Mitragyna speciosa

Mitragyna speciosa is an evergreen tree in the genus Mitragyna that can grow to a height of . Its trunk may grow to a diameter. The calyx-tube is long and has five lobes; the corolla-tube is long. Mitragyna speciosa is indigenous to Thailand, Indonesia, Malaysia, Myanmar, and Papua New Guinea. It was first formally described by the Dutch colonial botanist Pieter Korthals in 1839, who named it Stephegyne speciosa; it was renamed and reclassified several times before George Darby Haviland provided the final name and classification in 1859. ==Uses of the leaves==

Kratom is often used by workers in laborious or monotonous occupations to stave off exhaustion and as a mood-enhancer and painkiller. The herb is bitter and is generally combined with a sweetener. Opioid withdrawal Because the withdrawal effects of kratom are often reported to be less severe than those associated with traditional opioids, though no clinical trials have been done supporting this use. , there have been no formal trials to study the efficacy or safety of kratom to treat opioid addiction. While some literature reviews claim that kratom has less potential for dependence or overdose than traditional opioids, other reviews note that kratom withdrawal itself can still be quite severe. At higher doses, kratom produces opioid-like effects. In Thailand, a 2007 survey found that the lifetime, past year, and past 30 days kratom consumption rates were 2.32%, 0.81% and 0.57%, respectively, among respondents aged 12–65 years, Starting in the 2010s, a tea-based cocktail known as "4×100" became popular among some young people across Southeast Asia and especially in Thailand. It is a mix of kratom leaves, cough syrup, Coca-Cola, and ice. Around 2011, people who consumed the cocktail were often viewed more negatively than users of traditional kratom, but not as negatively as users of heroin. As of 2012, use of the cocktail was a severe problem among youth in three provinces along the border of Malaysia and southern Thailand. In the U.S., , kratom was available in outlets such as head shops and over the Internet; the prevalence of its U.S. use was unknown at the time. By 2020, it was estimated that 15 million people worldwide use kratom. ==Adverse effects==

Mitragyna speciosa may cause many adverse effects, and in November 2017 the FDA issued a public health advisory for the drug. Given that kratom products may vary greatly in potency, there is no standard dosing system. At relatively low doses (1–5 g of raw leaves), at which there are mostly stimulant effects, side effects include contracted pupils and blushing; adverse effects related to stimulation include anxiety and agitation, and opioid-related effects such as itching, nausea, loss of appetite, and increased urination begin to appear. Long-term use of high doses of kratom may lead to development of tolerance, dependence, and withdrawal symptoms, including loss of appetite, weight loss, decreased libido, insomnia, muscle spasms, muscle and bone pain, increased yawning and/or sneezing, myoclonus, watery eyes, hot flashes, fever, diarrhea, restlessness, anger, and sadness. Frequent use of high doses of kratom may cause tremors, anorexia, weight loss, seizures, psychosis and other mental health conditions. Kratom use has a small but statistically significant association with externalizing mental health disorders. Kratom use may worsen existing mental health conditions. Serious toxicity is relatively rare and generally appears at high doses or when kratom is used with other substances. In July 2016, the Centers for Disease Control issued a report stating that between 2010 and 2015, US poison control centers received 660 reports of exposure to kratom. Medical outcomes associated with kratom exposure were reported as minor (minimal signs or symptoms, which resolved rapidly with no residual disability) for 162 (24.5%) exposures, moderate (non-life-threatening, with no residual disability, but requiring some form of treatment) for 275 (41.7%) exposures, and major (life-threatening signs or symptoms, with some residual disability) for 49 (7.4%) exposures. Overall, 92.6% of outcomes were resolved with no residual disability. An analytical method using whole genome sequencing applied to samples from the infected users indicated that the salmonella outbreak likely had a common kratom source. A survey by Stanciu et al. of kratom consumers found that 25.5% of respondents reported symptoms consistent with a substance use disorder diagnosis based on the Diagnostic and Statistical Manual's criteria. After controlling for variables such as age, gender, daily kratom use frequency, and a history of substance use disorders or mental health conditions, individuals with a concurrent diagnosis of another substance use disorder (SUD) had 2.83 times the odds of meeting criteria for kratom addiction compared to those without a concurrent SUD diagnosis. Kratom addiction carries a relapse risk as high as 78% to 89% at three months post-cessation. In cases of severe addiction, an approach similar to the treatment of opioid addiction may be warranted. Respiratory depression Respiratory depression is the leading cause of death from opioid use. Although evidence is sparse, the risk of respiratory depression caused by taking kratom appears to be low, but, , the Food and Drug Administration listed respiratory depression as a concern. A 2018 review found that the alkaloids in kratom do not induce respiratory depression. Liver toxicity Chronic use of kratom can be hepatotoxic, and may cause acute liver injury; symptoms include abdominal discomfort, dark urine, itching and jaundice. These infants display similar symptoms to infants born with opioid withdrawal syndrome, such as jitteriness, reduced feeding, irritability, and sleeplessness. Infants impacted by kratom withdrawal may require hospitalization and pharmacologic weaning using morphine. Over 18 months in 2016 and 2017, 152 overdose deaths involving kratom were reported in the United States, with kratom as the primary overdose agent in 91 of the deaths, and 7 with kratom being the only agent detected. Nine deaths occurred in Sweden during 2010–11 relating to use of Krypton, a mixture of kratom, caffeine and O-desmethyltramadol, a metabolite of the opioid analgesic tramadol. ==Pharmacology==

Kratom contains at least 54 alkaloids. These include mitragynine, 7-hydroxymitragynine (7-HMG), speciociliatine, paynantheine, corynantheidine, speciogynine, mitraphylline, rhynchophylline, mitralactonal, raubasine, and mitragynaline. Both mitragynine and 7-HMG readily cross the blood-brain barrier. Mitragynine also appears to inhibit COX-2, block L-type and T-type calcium channels, and interact with other receptors in the brain including 5-HT2C and 5-HT7 serotonin receptors, D2 dopamine receptors, and A2A adenosine receptors. Mitragynine is metabolized in humans via phase I and phase II mechanisms with the resulting metabolites excreted in urine. In in vitro experiments, kratom extracts inhibited CYP3A4, CYP2D6, and CYP1A2 enzymes, which results in significant potential for drug interactions. == Chemistry ==

Many of the key psychoactive compounds in M. speciosa are indole alkaloids related to mitragynine, which is a tetracyclic relative of the pentacyclic indole alkaloids, yohimbine and voacangine. At least 40 other compounds have been isolated from M. speciosa leaves, In addition to alkaloids, M. speciosa produces many other secondary metabolites. These include various saponins, iridoids and other monoterpenoids, triterpenoids such as ursolic acid and oleanic acid, as well as various polyphenols including the flavonoids apigenin and quercetin. Although some of these compounds possess antinociceptive, anti-inflammatory, gastrointestinal, antidepressant, antioxidant, and antibacterial effects in cells and non-human animals, there is no sufficient evidence to support the clinical use of kratom in humans. Blood mitragynine concentrations are expected to be in a range of 10–50 μg/L in persons using the drug recreationally. Detection in body fluids is typically by liquid chromatography-mass spectrometry. ==Regulation==

, neither the plant nor its alkaloids were listed in any of the Schedules of the United Nations Drug Conventions. ASEAN , kratom was listed by ASEAN in its annex of products that cannot be included in traditional medicines and health supplements that are traded across ASEAN nations. Australia and New Zealand Mitragyna speciosa is a prohibited substance in Australia. In New Zealand, Mitragyna speciosa is designated a prescription medicine, and its use in herbal remedies is prohibited under section 2 of the Medicines Act 1981. Canada , Health Canada disallowed marketing of kratom for any use by ingestion and has taken action against companies marketing it for such purposes. Kratom can be marketed for other uses, such as incense. Europe , the plant was controlled in Denmark, Latvia, Lithuania, Poland, Romania, and Sweden. In the Czech Republic, regulated sales of kratom and kratom extracts became legal starting in July 2025. In Finland, scheduled in the "government decree on psychoactive substances banned from the consumer market". In the Republic of Ireland in 2017, kratom was designated a Schedule 1 illegal drug (the highest level), under the names 7-hydroxymitragynine and mitragynine. In the UK, the sale, import, and export of kratom is prohibited under the Psychoactive Substances Act 2016, which broadly bans any substance that "produces a psychoactive effect". South America Chile banned Kratom in 2021. Argentina banned Kratom in 2017. Brazil listed kratom as a New Psychoactive Substance (NPS) in 2020. However, it remains legal until it is included among prohibited substances. Indonesia Kratom was previously scheduled to become an illegal substance in Indonesia in 2024 once new regulations from the Indonesian National Narcotics Agency (BNN) go into effect. However, in 2024, a revision to a regulation by Ministry of Trade legalized production and export of kratom leaves. Later in September 2024, Indonesia's Ministry of Cooperatives and Small Medium Business stated that Indonesia will start building downstream industries for kratom exports. These developments made kratom legal to export and manufacture in Indonesia. Malaysia The use of kratom leaves, known locally as ketum or Biak is prohibited to use, import, export, manufacture, compound, mix, dispense, sell, supply, administer or possess in Malaysia under Section 30(3) of the Poisons Act 1952, and will be punished by imprisonment or fine or both. Although prohibited by statute, the use of kratom remains widely spread especially in Northern and East Coast region of Malaysia's Peninsula because the tree grows natively and tea decoctions are readily available in local communities. Certain parties have urged the government to penalize the use of kratom under the Dangerous Drugs Act instead of the Poisons Act, which would carry heavier penalties. Thailand Possession of kratom was illegal in Thailand until 2018. The Thai government had passed the Kratom Act 2486, effective 3 August 1943, which made planting the tree illegal, The Thai government has considered legalizing kratom for recreational use in 2004, 2009, 2013, and 2020. In 2018, Thailand became the first Southeast Asian country to legalize kratom for medical purposes. United States In 2014, the United States Food and Drug Administration (FDA) banned the import of kratom into the U.S. due to a lack of evidence for its safety. As of early 2026, the states of Iowa, Nebraska, and South Dakota introduced bills with legislation that would ban kratom, while Iowa and Nebraska would also classify kratom as a Schedule I drug. In 2025, it was banned in the following Massachusetts communities: Belchertown, Canton, Chelmsford, Dracut, Kingston, Lowell, Marlborough, and Northampton. As of December 12, 2025, the state of Ohio temporarily banned kratom-related products for 180 days, with the Ohio Board of Pharmacy moving toward a permanent ban on all forms of kratom by mid-2026. In late 2025, California Governor Gavin Newsom's administration began warning retailers that it is illegal to sell or manufacture kratom, which led to Los Angeles County banning kratom and Orange County significantly restricting kratom by banning synthetic or concentrated kratom products containing more than 2% 7-hydroxymitragynine. In 2016, kratom was banned in the cities of San Diego and Oceanside in the state of California. There was consideration in late 2017 to make kratom a Schedule I drug. In 2019, the FDA warned consumers that kratom remains unapproved for interstate commerce for use as a drug, may be unsafe in commercially available products, and is on an import alert, which can lead to confiscation of imported supplies. On August 13, 2025, Florida Attorney General James Uthmeier announced an emergency rule placing 7-hydroxymitragynine into Schedule I status under Florida state law, without any mention of a carve out or any exclusions for Mitragyna speciosa which contains low amounts of 7OH, effectively making kratom illegal in Florida. FDA assessment In April 2019, the FDA issued a statement declaring that kratom was not approved for any medical use, was potentially unsafe in commercial products available in the United States, and remained on an import alert where imported supplies would be confiscated. Samples of the products, manufactured by Triangle Pharmanaturals, and marketed under the brand name 'Raw Form Organics', tested positive for contamination and the manufacturer did not comply with federal requests for voluntary recall. FDA Commissioner Gottlieb stated that the recall was "...based on the imminent health risk posed by the contamination of this product with salmonella" and not related to other regulatory concerns. On February 26, the FDA warned a California manufacturer of a kratom product called "Mitrasafe" that the supplement was not confirmed as safe, was not approved as a dietary supplement or drug, and was illegal for interstate commerce. DEA scheduling On August 30, 2016, the Drug Enforcement Administration (DEA) announced its intention to place the active materials in the kratom plant into Schedule I of the Controlled Substances Act as a warning about an imminent hazard to public safety, citing over 600 calls to poison control centers between 2010 and 2015 and 15 kratom-related deaths between 2014 and 2016. This drew strong protests among those using kratom to deal with chronic pain or wean themselves off opioids or alcohol. A group of 51 members of the U.S. House of Representatives and a group of nine Senators each sent letters to acting DEA administrator Chuck Rosenberg protesting the listing and around 140,000 people signed an online White House Petition protesting it. The DEA noted the responses but said that it intended to go forward with the listing; a spokesman said: "We can't rely upon public opinion and anecdotal evidence. We have to rely upon science." In October 2016, the DEA withdrew its notice of intent while inviting public comments over a review period ending on December 1, 2016. As of July 2016, Alabama, Arkansas, Indiana, Vermont, and Wisconsin had made kratom illegal, and the US Army had forbidden soldiers from using it. Between February 2014 and July 2016, U.S. law-enforcement authorities "encountered 55 tons of kratom," or roughly "50 million individual doses," according to the International Narcotics Control Board. Public response The FDA's arguments for the federal prohibition of kratom have drawn both criticism and support. FDA commissioner Gottlieb responded to criticism in 2018 by stating that "The FDA has done an exhaustive review of adverse event reports, clinical literature and other sources of information related to kratom." Former commissioner Gottlieb continued to defend the agency's position in 2021, stating that he was convinced that kratom was fueling the U.S. opioid epidemic, though Gottlieb's partiality has been called into question as he has since gone on to become a member of the board of directors of Pfizer Inc., a company that has been heavily criticized for its sale and marketing of opioid drugs. == Research==

Kratom is under preliminary research for possible antipsychotic and antidepressant properties, as well as pain management, withdrawal management, and dependence reduction. Kratom use has not been shown to positively affect mental health and shows a very small association with negative indicators (mainly externalizing disorders). == See also ==