A Case Report of Kratom Addiction and Withdrawal

[justin2016]

• • •

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

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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.

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Center, Thailand: a five-year experience. J Psychoactive Drugs. 2013;45(5):404-408.

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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

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