Kratom consumption can be addictive and have adverse health effects

Document Type : Review

Author

Department of Food and Nutrition, Consumer Centre of the German Federal State of Bavaria, Munich, Germany

Abstract

Kratom, also known as herbal speed, is the powdered leaves of the Asian kratom tree (Mitragyna speciosa Korth). The consumption of kratom powder or kratom tea for diarrhea, inflammation, fever, and pain, but also for anxiety and depression is based on traditional experiences from East Asian herbal medicine.
Pharmacologically, kratom is an intoxicant or narcotic. In low doses, the leaves have a stimulating effect, in high doses, they are depressant and psychoactive like opioids. There is a steadily increasing popularity of the herbal drug kratom and its psychoactive compounds mitragynine and 7-hydroxymitragynine around the world. To date, no randomized controlled human intervention study has evaluated the safety and efficacy of kratom ingestion. In addition, there are increasing reports of kratom-associated adverse effects including herb-induced liver toxicity and nephrotoxicity, cardiovascular and neurological symptoms, and withdrawal syndrome.
The still unsatisfactory lack of regulatory control and easy availability via internet providers will continue to increase kratom use in many countries. Clinicians should be aware that kratom use can be addictive and have potentially serious side effects. It is important to determine the consumption of dietary and herbal supplements when taking the patient's medical history.

Keywords


  1. Hanapi NA, Chear NJ, Azizi J, Yusof SR. Kratom Alkaloids: Interactions with Enzymes, Receptors, and Cellular Barriers. Front Pharmacol. 2021;12:751656 doi:10.3389/fphar.2021.751656 PMid:34867362 PMCid:PMC8637859
  2. Papadi G, Bakhiya N, Ildico Hirsch-Ernst K. Assessment of the possible health risks associated with the consumption of botanical preparations of Mitragyna speciosa (kratom). EFSA J. 2022;20(Suppl 1):e200415. doi:10.2903/j.efsa.2022.e200415 PMid:35634550 PMCid:PMC9131591
  3. Swogger MT, Smith KE, Garcia-Romeu A, Grundmann O, Veltri CA, Henningfield JE, et al. Understanding Kratom Use: A Guide for Healthcare Providers. Front Pharmacol. 2022;13:801855 doi:10.3389/fphar.2022.801855 PMid:35308216 PMCid:PMC8924421
  4. Warner ML, Kaufman NC, Grundmann O. The pharmacology and toxicology of kratom: from traditional herb to drug of abuse. Int J Legal Med. 2016;130(1):127-38. doi:10.1007/s00414-015-1279-y PMid:26511390
  5. Hartley C 2nd, Bulloch M, Penzak SR. Clinical Pharmacology of the Dietary Supplement Kratom (Mitragyna speciosa). J Clin Pharmacol. 2022;62(5):577-93. doi:10.1002/jcph.2001 PMid:34775626
  6. Shah K, Tankersley W, Mekala H. Kratom: An Emerging Issue and Need for Regulations in the United States. Prim Care Companion CNS Disord. 2021;23(1):20r02770 doi:10.4088/PCC.20r02770
  7. Henningfield JE, Wang DW, Huestis MA. Kratom Abuse Potential 2021: An Updated Eight Factor Analysis. Front Pharmacol. 2022; 12: 775073. doi:10.3389/fphar.2021.775073 PMid:35197848 PMCid:PMC8860177
  8. Sharma V, Cottler LB, Bares CB, Lopez-Quintero C. Kratom Use Among U.S. Adolescents: Analyses of the 2019 National Survey on Drug Use and Health. J Adolesc Health. 2022;70(4):677-81 doi:10.1016/j.jadohealth.2021.10.009 PMid:34836801 PMCid:PMC9328154
  9. Tanna RS, Tian DD, Cech NB, Oberlies NH, Rettie AE, Thummel KE, et al. Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations. J Pharmacol Exp Ther. 2021;376(1):64-73 doi:10.1124/jpet.120.000270 PMid:33093187 PMCid:PMC7745086
  10. Aldyab M, Ells PF, Bui R, Chapman TD, Lee H. Kratom-Induced Cholestatic Liver Injury Mimicking Anti-Mitochondrial Antibody-Negative Primary Biliary Cholangitis: A Case Report and Review of Literature. Gastroenterol Res. 2019;12(4):211-15 doi:10.14740/gr1204 PMid:31523332 PMCid:PMC6731044
  11. Fernandes CT, Iqbal U, Tighe SP, Ahmed A. Kratom-Induced Cholestatic Liver Injury and Its Conservative Management. J Investig Med High Impact Case Rep. 2019;7:2324709619836138 doi:10.1177/2324709619836138 PMid:30920318 PMCid:PMC6440031
  12. Ahmad J, Odin JA, Hayashi PH, Fontana RJ, Conjeevaram H, Avula B, et al. Liver injury associated with kratom, a popular opioid-like product: Experience from the U.S. drug induced liver injury network and a review of the literature. Drug Alcohol Depend. 2021; 218: 108426. doi:10.1016/j.drugalcdep.2020.108426 PMid:33257199 PMCid:PMC8113016
  13. Botejue M, Walia G, Shahin O, Sharma J, Zackria R. Kratom-Induced Liver Injury: A Case Series and Clinical Implications. Cureus. 2021;13(4):e14679. doi:10.7759/cureus.14679
  14. Antony A, Lee TP. Herb-Induced Liver Injury With Cholestasis and Renal Injury Secondary to Short-Term Use of Kratom (Mitragyna speciosa). Am J Ther. 2019;26(4):e546-47 doi:10.1097/MJT.0000000000000802 PMid:29927773
  15. Khan MZ, Saleh MA, Alkhayyat M, Roberts DE, Lindenmeyer CC. Multiorgan Dysfunction Related to Kratom Ingestion. ACG Case Rep J. 2021;8(8):e00647 doi:10.14309/crj.0000000000000647 PMid:34476274 PMCid:PMC8389947
  16. Sangani V, Sunnoqrot N, Gargis K, Ranabhotu A, Mubasher A, Pokal M. Unusual Presentation of Kratom Overdose With Rhabdomyolysis, Transient Hearing Loss, and Heart Failure. J Investig Med High Impact Case Rep. 2021; 9: 23247096211005069. doi:10.1177/23247096211005069 PMid:33764201 PMCid:PMC8767650
  17. Jasim RK, Hassan Z, Singh D, Boyer E, Gam LH. Characterization of urinary protein profile in regular kratom (Mitragyna speciosa korth.) users in Malaysia. J Addict Dis. 2022; 40(2):235-46. doi:10.1080/10550887.2021.1981122 PMid:34747343
  18. Tobarran N, Wolf C, Cumpston KL, Wills BK. Pressure Necrosis Requiring Fasciotomy After Kratom Overdose. J Addict Med. 2022; 16(2):252-53. doi:10.1097/ADM.0000000000000873 PMid:34001773
  19. Maria-Rios JC, Darrabie M, Martin A. Severe Rhabdomyolysis Complicated with Compartment Syndrome Likely Associated to Recent Kratom Use. Am J Respir Crit Care Med. 2022; 205: A1578. doi:10.1164/ajrccm-conference.2022.205.1_MeetingAbstracts.A1578
  20. Torres-Ortiz A, Al Zein S, Alqudsi M. A Case of Hyperkalemia Induced by Kratom (Mitragyna speciosa). Cureus. 2022; 14 (4): e24036. doi:10.7759/cureus.24036
  21. Eggleston W, Stoppacher R, Suen K, Marraffa JM, Nelson LS. Kratom Use and Toxicities in the United States. Pharmacotherapy. 2019;39(7):775-77. doi:10.1002/phar.2280 PMid:31099038
  22. Post S, Spiller HA, Chounthirath T, Smith GA. Kratom exposures reported to United States poison control centers: 2011-2017. Clin Toxicol (Phila). 2019;57(10):847-54. doi:10.1080/15563650.2019.1569236 PMid:30786220
  23. Davidson C, Cao D, King T, Weiss ST, Wongvisavakorn S, Ratprasert N, et al. A comparative analysis of kratom exposure cases in Thailand and the United States from 2010-2017. Am J Drug Alcohol Abus. 2021;47(1):74-83 doi:10.1080/00952990.2020.1836185 PMid:33232183
  24. Leong Bin Abdullah MFI, Singh D. The Adverse Cardiovascular Effects and Cardiotoxicity of Kratom (Mitragyna speciosa Korth.): A Comprehensive Review. Front Pharmacol. 2021; 12: 726003. doi:10.3389/fphar.2021.726003 PMid:34646135 PMCid:PMC8504575
  25. Abdullah HMA, Haq I, Lamfers R. Cardiac arrest in a young healthy male patient secondary to kratom ingestion: is this 'legal high' substance more dangerous than initially thought? BMJ Case Rep. 2019;12(7):e229778. doi:10.1136/bcr-2019-229778 PMid:31326902 PMCid:PMC6663180
  26. Wolfer H, Gerona R, Blumenberg A. Evidence of a potential mechanism for Kratom-related cardiac arrest. Clin Toxicol (Phila). 2020;58(8):851-52. doi:10.1080/15563650.2019.1687907 PMid:31718341
  27. Sheikh M, Ahmed N, Gandhi H, Chen O. Report of ventricular fibrillation in a 44-year-old man using kratom. BMJ Case Rep. 2021;14(3):e237837. doi:10.1136/bcr-2020-237837 PMid:33758039 PMCid:PMC7993157
  28. Demick DS, Lee TT, Summers AT, El-Mallakh RS. Kratom: A growing substance of abuse in the United States. Ann Clin Psychiatry. 2020;32(4):275-80. doi:10.12788/acp.0012 PMid:32722734
  29. Burke DJ, Mahonski SG, Van Cott AC. Breakthrough Seizure Associated With Kratom Use in Patients With Epilepsy. Neurol Clin Pract. 2021;11(1):78-84 doi:10.1212/CPJ.0000000000000846 PMid:33968476 PMCid:PMC8101317
  30. Halim SA, Low JH, Chee YC, Alias MR. Seizures among young adults consuming kratom beverages in Malaysia: A case series. Epilepsy Behav. 2021;121(Pt A):108057. doi:10.1016/j.yebeh.2021.108057 PMid:34052638
  31. Zuberi M, Guru PK, Bansal V, Diaz-Gomez J, Grieninger B, Alejos D. Undifferentiated Shock and Extreme Elevation of Procalcitonin Related to Kratom Use. Indian J Crit Care Med. 2019;23(5):239-41. doi:10.5005/jp-journals-10071-23170 PMid:31160844 PMCid:PMC6535991
  32. Singh V, Mulla N, Wilson JL, Umansky A, Lee J, Stead T, et al. Intractable nausea and vomiting in naïve ingestion of kratom for analgesia. Int J Emerg Med. 2020;13(1):42. doi:10.1186/s12245-020-00301-0 PMid:32758124 PMCid:PMC7409412
  33. Stanciu CN, Gnanasegaram SA, Ahmed S, Penders T. Kratom Withdrawal: A Systematic Review with Case Series. J Psychoactive Drugs. 2019;51(1):12-8 doi:10.1080/02791072.2018.1562133 PMid:30614408
  34. Wright ME, Ginsberg C, Parkison AM, Dubose M, Sherbondy M, Shores E. Outcomes of mothers and newborns to prenatal exposure to kratom: a systematic review. J Perinatol. 2021;41 (6): 1236-43. doi:10.1038/s41372-021-00952-8 PMid:33589723 PMCid:PMC8225511
  35. Smith KE, Dunn KE, Rogers JM, Garcia-Romeu A, Strickland JC, Epstein DH. Assessment of Kratom Use Disorder and Withdrawal Among an Online Convenience Sample of US Adults. J Addict Med. 2022 doi:10.1097/ADM.0000000000000986 PMid:35220331 PMCid:PMC9402806
  36. Jittasopa W, Srisont S. The Causes of Death and Pathological Findings of Kratom Users: A 5-Year Retrospective Analysis. Am J Forensic Med Pathol. 2021;42(4):335-40.
    doi:10.1097/PAF.0000000000000691 PMid:34054017
  37. Nsubuga J, Baugher J, Dahl E, Schwensohn C, Blessington T, Aguillon R, et al. Multistate Outbreak Investigation of Salmonella Infections Linked to Kratom: A Focus on Traceback, Laboratory, and Regulatory Activities. J Food Prot. 2022;85(5): 747-54. doi:10.4315/JFP-21-319 PMid:35114689
  38. Prozialeck WC, Edwards JR, Lamar PC, Plotkin BJ, Sigar IM, Grundmann O, et al. Evaluation of the Mitragynine Content, Levels of Toxic Metals and the Presence of Microbes in Kratom Products Purchased in the Western Suburbs of Chicago. Int J Environ Res Public Health. 2020;17(15):5512 doi:10.3390/ijerph17155512 PMid:32751712 PMCid:PMC7432033
  39. Prozialeck W, Fowler A, Edwards J. Public Health Implications and Possible Sources of Lead (Pb) as a Contaminant of Poorly Regulated Kratom Products in the United States. Toxics. 2022; 10 (7):398. doi:10.3390/toxics10070398 PMid:35878303 PMCid:PMC9320411
  40. Sekar A, Velani S, Katzman S, O'Donnell M, Conway KS. Suspected Fanconi syndrome from cadmium toxicity exacerbated by heavy kratom use. A rare occurrence. Clin Toxicol (Phila). 2022;60(7):888-89 doi:10.1080/15563650.2022.2046774 PMid:35323068
  41. Fleming J, Poklis J, Peace MR, Alves EA. The Analysis of Commercially Available Kratom Products in Richmond, Virginia. Graduate Research Posters 2022. Poster 142. Available at: https://scholarscompass.vcu.edu/gradposters/142/
  42. S. Food and Drug Administration (FDA). FDA announces seizure of adulterated dietary supplements containing kratom. May 21, 2021. Available at: https://www.fda.gov/news-events/press-announcements/fda-announces-seizure-adulterated-dietary-supplements-containing-kratom
  43. Commission on Narcotic Drugs. Summary of assessments, findings, and recommendations of the 44th World Health Organization's (WHO) Expert Committee on Drug Dependence (ECDD), 11-15 October 2021. E/CN.7/2021/CRP.12. December 2021. Available at: https://www.unodc.org/documents/commissions/CND/CND_Sessions/CND_64Reconvened/ECN72021_CRP12_V2108992.pdf
  44. Lautenschlager F, Weiss M, Feuerer S, Wodarz N. Kratom - eine kurze ┼░ersicht für die Schmerzmedizin [Kratom - a short review for pain medicine]. Schmerz. 2022;36(2):128-34. doi:10.1007/s00482-021-00588-9 PMid:34533652 PMCid:PMC8447806