Kratom Research Analysis

Q: How is kratom regulated?

Oftentimes there is no guarantee of the quality, potency, and claims of kratom products on the market. For the most part, kratom products are not monitored by regulatory bodies, partly because kratom is not considered a supplement, a food, or a drug in the regulatory definitions of many countries. Thailand initially banned the use of kratom because of its addictive properties. Recently, kratom was removed from Thailand’s illegal substances list but still remains highly regulated.[9] Although it is still illegal to use kratom in Malaysia, its use remains high because the plant is geographically native.[10] The Drug Enforcement Administration (DEA) in the U.S. intended to classify kratom and its ingredients mitragynine and 7-hydroxymitragynine as schedule 1 controlled substances but withdrew this motion after opposition. The U.S. Food and Drug Administration (FDA) has issued numerous public warnings about kratom’s effects and also about the risk of contamination and adulteration of kratom products. These factors make for unfavorable conditions under which to conduct clinical research and to consistently regulate the quality of kratom products.[11][12] Potential quality concerns related to kratom products include contamination with toxins such as lead, adulteration with drugs, and inaccurate statements about product potency and effects.[13][14][15] It is important to be aware of these quality concerns when trying a kratom product.

Q: What’s the difference between kratom powder and kratom extract?

Generally, an equal weight of kratom extract contains more active ingredients and is more potent than kratom powder. Kratom powder usually refers to dried powdered leaves, whereas kratom extract is an end product of processing kratom leaves with a solvent to make a higher yield of active ingredients (such as mitragynine). The extract potency can vary greatly depending on the extraction solvent and process. For example, in a laboratory study, 600 mg of powdered kratom leaves extracted with water, ethanol, and methanol yielded approximately 60 mg of extract containing mitragynine at concentrations of 3.9 mg/g, 58.8 mg/g, and 35.9 mg/g, respectively.[21]

Q: Does kratom help manage opioid dependence?

In short, we don’t know. There is no human clinical research assessing the use of kratom for managing symptoms of opioid dependence and withdrawal. However, in a cross-sectional survey study in 136 chronic kratom users living in Malaysia, users reported taking an average of 3 glasses of kratom tea daily to reduce opioid intake and to manage withdrawal symptoms.[16] There are also some promising preclinical studies of kratom use in mice with opioid dependence.[19]

Q: How was kratom used traditionally?

In Southeast Asian countries such as Thailand and Malaysia, kratom has been traditionally used for centuries for conditions such as fever, cough, diarrhea, diabetes, hypertension, pain and also for opioid and alcohol withdrawal. It has also been used to increase energy and to increase sexual desire. Although regulatory authorities have been restraining kratom use in Thailand and Malaysia, it remains widely used, especially in rural areas.[3][20]

Q: Does kratom work for pain?

Informal surveys suggest that kratom is commonly used in the Western countries for pain relief, but research in humans is very limited.[22] To date, one randomized clinical trial in 26 male chronic Kratom users living in Malaysia showed that drinking a kratom tea decoction increases pain tolerance one hour after ingestion compared to drinking a placebo. Increased pain tolerance was measured because participants who ingested a kratom drink were able to keep their hand in an ice-cold bath for about 10 seconds longer compared to those who consumed a placebo.[23] However, there is animal research showing that kratom and its main ingredient mitragynine can reduce acute and chronic pain. At least 23 studies in animals (mice, rats, or dogs) suggest that kratom extract and its ingredient mitragynine have therapeutic effects in alleviating experimentally induced acute pain (via thermal or mechanical stimulus), and at least two animal studies suggest that it is beneficial for chronic neuropathic pain.[22]

Q: Does kratom cause liver toxicity?

There is emerging evidence of kratom (tea, powder, tablets) ingestion leading to liver toxicity and injury in rare cases. Kratom-induced liver injury is usually cholestatic (notable reduced/stopped bile flow) or mixed – a combination of cholestatic and hepatocellular (notable death and inflammation of liver cells). People often recover from this liver injury after stopping kratom use and receiving emergency supportive treatment. Corticosteroids, sometimes in combination with N-acetylcysteine (which is also used to treat other drug-induced liver toxicities), have been given for kratom-induced hepatotoxicity, but there is no evidence that these agents actually improve recovery. In previous cases, it took anywhere from 1 to 8 weeks for symptoms of liver injury to start showing (e.g. fatigue, nausea, itching, dark urine, jaundice).[7] In a more recent case series of 11 people (mostly male, ages 25–70), severe liver injury symptoms that required hospitalization started showing after 5 to 28 days of kratom use. In 3 of those 11 cases, the kratom product was available for analysis and was found to contain 0.8–2.0 mg of mitragynine per gram.[8] LiverTox a website that provides information related to liver injury rates Kratom as a likely cause of clinically apparent liver injury, although cases are rare.[7] More research is needed to determine whether certain doses, usage patterns, concomitant substance use, or preexisting conditions predispose a person to developing liver toxicity with kratom.

Marina Shkayeva

Kratom

•Last Updated: February 28, 2023

Kratom is an evergreen tree native to Southeast Asia whose leaves contain chemicals with partial opioid effects. Although kratom leaves have been used traditionally for hundreds of years, research on its safety and efficacy is limited. Anecdotally, kratom is used for pain, opioid use disorder, anxiety, and other conditions. Kratom may lead to dependence and withdrawal and can cause serious adverse effects in high doses.

Dosage

Kratom is most often used for

:

Marina Shkayeva, PharmD

:

Shyam Jayaraman, MD

•

Morgan Pfiffner, MS

Last Updated:February 28, 2023

Dosage Information
Frequently asked questions
References

What is kratom?

Kratom is an evergreen tree native to Southeast Asia (Thailand, Indonesia, Malaysia, etc.), with dose-dependent sedating and stimulant effects. It is typically consumed as tea or powder. Although kratom leaves have been used traditionally for hundreds of years, research on its safety and efficacy is limited.^[2]

How is kratom regulated?

What’s the difference between kratom powder and kratom extract?

What are kratom’s main benefits?

Kratom is used for pain, opioid use disorder, anxiety, and other conditions. However, these uses have not been studied in clinical trials. Reportedly, at lower doses, kratom produces stimulant effects (increased alertness and energy), whereas at higher doses, kratom produces sedative and pain-relieving effects. The exact doses at which kratom causes these effects is not well researched.^[3]

Does kratom help manage opioid dependence?

How was kratom used traditionally?

Does kratom work for pain?

What are kratom’s main drawbacks

Nausea and constipation may occur after kratom ingestion, especially if taken in higher amounts and/or more frequently.^[4] High doses of kratom might also trigger rare serious adverse events such as hallucinations, tremor, seizure, coma, and respiratory depression. The active alkaloid in kratom (mitragynine) has been found in a number of postmortem analyses, in addition to other substances (e.g., fentanyl, heroin, benzodiazepines). Because of the presence of these other substances, it is unknown whether and how kratom contributed to the cause of death. Finally, chronic kratom use can lead to dependence and precipitate an opioid-like withdrawal, including symptoms of agitation, nausea, and vomiting.^[5]

Does kratom cause liver toxicity?

Can an individual get addicted to kratom?

How does kratom work?

Kratom contains over 40 different alkaloids, of which the main active alkaloids include mitragynine and 7-hydroxymitragynine, and the latter is the more potent form. These alkaloids act as partial agonists of the mu-opioid and delta-opioid receptors and are thought to be responsible for kratom’s pain relieving and sedating effects. These effects have been shown to be reversed with an opioid antagonist in animal models and in some clinical case studies where respiratory depression was the main symptom.^[6] Mitragynine has also been shown to interact with adrenergic, serotonergic and dopamine receptors, but the exact impact in humans is not yet known.^[3] ^[5]

What else is Kratom known as?

Note that Kratom is also known as:

Thang
Kakuam
Thom
Ketum
Biak
Mambog
ithang
thom (Thailand)
ithang (Thailand)
bai krathom (Thailand)
gratom (Thailand)
kakaum (Thailand)
kadamba (Indonesia)
purik (Indonesia)
keton (Indonesia)
ketum (Malaysia)
biak-biak (Malaysia)
sepat (Malaysia)
kutum (Malaysia)
mambog (Philippines)
lugug (Philippines)
polapupot (Philippines)

Kratom should not be confused with:

kratom acetate
mitragynine acetate
Krypton
other species of the Mitragyna genus

Dosage information

Because kratom has been studied in very few clinical trials, most of the information about how it is used comes from surveys and traditional use. Traditionally, kratom leaves are chewed and can also be boiled to make tea. In Western countries, kratom is usually available as a powder to be mixed with liquids and also in capsule form.^[1]

In a survey of 129 regular kratom users in the U.S., most consumed kratom daily, and most consumed 1-3 grams of kratom per dose. Some users consumed 4–6 grams per dose (33%). Of the 129 regular users, 37% consumed kratom as a beverage, 43.6% ingested raw kratom powder, and 18.9% took kratom capsules.^[1]

References

^Smith KE, Rogers JM, Dunn KE, Grundmann O, McCurdy CR, Schriefer D, Epstein DHSearching for a Signal: Self-Reported Kratom Dose-Effect Relationships Among a Sample of US Adults With Regular Kratom Use Histories.Front Pharmacol.(2022)
^Jentsch MJ, Pippin MMKratomStatPearls.(2022-08)
^Ahmad I, Prabowo WC, Arifuddin M, Fadraersada J, Indriyanti N, Herman H, Purwoko RY, Nainu F, Rahmadi A, Paramita S, Kuncoro H, Mita N, Narsa AC, Prasetya F, Ibrahim A, Rijai L, Alam G, Mun'im A, Dej-Adisai SSpecies as Pharmacological Agents: From Abuse to Promising Pharmaceutical Products.Life (Basel).(2022-Jan-27)
^Grundmann OPatterns of Kratom use and health impact in the US-Results from an online survey.Drug Alcohol Depend.(2017-Jul-01)
^WHO Expert Committee on Specifications for Pharmaceutical Preparations. Forty-fourth report
^Overbeek DL, Abraham J, Munzer BWKratom (Mitragynine) Ingestion Requiring Naloxone Reversal.Clin Pract Cases Emerg Med.(2019-Feb)
^KratomLiverTox: Clinical and Research Information on Drug-Induced Liver Injury.(2012-04)
^Ahmad J, Odin JA, Hayashi PH, Fontana RJ, Conjeevaram H, Avula B, Khan IA, Barnhart H, Vuppalanchi R, Navarro VJ,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-Jan-01)
^Charoenratana S, et alAttitudes towards Kratom use, decriminalization and the development of a community-based Kratom control mechanism in Southern Thailand.Int. J. Drug Policy.(2021-9)
^Khalil S, et alEnforcement status of the poison act 1952 against offenses related to kratom (Mitragyna speciosa korth) misuse in Malaysia.UUM Journal of Legal Studies.(2020-10)
^Grundmann O, Hendrickson RG, Greenberg MIKratom: History, pharmacology, current user trends, adverse health effects and potential benefits.Dis Mon.(2022-Jun-19)
^Prozialeck W, Fowler A, Edwards JPublic Health Implications and Possible Sources of Lead (Pb) as a Contaminant of Poorly Regulated Kratom Products in the United States.Toxics.(2022-Jul-19)
^Lydecker AG, Sharma A, McCurdy CR, Avery BA, Babu KM, Boyer EWSuspected Adulteration of Commercial Kratom Products with 7-Hydroxymitragynine.J Med Toxicol.(2016-Dec)
^Prozialeck WC, Edwards JR, Lamar PC, Plotkin BJ, Sigar IM, Grundmann O, Veltri CAEvaluation 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-Jul-30)
^Ng JY, Ans M, Marwaha AAssessing the quality of information provided on websites selling Kratom (Mitragyna speciosa) to consumers in Canada.Subst Abuse Treat Prev Policy.(2021-Mar-19)
^Vicknasingam B, Narayanan S, Beng GT, Mansor SMThe informal use of ketum (Mitragyna speciosa) for opioid withdrawal in the northern states of peninsular Malaysia and implications for drug substitution therapy.Int J Drug Policy.(2010-Jul)
^Singh D, Narayanan S, Müller CP, Swogger MT, Rahim AA, Leong Bin Abdullah MFI, Vicknasingam BKSeverity of Kratom (Mitragyna speciosa Korth.) Psychological Withdrawal Symptoms.J Psychoactive Drugs.(2018)
^Singh D, Müller CP, Vicknasingam BKKratom (Mitragyna speciosa) dependence, withdrawal symptoms and craving in regular users.Drug Alcohol Depend.(2014-Jun-01)
^Wilson LL, Harris HM, Eans SO, Brice-Tutt AC, Cirino TJ, Stacy HM, Simons CA, León F, Sharma A, Boyer EW, Avery BA, McLaughlin JP, McCurdy CRLyophilized Kratom Tea as a Therapeutic Option for Opioid Dependence.Drug Alcohol Depend.(2020-Nov-01)
^Rosenbaum CD, Carreiro SP, Babu KMHere 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-Mar)
^Limcharoen T, Pouyfung P, Ngamdokmai N, Prasopthum A, Ahmad AR, Wisdawati W, Prugsakij W, Warinhomhoun SInhibition of α-Glucosidase and Pancreatic Lipase Properties of (Korth.) Havil. (Kratom) Leaves.Nutrients.(2022-Sep-21)
^Prevete E, Kuypers KPC, Theunissen EL, Corazza O, Bersani G, Ramaekers JGA systematic review of (pre)clinical studies on the therapeutic potential and safety profile of kratom in humans.Hum Psychopharmacol.(2022-Jan)
^Vicknasingam B, Chooi WT, Rahim AA, Ramachandram D, Singh D, Ramanathan S, Yusof NSM, Zainal H, Murugaiyah V, Gueorguieva R, Mansor SM, Chawarski MCKratom and Pain Tolerance: A Randomized, Placebo-Controlled, Double-Blind Study.Yale J Biol Med.(2020-Jun)

Primary Use

Pain

[ref-1] ^Smith KE, Rogers JM, Dunn KE, Grundmann O, McCurdy CR, Schriefer D, Epstein DHSearching for a Signal: Self-Reported Kratom Dose-Effect Relationships Among a Sample of US Adults With Regular Kratom Use Histories.Front Pharmacol.(2022)

[ref-2] ^Jentsch MJ, Pippin MMKratomStatPearls.(2022-08)

[ref-3] ^Ahmad I, Prabowo WC, Arifuddin M, Fadraersada J, Indriyanti N, Herman H, Purwoko RY, Nainu F, Rahmadi A, Paramita S, Kuncoro H, Mita N, Narsa AC, Prasetya F, Ibrahim A, Rijai L, Alam G, Mun'im A, Dej-Adisai SSpecies as Pharmacological Agents: From Abuse to Promising Pharmaceutical Products.Life (Basel).(2022-Jan-27)

[ref-4] ^Grundmann OPatterns of Kratom use and health impact in the US-Results from an online survey.Drug Alcohol Depend.(2017-Jul-01)

[ref-5] ^WHO Expert Committee on Specifications for Pharmaceutical Preparations. Forty-fourth report

[ref-6] ^Overbeek DL, Abraham J, Munzer BWKratom (Mitragynine) Ingestion Requiring Naloxone Reversal.Clin Pract Cases Emerg Med.(2019-Feb)

[ref-7] ^KratomLiverTox: Clinical and Research Information on Drug-Induced Liver Injury.(2012-04)

[ref-8] ^Ahmad J, Odin JA, Hayashi PH, Fontana RJ, Conjeevaram H, Avula B, Khan IA, Barnhart H, Vuppalanchi R, Navarro VJ,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-Jan-01)

[ref-9] ^Charoenratana S, et alAttitudes towards Kratom use, decriminalization and the development of a community-based Kratom control mechanism in Southern Thailand.Int. J. Drug Policy.(2021-9)

[ref-10] ^Khalil S, et alEnforcement status of the poison act 1952 against offenses related to kratom (Mitragyna speciosa korth) misuse in Malaysia.UUM Journal of Legal Studies.(2020-10)

[ref-11] ^Grundmann O, Hendrickson RG, Greenberg MIKratom: History, pharmacology, current user trends, adverse health effects and potential benefits.Dis Mon.(2022-Jun-19)

[ref-12] ^Prozialeck W, Fowler A, Edwards JPublic Health Implications and Possible Sources of Lead (Pb) as a Contaminant of Poorly Regulated Kratom Products in the United States.Toxics.(2022-Jul-19)

[ref-13] ^Lydecker AG, Sharma A, McCurdy CR, Avery BA, Babu KM, Boyer EWSuspected Adulteration of Commercial Kratom Products with 7-Hydroxymitragynine.J Med Toxicol.(2016-Dec)

[ref-14] ^Prozialeck WC, Edwards JR, Lamar PC, Plotkin BJ, Sigar IM, Grundmann O, Veltri CAEvaluation 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-Jul-30)

[ref-15] ^Ng JY, Ans M, Marwaha AAssessing the quality of information provided on websites selling Kratom (Mitragyna speciosa) to consumers in Canada.Subst Abuse Treat Prev Policy.(2021-Mar-19)

[ref-16] ^Vicknasingam B, Narayanan S, Beng GT, Mansor SMThe informal use of ketum (Mitragyna speciosa) for opioid withdrawal in the northern states of peninsular Malaysia and implications for drug substitution therapy.Int J Drug Policy.(2010-Jul)

[ref-17] ^Singh D, Narayanan S, Müller CP, Swogger MT, Rahim AA, Leong Bin Abdullah MFI, Vicknasingam BKSeverity of Kratom (Mitragyna speciosa Korth.) Psychological Withdrawal Symptoms.J Psychoactive Drugs.(2018)

[ref-18] ^Singh D, Müller CP, Vicknasingam BKKratom (Mitragyna speciosa) dependence, withdrawal symptoms and craving in regular users.Drug Alcohol Depend.(2014-Jun-01)

[ref-19] ^Wilson LL, Harris HM, Eans SO, Brice-Tutt AC, Cirino TJ, Stacy HM, Simons CA, León F, Sharma A, Boyer EW, Avery BA, McLaughlin JP, McCurdy CRLyophilized Kratom Tea as a Therapeutic Option for Opioid Dependence.Drug Alcohol Depend.(2020-Nov-01)

[ref-20] ^Rosenbaum CD, Carreiro SP, Babu KMHere 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-Mar)

[ref-21] ^Limcharoen T, Pouyfung P, Ngamdokmai N, Prasopthum A, Ahmad AR, Wisdawati W, Prugsakij W, Warinhomhoun SInhibition of α-Glucosidase and Pancreatic Lipase Properties of (Korth.) Havil. (Kratom) Leaves.Nutrients.(2022-Sep-21)

[ref-22] ^Prevete E, Kuypers KPC, Theunissen EL, Corazza O, Bersani G, Ramaekers JGA systematic review of (pre)clinical studies on the therapeutic potential and safety profile of kratom in humans.Hum Psychopharmacol.(2022-Jan)

[ref-23] ^Vicknasingam B, Chooi WT, Rahim AA, Ramachandram D, Singh D, Ramanathan S, Yusof NSM, Zainal H, Murugaiyah V, Gueorguieva R, Mansor SM, Chawarski MCKratom and Pain Tolerance: A Randomized, Placebo-Controlled, Double-Blind Study.Yale J Biol Med.(2020-Jun)

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