Plant species, recreational drug (kratom)
 ;templatestyles src="Template:Taxobox/core/styles.css" / ;
Mitragyna speciosa is a tropical evergreen tree of the Rubiaceae family (coffee family) native to Southeast Asia. It is indigenous to Cambodia, Thailand, Indonesia, Malaysia, Myanmar, and Papua New Guinea, where its leaves, known as kratom, have been used in herbal medicine since at least the 19th century. They have also historically been consumed via chewing, smoking, and as a tea. Kratom has opioid-like properties and some stimulant-like effects.
As of 2018[ [update]], the efficacy and safety of kratom are unclear. In 2019, the United States Food and Drug Administration (FDA) stated that there is no evidence that kratom is safe or effective for treating any condition. Some people take it for managing chronic pain, for treating opioid withdrawal symptoms, or for recreational purposes. The onset of effects typically begins within five to ten minutes and lasts for two to five hours.
Anecdotal reports describe increased alertness, physical energy, talkativeness, sociability, sedation, changes in mood, and pain relief following kratom use at various doses. Common side-effects include appetite loss, erectile dysfunction, nausea and constipation. More severe side-effects may include respiratory depression (decreased breathing), seizure, psychosis, elevated heart rate and blood pressure, trouble sleeping, and, rarely, liver toxicity. Addiction is a possible risk with regular use: when use is stopped, withdrawal symptoms may occur. A number of deaths have been attributed to the use of kratom, both by itself and mixed with other substances. Serious toxicity is relatively rare and generally appears at high doses or when kratom is used with other substances.
As of 2018, kratom is a controlled substance in 16 countries. 
There is growing international concern about a possible threat to public health from kratom use. In some jurisdictions its sale and importation have been restricted, and several public health authorities have raised alerts.
 ;templatestyles src="Template:TOC limit/styles.css" / ;
Description.
"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 trunk is generally straight, and the outer bark is smooth and grey. The leaves, ovate-acuminate in shape and opposite in growth pattern, are dark green, glossy on their upper surfaces, and can grow to over long and wide. They have 12 to 17 pairs of veins. The spherical inflorescences, which are deep yellow, grow in clusters of three at the ends of the branches. 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.
As of 2013[ [update]], kratom has been studied in cells and in animals, but no clinical trials have been conducted in the United States. The U.S. Drug Enforcement Administration (DEA) stated in 2013 that there is no legitimate medical use for kratom, and in 2019, the U.S. Food and Drug Administration (FDA) said that there is no evidence that kratom is safe or effective for treating any condition, and that there are no approved clinical uses for kratom.
Kratom is commonly ingested by chewing, as a tea, powdered in capsules or pills, or extracted for use in liquids. Kratom is rarely smoked. Different varieties of kratom contain different relative proportions of alkaloids such as mitragynine.
Traditional use.
In cultures where the plant grows, kratom has been used in traditional medicine. The leaves are chewed to relieve musculoskeletal pain and increase energy, appetite, and sexual desire in ways similar to khat and coca. The leaves, or extracts from them, are used to heal wounds and as a local anesthetic. Extracts and leaves have been used to treat coughs, diarrhea, and intestinal infections. They are also used as intestinal deworming agents in Thailand.
Kratom is often used by workers in laborious or monotonous occupations to stave off exhaustion and as a mood-enhancer and painkiller. In Thailand, kratom was "used as a snack to receive guests and was part of the ritual worship of ancestors and gods". 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, some people use kratom in the attempt to manage opioid use disorder, though no clinical trials have been done supporting this use. As of 2018[ [update]], there have been no formal trials to study the efficacy or safety of kratom to treat opioid addiction. Kratom is not approved for this or any other medical use. Stanciu et al. conducted a review of all literature and found insufficient evidence for any conclusions concerning whether kratom is harmful or whether can serve as harm reduction for those with 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.
Data on how widely it is used worldwide are lacking, as it is not detected by typical drug screening tests. Rates of kratom use appear to be increasing among those who have been self-managing chronic pain with opioids purchased without a prescription and are cycling (but not quitting) their opioid use.
In 1836, kratom was reported to have been used as an opium substitute in Malaysia. Kratom was also used as an opium substitute in Thailand in the 19th century.
Recreational uses.
At low doses, kratom produces euphoric effects comparable to those of coca. At higher doses, kratom produces opioid-like effects. The onset of effects typically begins within five to ten minutes and lasts for two to five hours. Some anecdotal reports describe increased work capacity, alertness, talkativeness, sociability, increased sexual desire, positive mood, and euphoria following the consumption of kratom.
According to the U.S. DEA and a 2020 survey, kratom is used to alleviate pain, anxiety, depression, or opioid withdrawal.
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, and that kratom was the most widely used recreational drug in Thailand.
Kratom may be mixed with other psychoactive drugs, such as caffeine and codeine. 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[ [update]], 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., as of 2015[ [update]], 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. In the United States, kratom use increased rapidly between 2011 and 2017. By 2020, it was estimated that 15 million people in the U.S. 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. The side effects of kratom appear to be dose-dependent and are more common with doses that exceed 8 g. While the incidence of adverse effects in people who use kratom is unknown, a 2019 review of 935 kratom exposures reported to U.S. poison control centers over a seven-year period listed the following signs and symptoms: agitation (18.6%), tachycardia (16.9%), drowsiness (13.6%), vomiting (11.2%), confusion (8.1%), seizures (6.1%), withdrawal symptoms (6.1%), hallucinations (4.8%), respiratory depression (2.8%), coma (2.3%), and cardiac or respiratory arrest (0.6%). The study also reported two deaths and four cases of neonatal abstinence syndrome. A different 2019 review listed as common side effects: decreased appetite, weight loss, erectile dysfunction, insomnia, sweating, hyperpigmentation, hair loss, tremor, and constipation.
Kratom products in the U.S. are commonly used in doses of 2–6 g of dried leaf, and doses exceeding 8 g are relatively uncommon. 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. At moderate to high doses (5–15 g of raw leaves), at which opioid effects generally appear, additional adverse effects include tachycardia (an increased stimulant effect) as well as the opioid side effects of constipation, dizziness, hypotension, dry mouth, and sweating.
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. This may lead to resumption of use.
Frequent use of high doses of kratom may cause tremors, anorexia, weight loss, seizures, psychosis and other mental health conditions. Kratom use may worsen existing mental health conditions. In case reports associating kratom use with psychosis, it remains unclear whether kratom use directly caused psychosis or simply unmasked the condition. Serious toxicity is relatively rare and generally appears at high doses or when kratom is used with other substances. Herb–drug interactions may result when kratom is combined with alcohol, sedatives, benzodiazepines, opioids, caffeine, cocaine, yohimbine, or monoamine oxidase inhibitors (MAOIs). Rhabdomyolysis is one of the rare and serious complications of this herb at high dosage.
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. One death was reported in a person who was exposed to the medications paroxetine (an antidepressant) and lamotrigine (an anticonvulsant and mood stabilizer) in addition to kratom. For 173 (26.2%) exposure calls, no effects were reported, or poison center staff members were unable to follow up regarding effects.
A 2019 report from the American Association of Poison Control Centers (AAPCC) noted that kratom use was increasing rapidly, with 1807 kratom exposures and a 52-fold increase occurring over the years 2011 to 2017. Most exposures occurred intentionally by adult males in their homes, with 32% of the incidents requiring admission to a health care facility and half of the admissions as a serious medical condition. Multiple-substance exposures were associated with a higher number of hospitalizations than kratom-only exposures and involved 11 deaths, including two due to kratom alone. Post-mortem toxicology testing detected multiple substances for almost all those who died, with fentanyl and fentanyl analogs being the most frequently identified co-occurring substances.
Overdoses of kratom are managed similarly to opioid overdoses, and naloxone can be considered to treat an overdose that results in a reduced impulse to breathe, despite mixed results for its utility, based on animal models.
From October 2017 to February 2018 in the United States, 28 people in 20 different states were infected with salmonella, an outbreak linked to the consumption of contaminated pills, powder, tea, or unidentified sources of kratom. 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.
Addiction.
Kratom is a botanical with a known addiction liability and, in vulnerable individuals, dependence may develop rather quickly with tolerance noted at three months and four- to ten-fold dose escalations required within the first few weeks. 
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