What is Kratom?
Kratom is the common name for the tropical tree named Mitragyna speciosa, an evergreen member of the coffee family. Native to Southeast Asia, it has been used in herbal medicine in Myanmar, Indonesia, Papua New Guinea, Malaysia, and Thailand, where it grows wild, since at least the nineteenth century. Kratom has both stimulant-like and opioid effects.
Street names for kratom include biak, kakuam, ketum, thang, and thom.
A 2018 research review of work on kratom concluded that the poor quality of the research into the substance’s safety and efficacy preclude approval as a therapeutic agent. Since 2019, the United States Food and Drug Administration (FDA) has warned US consumers not to use kratom, indicating that there is no evidence that it is safe or effective to treat any disease or condition with the plant.
However, as the Research section below indicates, the latest research into kratom is very promising.
Perhaps this is why kratom is trending, although people take it for different reasons. Some use kratom recreationally, and many others use it to treat opioid withdrawal symptoms, or to manage chronic pain. Expect the effects from kratom to start within several minutes of using it, and last for two to five hours.
Users report a number of effects from kratom, including:
- increased alertness
- sociability, talkativeness
- mood changes
- more physical energy
- pain relief
Possible side effects from kratom include
- appetite loss
- erectile dysfunction
- hair loss
- decreased breathing/respiratory depression
- difficulty sleeping
- high blood pressure
- high heart rate
- liver toxicity (rare)
Withdrawal symptoms may occur when use is stopped. Kratom alone or mixed with other substances has caused death, although rarely. Serious toxicity typically appears when kratom is used with other substances and/or at very high doses and is relatively rare.
A controlled substance in at least 16 countries, the FDA has banned the manufacture and import of kratom as a dietary supplement.
Kratom Tree Appearance and Description
The evergreen tree Mitragyna speciosa can reach a height of 82 feet or 25 meters. Trees that reach those heights may have trunks that are 3 feet or almost a meter in diameter.
Pieter Korthals, a Dutch colonial botanist, first formally described the kratom tree in 1839. He named the plant Stephegyne speciosa, but it was reclassified and renamed several times before its final name and classification in 1859 as Mitragyna speciosa, provided by George Darby Haviland.
The trunk of the kratom tree is generally tall, long, and straight, with smooth, gray outer bark. Kratom leaves on the tree are glossy and dark green. The ovate-acuminate shaped leaves can reach sizes of over 5.5 to 7.9 inches long and 2.8 to 4.7 inches wide when opened fully. Leaves have 12 to 17 pairs of veins running through them which take on different colors. Deep yellow kratom flowers grow at the ends of the branches in clusters of three.
Chemistry and Pharmacology of Kratom
Kratom is an agonist that binds to the brain’s mu-opioid receptors, those that are activated by opioids such as heroin or prescription painkillers. In that sense, kratom is a natural opioid, and although its structure mitigates against some of the work risks that all opioids carry with them—it does carry inherent risk of tolerance, dependence, and withdrawal.
Many of Mitragyna speciosa’s main psychoactive compounds are indole alkaloids related to mitragynine. The alkaloid mitragynine is tetracyclic, similar to the indole alkaloids voacangine and yohimbine which are pentacyclic.
Significant proportions of the isolable natural products that occur in Mitragyna speciosa are composed of mitragynine and 7-hydroxymitragynine (7-HMG). Mitragynine makes up 12 to 66 percent of leaf source weight depending on whether the leaf sources are Malaysian or Thai, and 7-hydroxymitragynine constitutes around 2 percent by weight.
Scientists have also isolated at least 40 other compounds from kratom leaves, including approximately 25 additional alkaloids. Among those are corynantheidine, also found in Pausinystalia johimbe; raubasine/ajmalicine, isolated originally from Rauvolfia serpentina; as well as mitragynine pseudoindoxyl, mitraphylline, and rhynchophylline.
Mitragyna speciosa produces various other secondary metabolites in addition to alkaloids. These include triterpenoids such as oleanic acid and ursolic acid; various iridoids, saponins, and other monoterpenoids; as well as various polyphenols including quercetin and apigenin, which are flavonoids. Some of these compounds possess anti-inflammatory, antinociceptive, antioxidant, antidepressant, antibacterial, and gastrointestinal effects in cells and in animals.
How Long Does Kratom Stay In Your System?
Kratom’s precise half-life is still uncertain; more research will be needed to determine that number. Several factors influence how long kratom stays in your system, as is true for other substances. Some of the most important are biological factors about the user such as age, genetics, body fat, and metabolic rate; lifestyle factors such as frequency of use, and intake of food and water; and source factors such as the type of kratom and the dose.
Detection of kratom in body fluids
Typical drug screening panels do not detect the plant’s metabolites and active compounds, but more specialized testing can detect them. Liquid chromatography-mass spectrometry is the most common means to detect kratom (or its results) in body fluids. Most testers expect blood mitragynine concentrations in recreational users to range from 10 to 50 μg/L.
Pharmacology of Kratom
There are at least 40 alkaloids in kratom, including: mitragynine, 7-hydroxymitragynine (7-HMG), corynantheidine, mitragynaline, mitraphylline, paynantheine, rhynchophylline, mitralactonal, raubasine, speciociliatine, and speciogynine. Although most kratom’s complex effects are produced by the alkaloids mitragynine and 7-hydroxymitragynine, the other alkaloids may help to create a sort of synergistic effect that does contribute.
Both mitragynine and 7-HMG are competitive antagonists of the δ-opioid receptor and partial agonists of the μ-opioid receptor, with low affinity for the κ-opioid receptor. Both readily cross the blood-brain barrier. Mitragynine appears to have lower affinity at the μ-opioid receptor than 7-HMG. These compounds do not activate the β-arrestin pathway as they are functionally selective, so they are less likely to cause side effects associated with traditional opioids such as constipation, respiratory depression, and sedation.
Mitragynine inhibits block L-type, COX-2, and T-type calcium channels. Mitragynine also interacts with other brain receptors including D2 dopamine receptors, serotonin receptors 5-HT2C and 5-HT7, and A2A adenosine receptors.
However, perhaps because mitragynine stimulates α2-adrenergic receptors, which inhibits the release of norepinephrine, kratom used in combination with other sedatives can be dangerous. Other compounds in this class include clonidine, prescribed to manage some symptoms of opioid withdrawal and anxiety, and dexmedetomidine, used for sedation. Kratom also contains the non-competitive NMDA receptor antagonist rhynchophylline, perhaps in response to this activity.
Humans metabolize mitragynine via phase I and phase II mechanisms, and users excrete metabolites in urine.
Kratom Side Effects
Mitragyna speciosa may cause side effects, some of them more adverse than others. However, the nature and extent of these side effects remains in dispute.
In November 2017 the FDA issued a public health advisory urging citizens to avoid using kratom entirely. In 2018, FDA Commissioner Scott Gottlieb issued a statement underscoring kratom’s potential for abuse. However, side effects connected to kratom appear to be dose-dependent, with higher doses exceeding 8 grams producing more frequent adverse effects.
A comprehensive set of numbers for adverse side effects in kratom users is unknown. However, a 2019 review in Pharmacotherapy of kratom exposures reported over a seven-year period to US poison control centers along with several other recent studies (cited above) list these possible adverse side effects from kratom—alone in some cases, used with other drugs in other cases:
- contracted pupils
- decreased appetite
- dry mouth
- hair loss
- high blood pressure
- hyperpigmentation/discoloration of the cheeks
- increased social behavior
- increased urination
- poor concentration
- sensitivity to sunburn
- temporary erectile dysfunction
- weight loss
And these symptoms have been reported by kratom users, but it’s unclear that any of these are actually directly attributable to kratom use:
- respiratory depression
- cardiac or respiratory arrest
- neonatal abstinence syndrome
Risks from higher potency concentrated extracts appear to be higher, and risk also increases when kratom is mixed with other drugs, psychoactive substances, or adulterants, or when people with a history of heroin use, alcohol use disorders, or some health problems take it.
Kratom products with 2 to 6 grams of dried leaf per dose are most commonly used in the US, with doses over 8 grams being fairly unusual. However, the potency of kratom products often varies greatly as there are no standards for dosing.
There are mostly stimulant effects resembling those of coca products at relatively low doses—those would be 1 to 5 grams of raw leaves. Kratom side effects at low doses include blushing, contracted pupils, and adverse stimulation effects such as agitation and anxiety. At low doses kratom may also produce opioid-related side effects such as nausea, itching, loss of appetite, and increased urination.
More prominent opioid effects generally appear at moderate to high doses of kratom, typically 5 to 15 grams of raw leaves. At these moderate to higher doses, users risk additional adverse stimulant and opioid side effects such as constipation, dizziness, dry mouth, hypotension, sweating, and tachycardia.
Repeated use of high doses of kratom over the long term may lead to development of dependence, tolerance, and symptoms of withdrawal upon stopping, including weight loss, loss of appetite, trouble sleeping, decreased sexual drive, muscle and bone pain, muscle spasms, jerky movement, hot flushes, watery eyes, diarrhea, fever, anger, restlessness, and sadness. The difficulty of enduring these kinds of symptoms can cause people to start using again, even if they’d rather not.
There are a few other risks to keep in mind based on the research on kratom we cited:
- Frequent use of high doses of kratom may cause tremors, anorexia, weight loss, and seizures.
- There are reports that high and frequent doses of kratom is associated with psychosis as well, but it is unclear whether kratom use revealed existing psychosis or directly caused the condition.
- Serious toxicity is rare and typically occurs when kratom is used with other substances, at high doses, or when both conditions are met.
- Kratom mixed with other substances—legal and illegal—may cause herb-drug interactions, including alcohol, benzodiazepines, caffeine, cocaine, monoamine oxidase inhibitors (MAOIs), opioids, sedatives, or yohimbine.
Can You Overdose on Kratom?
Although multiple death reports mention ingestion of kratom, the vast majority of these involve other substances. A 2019 paper analyzed National Poison Data System data and found that there were only 11 deaths even linked to kratom exposure between 2011 and 2017, and nine of the 11 deaths involved kratom and other medicines or drugs, such as alcohol, diphenhydramine (an antihistamine), benzodiazepines, caffeine, cocaine, and fentanyl.
The FDA identified at least 44 deaths related to kratom by 2018, with one possible pure kratom case among them. The FDA findings indicate that many of the kratom-associated deaths were caused by taking kratom with other potent substances, including alcohol, benzodiazepines, gabapentin, illicit drugs, opioids, and OTC medications such as cough syrup, or by taking adulterated kratom products. The FDA also found reports of kratom laced with other deadly compounds.
Medical teams manage kratom overdoses similarly to opioid overdoses, and despite mixed results for its utility, naloxone can be used to treat an overdose that results in respiratory depression.
In 2017 and 2018, 28 people in the US were infected with a multistate outbreak of salmonella from using contaminated kratom. According to whole genome sequencing, a common kratom source probably caused the salmonella outbreak.
The leading risk of death from opioid use, respiratory depression from taking Mitragyna speciosa appears to be low. A 2018 study found that kratom and its active ingredients do not cause the kind of significant respiratory depression that makes opioids so dangerous. However, the FDA continues to list respiratory depression as a risk or area of concern regarding kratom.
Kratom has been connected to rare instances of acute liver injury that are clinically apparent. Symptoms include pruritus, nausea, fatigue, and dark urine with jaundice as the last appearing symptom.
Most kratom related deaths involve other substances. That 2019 paper on National Poison Data System data we mentioned above found only two deaths that might have been solely caused by kratom—and that link was not proven.