Kratom

Common Names

  • Kratom; Cratom
  • Ketum; Kakuam
  • Biak
  • Mitragyne; Mitragyna; Mitragynine
  • Thang; Thom

For Patients & Caregivers

Kratom is an herbal supplement that has properties similar to other opioids. It is not recommended as a treatment for pain at this time due to lack of research, harmful side effects, and product contamination.

Kratom is an herbal supplement known to have both stimulant and calming effects. It may also have pain-relieving properties similar to opioids. However, kratom cannot be used as a substitution for prescription pain medications, because studies on its safety or usefulness in humans have not been conducted. Its use is banned in some countries and US states due to potential for abuse. Moreover, some kratom products were recalled due to contamination.

In general there are very limited data on effects in humans for all uses. More research is needed to determine the safety and effectiveness of this herbal supplement.

Anxiety
Although animal studies suggest kratom may relieve anxiety, it may also cause anxiety in humans during withdrawal.

Insomnia
Kratom appears to have sedative effects at higher doses.

Pain relief
Kratom appears to have pain-relieving effects at higher doses.

Stimulant
Lower doses of kratom have been traditionally used for its stimulating effects. It may also cause appetite suppression.

  • The FDA recently recalled powdered kratom supplements for salmonella contamination and issued a public health advisory against kratom. It also issued warnings of addiction and overdose risks similar to that of other opioids.
  • The Drug Enforcement Administration includes kratom on its Drugs of Concern list. These substances are not currently regulated by the Controlled Substances Act, but pose risks to persons who abuse them. In addition, the National Institute of Drug Abuse identified kratom as an emerging drug of abuse.
  • You have heart problems: Laboratory studies and case reports suggest kratom could worsen heart problems.
  • You are taking CYP450 or UGT substrate drugs: Kratom may affect the clearance of these drugs.

Withdrawal symptoms: Flu-like symptoms such as nausea, vomiting, chills, sweats, muscle spasms and pain, decreased appetite, or diarrhea; anxiety, irritability, depressed mood, hot flashes, sleeping difficulty. Symptoms are more likely with heavier use.

Case reports

  • Addiction and severe opioid-like withdrawal: In a middle-aged woman who had to be medically treated.
  • Overdose and withdrawal: In a young man with no evidence of other drug use.
  • Liver damage: From prolonged kratom use.
  • Heart attack: In a 26-year-old man; considered to be caused by kratom as no other cause was identified.
  • Other fatalities/cardiotoxicities: Involving kratom and mitragynine.
  • Deaths: Associated with kratom-containing products or use of multiple drugs in which kratom may have contributed. However, conclusions about which specific drugs caused the deaths could not be determined.
  • Several countries and US states have banned kratom.
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For Healthcare Professionals

Mitragyna speciosa

Mitragyna speciosa, commonly known as kratom, is indigenous to Southeast Asia. The leaves have been used in traditional medicine to treat pain, fatigue, fever, diarrhea, and wounds (1), while its extracts are known for their psychoactive properties, especially morphine-like effects (2). Kratom has gained popularity as a supplement to improve mood, and decrease anxiety and pain. It has also been a source of significant controversy. The FDA has issued numerous statements against kratom, citing adverse events, potentially related deaths, risk of addiction or overdose, and incidences of contaminated supplements (3) (4) (5).

Kratom has both stimulant and sedative properties (6). The main psychoactive constituents are mitragynine and 7-hydroxymitragynine (7). In vivo studies of derivative compounds and analogs from kratom demonstrate antinociceptive effects (8). Animal models suggest that kratom has muscle relaxant (9), anti-inflammatory (10), analgesic (11), and anorectic (12) properties. Mitragynine has also shown antioxidant and antiproliferative effects in a few cancer cell lines (13).

Data on the use and safety of kratom in humans are very limited. Stimulant effects occur at lower doses, while sedative and pain-relieving effects occur at higher doses (14). Kratom users may develop physiological dependence and experience withdrawal (15), but this risk has not yet been adequately quantified (16). More research on the therapeutic uses for kratom and its constituents, as well as its toxic effects and abuse potential is needed.

The biological activities of kratom in humans are still poorly characterized (17). Because of its potential interactions with other drugs (18) (19) and possible side effects (20), kratom should not be used as a substitution for prescription pain medications. Several countries and US states have banned the use of kratom due to its potential for abuse (21) (22).

  • Anxiety
  • Insomnia
  • Pain relief
  • Stimulant

The main active alkaloids in kratom are mitragynine and 7-hydroxymitragynine (7-HMG), which is thought to have analgesic effects comparable to morphine (11) (23). Through monoaminergic and opioid receptors, both compounds produce a range of CNS stimulant and depressant effects (23) (24) (25).

Although structurally different (26), mitragynine administration causes cognitive impairment and addiction profiles that closely resemble those of morphine (27). Other research also suggests these compounds share classic opioid characteristics—affinity for opioid receptors, analgesic cross-tolerance, and competitive interaction with naloxone–while possessing other novel attributes (28).

In animal models, anxiolytic-like effects are attributed to opioidergic, GABAergic, and dopaminergic interactions in brain regions (29). Mitragynine may also obstruct neuronal calcium channels (30).

  • The FDA recently recalled powdered kratom supplements for salmonella contamination (5) and issued a public health advisory against kratom (3), with warnings of addiction and overdose risks similar to that of other opioids (4).
  • The Drug Enforcement Administration includes kratom on its Drugs of Concern list. These substances are not currently regulated by the Controlled Substances Act, but pose risks to persons who abuse them. In addition, the National Institute of Drug Abuse identified kratom as an emerging drug of abuse (31).
  • Herbal mixtures that contain synthetic compounds and kratom have been linked to multiple deaths (32) (33).
  • Patients with tachycardia should avoid using kratom as laboratory studies suggest the potential for cardiotoxicity or exacerbation of Torsade de Pointes (34).

Withdrawal symptoms: Flu-like symptoms such as nausea, vomiting, chills, sweats, muscle spasms and pain, decreased appetite, or diarrhea; anxiety, irritability, depressed mood, hot flashes, sleeping difficulty; symptoms are more likely with heavier use (15) (16) (35).

Case reports
Addiction and severe opioid-like withdrawal syndrome: In a 37-year-old woman that was treated with clonidine and hydroxyzine (36).
Overdose and withdrawal: In a young man with negative toxicology screens (14).
Liver damage: From prolonged kratom use (37).
Cardiorespiratory arrest: In a 26-year-old man and considered a direct result of kratom ingestion in the absence of other identified causes (38).
Other fatalities/cardiotoxicities: Involving kratom and mitragynine (34) .
Deaths: Associated with the use of kratom-containing products or polydrug use in which kratom was suspected to have possibly contributed (3) (39) (40) (33) (41) (31). The multi-drug circumstances confound conclusive interpretation (42).

  • Cytochrome P450 (CYP 450) substrates: Increased clearance of drugs metabolized by CYP450s (18) (19) . Kratom may also inhibit CYP2D6 (43), and induce CYP1A2 (44).
  • UGT (Uridine 5’-diphospho-glucuronosyltransferase) substrates: Increased clearance of drugs metabolized by UGT1A6 with kratom use (18).

  1. 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. Feb 2013;37(2):138-151.

  2. Sabetghadam A, Ramanathan S, Sasidharan S, et al. Subchronic exposure to mitragynine, the principal alkaloid of Mitragyna speciosa, in rats. J Ethnopharmacol. Apr 19 2013;146(3):815-823.

  3. U.S. Food and Drug Administration. FDA orders mandatory recall for kratom products due to risk of salmonella. April 3, 2018.

  4. Fluyau D, Revadigar N. Biochemical Benefits, Diagnosis, and Clinical Risks Evaluation of Kratom. Front Psychiatry. 2017;8:62.

  5. Griffin OH, 3rd, Daniels JA, Gardner EA. Do You Get What You Paid For? An Examination of Products Advertised as Kratom. J Psychoactive Drugs. Nov-Dec 2016;48(5):330-335.

  6. Chittrakarn S, Keawpradub N, Sawangjaroen K, et al. The neuromuscular blockade produced by pure alkaloid, mitragynine and methanol extract of kratom leaves (Mitragyna speciosa Korth.). J Ethnopharmacol. Jun 16 2010;129(3):344-349.

  7. Shaik Mossadeq WM, Sulaiman MR, Tengku Mohamad TA, et al. Anti-inflammatory and antinociceptive effects of Mitragyna speciosa Korth methanolic extract. Med Princ Pract. 2009;18(5):378-384.

  8. Goh TB, Koh RY, Mordi MN, et al. Antioxidant value and antiproliferative efficacy of mitragynine and a silane reduced analogue. Asian Pac J Cancer Prev. 2014;15(14):5659-5665.

  9. Diep J, Chin DT, Gupta S, et al. Kratom, an Emerging Drug of Abuse: A Case Report of Overdose and Management of Withdrawal. A A Case Rep. Oct 26 2017.

  10. Singh D, Muller CP, Vicknasingam BK. Kratom (Mitragyna speciosa) dependence, withdrawal symptoms and craving in regular users. Drug Alcohol Depend. Jun 1 2014;139:132-137.

  11. Swogger MT, Walsh Z. Kratom use and mental health: A systematic review. Drug Alcohol Depend. Feb 1 2018;183:134-140.

  12. Maurer HH. Chemistry, pharmacology, and metabolism of emerging drugs of abuse. Ther Drug Monit. Oct 2010;32(5):544-549.

  13. Lydecker AG, Sharma A, McCurdy CR, et al. Suspected Adulteration of Commercial Kratom Products with 7-Hydroxymitragynine. J Med Toxicol. Dec 2016;12(4):341-349.

  14. 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). Feb 2018;235(2):573-589.

  15. 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.

  16. Warner ML, Kaufman NC, Grundmann O. The pharmacology and toxicology of kratom: from traditional herb to drug of abuse. Int J Legal Med. Jan 2016;130(1):127-138.

  17. Rech MA, Donahey E, Cappiello Dziedzic JM, et al. New drugs of abuse. Pharmacotherapy. Feb 2015;35(2):189-197.

  18. Suhaimi FW, Yusoff NH, Hassan R, et al. Neurobiology of Kratom and its main alkaloid mitragynine. Brain Res Bull. Sep 2016;126(Pt 1):29-40.

  19. Prozialeck WC, Jivan JK, Andurkar SV. Pharmacology of kratom: an emerging botanical agent with stimulant, analgesic and opioid-like effects. J Am Osteopath Assoc. Dec 2012;112(12):792-799.

  20. Yusoff NH, Suhaimi FW, Vadivelu RK, et al. Abuse potential and adverse cognitive effects of mitragynine (kratom). Addict Biol. Jan 2016;21(1):98-110.

  21. Raffa RB, Beckett JR, Brahmbhatt VN, et al. Orally active opioid compounds from a non-poppy source. J Med Chem. Jun 27 2013;56(12):4840-4848.

  22. Hazim AI, Ramanathan S, Parthasarathy S, et al. Anxiolytic-like effects of mitragynine in the open-field and elevated plus-maze tests in rats. J Physiol Sci. May 2014;64(3):161-169.

  23. European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Kratom (Mitragyna speciosa) drug profile. January 2015.

  24. 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. Jul 29 2016;65(29):748-749.

  25. Arndt T, Claussen U, Gussregen B, et al. Kratom alkaloids and O-desmethyltramadol in urine of a “Krypton” herbal mixture consumer. Forensic Sci Int. May 20 2011;208(1-3):47-52.

  26. Kronstrand R, Roman M, Thelander G, et al. Unintentional fatal intoxications with mitragynine and O-desmethyltramadol from the herbal blend Krypton. J Anal Toxicol. May 2011;35(4):242-247.

  27. Grundmann O. Patterns of Kratom use and health impact in the US-Results from an online survey. Drug Alcohol Depend. Jul 1 2017;176:63-70.

  28. Galbis-Reig D. A Case Report of Kratom Addiction and Withdrawal. WMJ. Feb 2016;115(1):49-52; quiz 53.

  29. Dorman C, Wong M, Khan A. Cholestatic hepatitis from prolonged kratom use: A case report. Hepatology. Nov 22 2014.

  30. Aggarwal G, Robertson E, McKinlay J, et al. Death from Kratom toxicity and the possible role of intralipid. J Intensive Care Soc. Feb 2018;19(1):61-63.

  31. Neerman MF, Frost RE, Deking J. A drug fatality involving Kratom. J Forensic Sci. Jan 2013;58 Suppl 1:S278-279.

  32. Holler JM, Vorce SP, McDonough-Bender PC, et al. A drug toxicity death involving propylhexedrine and mitragynine. J Anal Toxicol. Jan 2011;35(1):54-59.

  33. Karinen R, Fosen JT, Rogde S, et al. An accidental poisoning with mitragynine. Forensic Sci Int. Oct 24 2014;245c:e29-e32.

  34. Domingo O, Roider G, Stover A, et al. Mitragynine concentrations in two fatalities. Forensic Sci Int. Feb 2017;271:e1-e7.

  35. Hanapi NA, Ismail S, Mansor SM. Inhibitory effect of mitragynine on human cytochrome P450 enzyme activities. Pharmacognosy Res. Oct 2013;5(4):241-246.

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