Journal of Toxicology and Pharmacology

Case Report | J Toxic Pharm 2017; 1:003 | Open Access

Intravenous Kratom Use in a Patient with Opioid Dependence

Alicia G. Lydecker1*, Matthew D. Zuckerman2, Jason B. Hack3, Bruce Becker4, Joseph K. Cherkes5, Edward W. Boyer1 and Kavita M. Babu1

1Division of Medical Toxicology, Department of Emergency Medicine, University of Massachusetts Medical School, USA
2Division of Medical Toxicology, Department of Emergency Medicine, University of Colorado School of Medicine, USA
3Division of Medical Toxicology, Department of Emergency Medicine, Warren Alpert School of Medicine, Brown University, USA
4Departments of Emergency Medicine and Behavioral and Social Science, Warren Alpert School of Medicine, Brown University, USA
5Department of Toxicology, Rhode Island Hospital, USA

*Correspondence to:alicia.lydecker@gmail.com

Copyright:© 2017 The Authors. Published by Scientific Open Access Journals LLC.

Citation:Lydecker AG, Zuckerman MD, Hack JB, et al. Intravenous Kratom Use in a Patient with Opioid Dependence. J Toxicol Pharmacol 2017; 1:003.

Received: 02 January 2017; Accepted: 24 January 2017; Published: 03 February 2017

Abstract

Kratom, derived from Mitragyna speciosa Korth, has gained popularity as a natural product that can ameliorate opioid withdrawal symptoms. Compulsive Kratom ingestion is well-documented; however, there are no reports in the medical literature of parenteral Kratom use. We report the case of a 29-year-old man who transitioned from oral use to injecting various forms of Kratom. He presented to the emergency department with acute thrombophlebitis at an injection site.

Keywords:Kratom; Mitragynine; 7-hydroxymitragynine; Opioid withdrawal; Injection drug use; Abuse liability

Introduction

Kratom, a natural product with activity at opioid receptors, is available via the Internet without a prescription. Derived from Mitragyna speciosa Korth, a Southeast Asian tree, Kratom has been used for centuries for its dual stimulant and opioid-like properties. For various reasons, its use was banned in parts of Southeast Asia in the mid-20th century; however, because it is indigenous to many areas and culturally engrained, its use has not declined [1]. Increasingly, Kratom leaves and extract are used in the United States for the self-treatment of opioid withdrawal. Little is known about the abuse potential of these forms of Kratom. We report the first case of a patient whose addiction to Kratom escalated to intravenous use.

Case Report

A 29 year-old man with a history of substance abuse disorder presented to the emergency department complaining of pain in his arms. He reported that he had been purchasing Kratom extract via the Internet and injecting it intravenously several times daily. His last reported use was six hours prior to presentation. He denied using tobacco, ethanol, or illicit drugs. On arrival, he was afebrile with a pulse of 95 beats per minute, blood pressure of 138/82 mm Hg, respiratory rate of 18 breaths per minute, and pulse oximetry of 99% on room air. On physical exam, his cubital fossae were notable for erythema and induration, consistent with superficial thrombophlebitis. There were no “track marks.” He was alert and oriented with a normal mental status without evidence of acute intoxication. His laboratory evaluation was significant for a white blood cell count of 12.1 cells/microliter. He was treated with one gram of intravenous cefazolin.

The patient related a long history of substance use. He had initially become addicted to the prescription opioids hydrocodone and oxycodone. He subsequently began using heroin and cocaine. He entered opioid replacement treatment with methadone and later buprenorphine. For four years he abstained from heroin and cocaine use. He ultimately decided to stop his opioid replacement, as he was hoping to work in healthcare.

He read about making tea from Kratom leaves on the Internet and was attracted to its legal status and ability to elude detection on most standard urine drug screens. He initially noted its stimulant effects which allowed him to work faster and longer than his colleagues. Over time, this effect waned and he increased the use of the product to compensate. He was initially drinking Kratom tea daily, then several times daily, until he found a way to inject it intravenously.

He began buying Kratom extract in alcohol. He let the alcohol evaporate in a spoon, and then dissolved the remaining resin in water to inject. Subsequently, he began cooking off the alcohol with heat. Finally, the patient said that he was impatient, and began injecting the extract directly. At the time of presentation, he was buying Kratom extract from multiple online vendors, and injecting 1 ml of extract six times daily.

The patient was distressed by his increasing use and attempted to stop using the Kratom extract. He noted increasing withdrawal symptoms: “runny nose, watery eyes, goosebumps, the pukes and the shakes.” He described his Kratom withdrawal as less intense than that experienced with heroin. He attempted to use meprobamate, tramadol, and diphenhydramine to ameliorate his withdrawal symptoms.

During his evaluation in the emergency department, he requested admission to an opioid detoxification program. Discussions between medical staff and the local opioid detoxification program made it clear that he would be eligible for inpatient treatment despite the program’s lack of familiarity with the drug. As no beds were available, the patient was discharged with plans to contact the program and was subsequently lost to follow up.

A comprehensive urine drug test via GC/MS was used to analyze his urine. The analysis was positive for tramadol and metabolite, meprobamate, diphenhydramine, and acetaminophen, but negative for mitragynine and 7-hydroxymitragynine.

Discussion

Derived from the leaves of the Mitragyna speciosa Korth (a tree native to Southeast Asia), Kratom has been used for centuries as both a stimulant and an analgesic. The possession and sale of Kratom is illegal in Thailand and Malaysia, amongst a growing number of additional countries, although use persists [2]. Kratom is currently unscheduled in the United States and easily purchased online. It’s used as an opioid substitute for both recreational purposes and to ameliorate withdrawal symptoms [3,4]. During recent years, Kratom use has become increasingly popular in the U.S [5-7].

Kratom products are available as raw leaves, powder, chewing gum, extracts, and capsules. The leaves are oval, dark green, and approximately 1-2 cm in size. The central vein of the leaves may be either greenish-white or red, with reports of increased potency in the red-veined leaves [2]. The leaves are typically smoked or brewed into tea. Effects and duration are dose-dependent, with stimulant effects predominating at lower doses (few grams of dried leaves) while higher doses (10-25 grams dried leaves) result in sedation, dysphoria, and euphoria. Symptoms begin 5 to 10 minutes after consumption, and last one to six hours following exposure [2,8].

Of note, while Kratom use in Southeast Asia has traditionally been limited to tea or chewing leaves, more recent reports include use of “4 × 100” a Kratom cocktail popular with young adults [9]. The cocktails consist of Kratom leaves, a caffeinated soft drink, and codeine or diphenhydramine containing cough syrup. This parallels the development of similar codeine containing cocktails in the United States, although current reports are limited to Southeast Asia.

Among the dozens of alkaloids identified in Kratom, mitragynine and 7-hydroxymitragynine are considered to be most responsible for Kratom's opioid-like effects [10]. Additionally, mitragynine acts at supraspinal mu- and delta-opioid receptors, stimulates post-synaptic alpha-2 adrenergic receptors, and blocks stimulation of 5-HT2A receptors [11]. Adverse events associated with the ingestion of Kratom include seizures and hepatic injury [12-14]. Deaths associated with Kratom have been associated with contaminated products or coingestants [9,15-18].

We did not detect mitragynine in the patient's urine, despite his reported last use of intravenous Kratom six hours prior to his emergency department visit. At that time, mitragynine and 7-hydroxymitragynine were not included in the library of substances able to be detected by our institution's comprehensive urine drug screen by GC/MS. Likewise, a mitragynine-specific assay such as High Performance Liquid Chromatography (HPLC) was unavailable to us at the time of the patient’s original presentation, as was LC-MS/MS, the analytical technique previously described for identifying mitragynine and congeners [14].

Addiction to Kratom has been well described. The withdrawal syndrome among chronic Kratom users parallels opioid withdrawal, with irritability, yawning, rhinorrhea, and diarrhea [8]. A more contemporary case report described a patient with "anxiety, restlessness, tremor, sweating and cravings for the substance” after discontinuing Kratom use [19]. Cross-tolerance between opioids and Kratom has been described.

Our patient spontaneously self-reported features of tolerance, dose escalation, functional decline, and withdrawal in the setting of chronic Kratom use. Additionally, his usage pattern changed from oral Kratom use to intravenous Kratom use with a prepared extract to direct injection of extract. His emergency department presentation with superficial thrombophlebitis directly stemmed from complications of his Kratom addiction. It is unclear if risk of Kratom addiction is increased in patients with prior substance use disorders, however this case is an important reminder of the chronic nature of opioid addiction, which has a high rate of relapse. As Kratom becomes more popular in patients seeking abstinence from opiates, including heroin, such intravenous use may also increase.

Conflicts of Interest

Authors AL, MZ, JH, BB, and JC declare that they have no conflict of interest. Authors EB and KB provide medicolegal consultation and receive royalties from UpToDate. Author EB also participates in NIH-funded research on drugs of abuse.

Reference

  1. Tanguay P. Kratom in Thailand. Legislative Reform of Drug Policies 13. 2011; 1-16.
  2. Kratom (Mitragyna speciosa) drug profile. European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). 2015.
  3. Assanangkornchai S, Muekthong A, Samangsri N, Pattanasattayawong U. The Use of Mitragynine speciosa (“Krathom”), an Addictive Plant, in Thailand. Substance Use & Misuse. 2009; 42:2145-2157.
  4. Arndt T, Claussen U, Güssregen B, Schröfel S, Stürzer B, Werle A, et al. Kratom alkaloids and O-desmethyltramadol in urine of a “Krypton” herbal mixture consumer. Forensic Sci Int. 2011; 208:47-52.
  5. Anwar M, Law R, Schier J. Notes from the Field: Kratom ( Mitragyna speciosa) Exposures Reported to Poison Centers — United States, 2010–2015. MMWR Morb Mortal Wkly Rep. 2016; 65:748-749.
  6. Drugs of Abuse. U.S. Department of Justice Drug Enforcement Administration.
  7. Special Report: Opiates and Related Drugs Reported in NFLIS, 2009–2014. U.S. Department Of Justice, Drug Enforcement Administration, Office of Diversion Control. 2016.
  8. Suwanlert S. A study of kratom eaters in Thailand. Bull Narc.1975; 27:21-27.
  9. Tungtananuwat W, Lawanprasert S. Fatal 4x100: Homemade kratom juice cocktail. J Health Res. 2010; 24:43-47.
  10. Thongpradichote S, Matsumoto K, Tohda M, Takayama H, Aimi N, Sakai S, et al. Identification of opioid receptor subtypes in antinociceptive actions of supraspinally-administered mitragynine in mice. Life Sci. 1998; 62:1371-1378.
  11. Matsumoto K, Yamamoto LT, Watanabe K, Shingo Yanoc, Jie Shand, Peter K.T, et al. Inhibitory effect of mitragynine, an analgesic alkaloid from Thai herbal medicine, on neurogenic contraction of the vas deferens. Life Sci. 2005; 78:187-194.
  12. Kapp FG, Maurer HH, Auwärter V, Winkelmann M, Hermanns-Clausen M. Intrahepatic cholestasis following abuse of powdered kratom (Mitragyna speciosa). J Med Toxicol. 2011; 7:227-231.
  13. Roche KM, Hart K, Sangalli B. Kratom: a Case of a Legal High. Clinical Toxicol. 2008; 46:598.
  14. Philipp AA, Wissenbach DK, Weber AA, Zapp J, Zoerntlein SW, Kanogsunthornrat J, et al. Use of liquid chromatography coupled to low- and high-resolution linear ion trap mass spectrometry for studying the metabolism of paynantheine, an alkaloid of the herbal drug Kratom in rat and human urine. Anal Bioanal Chem. 2010; 396:2379-2391.
  15. 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.
  16. McIntyre IM, Trochta A, Stolberg S, Campman SC. Mitragynine “Kratom” related fatality: a case report with postmortem concentrations. J Anal Toxicol. 2015; 39:152-155.
  17. Holler JM, Vorce SP, McDonough-Bender PC, Magluilo J, Solomon CJ, Levine B. A drug toxicity death involving propylhexedrine and mitragynine. J Anal Toxicol. 2011; 35:54-59.
  18. Neerman MF, Frost RE, Deking J. A Drug Fatality Involving Kratom. Journal of Forensic Sciences. 2013; 58:S278-S279.
  19. McWhirter L, Morris S. A case report of inpatient detoxification after kratom (Mitragyna speciosa) dependence. Eur Addict Res. 2010; 16:229-231.