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Following “the Roots” of Kratom ( Mitragyna speciosa ): The Evolution of an Enhancer from a Traditional Use to Increase Work and Productivity in Southeast Asia to a Recreational Psychoactive Drug in Western Countries


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The use of substances to enhance human abilities is a constant and cross-cultural feature in the evolution of humanity. Although much has changed over time, the availability on the Internet, often supported by misleading marketing strategies, has made their use even more likely and risky. This paper will explore the case of Mitragyna speciosa Korth. (kratom), a tropical tree used traditionally to combat fatigue and improve work productivity among farm populations in Southeast Asia, which has recently become popular as novel psychoactive substance in Western countries. Specifically, it (i) reviews the state of the art on kratom pharmacology and identification; (ii) provides a comprehensive overview of kratom use cross-culturally; (iii) explores the subjective experiences of users; (iv) identifies potential risks and side-effects related to its consumption. Finally, it concludes that the use of kratom is not negligible, especially for self-medication, and more clinical, pharmacological, and socioanthropological studies as well as a better international collaboration are needed to tackle this marginally explored phenomenon.
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Research Article
Following (the Roots)of Kratom (Mitragyna speciosa):
The Evolution of an Enhancer from a Traditional Use to Increase
Work and Productivity in Southeast Asia to a Recreational
Psychoactive Drug in Western Countries
Eduardo Cinosi,1,2 Giovanni Martinotti,1,2 Pierluigi Simonato,1
Darshan Singh,3Zsolt Demetrovics,4Andres Roman-Urrestarazu,5,6
Francesco Saverio Bersani,1,7 Balasingam Vicknasingam,3Giulia Piazzon,1
Jih-Heng Li,8Wen-Jing Yu,8Máté Kapitány-Fövény,4,9,10 Judit Farkas,4,10
Massimo Di Giannantonio,2and Ornella Corazza1,7
Hateld, Her ts AL10 9AB, UK
2Department of Neuroscience, Imaging and Clinical Sciences, Gabriele D’Annunzio University, Chieti, Italy
3Centre for Drug Research, Universiti Sains, Penang, Malaysia
4Institute of Psycholog y, E¨
os Lor´
5London School of Economics and Political Science, LSE Health and Social Care, London, UK
6Department of Psychiatry, University of Cambridge, Cambridge, UK
7Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy
8School of Pharmacy and Ph.D. Program in Toxicology, Kaohsiung Medical University, Kaohsiung, Taiwan
9Faculty of Health Sciences, Semmelweis University, Budapest, Hungary
o Gyula Hospital, National Institute of Psychiatry and Addictions, Budapest, Hungary
Correspondence should be addressed to Ornella Corazza;
Received  August ; Revised  October ; Accepted  October 
Academic Editor: Yu-Ping Tang
Copyright ©  Eduardo Cinosi et al. is is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
e use of substances to enhance human abilities is a constant and cross-cultural feature in the evolution of humanity. Although
much has changed over time, the availability on the Internet, oen supported by misleading marketing strategies, has made their use
even more likely and risky. is paper will explore the case of Mitragyna speciosa Korth. (kratom), a tropical tree used traditionally
to combat fatigue and improve work productivity among farm populations in Southeast Asia, which has recently become popular
as novel psychoactive substance in Western countries. Specically, it (i) reviews the state of the art on kratom pharmacology and
identication; (ii) provides a comprehensive overview of kratom use cross-culturally; (iii) explores the subjective experiences of
users; (iv) identies potential risks and side-eects related to its consumption. Finally, it concludes that the use of kratom is not
negligible, especially for self-medication, and more clinical, pharmacological, and socioanthropological studies as well as a better
international collaboration are needed to tackle this marginally explored phenomenon.
1. Introduction
Kratom (Mitragyna speciosa Korth., of the Rubiaceae family)
is a –-metre high tropical tree, indigenous to Southeast
Asia, the Philippines, and New Guinea. Traditionally, in
certain regions of Southeast Asia, the chopped fresh or dried
leaves of the tree are chewed or made into tea by local manual
labourers to combat fatigue and improve work productivity
[]. In addition, kratom preparations have also been used
for centuries during socioreligious ceremonies and to treat
Hindawi Publishing Corporation
BioMed Research International
Volume 2015, Article ID 968786, 11 pages
BioMed Research International
1% 2%
Mitragynine (C23H30 N2O4)
Paynantheine (C23H28N2O4)
Hydroxymitragynine (C23H30N2O5)
Speciogynine (C23H30 N2O4)
Speciociliatine (C23H30N2O4)
F : An estimate of ai kratom extract composition. e
phytochemicals isolated from various parts of the tree include
overall  structurally related alkaloids as well as several avonoids,
terpenoid saponins, polyphenols, and various glycosides.
various medical conditions, such as morphine dependence
in ailand [], and as opium substitute in Malaya []. It
has been suggested that the genus was given the “Mitragyna
name by the Dutch botanist Korthals because the leaves and
the stigmas of the owers of the plant resemble the shape
of a bishop’s mitre []. However, considering its variety of
uses, it could be speculated that the term derives from the
“Mithraic cults,” seen as a source of spiritual transcendence
for thousands of years [].
Kratom preparations contain varying amounts of several
phytochemicals, making their pharmacological and toxi-
cological evaluation unique and dicult (Figure ). e
main psychoactive components in the leaves are alkaloids
mitragynine and -hydroxymitragynine both found only in
Mitragyna speciosa, but other analogues have been identied
(e.g., speciogynine, paynantheine, and speciociliatine) [,
] (Figure ). e eects of kratom in humans are dose-
dependent where small doses produce stimulatory eects
amphetamines, while larger dosages tend to be associated
with sedative-narcotic eects that resemble drugs such as
opiates [].
Imported to Western countries from Southeast Asia,
kratom has become in recent years a popular enhancer,
which could also be classied as novel psychoactive substance
(NPS) []. Beyond kratom, some of the most widely used
psychoactive plants, largely not under international control,
include Salvia divinorum,khat(Catha edulis), Hawaiian baby
woodrose seeds (Argyreia nervosa), y agaric (Amanita mus-
caria), “Magic Mushrooms” (Psilocybe and related species),
Peyote (Lophophora williamsii), Ayahuasca (Banisteriopsis
caapi and Psychotria viridis), and “Genie” (a smoking mixture
containing multiple plant materials and of dubious phar-
macognostical identity) []. Natural products oen used
as enhancers are exceptionally complex in terms of their
chemistry. is adds complexity of their pharmacological
eects, with a paucity of data relating to the toxicology of
these materials, and even less regarding their interactions
with conventional drugs of abuse []. is is further compli-
cated by the possibility of adulteration processes []. e level
of complexity, variability, and the unknown nature of these
choactive materials, could oer further risks of ill health by
misadventure, with potentially life-threatening consequences
[]. In this scenario, predictions of novel psychoactive drug
trends in Western countries specically suggest that kratom
e aim of the present study was to study this new
phenomenon by (i) reviewing the state of the art on kratom
pharmacology and identication; (ii) providing a compre-
hensive overview of kratom use cross-culturally, ranging
from its traditional use in native societies in Southeast Asia to
its more recent diusion as a NPS in Western countries; (iii)
exploring the subjective experience of users; (iv) identifying
risks and side-eects related to its consumption.
2. Materials and Methods
A collaborative and multidisciplinary eort to study the
rapid diusion of kratom was carried internationally by ten
research centres: the School of Life and Medical Sciences,
University of Hertfordshire (United Kingdom), Department
of Neuroscience, Imaging and Clinical Sciences, Gabriele
D’Annunzio University, Chieti (Italy), Centre for Drug
Research, Universiti Sains, Penang (Malaysia), Institute of
Psychology, E¨
os Lor´
and University, Budapest (Hungary),
London School of Economics and Political Science, LSE
Health and Social Care, London (United Kingdom), Depart-
ment of Psychiatry, University of Cambridge, Cambridge
(United Kingdom), Department of Neurology and Psychi-
atry, Sapienza University of Rome, Rome (Italy), School
of Pharmacy and Ph.D. Program in Toxicology, Kaohsiung
Medical University, Kaohsiung (Taiwan), Faculty of Health
Sciences, Semmelweis University, Budapest (Hungary), and
o Gyula Hospital National Institute of Psychiatry and
Addictions, Budapest (Hungary). A review of the literature
formed in three databases: PsycINFO, PubMed, and Med-
scape. Keywords used to carry out the database searches
included the following: “kratom”, “Mitragyna speciosa”,
“mitragynine”, and “-hydroxymitragynine”. Peer-review
data that emerged from the search were integrated with
an exploratory qualitative assessment of  websites, drug
fora, and other online resources (i.e., e-newsgroups, chat-
rooms, mailing lists, e-newsletters, and bulletin boards). is
was carried out on a regular weekly basis (between January
three languages (English, Italian, and Hungarian). Once the
substance availability of information was identied, further
specic searches were carried out for narratives focusing on
the following issues: (i) motivations behind its recreational
use and possible trends of misuse; (ii) the nature of its
eects on users, including adverse reactions and polydrug
misuse/idiosyncratic combinations; (iii) any other relevant
BioMed Research International
information. For the purpose of reporting the results in this
paper, any data collected from online fora, such as usernames
and complete URLs for specic threads that were considered
personal identiable, were anonymized. Additional searches
were conducted using the Global Public Health Intelligence
Network (GPHIN), a secure Internet-based early warning
system developed by Health Canada and the World Health
Organization (WHO), which monitors media reports in six
languages, Arabic, Chinese, English, French, Russian, and
Permission for the study was granted by the School of
Pharmacy Ethics Committee, University of Hertfordshire,
Hateld, United Kingdom (November ; PHAEC/-).
3. Results
 studies emerged from the literature review and were
critically analysed. Among these,  results were considered
not relevant (resulting duplicated, botanical studies, or stud-
ies focusing mainly on other selected chemical compounds)
and therefore excluded. e remaining  articles were
further qualitatively analysed and thematically divided in
three main areas of interest related to Mitragyna speciosa
and its main constituents: () in vitro and preclinical data
on pharmacology and behavioral eects (𝑁=51), ()
laboratoristic techniques for identication/characterization
(𝑁=26), and () epidemiological/toxicological reports on
humans (𝑁=18). Data on kratom that emerged from the
online searches were identied, monitored, and registered
into  categories: (1) epidemiology and motivation of use; (2)
legal status, methods of purchase, and typical price; (3) forms
of kratom use; (4) subjective pleasurable eects, adverse
eects, and fatal intoxications related to kratom; (5)pattern of
polyabuse. e results from the review of scientic literature
and online sources were comprehensively integrated and
summarized in the following three main subsections: (i)
preclinical data about pharmacology and identication of
kratom constituents; (ii) kratom use in humans in Southeast
Asia; (iii) kratom use in humans in Western countries.
3.1. Pharmacology and Identication of Kratom Constituents.
Kratom has both opioid- and psychostimulant-like subjective
eects []. e phytochemicals isolated from various parts
alkaloids [] of which mitragynine (Figure ) is the most
important with up to % purity in the extract of leaves
from ailand, and only % in kratom leaves from Malaysia.
is alkaloid is the one responsible for analgesic activity
opioid agonist property []. Although mitragynine can act
on the mu (𝜇), kappa (𝜅), and delta (𝛿) opioid receptors, it
is structurally dierent from morphine and other compo-
nents from the opioid family; the reason why it has been
suggested is that it might also present with a more broad
in kratom (including speciogynine (%), paynantheine (%),
and speciociliatine (%) (Figure )) are indole alkaloids of the
Corynanthe-type, possessing a monoterpene (iridoid) moiety
[]. Dierently, -hydroxymitragynine (Figure ), a minor
constituent (%) of M. speciosa, when isolated demonstrates
a potent antinociceptive activity in mice []. It is now
considered to be a major contributory factor for the analgesic
properties of M. speciosa due to its selectivity for 𝜇-and
𝜅-opioid receptors []. e presence of a hydroxyl group
at C- increases the potency of -hydroxymitragynine to
be - and -fold higher than morphine and mitragynine,
respectively, both in vitro and in vivo [, , ]. is might
be one of the main pharmacological markers of kratom
products’ quality and potency. Recent studies further revealed
how complex is kratom’s pharmacology, involving a 𝜅-opioid
and dopamine D receptors interaction in its various eects
[]. Serotonergic and adrenergic pathways have also been
involved in the eects of mitragynine, mostly due to its broad
anity to dierent receptors []. Indeed, the pharmacologi-
cal mechanisms responsible for stimulant activity are yet to be
clearly established []. Another confounding factor might be
the action of some other isolated compounds(speciociliatine,
speciogynine, and paynantheine), for example, whose eects
were not inhibited by naloxone in animal studies [, ].
It is possible that mitragynine is relatively safe at lower
subchronic dose but exhibits toxicity at a highest dose
[]. However, the erratic pharmacology of kratom makes
it dicult to dene a specic dose threshold. According to
online reports and traditional experiences, subjective eects
of kratom depend on the dosage: at low to moderate dose
(–g) it has a mild pleasant stimulant eect; at moderate-
high dose (– g) the compound has opioid-like analgesia
and sedation [, ]. No studies have been conducted so
far to determine the blood concentration in patients, and
future approach should consider this point in order to prevent
overdose, considering the possible risk of no response to
naloxone [, ]. e standard half-life of mitragynine is
. ±∼ hr, depending upon the individuals natural levels
of enzymes and other factors [, ]. -Hydroxymitragynine
has quite a bit shorter duration, with an average half-life of
. ±. hours [, ]. Recent evidences suggest that the
hydrophobicity, poor water solubility, high variability of drug
release in simulated biological uids, and acid degradable
characteristics of mitragynine probably further inuence the
large variability of its pharmacological responses reported
and brain histopathological changes, as well as hematological
and biochemical changes in mice []. Mitragynine, -
hydroxymitragynine, and mitraphylline exhibit high plasma
protein binding (>%) determined by equilibrium dialysis
clinical eects on CYPA activity, on the other hand
mitragynine might inhibit other cytochrome P enzyme
activities, specically CYPD [, ]. ese data indicate
the possibility of a drug interaction if mitragynine and -
hydroxymitragynine are coadministered with drugs that are
P-glycoprotein substrates [].
Current preclinical information on kratom suggests that
this ethnodrug, containing several dierent active alkaloids,
has a harmful toxicological prole and must be studied in
detail in order to better dene its potential as therapeutic
drug []. Acute administration of mitragynine produces
BioMed Research International
anxiolytic-like eects attributed to the interactions among
opioidergic receptor systems []. Other authors attempted
to reveal a possible link with the stress-related corticotropin
pathway []. Other evidences show that mitragynine exerts
an antidepressant eect in animal behavioral model inter-
acting with neuroendocrine HPA axis systems []. Among
its potential benets, in addition to analgesic activity [,
], mitragynine seems to be also a key component for
the anti-inammatory properties of kratom by suppressing
prostaglandin E (PGE-) production in the cyclooxygenase
 (COX-) pathway []. Moreover, some authors claim
that kratom might be promising antioxidant and anticancer
or chemopreventive compounds []. Kratom extracts and
mitragynine have been shown to possess cytotoxicity to some
human cancer cell lines, namely, SH-SYY cells (neuronal
cells), [] and avoid the tolerance and dependence on
chronic morphine treatment in mice as well as in human
neuroblastoma SK-N-SH cell [, ]. Other interesting prop-
erties of the compound might be the capability to modulate
muscle neurogenic contraction [–] and gastric secretion
developed as new therapeutic agents, there are also possible
serious adverse eects of these materials under investigation.
ere have been dierent studies showing serious conditions
aer repeated administration as elevated blood pressure,
nephrotoxic eects [], impaired cognition and behaviour
[, ], dependence potential [], and hepatic failure [,
]. e onset of liver injury is described to occur within
 to  weeks of starting regular use of kratom powder or
tablets, with symptoms of fatigue, nausea, pruritus, and dark
seems to be typically cholestatic and can be severe with
serum bilirubin levels rising above  mg/dL []. Kratom
constituents were also identied to be potentially cardiotoxic,
ideally potentiating Torsade de Pointes through inhibition
of rapid delayed rectier potassium current (IKr) in human
cardiomyocytes [].
At present, kratom constituents are not detected by
conventional drug screening tests: advanced tests like liq-
uid chromatography-tandem or ion-mass spectrometry are
required [].
3.2. Kratom Use in Southeast Asia
3.2.1. Diusion and Modalities of Consumption. Mitragyna
speciosa (Rubiaceae) is an indigenous plant of Southeast Asia.
or “biak” (Malaysia), or as “krathom” (ailand, “thom”
in Southern ailand) and has been used for millennia (a)
as a stimulant; (b) as a remedy in traditional medicine;
and (c) in social context [, ]. Historically, manual
labourers (e.g., sherman, farmers, and rubber-tappers) in
northern Malaysia and southern ailand commonly used
ketum leaves to improve their work productivity under the
sweltering sun and to relieve fatigue []. Rural folk have
traditionally ingested ketum leaves to self-treat common
medical problems (e.g., diabetes, diarrhoea, fever, and pain)
as an opium substitute in Malaya during opium scarcity [].
It is still popularly consumed in Asian communities during
social gatherings in the village [].
Traditionally, the fresh or dried leaves of kratom are
chewed or brewed into tea or smoked []. Ketum is bitter
and sugar or sweet beverages are commonly added to mask
its taste []. To experience vigour and euphoria, traditional
“kratom eaters” chew one to three fresh leaves at a time
[, ]. Regular and addicted users chew – times a day [].
about . g and a dry leaf about . g and twenty kratom
leaves contain about mg of mitragynine; no information
is available on other active compounds of the plant. Ketum
is currently widely available in many Asian countries (e.g., in
Malaysia) where it can be easily bought from ketum traders
in the community []. Consumers can be classied into two
improve physical tolerance to laborious work and the second
polydrug users who attempt to manage drug withdrawal
symptoms or reduce the intake of other opiates like heroin
[]. A recent study showed that out-of-treatment opiate users
in Malaysia oen use ketum to reduce their dependence
on illicit opiate as well as to ameliorate opiate withdrawal
symptoms [].
At present, there is no systematic data on the prevalence
of ketum use in all the native countries, but it seems to
be considerable in Malaysia and ailand. A survey per-
formed in  investigating kratom use in ailand (,
respondents aged – years) indicated that the lifetime,
past year, and past  days prevalences for kratom were
.%, .%, and .%, respectively []. ese gures, with
the exception of lifetime use, were signicantly higher than
those for cannabis making kratom the most widely used illicit
drug in ailand. Again in ailand past -day prevalence
studies among –-year-old students (𝑛 = 8 70812148)
in , , and  showed an increase in the lifetime
use of kratom (from .% to .%) []. Another study
in ailand in  showed a prevalence of psychoactive
drugs in , motor vehicle drivers: .% were positive to
mitragynine []. Overall, reported seizures linked to kratom
quintupled in ailand from  to , far higher than
those reported for any other drug []. Kratom reported
seizures in Malaysia and Myanmar also reached record levels
in , at roughly one ton each []. Conversely, in Taiwan,
heroin, methamphetamine, and some new drugs such as syn-
thetic cathinones (methylone, mephedrone, and MDPV) and
synthetic cannabinoids (K) have been identied since s
according to the Substance Abuse Monitoring and Reporting
Systems (SAMRS), which is a national data collection system
for substance abuse []. However, use of kratom and its
major alkaloid mitragynine has not been detected via the
collected information from the SAMRS []. erefore, it
could be suggested that kratom may not yet be a drug of
choice in Taiwan and might still be considered a rather
culture-bounded phenomenon in Asian countries.
e possession of kratom leaves has been illegal in
ailand since  []. Kratom is also controlled in a few
other countries in the region (Malaysia and Myanmar) and
elsewhere (Australia, Bhutan) []. In parallel, kratom-related
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arrests more than doubled between  and  in both
Myanmar and ailand []. To control its widespread abuse,
ketum was banned in Malaysia and regulated under the
Poisons Act  []. ose caught for possessing or pro-
cessing ketum leaves can be ned for approximately RM
, (US ) or imprisoned if found guilty []. e
Malaysian government is in the midst of regulating ketum
under the Dangerous Drugs Act , which will consider the
substances as harmful as opiates and amphetamines [].
3.2.2. Stigma and Side-Eects. Among rural folk, the believe
that kratom is a better alternative to illicit drugs, such
as heroin and methamphetamine, is still diuse and it is
mainly used for its invigorating-like eects [, ]. Five
to ten minutes aer kratom consumption users describe
themselves as feeling happy, strong, and active, especially
among those working in the agricultural sector []. ey
claim that “their mind is calm” aer the consumption of
the drug []. Overall, there is no real social stigma towards
ketum users and being dependent on ketum is not seen as
a major problem or taboo in Malaysia, at least for men.
their family but do not accept female addicts []. Moreover, it
seems that ketum dependents are not neglecting their family
and the impairment of their social functioning is still under
debate []. A recent cross-sectional survey in three northern
states of Peninsular Malaysia investigated  regular kratom
consumers []. Findings showed that regular kratom users
do not seem to experience major impairments in their
social functioning, despite being dependent on kratom for
prolonged periods []. Furthermore, ketum use does not
imply risky behaviours such as needle sharing, common in
heroin dependents []. On the other hand, evidence shows
that kratom can generate addiction problems and lead to
other social issues []. Considering how kratom use is
consistent, gures for treatment admissions for its use appear
rather low, accounting for, for example,  percent of all
drug treatment admissions in ailand in  (Figure ).
Kratom-related treatment admissions almost tripled between
 and  (Figure ) []. is could be also partially due
to a more strict antidrug policy, where individuals caught
with kratom are obliged to engage in treatment programs.
Surely, ndings show that regular kratom use is associated
with drug dependency, development of withdrawal symp-
toms, and craving []. Many regular users declare their
diculty to abstain from kratom use and experiencing
sharp unpleasant symptoms during abstinence periods [].
Physical withdrawal symptoms include anorexia, weight loss,
decreased sexual drive, insomnia, muscle spasms and pain,
aching in the muscles and bones, jerky movement of the
limbs, watery eyes/nose, hot ushes, fever, decreased appetite,
and diarrhoea [, ]. Psychological withdrawal symptoms
commonly reported are nervousness, restlessness, tension,
anger, hostility, aggression, and sadness [, ]. Long-term
addicts are described to become thin and have skin pigmen-
tation on their cheeks, due to the capacity of mitragynine
to increase the production of melanocytes-stimulating sub-
stance [, ]. Regular ketum use is also reported to cause
2007 2008 2009 2010 2011
Kratom-related treatment admissions in ailand
F : Kratom-related treatment admissions in ailand almost
tripled between  and . Source: United Nations Oce on
Drugs and Crime, Patterns and Trends of Amphetamine-Type
Stimulants and Other Drugs: Asia and the Pacic— (Bangkok,
psychotic symptoms such as mental confusion, delusion, and
hallucination [].
Regarding polydrug abuse, in Asia, patterns of com-
plex cointaking involving kratom are also reported. Beyond
classic” substances and many NPS as synthetic phenylethy-
lamines and cathinones, peculiarly there have been cases
where codeine is added into kratom drinks to obtain a
better “high” or euphoria. In southern ailand, in recent
years, homemade ice-cold cocktails, called “ ×,” have
become popular for their alleged alcohol-mimicking eect
among young Muslim people []. e cocktails are made
from kratom leaves, a caeine-containing so drink, and
codeine- or diphenhydramine-containing cough syrup as the
three basic ingredients to which ice cubes, an anxiolytic, an
antidepressant, or an analgesic drug is added [, ].
So far, there have not been any mortality or toxicity
incidents directly related to ketum use reported in Asian
countries. One possibility is that ketum users in Asia nor-
Traditionally, ketum in Asia has been used for its stimulant
eects and the dose consumed might be lower than the
one consumed for recreational purposes []. But it is also
possible that local health care providers in Asia, perceiving
ketum as a safe traditional herbal drink, might not attribute
some of the medical problems reported by users to ketum use;
this factor may indeed contribute to the underreporting of
adverse eects among ketum users in Southeast Asia.
3.3. Kratom Use in Western Countries
3.3.1. Diusion, Modalities, and Reasons of Consumption. In
recent years kratom has become popular in the EU, US,
BioMed Research International
and other countries (e.g., Japan) as a recreational novel
compound[,,].AvarietyofMitragyna speciosa related
products are easily accessible from local smart shops and
increasingly available forsale on the Internet, in particular on
web based “legal highs” pharmacies, but their exact content is
not always veried [, ]. Many dierent formulations are
available, including raw leaves, capsules, tablets, powder, and
concentrated extracts []. Prices vary between countries,
depending on the type and amount of the purchased product,
X” extracts,  to  euros per  gram for dried kratom [],
or sometimes even for lower prices (from less than  euro per
gram for “kratom power”) [, –].
Mitragyna speciosa and/or mitragynine and/or -hydrox-
ymitragynine are currently controlled only in a small number
of EU Member States, such as Denmark, Latvia, Lithuania,
Poland, Romania, and Sweden []. Kratom is also largely
uncontrolled in the US at a federal level while at the state
level there are some exceptions such as Indiana, Iowa,
Louisiana, and Massachusetts. is means all parts of the
plant and its extracts are legal to cultivate, buy, possess, and
distribute without a license or prescription, and, when sold
as a supplement, sales must conform to US supplement laws
[]. Recently, in February , the Food and Drug Admin-
istration (FDA) issued “Import Alert -” that seems to
provide customs and border agents broad authority to seize
kratom products from a number of suppliers outside the US
As kratom is oen not monitored in national drug abuse
surveys, there is still little information on prevalence of its
use. An initial warning about this phenomenon has been
launched by the Drug Enforcement Administration (DEA)
as early as  []. Internet surveys conducted by the
EMCDDA in  indicated that kratom was one of the most
widely oered “legal highs” in % of the investigated 
online shops across the EU []. A more extensive EMCDDA
Internet survey in July  showed that kratom was the
most widely oered product with  out of  (or %) of
online retailers shipping it to the EU. A further online study
identied  online shops selling NPS that would dispatch
products to at least one EU Member State (United Kingdom
appeared to be the most common) []. Kratom and Salvia
divinorum were the most frequently oered NPS, available
in  and  online shops, respectively []. In  the term
“kratom” was found in more than two million results. Of the
rst  websites listed in the search results,  were primarily
focused on the sale of kratom, while  were focused on
disseminating information about kratom through the use of
discussion boards [].
3.3.2. Subjective Experience: Online Reports. Since , an
exponential growing number of kratom’s subjective experi-
ences have been posted online by users (Box ) [, –].
advantage over chewing or making a tea: the amount of leaves
that constitutes a typical dose is too much to be smoked
easily [, ]. A paste-like extract can be prepared by lengthy
boiling of fresh or dried leaves and the syrup produced can
pills and smoked in pipes (“madatin”) []. Small pellets of
dissolved in hot water and consumed alone or mixed with
other ordinary herbal teas to make it more palatable (the so-
beverages or to ingest it with food, mixing it with yoghurt or
preparing cookies, in order to contrast the bitterness of the
compound [, ]. Regarding desired/recreational eects of
kratom, users report that at low doses it is rather stimulant,
mind is “more alert,” physical energy and sometimes sexual
arousal are increased, and ability to do physical work may
be improved and they also described “entactogenic” eects,
like empathy and euphoria (Box ) [, , ]. Some people
nd this level edgy rather than pleasant [, ]. At higher
doses, experiences describe it as more sedative and analgesic;
users prefer to be less sensitive to physical or emotional
pain, to feel and look calm, and to have a general feeling of
comfortable pleasure [, ]. Others report an increase of
empathy feelings (Box ) [].
3.3.3. Side-Eects. A variety of less explored side-eects
experienced by users also emerged from our work (Table ).
ese frequently include nausea, constipation, sleep prob-
lems, temporary erectile dysfunction, itching, and sweating
and also hyperpigmentation and tremor and anorexia and
weight loss in long term [, –]. Some users describe
hair loss, probably related to a regular (daily) use of kratom
[]. Withdrawal symptoms are also common, including
muscle aches, irritability, mood disturbances, runny nose,
diarrhoea, and muscle jerking (Table ) []. Users describe
tolerance (requiring the consumption of higher doses to
achieve the same eects) and also a “cross-tolerance” to
both kratom and opiates aer repeated intake [, –].
Moreover, kratom is increasingly purchased from Internet
sources for self-medication [, ], especially by individuals
with chronic pain to self-manage opioid withdrawal [, ]
or heroin, methadone, or suboxone withdrawal symptoms
[], or for its anxiolytic and antidepressant eects [].
For this reason, it is oen advertised online as a cheaper
alternative to traditional opioid replacement therapies with
no need of medical prescription []. is could pose a
serious problem for doctors prescribing pain medication or
opioid substitution therapy to someone who is a regular
kratom user. Adverse eects and intoxications cases across
various countries have also been reported, including liver
toxicity, seizure, and coma [, –], reports of patients
suering from intrahepatic cholestasis aer two weeks of
kratom use [], Adult Respiratory Distress Syndrome [],
and hypothyroidism [] (Table ). Evidence also suggests
that kratom might be a deadly substance when mixed with
other compounds (Table ). Fatalities resulting from the use
of a kratom-based product known as “Krypton” have also
been reported [] with  documented cases in Sweden
[]. Subsequent forensic studies revealed that Krypton
contained high amounts of the exogenous pharmaceutical
agent O-desmethyltramadol, an opioid analgesic and the
main active metabolite of tramadol, and it had been added
to the plant material. e presence of this contaminant
in some online products is well documented [, , ].
BioMed Research International
“About twenty minutes aer ingesting the Kratom, I began to feel a nice, pleasant euphoria
identical to that of an opiate...I did notice the simultaneous stimulant/depressant eect like
I notice in hydrocodone or oxycodone”
“I start to feel this intense warmth come over my entire body, it feels like a combination of
my rst MDMA high with a nice OxyContin like twist, along with the social aspect of
“I felt my insides become so and pliable like the onset of most trippy drugs”
“I felt relaxed, sedated, and free of my normal back and thumb pain in my right hand which
I thought would never be possible. I also felt a nice fuzzy feeling all over which I get from
smoking pot sometimes”
“I began oating in and out of waking dreams, the ‘nod’, whatever you want to call it, where
you’re not really asleep but you still see dreamlets and dream fragments oating before your eyes.
is goes on for quite some time”.
“I lost track of time at this point, as I was completely lost in the music and my own thoughts. I
wasn’t really feeling euphoria or a ‘high,’ like when using marijuana. I did feel very ‘stoned’ though,
and I guess I would refer to my state as being high because of my total relaxation and
“When I’m at the peak, I feel a very pleasant body buzz, kind of like being wrapped around a warm,
so blanket all day long. On the comedown, I feel relaxed but scatterbrained and my
concentration takes a hit, and I can easily enter ‘waking dreams’ where I’m not sleeping but
dreaming while being unaware of either state of consciousness, which oen causes me to jolt
awake and open my eyes”
B : Qualitative analysis of kratom users’ experiences.
Even though mitragynine was also detected in the products,
it was not determined how the two substances may have
interacted to cause death. Other “deadly cases” are available:
an article described a fatal reaction that appeared to be asso-
ciated with mixing with propylhexedrine (an 𝛼-agonist and
amphetamine-like stimulant, used as decongestant inhalers);
another case indicated that a mix of kratom, over-the-counter
cold medications, and benzodiazepines was responsible for
the death of a -year-old boy; a postmortem detection of
kratom together with venlafaxine, diphenhydramine, and
mirtazapine was screened in a -year man found unrespon-
sive in bed; a middle aged man in therapy with zopiclone,
citalopram, and lamotrigine was found dead at home and
postmortem analysis of peripheral blood revealed high con-
centrations of mitragynine and -hydroxymitragynine and
therapeutic values of intake of the other compounds [, ,
It must also be noted that kratom is commonly taken
in combination with a variety of other recreational “classic
drugs” (e.g., alcohol, cannabis, benzodiazepines, methadone,
cocaine, amphetamine, and hallucinogenic mushrooms) and
NPS (e.g., kava, mephedrone, and other synthetic cathinones,
tryptamines, and phenylethylamines such as C-E, AL-LAD,
and -HO-MiPT) [].
4. Discussion and Conclusions
Indeed, the use of substances to enhance human abilities
is a constant and cross-cultural feature in the evolution of
cultures for therapeutic purposes, religious ceremonies, and
improvement or modication of the physical and mental
abilities. Although much has changed over time, the drive
for human enhancement has not diminished and drugs
availability on the Internet, oen supported by misleading
marketing strategies, has made their use even more likely and
risky []. In this context,the tropical tree Mitragyna speciosa
Korth. (kratom) has now planted its “roots” of use worldwide.
Although the phenomenon has only been marginally studied,
an exponential number of kratom’s subjective experiences
have been posted online on drug fora by users in the EU
and US and elsewhere. Kratom, still easily available in native
countries, is now just “a click” away and potentially available
BioMed Research International
T : Report of adverse/toxicological eects of kratom.
Short time use eects
Nausea, constipation, sleep problems,
temporary erectile dysfunction,
itching, or sweating
Long time use eects Anorexia, dry mouth, problems in
diuresis, darker skin, and hair loss
Hostility, aggression, aching of muscles
and bones, jerky movements of the
limbs, anorexia and weight loss, and
Infrequent eects
Seizures (individuals using high doses
of kratom, either alone or combined
with other drugs), intrahepatic
cholestasis, psychotic symptoms, Adult
Respiratory Distress Syndrome, and
Kratom mixed with other substances:
over-the-counter cold medications and
venlafaxine, diphenhydramine, and
zopiclone, citalopram, and lamotrigine
to wide range of new users, including vulnerable individuals.
As it emerged from our previous studies [, –], the web
serves also as a repository of information for selected groups,
who can share experiences and suggest new products or
novel modalities of intake via online fora, chat-rooms, blogs,
videos, and others.
Anthropologically, drug addiction history is the complex
history of human vicissitude and desire, as human being is a
desiring being, trying in every way to assuage suerings, to
enhance feelings of pleasure, and to satisfy inexhaustible and
incessant desires []. Even today, the line between socially
acceptable and unlawful use of a variety of psychoactive
products seems to be culture-bound. Kratom is a plant with
a well-established traditional use in South Asia to enhance
work abilities as well as support traditional medicine and
culture, even if ocially banned. At the same time, its rapid
diusion in Western societies, where it is oen considered a
“natural” and thus safer option than illicit drugs or an alter-
native to opioid treatment, is not devoid of risks. According
to preclinical data and case reports published in scientic
literature as well as anecdotal experiences posted online,
kratom is not a safe drug. Its consumption is associated
per se with drug dependency, development of withdrawal
symptoms, craving, serious adverse eects, and life-threating
eects, especially in a multidrug-intoxicating scenario [,
, , ]. Furthermore, the idea that legality can equate
with the safety of a product might still remain a common
insidious misbelief amongst drug users []. On the other
hand, Suwanlert has pointed out in  that “it is hoped
that drug education will be a more eective step towards
kratom use control” [], foreseeing the failure of the legislative
measures in South Asian countries.
Kratom pharmacology itself is complex and requires
future research: this compound in fact acts on opioid as well
as on dopaminergic, serotonergic, GABAergic, and adren-
ergic systems [, ]. erefore, subjective eects are very
peculiar ranging from psychostimulant to sedative-narcotic.
Pharmacological mechanisms responsible for several of its
alkaloids activity deserve yet to be clearly established in future
studies. Altogether, available data on kratom suggest caution:
this unregulated plant could exhibit a serious harmful poten-
tial, far beyond any “therapeutic” desired eect; in parallel, its
anxiolytic, antidepressant, and analgesic properties need to be
better explored by scientic research works, like, for example,
in large blind randomized controlled clinical trials [].
Potential users who tend to self-medicate and health
professionals working with them should be clearly aware of
the risks associated with kratom consumption []. As it
emerged from this and other previous studies [], kratom
is advertised and sold online as “cheaper alternative” to
traditional opioid replacement therapies, as a painkiller for
chronic pain, or as an anxiolytic remedy in psychiatric
population, with no need of medical prescription or supervi-
sion. is encourages a tendency to self-medicate and could
become a serious problem for unaware doctors prescribing
medication to a patient who is a regular kratom user or in
case of acute intoxication related to the substance. Another
issue of concern is the action of other isolated compounds
(e.g., speciociliatine, speciogynine, and paynantheine) whose
eects were not inhibited by naloxone in animal studies [,
], meaning a potentially very dicult management in case
of overdose. erefore, in this scenario, the risk of adverse
reactions or possible misdiagnosis might be very high. It
might also be worth adding that kratom use is not detected
by conventional drug screening tests as advanced tests, like
liquid chromatography-tandem or ion-mass spectrometry,
focusing and asking direct questions on the nature and
patterns of drug intake, including medical products diversion
and consumption of NPS, during clinical assessments [].
Given that nowadays polydrug use represents the norm rather
than the exception, especially in emergency settings [], the
simultaneous use of drugs should also be promptly iden-
tied, investigated, and well discriminated. Future studies
should explicitly examine the eects of the combination in
complex patterns of polydrug intake, including kratom, to
fully understand the synergistic eects and associated clinical
and toxicological implications. Attention should also be paid
to the motivations behind such behaviours, social norms,
stigma, availability, and other lifestyle factors.
Surely, a possible limitation of our analysis could be
given by the fact that publicly available websites, fora, and
similar sources were also considered and included together
with a systematic literature review. One could wonder about
the limitations of carrying out a risk assessment of a drug
while taking into account also the online comments. It may
be inappropriate to trust information obtained from the
Internet without independent verication and we did not
have any possibility here to ascertain if the substance the
online alleged drug users were taking was indeed kratom. On
the other hand, online reports about kratom seem genuine
BioMed Research International
and many users illustrate their detailed experiences as proper
experiments on themselves. us, in the lack of relevant peer-
reviewed data, the online monitoring seems to be indeed a
very useful method to obtain preliminary information about
new and emergent phenomena []. Further, as demon-
strated by the outcomes of this study, a better international
collaboration is necessary to tackle this rapidly growing drug
Conflict of Interests
e authors declare that there is no conict of interests
regarding the publication of this paper.
is publication arises from collaborative activities and
sta exchanges among collaborating institutions funded by
the European Commission. e authors would also like
to acknowledge the contribution of the Canadian Centre
on Substance Abuse (CCSA), the Public Health Agency of
Canada, and the World Health Organization (WHO) for
granting access to the Global Public Health Intelligence
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... Kratom, also known as Mitragyna speciosa, is a member of the coffee family and has been used as a form of traditional medicine in Southeast Asia, particularly in Thailand, Malaysia, and Indonesia, for centuries [1]. Traditionally, it was consumed by chewing or brewing the leaves into tea [1]. ...
... Kratom, also known as Mitragyna speciosa, is a member of the coffee family and has been used as a form of traditional medicine in Southeast Asia, particularly in Thailand, Malaysia, and Indonesia, for centuries [1]. Traditionally, it was consumed by chewing or brewing the leaves into tea [1]. Its use as a recreational drug can be traced back to the early 19th century when it was first used to relieve fatigue, pain, and enhance productivity [2]. ...
... Drug effects vary depending on the dose, with low doses producing a stimulant-like effect and higher doses producing sedative effects. Due to its opioid-like effects, kratom is used to manage chronic pain, anxiety, and depression with high rates of user self-reported effectiveness [1]. Despite its potential benefits, kratom is also known to have addictive properties, and its use has been associated with adverse effects, such as confusion, hallucinations, and seizures [2]. ...
Kratom is an unregulated herbal supplement that is growing in popularity in the United States. Its primary active ingredients, mitragynine, and 7-hydroxymitragynine, are partial agonists that act on mu- and delta-opioid receptors in the central nervous system, producing analgesia and a sense of euphoria. Kratom use can lead to addiction and adverse side effects, such as seizures, hallucinations, and coma. This case report presents a male in his 40s with a history of kratom use, who presented to the clinic seeking help for his addiction. The patient had been using kratom for several years to self-medicate for his anxiety and depression and gradually developed a kratom addiction. The patient was successfully treated with buprenorphine/naloxone, which helped alleviate his withdrawal symptoms and allowed him to abstain from kratom. This case underscores the growing issue of kratom addiction in the United States and the critical need for physician awareness in treating withdrawal.
... Relative to other species, only M. speciosa has been extensively cultivated and used for medicinal benefits. The United States market is dominated by plant products imported from Southeast Asia (Cinosi et al., 2015). At low doses (1-5 g of dried leaf powder), kratom is said to have stimulant properties, while at higher doses (>10 g of dried leaf powder), opioid-like effects ensue. ...
... Dried kratom leaf powder is consumed in western countries as a capsule, pill, or tea (Cinosi et al., 2015). The powder is also swallowed with a drink, otherwise known as the "toss and wash method". ...
Kratom is a botanical natural product belonging to the coffee family, with stimulant effects at low doses and opioid-like effects at higher doses. During the last two decades, kratom has been purported as a safer alternative to pharmaceutical and illicit drugs to self-manage pain and opioid withdrawal symptoms. Kratom alkaloids, typically mitragynine, have been detected in biological samples from overdose deaths. These deaths are often observed in combination with other drugs and are suspected to result from polyintoxications. This review focuses on the potential for kratom to precipitate pharmacokinetic interactions with object drugs involved in these reported polyintoxications. The legal status, chemistry, pharmacology, and toxicology are also summarized. The aggregate in vitro and clinical data identified kratom and select kratom alkaloids as modulators of cytochrome P450 (CYP) enzyme activity, notably as inhibitors of CYP2D6 and CYP3A, as well as P-glycoprotein-mediated efflux activity. These inhibitory effects could increase the systemic exposure to co-consumed object drugs, which may lead to adverse effects. Collectively, the evidence to date warrants further evaluation of potential kratom-drug interactions using an iterative approach involving additional mechanistic in vitro studies, well-designed clinical studies, and physiologically based pharmacokinetic modeling and simulation. This critical information is needed to fill knowledge gaps regarding the safe and effective use of kratom, thereby addressing ongoing public health concerns. Significance Statement The botanical kratom is increasingly used to self-manage pain and opioid withdrawal symptoms due to having opioid-like effects. The legal status, chemistry, pharmacology, toxicology, and drug interaction potential of kratom are reviewed. Kratom-associated polyintoxications and in vitro-in vivo extrapolations suggest that kratom can precipitate pharmacokinetic drug interactions by inhibiting CYP2D6, CYP3A, and P-gp. An iterative approach that includes clinical studies and PBPK modeling and simulation is recommended for further evaluation of the drug interaction potential of this increasingly popular botanical.
... Kratom is known to improve the quality of life and well-being of community residents throughout South Thailand and is closely embedded in traditions and customs. Kratoms are also used to combat fatigue, enhance endurance, and activate psychoactive discrimination [4]. Traditionally, folk healers have combined kratom with several mixtures of Thai herbs to induce health-promoting effects [5]. ...
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Kratom (Mitragyna speciosa) leaves are commonly used to enhance endurance and treat various diseases. This study evaluated the effect of kratom leaf fermentation with Lactobacillus rhamnosus. Antibacterial activity was investigated against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Escherichia coli, and E. coli O157:H7. Biofilm inhibition and eradication assays were also performed. Antioxidant properties were determined by measuring the total phenolic and flavonoid content and DPPH and ABTS scavenging activities. Nitric oxide and TNF-α, IL-1β, and IL-6 expressions in LPS-stimulated RAW 264.7 macrophage cells were also measured. Aqueous kratom extract exhibited promising effects against free radicals and pro-inflammatory cytokines. Notably, all fermented kratoms showed significant antibacterial activity against the tested pathogens and antibiofilm formation by S. aureus and MRSA. Furthermore, the eradication of established biofilms of fermented kratoms was observed in S. aureus (day 2, 50 mg/mL) and E. coli (day 2, 100 mg/mL and day 4, 50 mg/mL). To the best of our knowledge, this study is the first to report that fermented and non-fermented kratoms could be nutraceutical sources of antibacterial, antibiofilm, antioxidant, and anti-inflammatory substances against related diseases and can be applied further in dietary or cosmetic products with health-promoting effects.
... Mitragyna speciosa, colloquially known as kratom, is a tree that grows natively in several Southeast Asian countries, including Indonesia, Malaysia, and Thailand. In these countries, the human consumption of kratom dates back several centuries and has had medicinal and recreational motives [1,2]. Locals ingest the crude plant products either by directly chewing on the leaves, or by using the leaves as an ingredient in tea and other drink concoctions [3]. ...
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Kratom (Mitragyna speciosa) is a Southeast Asian plant containing various alkaloids that induce pharmacological effects in humans. In Western countries, online vendors sell a variety of different kratom strains which are marketed to have distinct effect profiles. However, as of yet such marketing claims are unsubstantiated, and therefore the current study investigated whether differently colored kratom products can induce distinct effects, as self-reported by users. Six hundred forty-four current kratom users were anonymously surveyed to compare the self-reported effects of and motivations for using kratom products sold as red, green, and white strains. Most of the survey respondents were customers of the same kratom vendor, the products of which had been analyzed for their alkaloid content by an independent laboratory. The survey respondents reported distinct subjective experiences for different kratom strains, in a manner congruent with common marketing descriptions. However, the product analyses revealed no significant cross-strain differences in alkaloid content, suggesting that the reported effect differences might be disproportionally influenced by marketing narratives and anecdotal reports. Future studies should engage a more diverse population and include kratom strains from various vendors. Controlled, blinded experiments could assess whether the reported effect differences stem from a placebo effect or from alternative factors, e.g., minor alkaloids and terpenes.
... In these countries, the human consumption of kratom dates back several centuries and has had medicinal and recreational motives. [1,2] Locals ingest the crude plant products either by directly chewing on the leaves, or by using the leaves as an ingredient in tea and other drink concoctions. [3] Through these routes of administration, the plantʹs analgesic properties have been utilized to combat chronic pain, whereas its energizing effects have been popular among farming communities where kratom is used to prolong physical labor. ...
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Kratom (Mitragyna speciosa) is a Southeast Asian plant containing various alkaloids which induce pharmacological effects in humans. In Western countries, online vendors sell a variety of different kratom strains which are marketed to have distinct effect profiles. However, as of yet such marketing claims are unsubstantiated, and therefore the current study investigated whether differently colored kratom products can induce unique effects, as self-reported by users. 644 current kratom users were anonymously surveyed to compare the self-reported effects and motivations for using kratom products sold as red, green, and white strains. Most of the survey respondents were customers of the same kratom vendor, the products of which had been assessed for their alkaloid content by an independent laboratory. The survey respondents reported distinct subjective experiences for different kratom strains, in a manner congruent with common marketing descriptions. However, the product analyses revealed no significant cross-strain differences in alkaloid content, suggesting that the reported effect differences might be disproportionally influenced by marketing narratives and anecdotal reports. Future studies should engage a more diverse population and include kratom strains from various vendors. Controlled, blinded experiments could assess whether the reported effect differences stem from a placebo effect or from alternative factors, e.g. minor alkaloids and terpenes.
... Kratom is the herbal substance derived from the leaves of Mitragyna speciosa, a large evergreen tree of the same name native to Southeast Asia, that has centuries of ethnobotanical use [1 • ]. Common preparations of dried or fresh leaves, either chewed or made into a tea, provide mild stimulation to ward off fatigue, akin to traditional South American use of coca leaf [2]. Larger doses may cause anxiolytic and opioidlike effects and is often used for managing pain and opioid dependence [3,4]. ...
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Purpose of Review Kratom, a preparation of the leaves collected from the Southeast Asian plant Mitragyna speciosa, has increased in use within the United States (US) predominantly due to its stimulant and opioid-like effects. It contains many active alkaloids, most notably mitragynine. Clinical pharmacological research and toxicological information are limited, hindering forensic interpretation and an understanding of the role kratom use may play in death. Despite arguments from some vocal proponents and vendors that kratom poses no risk to users, there is a growing body of evidence that kratom use can result in significant adverse events, including death. Recent Findings Toxicological data for blood specimens analyzed between January 2018 and September 2022 in postmortem and driving under the influence of drugs cases were reviewed for the presence of mitragynine, the primary alkaloid of Mitragyna speciosa. Reported blood mitragynine concentrations, compound positivity, and concomitant findings were evaluated. Summary The forensic interpretation of mitragynine continues to be challenging. Kratom has been implicated in an increasing number of overdoses and deaths, and its significance is difficult to ascertain due to a substantial number of confounding variables, including a limited scope of toxicological testing and frequent co-positivity with drugs of abuse. Mitragynine has been listed as the primary toxicological finding in several overdose deaths albeit at a lower frequency compared to overall positivity, particularly when present at elevated concentrations (> 1000 ng/mL); these cases provide forensic confirmation of harms due to kratom use.
... Kratom is used recreationally as a plant-based substance by some users. Its effects are described as psychostimulant in small dosages of up to 5 g of plant material and similar to opioids at higher doses of approximately 5 to 15 g [1,6]. However, its native use in South Asia has been associated with the nonmedical self-treatment of several conditions (i.e., substance use disorder (SUD) symptoms, such as opioid and other drugs' withdrawal, pain, and improving energy) described even in the West, as well as hypertension, stomach ailments, diarrhea, infections, and diabetes, among others [1,7,8]. ...
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Purpose of review: This work aims to provide an up-to-date review of the preclinical and clinical scientific literature on the therapeutic value of kratom to better understand the underlying mechanisms related to its use and inform future therapeutic applications. Recent findings: A growing number of studies, mainly of cross-sectional nature, describe the widespread use of kratom by individuals to self-treat pain, psychiatric symptoms, and substance use disorders (SUD) outside a controlled clinical setting. Preclinical evidence suggests kratom is effective as an analgesic agent and might decrease the self-administration of other drugs. A randomized controlled trial has further supported kratom's therapeutic value as an analgesic. Investigations in nonclinical samples of long-term kratom users also indicate its therapeutic benefit in managing SUD symptoms (e.g., craving) and long-term or acute symptoms (e.g., withdrawal) for alcohol, opioids, and other illicit drugs. However, episodes of kratom-related intoxications have also been reported, often due to the adulteration and the contamination of kratom products mainly sold online or mixed toxicities when consumed outside clinical and traditional settings. Summary: Evidence on the clinical implications of kratom use is still limited and uncertain, with kratom research constantly evolving. Therefore, further randomized trials are needed.
Background Kratom has been used for different reasons such as pain, opioid withdrawal, and relaxation. Kratom can cause dependence and overdose, and it’s classified under ‘drugs of concern’ by the US Drug Enforcement Administration. Despite these concerns, kratom is legal in most of the United States and many countries around the world with easy accessibility. Literature searches reveal recommendations to use buprenorphine (or buprenorphine-naloxone), which are medications to treat opioid use disorder, in order to treat patients with kratom use disorder; however, there are no formal guidelines available. Buprenorphine (or buprenorphine-naloxone) induction is recommended to be conducted under observation (i.e. in the clinic) in the United States, but COVID-19 has resulted in shifts toward telehealth. Objectives Describe case series of successful management of kratom use disorder using telehealth followed by unobserved buprenorphine-naloxone home induction and highlight implications for future management, including maintenance dosage and induction method. Methods We present 2 very similar kratom use disorder patients who reported taking 35 g of kratom per day who underwent unobserved buprenorphine-naloxone home induction. Results Both were seen via telehealth initially. They reported no adverse effects before, during, or after the unobserved home induction on buprenorphine-naloxone but stabilized on significantly different dosages. Conclusion Telehealth followed by unobserved buprenorphine-naloxone induction at home may be an alternative to traditional buprenorphine-naloxone induction where treatment accessibility is limited. In addition to daily doses of kratom use, other factors, such as duration of kratom use and individual psychological factors may determine the most comfortable dose of buprenorphine-naloxone.
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Mitragynine is a major bioactive compound of Kratom, which is derived from the leave extracts of Mitragyna speciosa Korth or Mitragyna speciosa (M. speciosa), a medicinal plant from South East Asia used legally in many countries as stimulant with opioid-like effects for the treatment of chronic pain and opioid-withdrawal symptoms. Fatal incidents with Mitragynine have been associated with cardiac arrest. In this study, we determined the cardiotoxicity of Mitragynine and other chemical constituents isolated using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The rapid delayed rectifier potassium current (IKr), L-type Ca2+ current (ICa,L) and action potential duration (APD) were measured by whole cell patch-clamp. The expression of KCNH2 and cytotoxicity was determined by real-time PCR and Caspase activity measurements. After significant IKr suppression by Mitragynine (10 µM) was confirmed in hERG-HEK cells, we systematically examined the effects of Mitragynine and other chemical constituents in hiPSC-CMs. Mitragynine, Paynantheine, Speciogynine and Speciociliatine, dosage-dependently (0.1∼100 µM) suppressed IKr in hiPSC-CMs by 67% ∼84% with IC50 ranged from 0.91 to 2.47 µM. Moreover, Mitragynine (10 µM) significantly prolonged APD at 50 and 90% repolarization (APD50 and APD90) (439.0±11.6 vs. 585.2±45.5 ms and 536.0±22.6 vs. 705.9±46.1 ms, respectively) and induced arrhythmia, without altering the L-type Ca2+ current. Neither the expression,and intracellular distribution of KCNH2/Kv11.1, nor the Caspase 3 activity were significantly affected by Mitragynine. Our study indicates that Mitragynine and its analogues may potentiate Torsade de Pointes through inhibition of IKr in human cardiomyocytes.
Novel Psychoactive Substances: Classification, Pharmacology and Toxicology provides readers with background on the classification, detection, supply and availability of novel psychoactive substances, otherwise known as "legal highs." This book also covers individual classes of novel psychoactive substances that have recently emerged onto the recreational drug scene and provides an overview of the pharmacology of the substance followed by a discussion of the acute and chronic harm or toxicity associated with the substance. Written by international experts in the field, this multi-authored book is a valuable reference for scientists, clinicians, academics, and regulatory and law enforcement professionals.
Taiwan currently has one of the most dynamic economies in the world and its record in public health achievement is no less impressive. Thus it is of great interest to note that Taiwan may present a unique example of how people within a rapidly developing economy can successfully fight against the AIDS epidemic. AIDS and STD control policies are coordinated at the central level by the Department of Health of the Executive Yuan (the Cabinet). The AIDS Advisory Committee appointed by the Central Government consists of academics physicians and health officials. This committee reviews national control policies and periodically provides recommendations. The National AIDS Control programme which is implemented at all levels of the Government provides the basic framework for the prevention and control of AIDS. (excerpt)
The pharmacological self-management of novel psychoactive substance (NPS)-induced psychopathological consequences represents a fast growing phenomenon. This is facilitated by the frequent sharing of NPS intake experiences online and by the ease of access to a range of psychotropic medications from both the online and street market. Olanzapine is anecdotally reported by Web users to be the most frequent self-prescribed medication to cope with NPS-induced psychoses. Hence, we aimed here at better assessing olanzapine use/misuse for this purpose. Exploratory qualitative searches of 163 discussion fora/specialized websites have been carried out in four languages (English, German, Spanish, and Italian) in the time frame November 2012-2013. Most NPS-users allegedly self administer with olanzapine to manage related psychotic crises/"bad trips". This may be typically taken only for a few days, at a dosage range of 5-50 mg/day. Only a few research studies have formally assessed the effectiveness of olanzapine and indeed of other second-generation antipsychotics to treat NPS-induced psychosis. Olanzapine was suggested here from a range of pro drug websites as being the "ideal" molecule to terminate "bad trips". Health professionals should be informed about the risks related to olanzapine misuse. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
The urge to gain information on a new drug marketed online as 'Psyclone' has emerged after the death of a 38-year-old man in Bolton (UK). The fatality appeared to be a consequence of smoking this psychoactive product. From October to December 2013, qualitative searches of the Web have been carried out in English and Italian, using the keywords 'Psyclone', 'Psyclone legal high', 'Psyclone incense' and 'Psyclone research chemical' on the Google search engine and on the database provided by the Global Public Health Intelligence Network. Our research highlighted the existence of two psychoactive products labelled as Psyclone but with different contents and packaging: a herbal blend containing two synthetic cannabinoids (AKB-48 and 5f-PB-22) and a research chemical containing 50% ethylphenidate, 30% caffeine and 20% lidocaine. Desired and side effects of both compounds are explored in the paper. Being sold as a legal product, Psyclone may appeal to recreational users, who remain unaware of its real content. This is a serious public health threat, which may lead to acute intoxications and fatalities. Further studies in the field, including Internet monitoring, are therefore required. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.