The goal of this website is to inform you about the herbal product kratom, which is also known by its Latin name Mitragyna speciosa in the coffee plant family (Rubiaceae). The information provided here is gathered from a range of scientific sources which have been reviewed by a team of experts. We strive to keep the information up to date.
Please be advised that the information provided on this website is not intended as health care advice. Rather, this is a forum for sharing scientific information.
Christopher McCurdy, Ph.D., a professor in the department of medicinal chemistry, is an internationally recognized expert on kratom and a broadly trained medicinal chemist, behavioral pharmacologist and pharmacist whose research focuses on the design, synthesis and development of drugs to treat pain and drug abuse.
Oliver Grundmann, Ph.D., a clinical associate professor in the department of medicinal chemistry, is interested in the search for new treatment options from natural products for Central Nervous System and gastrointestinal diseases such as anxiety and depressive disorders as well as the epidemiology of kratom use and related health patterns.
Jay McLaughlin, Ph.D., an associate professor in the department of pharmacodynamics, runs in vivo behavioral neuroscience and pharmacological tests to determine the effects of individual kratom alkaloids on behavior as mediated by receptor targets in the brain.
Department: Medicinal Chemistry
Christopher R McCurdy
Ph.D., F.A.A.P.S.
Professor And The Frank A. Duckworth Eminent Scholar Chair; Associate Dean For Faculty Development; Director Of The UF Translational Drug Development Core
Kratom is both the whole tree Mitragyna speciosa in the coffee family Rubiaceae as well as the leaves and extracts of the leaves that are used for medicinal and recreational purposes. The tree is native to Southeast Asia and primarily grown in Malaysia, Thailand, and Indonesia. It is occasionally cultivated in other countries including the U.S. It is also known as ketum, biak-biak, Maeng Da, thang, thom and kakuam, among others.
Kratom should not be confused with its single compounds mitragynine or 7-hydroxymitragynine. These are isolated substances with a defined chemical structure that are present in kratom extracts. Fresh kratom leaves contain mitragynine although the presence of 7-hydroxymitragynine in unprocessed leave material has not been confirmed.
News
Deadly Dose (published in the Tampa Bay Times, 2023)
Dr. Mercola interviews Dr. Christopher McCurdy about kratom, a traditional medicine known and used for centuries, and its potential benefits for pain relief and opioid withdrawal
In Southeast Asia, fresh kratom leaves were chewed to increase work efficiency and relieve fatigue for manual laborers. Fresh and dried leaves were also brewed into teas in Malaysia and Thailand for a range of ailments including diabetes, diarrhea, fever, pain and for use as a wound poultice. It has been used as a substitute for opium and to reduce opioid withdrawal symptoms in Asian countries and in western countries. There is no scientific information on traditional uses of kratom preparations before the 2000s outside of Asia.
Traditional use of kratom in Southeast Asia was first reported in 1836 but likely dates back further primarily for two reasons: as an opium substitute in Malaysia and as a stimulant to increase work efficiency in Thailand. Today, kratom is used alone or brewed in combination with cough syrup (often codeine) and Coca Cola, then referred to as 4×100 as a drug of abuse, in Southeast Asia.
Its first use in the U.S. remains unknown but cases emerged in the early 2000s describing kratom for self-treatment of opioid withdrawal symptoms, pain and mental conditions. The CDC reported an increase in calls to Poison Control Centers involving kratom and the FDA has warned consumers to avoid taking kratom. As of February 2019, the FDA recommends placing kratom’s active compounds, mitragynine and 7-hydroxymitragynine, in DEA schedule 1 because of its opioid-like effects and potential for dependence without any current medical indication in the U.S.
The scientific community is actively pursuing further research to evaluate the therapeutic versus adverse effect profile of these active compounds to determine their medicinal value. If they are shown to have therapeutic and medically useful effects, then less restrictive (Schedules 2-5) or no scheduling could be appropriate.
Information for Consumers
Is kratom safe?
Kratom products in the US are not fresh leaf material and therefore, not the exact same product that is found in Southeast Asia traditional use. This difference, which has not been fully investigated, comes from the fact that products available outside of the traditional use are usually dried or aged in ways that could possibly change the chemical composition of the leaf material. As is the case with any dietary supplement or drug-like substance, if one is interested in using kratom then it is recommended that you consult with your healthcare provider (physician, nurse, and/or pharmacist) beforehand.
Which kratom products are best to take?
Extracts of plants, in the case of kratom (leaf extracts), will have varying compositions of compounds depending on when the leaves were harvested, where the tree is grown, how old the leaves were, etc. Some of these factors can be controlled while others are difficult to be accounted for. The Food and Drug Administration, or FDA, has provided guidelines that supplement manufacturers can follow to ensure that their products meet good manufacturing practices. These guidelines ensure that the final product is free of contaminants and adulterants, meets the labeling standards of the FDA, and can be traced back to their origin from the point of purchase.
What is standardized kratom extract?
Some kratom extracts may be labeled as standardized to contain a certain amount of the proposed active ingredient mitragynine and/or 7-hydroxymitragynine. Standardization ensures that a given amount of the extract will contain the same amount of the compound that the extract has been standardized to (currently for kratom this will be mitragynine and/or 7-hydroxymitragynine). An example is a standardized extract of kratom containing 2% mitragynine. This means that for 1g of Kratom extract there will be 0.02g of mitragynine present. In some cases, there may be a range present or an upper limit. Standardization is another strategy to ensure a safer kratom product is made available to consumers.
When should I contact my health care provider if I take kratom?
As stated above, you should first consult with your health care provider before taking kratom. If your health care provider agrees or recommends taking kratom, you should contact them as soon as any concerning changes occur in your health status. Do not change the suggested dose or frequency of kratom on your own without consulting with your health care provider. If you feel unwell while taking kratom, stop taking the extract and contact your health care provider.
Is there a difference between the red, white or green vein kratom varieties?
The different vein colorations of the leaf are being advertised for their varying effects in the U.S. and in other western countries. This distinction has not been made in traditional use settings. The leaves are all collected from the same tree, Mitragyna speciosa, and to date there is no information on differences in terms of effects in animal or human scientific studies.
Information for Health Care Professionals
Dosage forms, dose range; differentiation between pure kratom and adulterated products
Kratom is primarily consumed orally. It is available in the US as powder, tablets, capsules, raw leaves (mostly dried), and concentrated extracts (most containing varying amounts of ethanol). The doses range widely based on the dosage form with powders usually suggesting a dose of 3-5 g while concentrated liquid extracts may only require 1-2 drops to be added to a beverage according to manufacturer recommendations. Users may administer the extracts several times per day to achieve improvement of their condition although a majority appear to use the extract 3 times/day in doses of 3-5 g. Self-dosing in combination with currently unregulated Kratom product quality results in highly variable concentrations of the putative active ingredients, mitragynine and 7-hydroxymitragynine. Pure kratom products should contain no more than 66% of mitragynine as the main alkaloid and 2% of 7-hydroxymitragynine in the alkaloid fraction of the extract or a total of approximately 2% of alkaloids (1.8-2% mitragynine and 0.02-0.03% 7-hydroxymitragynine) in the whole leaf extract. Adulterated kratom preparations have been found for sale in Western countries with various synthetic compounds including 7-hydroxymitragynine, O-desmethyltramadol (then referred to as “Krypton”), fentanyl, hydrocodone, and other prescription opioids.
Potential uses, what consumers and patients may use it for
Because of its many traditional uses as both a dose-dependent stimulant and analgesic, kratom preparations may be used for a wide range of self-treatment options by patients. Surveys and case reports describe the use for acute and/or chronic pain, mitigation of opioid, prescription and other drug dependency withdrawal symptoms, substitution of opioid medication or illicit opioid drugs, harm reduction measures in opioid withdrawal, depressive or anxiety disorders, attention deficit and hyperactivity disorders (ADHD/ADD), bipolar disorder, post-traumatic stress disorder (PTSD), and other conditions. In addition, a person may use kratom recreationally to obtain relaxation, improved mood, increased energy, or an altered state of consciousness (“high”).
Current known pharmacology, active pharmacological principles
Early investigations of whole kratom extracts indicated that the extract exerted a stimulant effect in both humans and animals but only a weak analgesic effect equivalent “in potency to that of codeine”. Following isolation of the indole alkaloids mitragynine and 7-hydroxymitragynine from enriched extracts, both were found to be partial agonists at the μ-opioid receptor. Mitragynine binds with much lower affinity to the receptor compared to morphine and has much lower efficacy (EC50=339 nM for mitragynine vs. EC50=3 nM for morphine) while 7-hydroxymitragynine is about 10 times more potent than mitragynine at the receptor with an EC50=35 nM in vitro. Other alkaloids from kratom may act as competitive antagonists to the μ-opioid receptor thus resulting in a potentially complex overall pharmacological response of the whole extract depending on the amount of alkaloids present. The binding affinities for mitragynine and 7-hydroxymitragynine at κ- and δ-opioid receptors as partial competitive antagonists has been reported in functional assays as much weaker (κ-opioid receptor: Ki=772 nM for mitragynine and Ki=188 nM for 7-hydroxymitragynine; δ-opioid receptor: Ki>10 μM for mitragynine and Ki=219 nM for 7-hydroxymitragynine). Mitragynine has been investigated in non-opioid receptor binding studies and has shown affinity for α2-adrenergic, adenosine A2a, dopamine D2, serotonin 5-HT2C, and 5-HT7receptors although it remains unclear if this activity is agonistic or antagonistic. Both in vitroand in vivostudies confirmed that the analgesic effects of mitragynine are reversible with the administration of naloxone, an opioid-receptor antagonist.
Known/reported adverse effects, toxicology (both general and specific to organ systems as applicable)
The most common adverse effects with the use of kratom are nausea, vomiting, constipation, stomach upset, and either drowsiness/dizziness or irritability/agitation. Dry mouth, sweating, sedation, and tachycardia have been reported in doses above 8 grams (powder). Intrahepatic cholestasis and hepatic liver enzyme elevation has been reported with chronic and frequent use (one month or longer) of kratom in high doses. Liver function returned to normal after cessation of kratom use. Withdrawal symptoms associated with kratom cessation are dose-dependent and may include decreased appetite, diarrhea, agitation, sedation, insomnia, hallucination, changes in heart rate and blood pressure, and seizures. Respiratory depression and hemorrhagic stroke which were reported in fatalities involving kratom could not be casually linked to the ingestion since they also involved other drugs and/or medications.
Known and suspected drug interactions
To date several case studies of drug interactions with kratom have been reported that relate to its CNS depressant effects. Both additive and synergistic effects are observed if kratom is used with benzodiazepines, barbiturates, alcohol, opioids, antidepressants, anxiolytics, and other CNS-active drugs. Because of unknown routes of metabolism, specific CYP enzyme interactions remain unknown but caution is advised if kratom is used in combination with drugs that are substrates of CYP isoforms 1A2, 2C19, 2D6, and 3A4. For a list of general known clinically relevant CYP substrates (not specific to Kratom interactions) see https://www.fda.gov/drugs/developmentapprovalprocess/ developmentresources/druginteractionslabeling/ucm093664.htm#table3-1. Few case reports indicate that some drugs (quetiapine, modafinil) may interact with kratom although it remains unknown if this can be attributed to a CYP interaction. In vitrostudies have shown that kratom and mitragynine are inhibitors of the multi-drug transporter P-gp that may lead to increased concentrations of a range of drugs that are substrates for this transporter. It is not known to what degree these metabolic interactions are clinically relevant.
Risks for misuse, abuse, and dependence to kratom; withdrawal symptoms
Like caffeine or nicotine, kratom poses a risk for dependence development if consumed in higher doses (more than 5g/dose and more than 3 times/day) on a frequent basis and does present with withdrawal symptoms. It is not clear if this risk is related to the variability of alkaloid concentration in marketed products. Studies in rats have shown that mitragynine, when administered as a single compound, does not appear to have abuse potential and may decrease opioid intake. In contrast, 7-hydroxymitragynine does have a strong abuse potential, when administered as a pure compound to rats. The variability of alkaloid concentrations in marketed kratom products therefore can lead to some products carrying a higher risk for dependence development. Additionally, the risk of dependence development appears to be higher if the extract is used for harm reduction to mitigate opioid and illicit drug withdrawal or for self-treatment of pain. Withdrawal symptoms are mild compared to opioids with anxiety, diarrhea, pain, insomnia, restlessness, mood changes, tension, anger, and nervousness presenting. The symptoms may last from 3-10 days following the last dose and withdrawal symptoms can be treated with short-term buprenorphine-naloxone substitution therapy.
Kratom use in pregnancy
Case reports have been published where mothers who used kratom during their pregnancy have given birth to newborns presenting with signs of neonatal abstinence syndrome (NAS) similar to opioids. This warrants more scientific studies and information around the use of kratom during pregnancy. There are no known reports of animal studies in pregnancy at the current time. With a lack of any scientific understanding of kratom use during pregnancy and the multiple case reports in the literature, it is strongly advised against the use of the supplement in this population.
Potential lab values in diagnostic and differential evaluation
There are currently no standard laboratory procedures for the measurement of kratom or its metabolites in a clinical setting. Methods for the measurement of mitragynine have been described in the scientific literature and a few forensic laboratories have implemented them as part of their screening and confirmatory testing. To make matters more complex, the plant produces three other compounds that are different stereoisomers of mitragynine, all with the same chemical composition by varying three-dimensional configurations, that can be mistakenly added to the quantification of mitragynine leading to an overestimation of actual mitragynine concentrations. It has been difficult to link blood concentrations of mitragynine to impairment or toxicity given the wide range of variability with the ingestion of kratom preparations and undetermined mitragynine levels. Reports of mitragynine blood levels vary from 0.02 to 0.24 μg/g in fatalities (often in combination with other drugs) but also 0.0194 to 0.158 μg/g in subjects who did not experience any serious side effects. Hepatotoxicity indicated through elevated levels of bilirubin, alkaline phosphatase (ALP), and alanine aminotransferase (ALT) have been reported with chronic high doses of kratom in individuals who take other medications that are potentially hepatotoxic indicating a potential drug interaction. This has not been observed if unadulterated kratom is taken alone.
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