2014
63
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Figure 1
Number of Google Searches for "Kratom"
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0
100
2004
2005
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18 Leaf Bark Root
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Number of Mitragyna species with Reported Uses

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Ethnomedicinal Use Category
Figure 6

Brown Lund Murch Ethnobotanika Mitragyna Speciosa

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A Botanical, Phytochemical and Ethnomedicinal

Paula N. Brown, Jensen A. Lund, Susan J. Murch

A Botanical, Phytochemical and Ethnomedicinal Review of the Genus Mitragyna

Aim of the Study

Materials and Methods

Keywords: Kratom, Mitragyna, M. speciosa, review, Mitragynine, 7-hydroxymitragynine

Although species of Mitrgayna possess a long history of ethnomedicinal use outside of

use despite harmful consequences that is often considered a hallmark of addiction

3.1. Taxonomy of Mitragyna

3.2. Identification of the genus Mitragyna

3.3 Substituion of species

4.0. Chemistry of Mitragyna

Proportions of alkaloid compounds can vary dramatically in Mitragyna plants depending

The pharmacology and toxicology of Mitragyna and phytochemicals isolated from

leading to production of COX-2 enzymes, suggesting a possible anti-inflammatory action (Utar

The effect of kratom and kratom alkaloids upon psychological disorders in a

In vitro study of mitragynine demonstrated cytotoxicity partially due to metabolic

6.0. Ethnomedical Uses of Plant Tissues

6.1 Fever, Malaria, and African sleeping sickness

6.3. Dermatological aid

6.4 Drug dddiction

6.5. Wasting syndrome, poor nutrition or stimulant

6.6. Gastrointestinal aid and parasites

6.7. Liver and kidney aid, jaundice, diabetes

6.8. Neurological aid

6.9. Pain, inflammation, rheumatism, and swelling

6.10. Pregnancy and reproductive aid

6.11. Respiratory aid

6.12. Urogenital aid

6.14. Other therapeutic activity

Despite growing interest towards species of Mitragyna as either a susbstitutes for M.

As previously mentioned, there is growing evidence to support that products sold as

M. speciosa’s utility in pain relief and treatment of opiate addiction in traditional

Given taxonomic re-arrangement for members in the genus Mitragyna as well as

Bouquet, A., 1969. Féticheurs et médecines traditionnelles du Congo (Brazzaville). Mémoires

Polygenis-Bigendako, M-J., 1990. Recherches ethnopharmacognosiques sur les plantes utilisées en

Puff, C., 2007. Flora of Thailand: Rubiaceae. Electronic document,

Razafinmandimbison, S.G., Bremer, B., 2011. Tribal delimitation of Naucleeae (Cinchonoideae,

US Drug Enforcement Administration, 2016b. Withdrawal of Notice of Intent to Temporarily Place

Yearsley, C., 2016. Kratom: Medicine or Menace? HerbalGram 112, 46-59.

Figure 3: Indole alkaloids found in Mitragyna leaf.

Figure 4: Oxindole alkaloids found in Mitragyna leaf.

Figure 5: Distribution of references by species and plant part.

Table 1: Botanical Nomenclature for the genus Mitragyna

Species Synonyms Heteronyms Distribution

Nauclea africana Willd.;

Nauclea africana Willd.;

Table 2: Alkaloids described in leaf materials of Mitragyna

M. mitrafoline, mitradiversifoline, specionoxeine-N(4)-oxide, 7- Badger et al., 1950; Cao et al., 2013

M. hirsuta mitraphylline, isomitraphylline , isomitraphylline N-oxide, Kitajima et al., 2007; Phillipson et

M. mitraciliatine, rhynchophylline, rhynchociline, cilaphylline, Beckett et al., 1963

M. mitraphylline, isomitraphylline, rhynchophylline, isorhynchophylline, Barger et al., 1939; Houghton and

M. mitraphylline, isomitraphylline, rotundifoline, isorotundifoline, Hendrickson et al., 1993; Shellard

isomitraphylline, ciliaphylline N-oxide Rungsiyakul, 1973;

Table 3: Summary of pharmacological effects for Mitragyna alkaloids

2005 deferens 2. Mitragynine was found to block T- and L-

1. Mitragynine, paynantheine, speciogynine,

1. "Mitragynine produced antinociceptive

Table 4: Summary of Ethnomedicinal Data for Leaves of Mitragyna

fatigue, Thoen and

Table 5: Summary of Ethnomedicinal Data for Bark of Mitragyna

decoction taken orally Doka et al., 2009