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Presented by: UT El Paso / Austin Cooperative Pharmacy Program & Paso del Norte Health Foundation

Kratom


Compilation by Armando Gonzalez Stuart, PhD.
Kratom

Scientific Name:

Mitragyna speciosa

Botanical Family:

Rubiaceae

Other Common Name:

Biak-biak, giam, gra-tom, kadamba. ketum, akuam, kraton, ithang, lugub, thom, mambog, puri (Pantano et al, 2016; Quattrocchi, 2012).

Common names in Spanish:

Unknown.

Where is it found?

Kratom is a medium-sized tree that is native to Southeast Asia (Mabberley, 2008; Ratsch, 2005), but related species (M. ciliata, M. stipulosa, and M. inermis, for example) can be found in tropical Africa as well (Iwu, 2014; Assi and Guinko, 1991).

Parts of the plant used:

Principally the leaves.

How is it used?

The leaves are steeped in hot water to make a tea (with honey or other sweeteners in order to reduce its bitter taste), as well as heated and pounded to be applied externally as poultices, or pulverized and taken as capsules. The leaves are smoked and can also be chewed fresh or dried. Some botanical supplements may contain kratom alone or in combination with other plants (Pantano et al., 2016; Quattrocchi, 2012; Ratsch, 2005).

What is it used for?

The leaves contain various active ingredients (mainly alkaloids) that are hallucinogenic, and can cause psychosis, stimulation (euphoria), and sedation as well. Additionally, the phytochemicals contained in the plant have analgesic, astringent, stimulant, and tonic actions. The plant has been popularly used as a substitute for opium, but has been banned in various countries across the globe due to the potentially addictive nature of some of its components (Anwar, 2016; Pantano, 2016). Kratom contains chemical substances that posses opioid (analgesic or sedative) effects. Additionally, this species contains two psychoactive chemicals, which have both stimulant (mitragynine) as well as sedating or narcotic (7-hydroxymitragynine) effects (Griffin, 2016; Ratsch, 2011).

Studies by Váradi et al. (2016), suggest that the chemical compounds and their analogs contained in kratom could potentially be a promising new generation of novel pain relievers. Until the discovery of kratom’s chemical constituents, opioid compounds were thought to be found only in the opium poppy (Papaver somniferum - Papaveaceae. However, some sources mention that kratom use could potentially be more dangerous than that of opium (Ismail et al., 2017; Mabberley, 2017).

Kratom preparations are also used in Asia as local anesthetics, as well as to treat various health problems such as hypertension, diabetes, dysentery, gastrointestinal parasites, and stomachaches. The leaves are also applied externally as poultices, alone to treat wounds or in combination with other medicinal plants for splenomegaly (abnormal enlargement of the spleen). Natives in various Asian countries consume the leaves for their stimulant ability, as well as to combat fatigue and as a substitute for opium. The plant chemicals exert a morphine-like effect at high doses (Pantano et al., 2016; Ismail et al., 2017).

Kratom’s main alkaloids, mitragynine and 7-hydroxymitragynine, modulate opioid receptors, and exert their effects as partial agonists at mu-opioid receptors and competitive antagonists at kappa- and delta-opioid receptors. These phytochemicals also seem to exert diverse activities at other brain receptors, including adrenergic, serotonergic, and dopaminergic receptors, for example. This could provide an explanation for the complex pharmacological profile of the plant’s raw extracts (Krugel and Grundmann, 2017).

Very high doses of mitragynine were found in two people who died after ingesting a product containing kratom, although the cause of death was not due primarily to this compound in either case (Domingo et al., 2017).

Kratom has also been used as a treatment against opium addiction (Wiart, 2002; Ismail et al., 2017). Products made from this plant are used in Thailand and Malaysia to treat various health problems, including intestinal worms, cough, diabetes, hypertension, chronic musculoskeletal pain, and gastroenteritis. The leaves are also used for their antipyretic (fever reducing), anti-inflammatory, and analgesic effects. Even though the plant has been proven to possess important medicinal applications, the irresponsible “recreational” use of kratom, alone or in combination with other substances (including caffeine, alcohol, and certain pharmaceutical drugs), has spread to various countries around the world, including the United States (Anwar et al., 2016).

Reports from Thailand mention that a combination (“cocktail”) of kratom with various other chemical substances, including certain pharmaceuticals, has caused various deaths. Additionally, in Sweden, a product purportedly containing kratom as well as caffeine, and a pharmaceutical analgesic (O-desmethyltramadol), caused the death of nine people (Pantano et al., 2016). Various kratom products advertised on the internet purportedly contain some of its main active ingredients (Griffin et al., 2016).

Anwar et al. (2016) evaluated the calls made to U.S. poison centers related to exposure to kratom in a five-year period (from 2010 to 2015). There was a tenfold increase in the number of calls (from 26 in 2010 to 263 in 2015). Approximately 90.2% (595) of the people who called stated they had ingested the plant. Within these calls, some reported using kratom combined with other substances (multiple exposures). The other substances commonly reported included ethanol (alcohol), other plants, benzodiazepinic drugs, narcotics, and acetaminophen (paracetamol).

A 23-year-old male was admitted to a hospital’s emergency room complaining that for the past 4 days, he had painless jaundice, light stools, and dark urine. This was 7 days after his last ingestion of a kratom product. This case is another example of the plant’s potential toxicity to the liver. Some people employ kratom as a psychostimulant since its use is currently legal in various countries (Drago et al., 2017).
A case of acute hepatitis in a 31-year-old male caused by the ingestion of a kratom herbal tea was successfully treated with N-acetylcysteine (Mousa et al., 2017).

Fluyau and Rivadigar (2017) mention that the plant’s bioactive ingredients show certain benefits such as stimulant and sedative actions and also antinociceptive (pain relieving) effects. The compounds contained in kratom apparently inhibit pro-inflammatory mediator release and vascular permeability and may stimulate the immune system. Additionally, the plant possesses antidepressant and anorectic actions. Despite certain beneficent effects, kratom may also have a negative side, causing arrhythmias, seizures, memory impairment, hepatic cholestasis, coma, and, in certain cases, death. Kratom use can also elicit diverse and contradictory psychological manifestations ranging form euphoria and feeling relaxed to manifestation of serious symptoms including psychosis, hostility, and aggressive behavior.

A 22-year old male presented with severe headache, disorientation, and aphasia after ingesting Adderall and a product containing kratom. The patient’s initial blood pressure was high but returned to normal after his admission to the hospital. This case scenario suggests that ingesting products containing kratom could cause posterior reversible encephalopathy syndrome. This should be taken into account when patients are admitted to hospital emergency centers presenting symptoms such as cephaleas (headaches), confusion, and visual disturbances (Castillo et al., 2017).

A study undertaken by Lydecker et al. (2016) found multiple packaged commercial Kratom products that likely contained artificially elevated concentrations of 7-hydroxymitragynine. This alkaloid is the plant’s main bioactive ingredient associated with some of the deleterious side effects on users. Since the quality control of various herbal products in many countries is less than optimal, the authors of the study emphasized the great importance of increased dietary supplement oversight of herbal supplements containing kratom.

Safety / Precautions

  • The irresponsible use of kratom can lead to severe adverse health effects, especially when the plant is consumed along with alcohol and / or other drugs for “recreational purposes” (Anwar et al., 2016; Drago, et al., 2017).
  • The Drug Enforcement Agency (DEA) announced on August 30, 2016 its intention to classify kratom as a Schedule I drug (a dangerous substance with no known medical properties). However, on October 12 of the same year, the DEA withdrew its intent owing to a public and congressional groundswell in support of kratom (Griffith and Webb, 2017).
  • In its Drugs of Abuse publication, the DEA lists Kratom as a “drug of concern” (DEA, 2017).
  • Various researchers mention that due to the increasing concern in various countries regarding the plant’s abuse potential, it is necessary to undertake a judicious assessment of its possible benefits and hazards (Warner et al., 2016; Brown et al., 2017).
  • According to Fluyau and Rivadigar (2017) kratom’s potential side effects offset its benefits, since it can cause serious physiological and psychological health hazards that could potentially be fatal.
  • Fatal intoxications usually do not involve ingesting kratom alone, but in combination with various other products, including certain adulterants and medications (Anwar et al., 2016; Lydecker et al., 2016; Domingo et al., 2017; Kruegel and Grundemann, 2017).
  • Before you decide to take any medicinal herb or herbal supplement, be sure to consult with a health care professional first. Avoid self-medication and self-diagnosis: Always be on the safe side!

References:

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. DOI: http://dx.doi.org/10.15585/mmwr.mm6529a4.

Assi LA, Guinko S. Plants used in traditional medicine in West Africa. Basel, Switzerland: Editiones Roche; 1991; pp. 116-117.

Brown PN, Lund JA, Murch SJ. A botanical, phytochemical and ethnomedicinal review of the genus Mitragyna korth: Implications for products sold as kratom. J Ethnopharmacol. 2017; 202:302-325. doi: 10.1016/j.jep.2017.03.020.

Castillo A, Payne JD, Nugent K. Posterior reversible leukoencephalopathy syndrome after kratom ingestion. Proceedings (Baylor University Medical Center). 2017; 30(3):355-357.

Domingo O, Roider G, Stöver A, Graw M, Musshoff F, Sachs H, Bicker W. Mitragynine concentrations in two fatalities. Forensic Sci Int. 2017;271:e1-e7. doi: 10.1016/j.forsciint.2016.12.020.

Drago JZ, Lane B, Kochav J, Chabner B. The Harm in Kratom. Oncologist. 2017 Jul 24. pii: theoncologist.2017-0279. doi: 10.1634/theoncologist. 2017-0279.

Drug Enforcement Administration (DEA). DEA Announces Intent to Schedule Kratom. https://www.dea.gov/divisions/hq/2016/hq083016.shtml. Retrieved October 11, 2016.

Drug Enforcement Administration (DEA). Drugs of Abuse. https://www.dea.gov/pr/multimedia-library/publications/drug_of_abuse.pdf Accessed November 16, 2017.

Fluyau D, Revadigar N. Biochemical Benefits, Diagnosis, and Clinical Risks Evaluation of Kratom. Front Psychiatry. 2017; 8:62. doi: 10.3389/fpsyt.2017.00062.

Griffin OH, Daniels JA, Gardner EA. Do You Get What You Paid For? An Examination of Products Advertised as Kratom. J Psychoactive Drugs. 2016, 26:1-6.

Griffin OH, Webb ME. The Scheduling of Kratom and Selective Use of Data. J Psychoactive Drugs. 2017; 22:1-7. doi: 10.1080/02791072.2017.1371363.]

Ismail I, Wahab S, Sidi H, Das S, Lin LJ, Razali R. Kratom and Future Treatment for the Opioids Addiction and Chronic Pain: Periculo Beneficium? Curr Drug Targets. 2017 Apr 25. doi: 10.2174/1389450118666170425154120.

Iwu M. Handbook of African Medicinal Plants 2nd ed. Boca Raton, FL: CRC Press; 2014; pp. 257-258.

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. 2017 Aug 19. pii: S0028-3908(17)30393-3. doi: 10.1016/j.neuropharm.2017.08.026.

Lydecker AG, Sharma A, McCurdy CR, Avery BA, Babu KM, Boyer EW. Suspected Adulteration of Commercial Kratom Products with 7-Hydroxymitragynine. J Med Toxicol. 2016 ;12(4):341-349.

Mabberley D J. Mabberley’s Plant Book 4th ed. London: Cambridge University Press; 2017; p. 592 .

Mousa MS, Sephien A, Gutierrez J, OʼLeary C. N-Acetylcysteine for Acute Hepatitis Induced by Kratom Herbal Tea. Am J Ther. 2017 Jul 6. doi: 10.1097/MJT.0000000000000631.

Pantano F, Tittarelli R, Mannocchi G, Zaami S, Ricci S5, Giorgetti R, Terranova D, Busardò FP, Marinelli E. Hepatotoxicity Induced by "the 3Ks": Kava, Kratom and Khat. Int J Mol Sci. 2016 ;17(4):580. doi: 10.3390/ijms17040580.

Quattrocchi U. World Dictionary of Medicinal and Poisonous Plants (Vol. 4). Boca Raton, FL: CRC Press; 2012; p. 172.

Ratsch C. Encyclopedia of Psychoactive Plants. Rochester, VT: Park Street Press; 2005; pp. 366-368.

Váradi A, Marrone GF, Palmer TC, Narayan A, Szabó MR, Le Rouzic V, Grinnell SG, Subrath JJ, Warner E, Kalra S, Hunkele A, Pagirsky J, Eans SO, Medina JM, Xu J, Pan YX, Borics A, Pasternak GW, McLaughlin JP, Majumdar S. Mitragynine/Corynantheidine Pseudoindoxyls As Opioid Analgesics with Mu Agonism and Delta Antagonism, Which Do Not Recruit β-Arrestin-2. J Med Chem. 2016; 59(18):8381-97. doi: 10.1021/acs.jmedchem.6b00748.

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
Wiart C. Medicinal Plants of Southeast Asia 2nd ed. Selangor, Malaysia: Prentice Hall; 2002; pp. 285-286.