ABSTRACT
Objective: To understand and highlight the current issues, emerging trends, and regulations of kratom in the United States.
Data Sources: PubMed and PubMed Central of the National Library of Medicine, MEDLINE, PsycINFO, and ClinicalTrials.gov databases were utilized.
Study Selection: Studies published between January 1, 2000, and June 30, 2020, were accessed by using the MeSH term mitragyna in the context of toxicity, safety, and legislation and jurisprudence.
Data Extraction: The final qualitative synthesis included 11 studies by following Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement guidelines.
Results: The US Drug Enforcement Administration (DEA) initially proposed to place kratom under Schedule I of the Controlled Substances Act, but the DEA later withdrew the intent, and kratom is still a legal substance in most of the United States. A low to moderate kratom dose produces mild stimulant properties, whereas large doses produce sedative effects that are identical to opiates. Its regular use at a higher dose is associated with dependence. Management of overdose is similar to that of patients presenting with opioid abuse, although kratom may potentially pose a higher risk for drug toxicity and organ injury compared to opioids due to intrinsic properties and adulteration. There is no clinical evidence for its safety and efficacy. The US Food and DEA do not recognize any legitimate medical use of kratom.
Conclusions: Kratom is an emerging public health concern and is abused as an alternative to opioids. Stringent policies and public awareness campaigns are required to curb the perception of its safe use, which needs to be substantiated with well-designed clinical trials.
Continue Reading...
Did you know members enjoy unlimited free PDF downloads as part of their subscription? Subscribe today for instant access to this article and our entire library in your preferred format. Alternatively, you can purchase the PDF of this article individually.
References (63)
- Müller CP, Schumann G. Drugs as instruments: a new framework for non-addictive psychoactive drug use. Behav Brain Sci. 2011;34(6):293–310. PubMed CrossRef NLM
- 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. PubMed CrossRef NLM
- Streatfeild D. Cocaine: An Unauthorised Biography. New York, NY: St. Martin’s Press; 2001.
- 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. PubMed CrossRef NLM
- Ingsathit A, Woratanarat P, Anukarahanonta T, et al. Prevalence of psychoactive drug use among drivers in Thailand: a roadside survey. Accid Anal Prev. 2009;41(3):474–478. PubMed CrossRef NLM
- Singh D, Narayanan S, Vicknasingam B. Traditional and non-traditional uses of mitragynine (kratom): a survey of the literature. Brain Res Bull. 2016;126(Pt 1):41–46. PubMed CrossRef NLM
- Veltri C, Grundmann O. Current perspectives on the impact of kratom use. Subst Abuse Rehabil. 2019;10:23–31. PubMed CrossRef NLM
- O’Neill-Dee C, Spiller HA, Casavant MJ, et al. Natural psychoactive substance-related exposures reported to United States poison control centers, 2000–2017 [published online ahead of print November 25, 2019]. Clin Toxicol (Phila). PubMed NLM
- The facts about kratom. Kratom Information and Resource Center. Updated September 1, 2020. Accessed September 5, 2020. https://kratominfocenter.org/the-facts-about-kratom/
- Prozialeck WC, Jivan JK, Andurkar SV. Pharmacology of kratom: an emerging botanical agent with stimulant, analgesic and opioid-like effects. J Am Osteopath Assoc. 2012;112(12):792–799. PubMed NLM
- Nicewonder JA, Buros AF, Veltri CA, et al. Distinct kratom user populations across the United States: a regional analysis based on an online survey. Hum Psychopharmacol. 2019;34(5):e2709. PubMed CrossRef NLM
- Grundmann O. Patterns of kratom use and health impact in the US—results from an online survey. Drug Alcohol Depend. 2017;176:63–70. PubMed CrossRef NLM
- 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(29):748–749. PubMed CrossRef NLM
- Kratom DrugFacts. What is kratom? National Institute on Drug Abuse. Updated April 2019. Accessed July 1, 2020. www.drugabuse.gov/publications/drugfacts/kratom
- Find Help. ATOD. Substance Abuse and Mental Health Services Administration. Updated April 23, 2020. Accessed July 1, 2020. https://www.samhsa.gov/find-help/atod
- Eastlack SC, Cornett EM, Kaye AD. Kratom-pharmacology, clinical implications, and outlook: a comprehensive review. Pain Ther. 2020;9(1):55–69. PubMed CrossRef NLM
- Likhitsathian S, Jiraporncharoen W, Aramrattana A, et al. Polydrug use among kratom users: findings from the 2011 Thailand National Household Survey. J Subst Use. 2018;23(4):384–389. CrossRef
- Suwanlert S. A study of kratom eaters in Thailand. Bull Narc. 1975;27(3):21–27. PubMed NLM
- Sethi R, Hoang N, Ravishankar DA, et al. Kratom (mitragyna speciosa): friend or foe? Prim Care Companion CNS Disord. 2020;22(1):19nr02507. PubMed CrossRef NLM
- Substance Abuse and Mental Health Services Administration. 2019. Accessed July 2, 2020. https://www.samhsa.gov/
- Moher D, Liberati A, Tetzlaff J, et al. PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. PubMed CrossRef NLM
- Dixon RB, Waggoner D, Davis M, et al. Contamination of some kratom products with salmonella. Ann Clin Lab Sci. 2019;49(5):675–677. PubMed NLM
- Eggleston W, Stoppacher R, Suen K, et al. Kratom use and toxicities in the United States. Pharmacotherapy. 2019;39(7):775–777. PubMed CrossRef NLM
- White CM. Pharmacologic and clinical assessment of kratom. Am J Health Syst Pharm. 2018;75(5):261–267. PubMed CrossRef NLM
- Henningfield JE, Fant RV, Wang DW. The abuse potential of kratom according the 8 factors of the controlled substances act: implications for regulation and research. Psychopharmacology (Berl). 2018;235(2):573–589. PubMed CrossRef NLM
- Sethi R, Miller KA, McAllister R. Kratom: is it the new illicit opiate on the market? Prim Care Companion CNS Disord. 2018;20(4):15l01895. PubMed CrossRef NLM
- Fluyau D, Revadigar N. Biochemical benefits, diagnosis, and clinical risks evaluation of kratom. Front Psychiatry. 2017;8:62. PubMed CrossRef NLM
- 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):127–138. PubMed CrossRef NLM
- Addictive Substance Called Kratom Becoming Popular in South Florida. Partnership to End Addiction. Published July 6, 2011. Accessed July 3, 2020. https://drugfree.org/learn/drug-and-alcohol-news/addictive-substance-called-kratom-becoming-popular-in-south-florida/
- Smith PA. Is Kratom a Performance Enhancer or a Lethal Opioid? Outside. Accessed July 3, 2020. https://www.outsideonline.com/2387546/kratom-safety
- Modernizing Drug Death Data. Centers for Disease Control and Prevention. Updated April 9, 2019. Accessed July 3, 2020. https://www.cdc.gov/surveillance/projects/improving-data-on-drug-overdose-deaths.html
- Yamamoto LT, Horie S, Takayama H, et al. Opioid receptor agonistic characteristics of mitragynine pseudoindoxyl in comparison with mitragynine derived from Thai medicinal plant Mitragyna speciosa. Gen Pharmacol. 1999;33(1):73–81. PubMed CrossRef NLM
- Babu KM, McCurdy CR, Boyer EW. Opioid receptors and legal highs: Salvia divinorum and kratom. Clin Toxicol (Phila). 2008;46(2):146–152. PubMed CrossRef NLM
- Azizi J, Ismail S, Mordi MN, et al. In vitro and in vivo effects of three different mitragyna speciosa korth leaf extracts on phase II drug metabolizing enzymes—glutathione transferases (GSTs). Molecules. 2010;15(1):432–441. PubMed CrossRef NLM
- Reagmongkhol CD, Keawpradup N, Sawangjaroen K. Effects of the extracts from mitragyna speciosa leaves on analgesic and neurobehavioural activities in experimental animals. Songklanakarin J Sci Technol. 2007;29(suppl 1):39–48.
- Roche KM, Hart K, Sangalli B, et al. Kratom:a case of legal high. Clin Toxicol. 2008;46(7):598.
- Nelsen JL, Lapoint J, Hodgman MJ, et al. Seizure and coma following kratom (mitragynina speciosa korth) exposure. J Med Toxicol. 2010;6(4):424–426. PubMed CrossRef NLM
- Hillebrand J, Olszewski D, Sedefov R. Legal highs on the Internet. Subst Use Misuse. 2010;45(3):330–340. PubMed CrossRef NLM
- Jansen KL, Prast CJ. Ethnopharmacology of kratom and the Mitragyna alkaloids. J Ethnopharmacol. 1988;23(1):115–119. PubMed CrossRef NLM
- Hassan Z, Muzaimi M, Navaratnam V, et al. From Kratom to mitragynine and its derivatives: physiological and behavioural effects related to use, abuse, and addiction. Neurosci Biobehav Rev. 2013;37(2):138–151. PubMed CrossRef NLM
- Hassan Z, Bosch OG, Singh D, et al. Novel psychoactive substances-recent progress on neuropharmacological mechanisms of action for selected drugs. Front Psychiatry. 2017;8:152. PubMed CrossRef NLM
- Kong WM, Chik Z, Ramachandra M, et al. Evaluation of the effects of mitragyna speciosa alkaloid extract on cytochrome P450 enzymes using a high throughput assay. Molecules. 2011;16(9):7344–7356. PubMed CrossRef NLM
- Porrogi P, Kóbori L, Kõhalmy K, et al. Limited applicability of 7-methoxy-4-trifluoromethylcoumarin as a CYP2C9-selective substrate. Pharmacol Rep. 2008;60(6):972–979. PubMed NLM
- Kikura-Hanajiri HR, Kawamura M, Maruyama T, et al. Simultaneous analysis of mitragynine, 7-hydroxylmitragynine and other alkaloids in the psychotropic plant “kratom” (mitragyna speciosa) by LC-ESI-MS. Forensic Toxicol. 2009;27:67–74. CrossRef
- Kratom. Drugs.com. Updated May 4, 2020. Accessed July 4, 2020. https://www.drugs.com/illicit/kratom.html
- NIH US National Library of Medicine. ClinicalTrials.gov. Accessed July 3, 2020. https://clinicaltrials.gov/ct2/results?cond=kratom&term=&cntry=&state=&city=&dist=
- Kruegel AC, Grundmann O. The medicinal chemistry and neuropharmacology of kratom: a preliminary discussion of a promising medicinal plant and analysis of its potential for abuse. Neuropharmacology. 2018;134(Pt A):108–120. PubMed CrossRef NLM
- Váradi A, Marrone GF, Palmer TC, et al. Mitragynine/corynantheidine pseudoindoxyls as opioid analgesics with mu agonism and delta antagonism, which do not recruit b-arrestin-2. J Med Chem. 2016;59(18):8381–8397. PubMed CrossRef NLM
- Daly J. FDA Declares Kratom an Opioid. TheScientist. Published February 7, 2018. Accessed July 4, 2020. https://www.the-scientist.com/news-analysis/fda-declares-kratom-an-opioid-were-here-to-explain-what-it-does-30306
- 2017 NSDUH Annual National Report. Substance Abuse and Mental Health Services Administration. Updated September 14, 2018. Accessed July 5, 2020. https://www.samhsa.gov/data/report/2017-nsduh-annual-national-report
- Vivolo-Kantor AM, Seth P, Gladden RM, et al. Vital Signs: trends in emergency department visits for suspected opioid overdoses—United States, July 2016–September 2017. MMWR Morb Mortal Wkly Rep. 2018;67(9):279–285. PubMed CrossRef NLM
- Speciosa.org. Mississippi steps back from regulating or outlawing kratom. Botanical Education Alliance website. Accessed July 5, 2020. https://speciosa.org/category/activism/botanical-education-alliance/
- The Authoritative Source For all Things Kratom. Kratom Science. Accessed July 5, 2020. https://www.kratomscience.com/
- Arndt T, Claussen U, Güssregen B, et al. Kratom alkaloids and O-desmethyltramadol in urine of a “Krypton” herbal mixture consumer. Forensic Sci Int. 2011;208(1–3):47–52. PubMed CrossRef NLM
- Khazaeli A, Jerry JM, Vazirian M. Treatment of withdrawal and addiction with buprenorphrine. J Addict Med. 2018;12(6):493–495. PubMed CrossRef NLM
- How to Treat Kratom Abuse and Withdrawal. American Addiction Centers. Updated November 13, 2019. Accessed July 5, 2020. https://americanaddictioncenters.org/kratom
- Kratom drug profile. European Monitoring Centre for Drugs and Drug Addiction. Accessed July 5, 2020. http://www.emcdda.europa.eu/publications/drug-profiles/kratom
- Kratom. United States Drug Enforcement Administration. Accessed July 6, 2020. https://www.dea.gov/factsheets/kratom
- FDA and Kratom. US Food & Drug Administration. Updated September 11, 2019. Accessed July 6, 2020. https://www.fda.gov/news-events/public-health-focus/fda-and-kratom
- Galbis-Reig D. A case report of kratom addiction and withdrawal. WMJ. 2016;115(1):49–52, quiz 53. PubMed NLM
- Sheleg SV, Collins GB. A coincidence of addiction to “Kratom” and severe primary hypothyroidism. J Addict Med. 2011;5(4):300–301. PubMed CrossRef NLM
- Swetliz I. HHS recommends that DEA makes kratom a schedule 1 drug, like LSD or heroin. STAT. Published November 9, 2018. Accessed July 6, 2020. https://www.statnews.com/2018/11/09/hhs-recommended-dea-ban-kratom-documents-show/
- Momentum Gains KCPA. in Mississippi and Oklahoma. American Kratom Association. Updated March 2, 2020. Accessed July 6, 2020. https://www.americankratom.org/advocacy/update/kcpa-momentum-gains-in-mississippi-and-oklahoma.html
Members enjoy free PDF downloads on all articles.
Save
Cite
Already a member? Login
Advertisement
GAM ID: sidebar-top