ArticlePDF AvailableLiterature Review

Pharmacology of Kratom: An Emerging Botanical Agent With Stimulant, Analgesic and Opioid-Like Effects

De Gruyter
Journal of Osteopathic Medicine
Authors:

Abstract and Figures

Kratom (Mitragyna speciosa) is a plant indigenous to Thailand and Southeast Asia. Kratom leaves produce complex stimulant and opioid-like analgesic effects. In Asia, kratom has been used to stave off fatigue and to manage pain, diarrhea, cough, and opioid withdrawal. Recently, kratom has become widely available in the United States and Europe by means of smoke shops and the Internet. Analyses of the medical literature and select Internet sites indicate that individuals in the United States are increasingly using kratom for the self-management of pain and opioid withdrawal. Kratom contains pharmacologically active constituents, most notably mitragynine and 7-hydroxymitragynine. Kratom is illegal in many countries. Although it is still legal in the United States, the US Drug Enforcement Administration has placed kratom on its "Drugs and Chemicals of Concern" list. Physicians should be aware of the availability, user habits, and health effects of kratom. Further research on the therapeutic uses, toxic effects, and abuse potential of kratom and its constituent compounds are needed.
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792 • JAOA • Vol 112 • No 12 • December 2012 Prozialeck et al • Special Communication
Pharmacology of Kratom: An Emerging Botanical Agent
With Stimulant, Analgesic and Opioid-Like Effects
Walter C. Prozialeck, PhD
Jateen K. Jivan, BS
Shridhar V. Andurkar, PhD
Kratom (Mitragyna speciosa) is a plant indigenous to
Thailand and Southeast Asia. Kratom leaves produce
complex stimulant and opioid-like analgesic effects. In
Asia, kratom has been used to stave off fatigue and to
manage pain, diarrhea, cough, and opioid withdrawal.
Recently, kratom has become widely available in the
United States and Europe by means of smoke shops and
the Internet. Analyses of the medical literature and select
Internet sites indicate that individuals in the United
States are increasingly using kratom for the self-man-
agement of pain and opioid withdrawal. Kratom contains
pharmacologically active constituents, most notably
mitragynine and 7-hydroxymitragynine. Kratom is illegal
in many countries. Although it is still legal in the United
States, the US Drug Enforcement Administration has
placed kratom on its “Drugs and Chemicals of Concern
list. Physicians should be aware of the availability, user
habits, and health effects of kratom. Further research on
the therapeutic uses, toxic effects, and abuse potential
of kratom and its constituent compounds are needed.
J Am Osteopath Assoc. 2012;112(12):792-799
Throughout history, humans have used plant-derived
materials (often referred to as “herbal” or “botanical”
remedies) to treat diseases, cope with the stresses of life,
and achieve altered states of awareness. Even with the
development of modern pharmaceuticals and medical
practices, many people still use herbal remedies either as
alternatives to or in conjunction with mainstream medical
care. Several years ago, Barnes et al1found that more than
30% of US patients had or were using some form of herbal-
based remedy. They also noted that the agents were being
used primarily for “musculoskeletal or other conditions
involving chronic pain.1
Even though the efficacies of most of these herbal
remedies have yet to be proven in controlled clinical trials,
it is clear that such products are being used extensively.
Whether they are consumed alone or in combination with
prescribed medications, herbal remedies have the potential
to cause toxic effects, interact with prescription drugs, and
complicate the diagnosis and treatment of disease.2At the
same time, however, herbal remedies may have substantial
therapeutic effects. Some evidence2suggests that certain
herbal products may, in fact, have therapeutic actions that
are equivalent to those of modern pharmaceuticals. More-
over, research on the effects of herbal supplements and
their active constituents may provide insight that could
lead to the development of new and more effective thera-
peutic agents.
Given the extensive use of herbal remedies, it is impor-
tant that physicians and other health care professionals
have some knowledge of their attendant issues. This topic
is especially relevant to osteopathic physicians because
the tenets of osteopathic medicine focus on a unified
approach to patient care, musculoskeletal health, and self-
healing.3Osteopathic physicians should be familiar with
common herbal remedies that their patients may be using.
One herbal remedy that has been receiving increased public
attention in recent years is kratom.4In the present article,
we discuss current patterns of usage, basic pharmacology,
legal standing, and medicinal potential of kratom.
From the Department of Pharmacology at the Midwestern University/Chicago
College of Osteopathic Medicine (Dr Prozialeck and Mr Jivan) and the Depart-
ment of Pharmaceutical Sciences at the Midwestern University, Chicago Col-
lege of Pharmacy (Dr Andurkar), both in Downers Grove, Illinois.
Financial Disclosures: None reported.
Address correspondence to Walter C. Prozialeck, PhD, Department of
Pharmacology, Midwestern University/Chicago College of Osteopathic Med-
icine, 555 31st St, Downers Grove, IL 60515-1235.
E-mail: wprozi@midwestern.edu
Submitted March 1, 2012; revision received August 24, 2012; accepted August
29, 2012.
JAOA Vol 112 • No 12 • December 2012 793Prozialeck et al • Special Communication
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Background
The term kratom refers to a group of tree-like plants belong-
ing to the Mitragyna genus of the Rubiaceae family.4-9
Other members of the Rubiaceae family include the coffee
and gardenia plants. From a medical perspective, the most
important species of kratom is Mitragyna speciosa, which
is indigenous to Thailand and surrounding countries in
Southeast Asia.7Images of a kratom plant and a kratom
leaf are shown in Figure 1.
Kratom has been widely used in Southeast Asia for
hundreds of years.5,6 In Thailand, kratom use typically
involves ingestion of the plant’s raw leaves or consumption
of teas that are brewed or steeped from the leaves.4,6,9
Kratom leaves are used for their complex, dose-dependent
pharmacologic effects.4,6,9-12 Low to moderate doses (1-5g)
of the leaves reportedly produce mild stimulant effects that
enable workers to stave off fatigue.6,9-11,13 Moderate to high
doses (5-15 g) are reported to have opioid-like effects.6,9-11,13
At these doses, kratom has been used for the management
of pain, diarrhea, and opioid withdrawal symptoms, as
well as for its properties as a euphoriant.5,6,9-11,14 Very high
doses (>15 g) of kratom tend to be quite sedating and can
induce stupor, mimicking opioid effects.4,5,9
Growth of Kratom Use in the West
Recent Research
Despite its long history and widespread use in Southeast
Asia, kratom has only recently begun to receive attention
and be used as an herbal remedy in the West. The emer-
gence of kratom as a product or drug of interest in the
United States is evident from the results of our literature
search. Our search of the US National Library of Medicine’s
PubMed database in February 2012, using the keyword
kratom,” yielded a total of 35 published articles and
reviews. Of those, 30 (86%) were published in or after 2004,
4 (11%) were published between 1988 and 1997, and 1
(3%) was published in 1975. Another PubMed search,
using the keywords Mitragyna speciosa, yielded a total
of 65 published articles. Of those, 49 (75%) were published
within the past 10 years.
In addition to these general trends in the number of
publications on kratom, we found that an increasing num-
ber of reports of adverse effects resulting from the use of
kratom have been published.15-19 Recent news reports
have highlighted the increasing level of kratom use, par-
ticularly among college-aged populations.20,21 Moreover,
published studies indicate that vast numbers of online
vendors and general information Web sites for kratom
have appeared in the past few years, suggesting that there
is a substantial demand for kratom products.22,23
Increased Internet Presence
In February 2012, we also conducted an Internet search
using the Google search engine. A search for the keyword
“kratom” found more than 2 million results. Of the first
100 Web sites listed in the search results, 78 were primarily
focused on the sale of kratom, while 22 Web sites primarily
focused on disseminating information about kratom
through the use of discussion boards. We want to strongly
emphasize that the scientific validity of the claims and
anecdotes reported on these Web sites has not been sub-
stantiated. Moreover, for the purpose of the present review,
we did not believe it was appropriate to cite all sources of
anecdotal information. However, we did find 3 Web sites
to be particularly informative: Erowid.org24; Sagewisdom
.org25; and WebMD.com26. These Web sites contain a variety
of information including the drug’s uses and effects, dis-
cussions of individuals’ personal experiences, and adverse
reactions when using kratom. Some of the Web sites24,25
even describe the biology of Mitragyna speciosa, including
optimal methods and conditions for growing. In addition,
an analysis by León et al7suggests cultivation exists here
in the United States. It is also important to note that much
of the content of these Web sites clearly indicates that kratom
is being used for medicinal purposes. Although some
sites24-26 portray users of kratom as recreational drug users,
many posts on kratom blogs are from patients dealing with
pain management issues.24-26 In some cases,24-26 individuals
report finding relief of various types of pain with kratom
use. In addition, recent publications have highlighted the
use of kratom products for the self-management of opioid
withdrawal symptoms.20,27 Although the anecdotal claims
reported on the aforementioned Web sites and publications
have not been substantiated, their existence indicates that
kratom is being used in these contexts.
AB
Figure 1. Images of a kratom plant (A) and a kratom leaf (B).
Images were obtained from the US Drug Enforcement Admin-
istration Web site.4,29
794 • JAOA • Vol 112 • No 12 • December 2012 Prozialeck et al • Special Communication
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Legal Status and Availability
Although the findings of our literature and Internet searches
strongly suggest a marked increase in kratom use in the
United States and Europe, kratom still appears to be some-
what of an “underground phenomenon.” During our
searches of the literature and the internet, we found no
evidence that kratom is currently marketed by any of the
large nutritional supplement chain stores in the United
States. However, a wide variety of kratom products—
including raw leaves, capsules, tablets, and concentrated
extracts—are readily available from Internet-based sup-
pliers.20,21 In addition, these products are often sold in spe-
cialty stores commonly known as “head shops” or “smoke
shops.” In February 2012, our own informal in-person and
telephone survey of 5 smoke shops in the metropolitan
Chicago area revealed that purported kratom products
were available in all of them. Figure 2 and Figure 3 show
images of several kratom products (ie, chopped leaves,
capsules, and pressed tablets) that were legally purchased
at a smoke shop in suburban Chicago.
From a legal standpoint, kratom is regulated as an
herbal product under US law and US Food and Drug
Administration and US Drug Enforcement Administration
(DEA) policies. As of this writing, Mitragyna speciosa
(kratom) is not prohibited by the Controlled Substances
Act28 and is considered a legal substance in the United
States. However, the DEA’s December 2010 version of the
Drugs and Chemicals of Concern list states that “there is
no legitimate medical use for kratom in the U.S.”29 There-
fore, it cannot legally be advertised as a remedy for any
medical condition.
Pharmacology of Kratom
Chemistry and Pharmacognosy
As the use of kratom in the West has grown during the
past 15 years,4,20,23,30 there have been increased efforts to
identify and characterize the active pharmacologic agents
that mediate the effects of kratom in the body. Thus far,
more than 20 active compounds have been isolated from
kratom, and considerable evidence shows that these com-
pounds do, in fact, have major pharmacologic effects.30,31
Various aspects of the medicinal chemistry and pharma-
cognosy of kratom have recently been reviewed by Adkins
et al.30 Accordingly, only a few key points regarding these
topics will be considered in the present article. The Table
shows the chemical structures and summarizes the major
pharmacologic actions of some of the kratom-derived com-
pounds that have been studied most extensively. The most
extensively-characterized of kratom’s active pharmacologic
ABC
Figure 2. Images of kratom products purchased at a “smoke shop” in suburban Chicago. The images show chopped
leaves (A), which are typically brewed into “kratom tea”, capsules containing finely chopped leaves (B), and compressed
tablets containing leaves or resin (C).
Figure 3. Warning label on the back of a package of kratom
capsules.
JAOA Vol 112 • No 12 • December 2012 795Prozialeck et al • Special Communication
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agents have been the mitragynine analogs.30 These agents
contain an indole ring and are, in some respects, structurally
similar to yohimbine.30 These agents have been shown to
produce a wide variety of pharmacologic effects, both in
vivo and in vitro.30 In the following sections, we will con-
sider the importance of these compounds as they relate
to the primary pharmacologic effects of kratom, particularly
analgesia and the ability to suppress symptoms of opioid
withdrawal.
Analgesic and Opioid-Like Effects
In Southeast Asia, kratom has long been used for the man-
agement of pain and opium withdrawal.6,9-11,14 In the West,
kratom is increasingly being used by individuals for the
self-management of pain or withdrawal from opioid drugs
such as heroin and prescription pain relievers.20,27 It is
these aspects of kratom pharmacology that have received
the most scientific attention. Although to our knowledge,
no well-controlled clinical studies on the effects of kratom
on humans have been published, there is evidence30-38 that
kratom, kratom extracts, and molecules isolated from
kratom can alleviate various forms of pain in animal mod-
els. Studies have used a variety of methods including hot
plate,35,37,39 tail flick,32,39 writhing,37,38 and pressure/inflam-
mation35,38 tests in mice32,35,38,39 and rats,35,37 as well as more
elaborate tests in dogs and cats.35 In addition, a variety of
chemical compounds have been isolated from kratom and
shown to exhibit opioid-like activity on smooth muscle
systems31,33,34 and in ligand-binding studies.39,40 Most
notably, many of the central nervous system and peripheral
effects of these kratom-derived substances are sensitive to
inhibition by opioid antagonists.31-34,39-41
Table.
Structures and Pharmacologic Activities of Compounds Isolated From Kratom
Compound Structure Pharmacology
Mitragynine30,33,34,39,40,44 Structurally similar to yohimbine
Activity on μ, , and κreceptors
Main activity on μreceptors creating opiate
and analgesic effects and physical dependence
Inhibits radioligand binding at central nervous
system receptors
Activates descending noradrenergic and
serotonergic pathways in spinal cord
Stimulates postsynaptic α2-adrenergic
receptors
Blocks stimulation of 5-hydroxytryptamine2A
receptors
7-Hydroxymitragynine30,33,34,39,40,44 13- and 46-fold higher potency than morphine
and mitragynine, respectively
Potency and quick-acting characteristics may be
caused by introduction of –OH group on C7
position
Induces clinically significant antinociceptive
responses in a dose-dependent manner
Speciociliatine30,44 C3 stereoisomer of mitragynine
Inhibits twitch contraction in naloxone-
insensitive manner
May inhibit acetylcholine release from
presynaptic nerve through means other than
opioid receptor
stimulation
Paynantheine40,44 Inhibits twitch contraction in naloxone-
insensitive manner
Inhibits muscarine receptors on ileal smooth
muscle
Speciogynine40,44 Inhibits twitch contraction in naloxone-
insensitive manner
Inhibits muscarine receptors in ileal smooth
muscle
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Most of the opioid-like activity of kratom has been
attributed to the presence of the indole alkaloids, mitrag-
ynine and 7-hydroxymitragynine. Both compounds have
been shown to have analgesic and antinociceptive effects
in animals, although 7-hydroxymitragynime is more
potent.30,32,40 These agents also produce opioid-like effects
on organs such as the intestines and male internal geni-
talia.33,34 Moreover, when they are given to animals for 5
days or longer, both compounds produce a state of physical
dependence, with withdrawal symptoms that resemble
those of opioid withdrawal.31,32,41 In addition, ligand-bind-
ing studies and those using opioid antagonists indicate
that these effects are largely mediated by means of actions
on μ- and δ-type opioid receptors.30,31,33 Along with these
various central nervous system effects, kratom also appears
to have anti-inflammatory activity.38Utar et al42recently
found that mitragynine can inhibit lipopolysaccharide-
stimulated cyclooxygenase-2 expression and prostaglandin
E2 production. In addition to direct mediation by means
of opioid receptors, the antinociceptive effects of mitrag-
ynine appear to involve the activation of descending nora-
drenergic and serotonergic pathways in the spinal cord.43
Additionally, animal studies have shown that mitragynine
may stimulate postsynaptic α2-adrenergic receptors and
possibly even block 5-hydroxytryptamine2A receptors.33
Although kratom contains lower levels of 7-hydroxymi-
tragynine than mitragynine, it has been suggested that
7-hydroxymitragynine is more potent and has better oral
bioavailability and blood brain-barrier penetration than
mitragynine,30,40 making it the predominant mediator of
analgesic effects of kratom in the body.
Other compounds that have been isolated from kratom
and implicated in some of its effects include speciociliatine,
speciogynine, and paynatheine.30,40 These compounds
have been shown to modulate intestinal smooth muscle
function and behavioral response in animals.33,34,40,44 How-
ever, these effects were not inhibited by the opioid receptor
antagonist naloxone, suggesting that they involve opioid-
independent mechanisms.40,44 It remains to be determined
how these compounds may contribute to the overall actions
of kratom in vivo.
Subjective Effects
In spite of the fact that kratom has been widely touted
and used as a “legal opioid,”23,31 few scientific studies
have addressed the psychoactive properties of
kratom.6,9,11,12 Most of the available information is based
on anecdotal reports and patient experiences. The general
subjective effects of kratom have been summarized in
various reviews.6,9,12,30 In addition, many individuals
have posted descriptions of their personal kratom expe-
riences on Web sites such as Erowid, Sagewisdom, and
WebMD.24-26 As noted previously, kratom produces an
unusual combination of stimulant- and opioid-like effects.
These effects are highly dependent on the dose of kratom
and can vary markedly from one individual to another.
Low to moderate doses (1-5 g of raw leaves) usually pro-
duce a mild stimulant effect that most individuals perceive
as pleasant but not as intense as those of amphetamine-
like drugs.24,25 Some individuals, however, report that
these low-dose effects are mainly characterized by an
unpleasant sense of anxiety and internal agitation.24-26 It
is noteworthy that those who have used kratom products
for pain management tend to view the stimulant effects
of kratom as being more desirable than the sedative effects
of traditional opioids.24-26
Opioid-like effects, such as analgesia, constipation,
euphoria, and sedation are typically associated with the
use of moderate-high doses of kratom (5-15 g). As with
the lower-dose effects, the higher-dose effects may be either
euphoric or dysphoric, depending on the individual. Of
note, the euphoric effects of kratom generally tend to be
less intense than those of opium and opioid drugs.6,10,11,25
Nevertheless, kratom is still sought by drug users.
Toxic Effects and Untoward Reactions
During the past 3 years, there have been an increasing
number of case reports15,17,29 describing unusual adverse
reactions in patients who had been using kratom or
kratom-based products. The acute adverse effects of
kratom experienced by many users appear to be a direct
result of kratom’s stimulant and opioid activities.6,9,11,30,31
Stimulant effects may manifest themselves in some indi-
viduals as anxiety, irritability, and increased aggression.
Opioid-like effects include sedation, nausea, constipation,
and itching. Again, these effects appear to be dose depend-
ent and to vary markedly from one individual to another.
Chronic, high-dose usage has been associated with several
unusual effects. Hyperpigmentation of the cheeks, tremor,
anorexia, weight loss, and psychosis have been observed
in individuals with long-term addiction.9Reports of serious
toxic effects are rare and have usually involved the use
of relatively high doses of kratom (>15 g).9,17,45,46 Of par-
ticular concern, there have been several recent reports of
seizures occurring in individuals who have used high
doses of kratom, either alone or in combination with other
drugs, such as modafinil.17,22,45 Kapp et al15 recently
described a case of intrahepatic cholestasis in a chronic
user of kratom.
It is important to note that in each of these case reports,
the patients may have had confounding health conditions,
may have been using other drugs along with kratom, or
both. One of the major problems in evaluating the potential
uses and safety of an herbal agent such as kratom is the
lack of understanding of how substances in kratom may
interact with prescription medications, drugs of abuse, or
JAOA Vol 112 • No 12 • December 2012 797Prozialeck et al • Special Communication
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even other herbal supplements. This issue is compounded
by the relative lack of regulations and standardization
related to the production and sale of kratom. These poten-
tial hazards were highlighted in several case reports of
deaths resulting from the use of a kratom-based product
known as “Krypton”.16,47 This agent, which was touted
as a very potent form of kratom, had been marketed in
Sweden. During the past 5 years, there have been reports
of 9 deaths related to the use of Krypton.16In a case series
by Kronstad et al,16subsequent forensic studies revealed
that Krypton contained high amounts of the exogenous
pharmaceutical agent O-desmethyltramadol, which has
opioid and neuromodulator activity. Evidently, the exoge-
nous O-desmethyltramadol had been added to the plant
material. Even though mitragynine was also detected in
the products, it was not determined how the 2 substances
may have interacted to cause death. Another recent report48
described a fatal reaction that appeared to be associated
with the use of a combination of propylhexedrine—an α
agonist and an amphetamine-like stimulant—and mitrag-
ynine. This latter case highlights the fact that extracts and
tinctures containing purified mitragynine, 7-hydroxymi-
tragynine, and 7-acetoxymitragynine have become available
for purchase by means of the Internet. These sources can
easily be found by conducting an Internet search using
the term “mitragynine purchase.” The possibility that these
highly concentrated mitragynine alkaloid extracts could
be used in conjunction with other psychoactive drugs (eg,
alcohol, sedatives, opioids, stimulants, cannabinoids) raises
the potential for serious drug interactions.
Kratom Abuse, Dependence, and Addiction
Potential
A large number of Internet posts refer to the use of kratom
as a euphoriant or “legal opioid.23-26 A major question
that remains unanswered is, “How addictive is kratom?”
Although many anecdotal reports suggest that it may be
less addictive than classical opioids, there are also numerous
reports that, in some individuals, it may be highly addictive.
For example, in Southeast Asia, it has long been recognized
that individuals will seek out and abuse kratom for its
euphoric and mind-altering effects and that chronic users
can become tolerant of, physically dependent on, and
addicted to kratom.9,10 Kratom addiction is considered
such a problem that many Southeast Asian countries have
outlawed the use of kratom.9,10
As kratom use has expanded to Europe and the United
States, there have been increasing reports of individuals
becoming physically dependent on or addicted to
kratom.22,30,31,45,46 Most published studies are case
reports22,31,45,46 of heavy, compulsive users of kratom. In
each case, the individual exhibited substantial tolerance
to the effects of kratom and showed overt symptoms of
withdrawal when kratom use was stopped. The symptoms
of withdrawal were similar to those from traditional opioids
and included irritability, dysphoria, nausea, hypertension,
insomnia, yawning, rhinorrhea, myalgia, diarrhea, and
arthralgias. In a recent report, McWhirter and Morris45
described the use of an opioid agonist (dihydrocodeine)
and an α-adrenergic antagonist (lofexidine) to successfully
manage symptoms of withdrawal in an individual who
was addicted to kratom.
Drug Screening and Analyses
Kratom and kratom-derived compounds such as mitrag-
ynine and 7-hydroxymitragynine are not detected in most
routine drug testing or screening procedures.49 Although
various tests for kratom-derived compounds have been
developed,49they are not yet widely available for general
use. Moreover, there are still some controversies regarding
the designation of drug-level cutoff points for defining
the tests.49 The analytical and forensic aspects of kratom
toxicology have been summarized in a review by Philipp
et al.49
Conclusion
Evidence suggests that kratom is being used extensively
for both medical and nonmedical purposes. Recent studies
have shown that kratom contains a variety of active com-
pounds that produce major pharmacologic effects at opioid
and other receptors. Kratom and kratom-derived drugs
may potentially be used for the management of pain,
opioid withdrawal symptoms, and other clinical problems.
At the same time, serious questions remain regarding the
potential toxic effects and the abuse and addiction potential
of kratom. This issue is further confounded by the lack of
quality control and standardization in the production and
sale of kratom products. The possibilities of kratom prod-
ucts being adulterated or interacting with other drugs are
also serious concerns. Until these issues are resolved, it
would not be appropriate for physicians to recommend
kratom for the treatment of patients. Nevertheless, physi-
cians need to be aware that patients may use kratom or
kratom-based products on their own. Further studies to
clarify the efficacy, safety, and addiction potential of kratom
are needed.
Acknowledgments
The authors thank Victoria Sears and Laura Phelps, MA, in the
Department of Pharmacology at Midwestern University for
their help in preparing the manuscript. The authors also thank
Susan Hershberg at Midwestern University for her assistance
in capturing the photographic images of the kratom products.
(continued)
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References
1.Barnes PM, Bloom B, Nahin RL. Complementary and alternative medicine use
among adults and children: United States, 2007. Natl Health Stat Report.2008(12):1-
23.
2.Denneky C, Tsouraunis C. Dietary supplements and herbal medications. In:
Katzung B, Masters S, Trevor A. Basic and Clinical Pharmacology. 12th ed. New
York, NY: McGraw Hill; 2011:1125-1137.
3. American Osteopathic Association. Tenets of osteopathic medicine. American
Osteopathic Association Web site. http://www.osteopathic.org/inside-aoa/about
/leadership/Pages/tenets-of-osteopathic-medicine.aspx. Accessed August 22, 2012.
4. US Drug Enforcement Administration. Special intelligence brief: kratom (Mitrag-
yna speciosa). Microgram Bulletin. 2006;39(3):30-32. http://www.justice.gov/dea/pr
/micrograms/2006/mg0306.pdf. Accessed November 12, 2012.
5.Grewal KS. Observations on the pharmacology of mitragynine. J Pharmacol
Exp Ther. 1932;46:251-271.
6.Jansen KL, Prast CJ. Ethnopharmacology of kratom and the Mitragyna alkaloids.
J Ethnopharmacol. 1988;23(1)115-119.
7.León F, Habib E, Adkins JE, Furr EB, McCurdy CR, Cutler SJ. Phytochemical char-
acterization of the leaves of Mitragyna speciosagrown in U.S.A. Nat Prod Commun.
2009;4(7):907-910.
8. Maruyama T, Kawamura M, Kikura-Hanajiri R, Takayama H, Goda Y. The botanical
origin of kratom (Mitragyna speciosa; Rubiaceae) available as abused drugs in
the Japanese markets. J Nat Med. 2009;63(3):340-344.
9. Suwanlert S. A study of kratom eaters in Thailand. Bull Narc. 1975;27(3):21-27.
10. Assanangkornchai S, Muekthong A, Sam-Angsri N, Pattanasattayawong U.
The use of Mitragynine speciosa (“Krathom”), an addictive plant, in Thailand.
Subst Use Misuse. 2007;42(14):2145-2157.
11. Jansen KL, Prast CJ. Psychoactive properties of mitragynine (kratom). J Psy-
choactive Drugs. 1988;20(4):455-457.
12. Shellard EJ. Ethnopharmacology of kratom and the Mitragyna alkaloids. J
Ethnopharmacol. 1989;25(1):123-124.
13. Pichainarong N, Chaveepojnkamjorn W, Khobjit P, Veerachai V, Sujirarat D.
Energy drinks consumption in male construction workers, Chonburi province. J
Med Assoc Thai. 2004;87(12):1454-1458.
14. Vicknasingam B, Narayanan S, Beng GT, Mansor SM. The informal use of
ketum (Mitragyna speciosa) for opioid withdrawal in the northern states of penin-
sular Malaysia and implications for drug substitution therapy. Int J Drug Policy.
2010;21(4):283-288.
15. Kapp FG, Maurer HH, Auwärter V, Winkelmann M, Hermanns-Clausen M.
Intrahepatic cholestasis following abuse of powdered kratom (Mitragyna speciosa).
J Med Toxicol. 2011;7(3):227-231.
16. Kronstrand R, Roman M, Thelander G, Eriksson A. Unintentional fatal intoxi-
cations with mitragynine and O-desmethyltramadol from the herbal blend Krypton.
J Anal Toxicol. 2011;35(4):242-247.
17. Nelsen JL, Lapoint J, Hodgman MJ, Aldous KM. Seizure and coma following
Kratom (Mitragynina speciosa Korth) exposure. J Med Toxicol. 2010;6(4):424-426.
18. Rosenbaum CD, Carreiro SP, Babu KM. Here today, gone tomorrow...and back
again? a review of herbal marijuana alternatives (K2, Spice), synthetic cathinones
(bath salts), kratom, Salvia divinorum, methoxetamine, and piperazines. J Med
Toxicol. 2012;8(1):15-32.
19. Sheleg SV, Collins GB. A coincidence of addiction to “Kratom” and severe pri-
mary hypothyroidism. J Addict Med. 2011;5(4):300-301.
20. Krauth D. Substance called “Kratom” becoming a growing problem. The Palm
Beach Post. July 1, 2011. http://www.palmbeachpost.com/health/substance-called-
kratom-becoming-a-growing-problem-1575630.html. Accessed February 25, 2012.
21. Osterhaus H. Natural herb flavors students’ day. The University Daily Kansan.
January 23, 2008. http://kansan.com/archives/2008/01/23/osterhaus-natural-herb-
flavors-students-day/. Accessed February 25, 2012.
22. Boyer EW, Babu KM, Adkins JE, McCurdy CR, Halpern JH. Self-treatment of
opioid withdrawal using kratom (Mitragynia speciosa korth). Addiction. 2008;
103(6):1048-1050.
23. Schmidt MM, Sharma A, Schifano F, Feinmann C. “Legal highs” on the net—
evaluation of UK-based websites, products and product information. Forensic Sci
Int. 2011;206(1-3):92-97.
24. Kratom dosage. The Vaults of Erowid Web site. http://www.erowid.org
/plants/kratom/kratom_dose.shtml. Accessed July 20, 2011.
25. The kratom user’s guide. Sage Wisdom Web site. http://www.sagewisdom.org
/kratomguide.html. Accessed July 20, 2011.
26. Kratom addiction?? [online forum]. WebMD Substance Abuse Community
Web site. http://forums.webmd.com/3/substance-abuse-exchange/forum/350/32#32.
Accessed July 20, 2011.
27. Ward J, Rosenbaum C, Hernon C, McCurdy CR, Boyer EW. Herbal medicines
for the management of opioid addiction: safe and effective alternatives to con-
ventional pharmacotherapy? CNS Drugs. 2011;25(12):999-1007. http://adisonline
.com/cnsdrugs/Fulltext/2011/25120/Herbal_Medicines_for_the_Management_of
_Opioid.2.aspx. Accessed February 29, 2012.
28. Controlled Substances Act, 21 USC §801 et seq.
29.US Department of Justice, Drug Enforcement Administration, Office of Diversion
Control. Drugs and chemicals of concern: kratom (Mitragyna speciosa korth).
Office of Diversion Control Web site. http://www.deadiversion.usdoj.gov/drugs
_concern/kratom.htm. Accessed October 30, 2011.
30. Adkins JE, Boyer EW, McCurdy CR. Mitragyna speciosa, a psychoactive tree
from Southeast Asia with opioid activity. Curr Top Med Chem. 2011;11(9):1165-
1175.
31. Babu KM, McCurdy CR, Boyer EW. Opioid receptors and legal highs: Salvia
divinorum and kratom. Clin Toxicol (Phila). 2008;46(2):146-152.
32. Matsumoto K, Horie S, Takayama H, et al. Antinociception, tolerance and
withdrawal symptoms induced by 7-hydroxymitragynine, an alkaloid from the
Thai medicinal herb Mitragyna speciosa. Life Sci. 2005;78(1):2-7.
33. Matsumoto K, Yamamoto LT, Watanabe K, et al. Inhibitory effect of mitra -
gynine, an analgesic alkaloid from Thai herbal medicine, on neurogenic contraction
of the vas deferens. Life Sci. 2005;78(2):187-194.
34. Matsumoto K, Hatori Y, Murayama T, et al. Involvement of μ-opioid receptors
in antinociception and inhibition of gastrointestinal transit induced by 7-hydroxy -
mitragynine, isolated from Thai herbal medicine Mitragyna speciosa. Eur J Phar-
macol. 2006;549(1-3):63-70.
35. Macko E, Weisbach JA, Douglas B. Some observations on the pharmacology
of mitragynine. Arch Int Pharmacodyn Ther. 1972;198(1):145-161.
36. Maurer HH. Chemistry, pharmacology, and metabolism of emerging drugs of
abuse. Ther Drug Monit. 2010;32(5):544-549.
37. Sabetghadam A, Ramanathan S, Mansor SM. The evaluation of antinociceptive
activity of alkaloid, methanolic, and aqueous extracts of Malaysian Mitragyna
speciosa Korth leaves in rats. Pharmacognosy Res. 2010;2(3):181-185.
38. Shaik Mossadeq WM, Sulaiman MR, Tengku Mohamad TA, et al. Anti-inflam-
matory and antinociceptive effects of Mitragyna speciosaKorth methanolic extract.
Med Princ Pract. 2009;18(5):378-384.
39. Takayama H, Ishikawa H, Kurihara M, et al. Studies on the synthesis and opioid
agonistic activities of mitragynine-related indole alkaloids: discovery of opioid
agonists structurally different from other opioid ligands. J Med Chem. 2002;45(9):
1949-1956.
40. Takayama H. Chemistry and pharmacology of analgesic indole alkaloids from
the rubiaceous plant, Mitragyna speciosa. Chem Pharm Bull (Tokyo). 2004;52(8):916-
928.
41. Thongpradichote S, Matsumoto K, Tohda M, et al. Identification of opioid
receptor subtypes in antinociceptive actions of supraspinally-administered mitra -
gynine in mice. Life Sci. 1998;62(16):1371-1378.
42. Utar Z, Majid MI, Adenan MI, Jamil MF, Lan TM. Mitragynine inhibits the COX-
2 mRNA expression and prostaglandin E2 production induced by lipopolysaccharide
in RAW264.7 macrophage cells. J Ethnopharmacol. 2011;136(1):75-82.
43. Matsumoto K, Mizowaki M, Suchitra T, et al. Central antinociceptive effects
of mitragynine in mice: contribution of descending noradrenergic and serotonergic
systems. Eur J Pharmacol. 1996;317(1):75-81.
JAOA Vol 112 • No 12 • December 2012 799Prozialeck et al • Special Communication
SPECIAL COMMUNICATION
44. Horie S, Koyama F, Takayama H, et al. Indole alkaloids of a Thai medicinal
herb, Mitragyna speciosa, that has opioid agonistic effect in guinea-pig ileum.
Planta Med. 2005;71(3):231-236.
45. Roche KM, Hart K, Sangali B, Lefberg J, Bayer M. Kratom: a case of a legal
high. Clin Tox. 2008;46(7):598. Abstract 41.
46. McWhirter L, Morris S. A case report of inpatient detoxification after kratom
(Mitragyna speciosa) dependence. Eur Addict Res. 2010;16(4):229-231.
47. Arndt T, Claussen U, Güssregen B, et al. Kratom alkaloids and O-desmethyl-
tramadol in urine of a “Krypton” herbal mixture consumer. Forensic Sci Int.
2011;208(1-3):47-52.
48. Holler JM, Vorce SP, McDonough-Bender PC, Magluilo J Jr, Solomon CJ, Levine
B. A drug toxicity death involving propylhexedrine and mitragynine. J Anal Toxicol.
2011;35(1):54-59. http://jat.oxfordjournals.org/content/35/1/54.long. Accessed Octo-
ber 29, 2012.
49. Philipp AA, Meyer MR, Wissenbach DK, et al. Monitoring of kratom or Krypton
intake in urine using GC-MS in clinical and forensic toxicology. Anal Bioanal Chem.
2011;400(1):127-135.
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... Psychopharmacology Kratom use has also expanded to Western countries, leading to a wide availability of kratom products (e.g., powder, capsules, tablets) online and in specialty shops (Hillebrand et al. 2010;Prevete et al. 2024;Prozialeck et al. 2012;Williams and Nikitin 2020). The main motivations for using kratom include recreational purposes and self-treatment of various mental and physical health conditions (Bath et al. 2020;Coe et al. 2019;Grundmann et al. , 2023Smith et al. 2024a). ...
... The main motivations for using kratom include recreational purposes and self-treatment of various mental and physical health conditions (Bath et al. 2020;Coe et al. 2019;Grundmann et al. , 2023Smith et al. 2024a). A small amount (< 5 g) of raw plant material has been reported to produce stimulatory effects such as increasing talkativeness, alertness, or physical energy (Henningfield et al. 2024;Kruegel and Grundmann 2018;Prozialeck et al. 2012;Singh et al. 2019a;Swogger et al. 2022). Doses above 5 g have been reported to produce inhibitoryanalgesic and sedative properties like opioids (Henningfield et al. 2024;Kruegel and Grundmann 2018;Prozialeck et al. 2012;Singh et al. 2019a;Swogger et al. 2022). ...
... A small amount (< 5 g) of raw plant material has been reported to produce stimulatory effects such as increasing talkativeness, alertness, or physical energy (Henningfield et al. 2024;Kruegel and Grundmann 2018;Prozialeck et al. 2012;Singh et al. 2019a;Swogger et al. 2022). Doses above 5 g have been reported to produce inhibitoryanalgesic and sedative properties like opioids (Henningfield et al. 2024;Kruegel and Grundmann 2018;Prozialeck et al. 2012;Singh et al. 2019a;Swogger et al. 2022). Moreover, it has been shown that kratom's stimulant and sedative effects can co-exist (Smith et al. 2023a), often at higher doses (Peran et al. 2023). ...
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Rationale Despite the growing scientific interest on mitragynine, the primary alkaloid in kratom (Mitragyna Speciosa), there is a lack of clinical trials in humans. Objectives This phase 1 study aimed to evaluate mitragynine’s safety profile and acute effects on subjective drug experience, neurocognition, and pain tolerance. Methods A placebo-controlled, single-blind, within-subjects study was conducted in two parts. In part A, eight healthy human volunteers received placebo and three doses of mitragynine (5, 10, and 20 mg) in a sequential dosing scheme, on separate days. In part B, a second group of seven volunteers received placebo and 40 mg of mitragynine. Vital signs, subjective drug experience, neurocognitive function, and pain tolerance were measured at regular intervals for 7 h after administration. Results Overall, mitragynine did not affect most of the outcome measures at any dose. Yet, the lowest dose (5 mg) of mitragynine increased subjective ratings of arousal and attention, accuracy in a sustained attention task, and motor inhibition. The highest dose (40 mg) of mitragynine increased subjective ratings of amnesia and produced mild psychopathological symptoms. Mitragynine did not significantly affect vital signs, and only mild, transient side effects were reported. Conclusion The present study suggests that low doses (5–10 mg) of mitragynine may cause subjective feelings of stimulation and enhance attention, while the highest dose (40 mg) may cause inhibitory feelings of amnesia and distress. Mitragynine doses up to 40 mg were well tolerated in this group.
... Among the studied literature, mitragynine has been the focus of more scientific studies than 7-hydroxymitragynine. Apart from elucidating its biological potential, extensive research has been performed to have a better understanding of the chemistry and pharmacological parameters associated with them. Both mitragynine and 7-hydroxymitragynine act on opioid receptors, however, their binding affinity differs significantly (Prozialeck et al., 2012). 7-hydroxymitragynine possesses 46 times more affinity compared to that of the mitragynine and 13 times higher affinity than morphine, while mitragynine shows less potent binding activity than morphine (Yamamoto et al., 1999;Matsumoto et al., 2004). ...
... The chemical structures of speciogynine, speciociliatine and mitraciliatine are shown in Fig. 3. hydroxy-8-methoxy-1,2,3,4,6,7,7α,12β-octahydroindolo[2,3-α]quinolizine-2-yl)-3-methoxyacrylate) (WHO ECDD, 2021) is a biologically active metabolite of mitragynine suggested by both in vitro and in vivo (mice model) studies (Kruegel et al., 2019). It has an empirical formula C 23 H 30 N 2 O 5 (414.5 Da) with a pKa 12.20 and its chemical structure was first elucidated in 1993 (Prozialeck et al., 2012;Ponglux et al., 1994). 7-hydroxymitragynine has an optical rotation [α]D = +47.9 ...
... [32] In addicted patients, withdrawal symptoms such as irritability, dysphoria, nausea, hypertension, insomnia, yawning, rhinitis, muscle pain, diarrhea, and arthralgia may occur upon discontinuation of use. [33] ...
Article
INTRODUCTION In recent years, there has been an increase in the use of herbal stimulants around the world. Many people cannot imagine life without coffee, a cup of this drink is often a mandatory part of the day. As the world moves faster and faster, people are looking for a way to keep up with it. Therefore, more and more plant and mushroom stimulants appear on the market, which help people replenish energy deficiencies and meet the challenge of constantly living on the run. Selected stimulants, the benefits associated with their use, and side effects are described in the work below. THE AIM The aim of this work is to discuss the properties that stimulate the human body. We have selected less and more known plants and mushrooms, describing their properties, benefits of their use, side effects, and contraindications to their use. MATERIALS AND METHODS In this work, we describe the impact of substances that stimulate the human body contained in selected plants and mushrooms. A review of the literature available in the National Library of Medicine database at https://pubmed.ncbi.nlm.nih.gov and Google Scholar was conducted. The articles were searched using keywords such as herbs stimulants, fungi, side effects, adaptogens, and advantages. SUMMARY There are many plants and fungi in nature containing substances that have a beneficial effect on the human body. They improve brain function, reduce stress, and increase concentration. We often reach for them because we really need an additional energy booster in today's world. However, it should be remembered that these agents in too high doses may also cause side effects. Therefore, these preparations should be selected individually, taking into account chronic diseases, conditions such as pregnancy and lactation, and medications taken.
... Kratom (Mitragyna speciosa) is a tropical evergreen tree from the Rubiaceae family, native to Southeast Asia, and its leaves have been used as herbal remedies since at least the mid-19th century [6]. The bioactive alkaloids in kratom may have favorable interactions with neurotransmitter receptors in the central nervous system (D2 dopamine, 5-hydroxytryptamine 2A {HT2A}, and 5-HT2C receptors), which could confer potential benefits for anxiety and other mental health conditions [7,8]. ...
... Various consumption methods include chewing fresh leaves, brewing tea, the "Toss and Wash" technique, encapsulation, and mixing with foods or beverages (DEA, 2023). Kratom is believed to exhibit stimulantlike effects at lower doses, providing increased energy and focus, with users reporting mood enhancement properties (Prozialeck et al., 2012). Higher doses may induce euphoria, contributing to recreational use, while excessive consumption can result in adverse effects such as nausea and vomiting (Singh et al., 2014). ...
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Tertiary students' knowledge of kratom predominantly focuses on its effects and legal implications, overlooking the crucial understanding of different kratom leaf veins. Recognizing these vein types is essential for comprehending the potential consequences of kratom misuse. This study addresses concerns about the likelihood of tertiary students engaging in kratom abuse due to its easy accessibility and affordability. This study aims to evaluate the knowledge levels of three types of kratom veins inhalants—white, red, and green—among male and female tertiary students, utilizing a cross-sectional design with quantitative data collected from 296 students through Google Forms. The analysis reveals gender-based disparities in knowledge percentages for each vein type. The analysis presented in Figure 1 accentuates significant disparities in knowledge levels between male and female respondents regarding various colours of kratom veins. Notably, males consistently exhibit superior knowledge, with a substantial percentage of 19.9% for the white vein compared to their female counterparts. This trend persists with the red vein, where males outperform females, achieving a knowledge percentage of 15.9%, indicating a persistent gender-based difference in understanding kratom vein colours among tertiary students. The examination extends to the green vein, with males demonstrating a higher knowledge percentage of 10.1% compared to females. Despite the widespread use of kratom, particularly among adolescents in substance abuse, a substantial knowledge gap exists among tertiary students regarding various kratom vein types. Tailoring educational efforts to consider these multifaceted factors is crucial for promoting inclusivity, equitable knowledge distribution, and fostering a comprehensive understanding of kratom within diverse populations. Abstrak: Pengetahuan pelajar-pelajar tertiari tentang kratom lebih cenderung kepada kesan dan implikasi undang-undang, dengan memahami pemahaman yang penting mengenai pelbagai jenis urat daun kratom. Pemahaman terhadap jenis-jenis urat ini adalah kunci untuk memahami kesan pengaruh kratom. Kajian ini menimbulkan kebimbangan mengenai kemungkinan pelajar tertiari terlibat dalam pengaruh dan harga yang mampu disebabkan kemudahan. Objektif kajian adalah menilai tahap pengetahuan terhadap tiga jenis urat kratom - putih, merah, dan hijau - di kalangan pelajar lelaki dan perempuan tertiari. Reka bentuk rentas-seksyen digunakan dengan mengumpulkan data kuantitatif daripada 296 pelajar melalui Google Forms. Analisis menunjukkan perbezaan berdasarkan jantina dalam peratusan pengetahuan bagi setiap jenis urat. Rajah 1 menunjukkan perbezaan yang ketara dalam tahap pengetahuan antara responden lelaki dan perempuan mengenai pelbagai warna urat kratom. Lelaki menunjukkan pengetahuan yang lebih tinggi secara konsisten, dengan peratusan ketara sebanyak 19.9% untuk urat putih berbanding perempuan. Trend ini berterusan dengan urat merah, di mana lelaki melebihi perempuan, mencapai peratusan pengetahuan sebanyak 15.9%, menunjukkan perbezaan yang berterusan berdasarkan jantina dalam pemahaman warna urat kratom di kalangan pelajar tertiari. Pemeriksaan melibatkan urat hijau, dengan lelaki menunjukkan peratusan pengetahuan yang lebih tinggi sebanyak 10.1% berbanding dengan perempuan. Walaupun penggunaan kratom yang meluas, terutamanya di kalangan remaja dalam pengaruh bahan, terdapat jurang pengetahuan yang besar di kalangan pelajar tertiari mengenai pelbagai jenis urat kratom. Penyesuaian usaha pendidikan untuk mengkaji faktor-faktor yang berbeza ini adalah penting untuk mempromosikan inklusiviti, pengagihan pengetahuan yang saksama, dan memahami pemahaman yang menyeluruh tentang kratom dalam kalangan populasi yang pelbagai.
... The physiological effects vary based on the dose that is taken as well as the particular strain of kratom that is consumed [3]. For example, the red vein strain of Mitragyna speciosa tends to induce a sedated state when ingested, whereas the green vein strain tends to cause a stimulating effect [6]. The use of kratom has historically been by people living in Southeast Asia [7]. ...
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The term "kratom" refers to a plant species formally known as Mitragyna speciosa. Kratom is composed of over 40 alkaloids, a type of organic compound that contains nitrogen. These compounds work primarily via binding to opioid receptors expressed on neurons, where they stimulate signal transduction mechanisms involving the activation of G proteins. Kratom has been shown to cause both a stimulant-like effect and a sedative effect in humans. These studies have shown that use is highest among European-American, middle-class men living in suburban areas. Additionally, individuals who have a history of opioid misuse are also more likely to take kratom. Kratom is used by many different people in the US for numerous different reasons. Some of the most often cited reasons include treating chronic pain conditions, depression, and anxiety. Individuals who used kratom for these reasons typically consumed kratom daily at a dose of 1-3 grams, with the kratom extracted into a powder to be consumed in a capsule. Additionally, there have been reports of kratom being used to treat opioid withdrawal symptoms, as kratom can bind to some of the same receptors as opioids. This manuscript specifically describes trends regarding the use of kratom in the US, pharmacokinetic and pharmacodynamic properties of kratom, potential therapeutic uses of kratom, adverse events caused by kratom, and case studies in the literature regarding patients using kratom.
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Mitragyna speciosa Korth is a medicinal plant indigenous to Thailand and Malaysia and has been known for its narcotic and coca-like effects. Many studies have been performed on the antinociceptive effect of the plant extracts of Thai origin; however, limited studies have been reported till date on M. speciosa extracts of Malaysian origin. Various concentrations of alkaloid (5-20 mg/kg), methanolic (50-200 mg/kg), and aqueous (100-400 mg/kg) extracts of Malaysian M. speciosa leaves were prepared and orally administered to nine groups of rats. Morphine (5 mg/kg, s.c.) and aspirin (300 mg/kg, p.o.) were used as control. Antagonism of the antinociceptive activity was evaluated by pretreatment with naloxone at a dose of 2 mg/kg (i.p.). Results showed that oral administration of the alkaloid (20 mg/kg), methanolic (200 mg/kg), and aqueous (400 mg/kg) extracts significantly prolonged the latency of nociceptive response compared with control groups in both hot plate and tail flick tests (P < 0.05). Antinociceptive action of the alkaloid (20 mg/kg), methanolic (200 mg/kg), and aqueous (400 mg/kg) extracts was significantly blocked by naloxone. In conclusion, these results suggest the presence of antinociceptive effect in various extracts of Malaysian M. speciosa leaves. In addition, the antinociceptive effective doses vary depending on the type of solvents used for extraction.
Article
Despite their widespread Internet availability and use, many of the new drugs of abuse remain unfamiliar to health care providers. The herbal marijuana alternatives, like K2 or Spice, are a group of herbal blends that contain a mixture of plant matter in addition to chemical grade synthetic cannabinoids. The synthetic cathinones, commonly called "bath salts," have resulted in nationwide emergency department visits for severe agitation, sympathomimetic toxicity, and death. Kratom, a plant product derived from Mitragyna speciosa Korth, has opioid-like effects, and has been used for the treatment of chronic pain and amelioration of opioid-withdrawal symptoms. Salvia divinorum is a hallucinogen with unique pharmacology that has therapeutic potential but has been banned in many states due to concerns regarding its psychiatric effects. Methoxetamine has recently become available via the Internet and is marked as "legal ketamine." Moreover, the piperazine derivatives, a class of amphetamine-like compounds that includes BZP and TMFPP, are making a resurgence as "legal Ecstasy." These psychoactives are available via the Internet, frequently legal, and often perceived as safe by the public. Unfortunately, these drugs often have adverse effects, which range from minimal to life-threatening. Health care providers must be familiar with these important new classes of drugs. This paper discusses the background, pharmacology, clinical effects, detection, and management of synthetic cannabinoid, synthetic cathinone, methoxetamine, and piperazine exposures.
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Striking increases in the abuse of opioids have expanded the need for pharmacotherapeutic interventions. The obstacles that confront effective treatment of opioid addiction - shortage of treatment professionals, stigma associated with treatment and the ability to maintain abstinence - have led to increased interest in alternative treatment strategies among both treatment providers and patients alike. Herbal products for opioid addiction and withdrawal, such as kratom and specific Chinese herbal medications such as WeiniCom, can complement existing treatments. Unfortunately, herbal treatments, while offering some advantages over existing evidence-based pharmacotherapies, have poorly described pharmacokinetics, a lack of supportive data derived from well controlled clinical trials, and severe toxicity, the cause for which remains poorly defined. Herbal products, therefore, require greater additional testing in rigorous clinical trials before they can expect widespread acceptance in the management of opioid addiction.
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Here we present a case of a coincidence of addiction to "Kratom" (botanically known as Mitragyna speciosa Korth) and developed severe primary hypothyroidism. We are discussing a possibility that high dose of indole alkaloid mitragynine (the major alkaloid identified from "Kratom") might reduce the normal response of the thyroid gland to thyroid-stimulating hormone resulting in primary hypothyroidism. Further experimental investigations of mitragynine as a possible suppressor of thyroid gland function would be a matter of interest.
Article
Kratom (Mitragyna speciosa) is a common medical plant in Thailand and is known to contain mitragynine as the main alkaloid. According to an increase in published reports and calls at German poison control centers, it has been used more frequently as a drug of abuse in the western hemisphere during the last couple of years. Despite this increase, reports of severe toxicity are rare within the literature. We describe a case of a young man who presented with jaundice and pruritus after intake of kratom for 2 weeks in the absence of any other causative agent. Alkaloids of M. speciosa were detected in the urine. While M. speciosa is gaining in popularity among illicit drug users, its adverse effects remain poorly understood. This is the first published case of intrahepatic cholestasis after kratom abuse.
Article
ETHOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa Korth (Rubiaceae) is one of the medicinal plants used traditionally to treat various types of diseases especially in Thailand and Malaysia. Its anti-inflammatory and analgesic properties in its crude form are well documented. In this study, the cellular mechanism involved in the anti-inflammatory effects of mitragynine, the major bioactive constituent, was investigated. The effects of mitragynine on the mRNA and protein expression of COX-1 and COX-2 and the production of prostaglandin E(2) (PGE(2)) were investigated in LPS-treated RAW264.7 macrophage cells. Quantitative RT-PCR was used to assess the mRNA expression of COX-1 and COX-2. Protein expression of COX-1 and COX-2 were assessed using Western blot analysis and the level of PGE(2) production was quantified using Parameter™ PGE(2) Assay (R&D Systems). Mitragynine produced a significant inhibition on the mRNA expression of COX-2 induced by LPS, in a dose dependent manner and this was followed by the reduction of PGE(2) production. On the other hand, the effects of mitragynine on COX-1 mRNA expression were found to be insignificant as compared to the control cells. However, the effect of mitragynine on COX-1 protein expression is dependent on concentration, with higher concentration of mitragynine producing a further reduction of COX-1 expression in LPS-treated cells. These findings suggest that mitragynine suppressed PGE(2) production by inhibiting COX-2 expression in LPS-stimulated RAW264.7 macrophage cells. Mitragynine may be useful for the treatment of inflammatory conditions.