A Case Report of Kratom Addiction and Withdrawal

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Author Affiliations: Wheaton Franciscan Healthcare–All Saints, Racine, Wis.
Corresponding Author: David Galbis-Reig, MD, Medical Director of
Addiction Services, Wheaton Franciscan Healthcare–All Saints, 1320
Wisconsin Ave, Racine, WI 53403; phone 262.687.2365; fax 501.423.1588;
e-mail dgalbisreig@aol.com.
CASE REPORT
VOLUME 115 • NO. 1 49
tom, a “nonaddictive, natural option” to
“pain killers,” could be a good alternative
to treat her pain. She gave the patient some
capsules containing dried, crushed kratom
leaves. The patient reports that it provided
her pain relief and also gave her a “boost
of energy.” Given the expense, however,
she decided to purchase the concentrated
extract off the Internet on the assumption
that it would last longer because it
would require less of the substance. Over
the course of the next 2 years, the patient
continued to purchase kratom extract
from a single Internet site based in Florida for $150 for a 20
ml bottle labeled only with the name of the company and the
country of origin (in this case Bali). The patient reported that
within 6 months she realized that she was using much more of
the kratom than she intended. When she attempted to cut back,
she discovered that she would experience cravings as well as significant
withdrawal symptoms consisting of severe abdominal
cramps, sweats, blurred vision, nausea, vomiting, and diarrhea.
Over the course of the next 1.5 years she attempted to detoxify
in the outpatient setting with medication support from 2 outpatient
providers using low dose clonidine, without success. By this
point, the patient had also lost a significant amount of weight,
stating that the kratom curbed her appetite. Her husband later
told the physician that she was hiding the fact that she had continued
to use kratom, was hiding the bottles around the home,
and had gone to significant lengths to ensure that he would not
discover that she had continued to order kratom online by having
the product shipped to local FedEx stores. The patient admitted
she was worried that she would lose her family if she did not
stop taking the kratom. Despite its effects on her health (weight
loss, insomnia, cravings, and decreased overall energy level) and
the conflict that her use had been creating in her marriage, she
had continued to take the kratom extract. Both her husband and
father gave her an ultimatum to stop using the kratom, which led
to her contacting the inpatient mental health and addiction unit
for assistance.
CASE PRESENTATION
A 37-year-old white woman with no previous history of substance
abuse treatment was admitted to the inpatient mental
health and addiction service after contacting the unit for treatment
of an “addiction to kratom.” The patient denied any past
medical history except for postpartum depression that was partially
responsive to sertraline, which the patient discontinued on
her own. The patient reported that she works as a teacher and
was first introduced to kratom 2 years prior to admission by a
fellow teacher who was using it to treat her fibromyalgia pain.
Because the patient had been in pain from recent carpal tunnel
surgery and was concerned about taking opioid analgesics due to
their “addictive potential,” her colleague convinced her that kraABSTRACT
Kratom, a relatively unknown herb among physicians in the western world, is advertised on the
Internet as an alternative to opioid analgesics, as a potential treatment for opioid withdrawal and
as a “legal high” with minimal addiction potential. This report describes a case of kratom addiction
in a 37-year-old woman with a severe opioid-like withdrawal syndrome that was managed
successfully with symptom-triggered clonidine therapy and scheduled hydroxyzine. A review of
other case reports of kratom toxicity, the herb’s addiction potential, and the kratom withdrawal
syndrome is discussed. Physicians in the United States should be aware of the growing availability
and abuse of kratom and the herb’s potential adverse health effects, with particular attention
to kratom’s toxicity, addictive potential, and associated withdrawal syndrome.
David Galbis-Reig, MD
A Case Report of Kratom Addiction and Withdrawal
CME available. See page 53 for more information.
50 WMJ • FEBRUARY 2016
nine, case reports suggest that side effects
of mitragynine, including risk of torsade
de pointes, appear to be dose dependent.1,2
The patient was started on the
opioid withdrawal protocol using symptom-triggered
clonidine at a dose of 0.1-
0.2 mg every 2 hours based on the Clinical
Opioid Withdrawal Scale (COWS) Score,
a validated scale that scores typical opioid
withdrawal symptoms such as pupillary
dilatation, diaphoresis, gastrointestinal distress,
anxiety, fever, bone and joint pains,
increased lacrimation or rhinorrhea, tremors,
and yawning based on the severity
of the symptoms. Scheduled hydroxyzine
50 mg by mouth every 6 hours also was
started, along with a 0.1 mg per day clonidine
patch to assist with withdrawal symptoms.
By 1 pm on the day of admission,
the patient’s withdrawal symptoms started
to increase rapidly as she developed myalgias,
bone pain, abdominal cramping pain,
nausea, and blurred vision due to rapid
pupillary dilatation. The patient developed
severe withdrawal symptoms by mid-afternoon,
which progressed rapidly requiring
up to 2 mg of oral clonidine over the next
36 hours as noted by the Clinical Opioid
Withdrawal Scale (COWS) Scores (Figure
1) and frequency and dose of clonidine
administered (Figure 2). Fortunately, the
hyperautonomic symptoms improved rapidly
over the course of 2 to 3 days. During previous attempts at
detoxification, the patient described a prolonged period of severe
depression and anxiety. Given the patient’s previous history of
postpartum depression only partially treated with sertraline, she
also was started on extended release venlafaxine beginning at a
dose of 37.5 mg and titrated daily up to 150 mg for her depression.
In order to avoid benzodiazepines, the patient was started
on pregabalin at a dose of 25 mg by mouth every 8 hours and
titrated to 50 mg every 8 hours prior to discharge for her anxiety.
The patient’s condition stabilized over the course of 3 days
in the hospital. After a family meeting with her husband and
father, the patient was discharged to home with an appointment
to begin participation in a dual partial hospital program. She
was provided with a prescription to start naltrexone 50 mg by
mouth daily for opioid antagonist therapy to begin no sooner
than 7 days after discharge to avoid precipitating any additional
withdrawal symptoms.
On presentation, the patient’s pupils measured approximately
2-3 mm in diameter and she complained only of mild diaphoresis.
She admitted to taking her last dose of kratom at 5 am on the
day of admission. She brought her last vial of kratom, which contained
approximately 2 ml of a clear fluid that she admitted was
concentrated kratom extract diluted with water. Unfortunately,
there was not enough of the diluted concentrate left in the bottle
for laboratory analysis. The initial examination was unremarkable
except for mild diaphoresis of the palms and back of the neck
and significant cachexia. Electrolytes, renal function, hemogram,
and liver studies were within normal limits. Urine toxicology by
immunoassay was negative for all drugs of abuse including oxycodone,
opioids, and methadone. A sample of urine was sent for
liquid chromatography-mass spectrometry (LC-MS) to detect
mitragynine (the active alkaloid in kratom), results of which
came back positive at a cutoff value of 10 ng/ml. While an exact
toxic concentration has not been clearly established for mitragyFigure
1. Clinical Opioid Withdrawal Scale Scores Over Time
Figure 2. Kratom Withdrawal Clonidine Dose Requirements
VOLUME 115 • NO. 1 51
At the present time, however, the clinical properties of mitragynine
and its potential for development as a therapeutic agent are
only in the early stages of investigation.
The Internet is ripe with sites and articles that proclaim the
analgesic and stimulant properties of kratom while downplaying
its adverse side effects and addictive potential. Numerous case
series and reports, however, have described the addictive potential
of kratom, both in herbal form and as an extract. The oldest of
these published articles dates back to 1975 with an early description
of kratom addiction in the Thai population.10 In a more
recent study carried out to determine the risk of suicide among
illicit drug users in Thailand, the investigators report that the primary
drug of abuse in their study was kratom (illegal in Thailand
since 1943), which was used by 59% of the 537 respondents
who admitted to illicit drug use, followed by methamphetamine
(24%).11 This epidemiological study, however, did not distinguish
between abuse and addiction.
More recently, a number of case series and reports of kratom
toxicity have started to surface in the United States and Europe
(Table). In one such report, a male patient abusing and addicted
to hydromorphone attempted to use kratom to prevent withdrawal
and was admitted to the hospital after he mixed the kratom
with modafanil and suffered a generalized tonic-clonic seizure.12
It is unclear if the seizure was a result of the kratom or
the combination of the 2 drugs. In a separate case series from
Sweden, investigators report on 9 cases of krypton intoxication
and death.13 Krypton is an herbal preparation of dried, crushed
kratom leaves mixed with another mu-opioid receptor agonist,
O-desmethyltramadol.13 The abuse potential, toxicity, and withdrawal
symptoms associated with kratom use have been described
in at least 3 case series.14-16 Three additional case reports also have
demonstrated the potentially fatal effects of kratom without the
addition of other mu-opioid agonists.17-19
DISCUSSION
Kratom (Mitragynia speciosa Korth) is an herb indigenous to
Thailand and other countries in Southeast Asia that has been
used by people in that part of the world for hundreds of years
to stave off fatigue and to manage pain, opioid withdrawal, and
cough.3 In the past decade, the herb has made its way around
the world via Internet sales as an alternative to opioids for pain
relief. Unfortunately, kratom is not well known by physicians in
the United States. Kratom contains a number of active phytochemicals,
but the chemical entity mitragynine (the plant’s primary
alkaloid) is widely regarded to produce the majority of the
plant’s psychoactive effects, with additional contributions from
other phytochemicals, including 7-hydroxymitragynine (7-HMG)
and mitraphylline.4,5 When ingested orally, the bioavailability of
mitragynine is estimated in the laboratory to be approximately
3.03% with an onset of action of approximately 5 to 10 minutes.2
The half-life of mitragynine is not known with certainty, but its
effects appear to last several hours consistent with the initiation of
withdrawal symptoms within 12 to 24 hours (as occurred in the
current case).2 At low doses, mitragynine has stimulant effects, but
at high doses, mitragynine behaves like an opioid and has been
shown to have agonist activity at the Mu and Kappa-opioid receptors.6
Kratom is not currently scheduled by the Drug Enforcement
Agency (DEA) but is listed on its “Drugs and Chemicals of
Concern” list and is sold on the Internet as a “nonaddictive” herbal
alternative for pain control.6,7 It also is used by many as a “legal
high” and to assist with withdrawal from opioids. Despite its nonscheduled
status with the DEA, in 2013 Wisconsin Act 351 classified
kratom as a schedule 1 controlled dangerous substance, making
it illegal to possess or use in Wisconsin.8,9 Mitragynine, the
primary active component of kratom, currently is being investigated
as a potential analgesic with a diminished risk of respiratory
depression in overdose compared to traditional opioid analgesics.6
Table. Literature Review of Kratom Case Reports, Case Series, and Investigations
Number of Type of
Authors Cases Article Outcome Comments
Nelson JL, et al7 1 Case report Generalized tonic-clonic seizure; Kratom combined with Modafanil
discharged to home
Kronstrand R, et al8 9 Retrospective Death All 9 cases involved combined kratom and O-desmethyltramadol
case series (Krypton).
Singh D, et al9 293 Cross-sectional survey Dose dependent effects of toxicity, First study to measure kratom dependence, withdrawal symptoms,
of kratom user addiction, and withdrawal and drug craving.
Forrester MB10 14 Retrospective All patients treated Retrospective case series of kratom exposure reports
case series and recovered to Texas Poison Centers.
Trakulsrichai S, et al11 52 Retrospective Most cases with Study describes toxicity and withdrawal reported to Ramathibodi Case
review series good prognostic outcome Poison Center in Thailand.
McIntyre IM, et al12 1 Case report Death Kratom overdose; tissue samples also demonstrated mirtazapine, venlafaxine,
and diphenhydramine.
Karinen R, et al13 1 Case report Death Kratom overdose; blood analysis also demonstrated citalopram,
zopiclone, and lamotrigine.
Neerman MF, et al14 1 Case report Death Kratom overdose; toxicology also revealed therapeutic levels
of over-the-counter cold medicine and benzodiazepine.
52 WMJ • FEBRUARY 2016
Funding/Support: None declared.
Financial Disclosures: Dr Galbis-Reig reports ownership of stock in GW
Pharmaceuticals and Cortex Pharmaceuticals, Pfizer Inc bonds, and spousal
ownership of stock options in Abbvie, Abbott Pharma, and Hospira.
Planners/Reviewers: The planners and reviewers for this journal CME activity
have no relevant financial relationships to disclose.
REFERENCES
1. Prozialeck W, Jivan J, Andurkar S. Pharmacology of kratom: an emergening
botanical agent with stimulant, analgesic, and opioid-like effects. Am Osteopath Assoc.
2002;112(12):792-799.
2. Manda V, Avula B, Ali Z, Khan I, Walker L, Khan S. Evaluation of the in vitro
absorption, distribution, metabolism, and excretion (ADME) properties of mitragynine,
7-hydroxymitragynine, and mitraphylline. Planta Med. 2014;80(7):568-576.
3. Le D, Goggin M, Janis G. Analysis of mitragynine and metabolites in human urine for
detecting the use of the psychoactive plant kratom. J Anal Toxicol. 2012;36(9):616-625.
4. Suwanlert S. A study of kratom eaters in Thailand. Bulletin Narcotics. 1975;27(3):21-27.
5. Kittirattanapaiboon P, Suttajit S, Junsirimongkol B, Likhitsathian S, Srisurapanont
M. Suicide risk among Thai illicit drug users with and without mental/alcohol use
disorders. Neuropsychiatr Dis Treat. 2014;10:453-458.
6. Nelson J, Lapoint J, Hodgman M, Aldous K. Seizure and coma following kratom
(Mitragynina speciosa Korth) exposure. J Med Toxicol. 2010;6:424-426.
7. Kronstrand R, Roman M, Thelander G, Eriksson A. Unintentional fatal intoxications
with mitragynine and O-desmethyltramadol from the herbal blend krypton. J Anal
Toxicol. 2011;35:242-247.
8. Greenemeier L. Should kratom use be legal? Scientific American. September 30,
2013. http://www.scientificamerican.com/artic ... -be-legal/. Accessed
January 14, 2016.
9. Drug Enforcement Administration, Office of Diversion Control. January 1, 2013. http://
http://www.deadiversion.usdoj.gov/drug_ ... kratom.pdf. Accessed January 14, 2016.
10. Singh D, Muller C, Vicknasingam B. Kratom (Mitragyna speciosa) dependence,
withdrawal symptoms, and craving in regular users. Drug Alcohol Depend.
2014;139:132-137.
11. Forrester M. Kratom exposures reported to Texas poison centers. J Addict Dis.
2013;32(4):396-400.
12. McIntyre I, Trochta A, Stolberg S, Campman S. Mitragynine ‘Kratom’ related fatality:
a case report with postmortem concentrations. J Anal Toxicol. 2015;39(2):152-155.
13. Karinen R, Fosen J, Rogde S, Vindenes V. An accidental poisoning with
mitragynine. Forensic Sci Int. 2014;245c:e29-e32.
14. Trakulsrichai S, Tongpo A, Sriapha C, et al. Kratom abuse in Ramathibodi Poison
Center, Thailand: a five-year experience. J Psychoactive Drugs. 2013;45(5):404-408.
15. Neerman M, Frost R, Deking J. A drug fatality involving kratom. J Forensic Sci.
2013;58(Suppl 1):S278-S279.
16. Harun N, Hassan Z, Navaratnam V, Mansor S, Shoaib M. Discriminative stimulus
properties of mitragynine (kratom) in rats. Psychopharmacology (Berl). 2015;232(13):
2227-2238.
17. Lu J, Wei H, Wu J, et al. Evaluation of the cardiotoxicity of mitragynine and its
analogues using human induced pluripotent stem cell-derived cardiomyocytes. PLoS
One. 2014;9(12):1-18.
18. Ulbricht C, Costa D, Dao J, et al. An evidence-based systematic review of kratom
(Mitragyna speciosa) by the Natural Standard Research Collaboration. J Diet Suppl.
2015;10(2):152-170.
19. Drug Enforcement Administration. Office of Diversion Control. KRATOM (Mitragyna
speciosa korth). January 2013. http://www.deadiversion.usdoj.gov/drug_chem_info/
kratom.pdf. Accessed January 14, 2016.
20. Synche Enterprises. Kratom Legal Status. February 9, 2015. http://www.synche.
com/tag/kratom-legal-status/. Accessed January 14, 2016.
21. Wisconsin State Legislature. 2013 Wisconsin Act 351. April 24, 2014. https://docs.
legis.wisconsin.gov/2013/related/acts/351. Accessed January 14, 2016.
The addictive potential of kratom (specifically mitragynine)
has been well described in a discriminative stimulus rat model
of addiction with properties similar to morphine and cocaine.20
While the toxicity and addictive potential of kratom and its
derivatives has not been well described in human populations,
several case series and reports describe a clear addiction potential
and a potentially severe, opioid-like withdrawal syndrome in
humans.14,16 Toxicity has included reports of palpitations, seizures,
and coma.12,16 The most extensive description of kratom withdrawal
suggests symptoms of physical withdrawal that include
myalgias, pupillary dilatation, insomnia, rhinorrhea, lacrimation,
fever, hot flashes, anorexia, and diarrhea as well as psychological
withdrawal symptoms that include agitation, anxiety, irritability,
and depression.14 Given the mu-opioid agonist effects of the alkaloids
mitragynine and 7-hydroxymitragynine found in kratom,
the symptom complex of kratom withdrawal is, not surprisingly,
similar to the opioid withdrawal syndrome. The investigators of
the aforementioned cross-sectional survey study declare that “kratom
use is associated with drug dependence, drug withdrawal,
and craving” consistent with drug addiction.14
Empirical evidence regarding how best to treat the kratom
withdrawal syndrome and assist with long-term maintenance of
sobriety from kratom is currently lacking, though the current case
report suggests that a combination of high dose alpha-2 agonist
therapy and hydroxyzine may provide relief from both the physical
and mental symptoms of kratom withdrawal. Theoretically,
buprenorphine and methadone agonist therapy also might be
utilized for long-term maintenance of sobriety in kratom addiction,
though kratom’s current classification as a distinct chemical
entity not related to the opioid class of chemicals creates some
medico-legal and regulatory issues that require consideration with
respect to opioid agonist therapy. As a result, and because there
are no regulatory issues with antagonist therapy, the patient was
prescribed oral naltrexone to assist with craving and maintenance
of sobriety from kratom.
CONCLUSION
Kratom (Mitragynia speciosa Korth), an herb originating in
Southeast Asia, which currently is not scheduled by the DEA,
but is classified as a schedule 1 dangerous controlled substance in
Wisconsin,21 possesses psychoactive properties that include both
stimulant and opioid-like effects. Kratom has grown, and continues
to grow, in popularity in the United States and in Wisconsin.
Withdrawal symptoms are mediated by the opioid properties of
the plant’s primary alkaloid compounds and can successfully be
treated using an alpha-2 agonist and hydroxyzine as demonstrated
by the current case report in which symptom-triggered clonidine
therapy was utilized with COWS in conjunction with scheduled
hydroxyzine. Physicians should be aware of the growing availability
of kratom and its potential adverse health effects, especially its
toxicity, addictive potential, and withdrawal syndrome.
The mission of WMJ is to provide a vehicle for professional communication and continuing education for
Midwest physicians and other health professionals.
WMJ (ISSN 1098-1861) is published by the Wisconsin Medical Society and is devoted to the interests of
the medical profession and health care in the Midwest. The managing editor is responsible for overseeing
the production, business operation and contents of the WMJ. The editorial board, chaired by the
medical editor, solicits and peer reviews all scientific articles; it does not screen public health, socioeconomic,
or organizational articles. Although letters to the editor are reviewed by the medical editor, all
signed expressions of opinion belong to the author(s) for which neither WMJ nor the Wisconsin Medical
Society take responsibility. WMJ is indexed in Index Medicus, Hospital Literature Index, and Cambridge
Scientific Abstracts.
For reprints of this article, contact the WMJ at 866.442.3800 or e-mail wmj@wismed.org.
© 2016 Wisconsin Medical Society

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