Mitragyna speciosa

Mitragyna speciosa
Scientific classification
Kingdom:	Plantae
(unranked):	Angiosperms
(unranked):	Eudicots
(unranked):	Asterids
Order:	Gentianales
Family:	Rubiaceae
Subfamily:	Cinchonoideae
Tribe:	Naucleeae
Genus:	Mitragyna
Species:	M. speciosa
Binomial name
Mitragyna speciosa (Korth.) Havil.
Synonyms
Nauclea korthalsii Steud. nom. inval. Nauclea luzoniensis Blanco Nauclea speciosa (Korth.) Miq. Stephegyne speciosa Korth.

Mitragyna speciosa also known as ketum, kratom and kratumum, is a tropical deciduous and evergreen tree in the coffee family (Rubiaceae) native to Southeast Asia in the Indochina and Malaysia floristic regions. Its leaves are used for medicinal properties. It is psychoactive, and leaves are chewed to uplift mood and to treat health problems. It is addictive according to the New York Times article, "Kratom, an Addict's Alternative, is Found to be Addictive Itself". There are only limited scientific studies to confirm that danger.

M. speciosa is indigenous to Thailand and, despite growing naturally in the country, has been outlawed for 70 years and was originally banned because it was reducing the Thai government's tax revenue from opium distribution.

Kratom behaves as a μ-opioid receptor agonist like morphine and is used in the management of chronic pain, as well as recreationally. Kratom use is not detected by typical drug screening tests, but its metabolites can be detected by more specialized testing. The pharmacological effects of kratom on humans, including its efficacy and safety, are not well-studied. Adverse effects such as psychosis, convulsions, hallucinations, sweating, nausea, vomiting, chest pain, dizziness and confusion have also been reported, albeit rarely. There has been a reported case in which chronic use of M. speciosa was associated with bowel obstruction, as well as reports stating that the plant carries the potential for addiction and can lead to withdrawal symptoms. In Thai it is called กระท่อม.

Taxonomy and etymology

Mitragyna Speciosa was first formally described by the Dutch colonial botanist Pieter Korthals in 1839. Unfortunately, the original source is not currently available on the internet, and can only be found in a few libraries around the world. However, Korthals' classification was reviewed and confirmed, and his original Latin description was included in a 1897 publication by George Haviland. The genus was named Mitragyna by Korthals because the stigmas in the first species he examined resembled the shape of a bishop's mitre. It is botanically related to the genera Corynanthe and Uncaria and shares some similar biochemistry.

Description

Young M. speciosa tree

Mitragyna speciosa trees usually grow to a height of 12–30 ft (3.7–9.1 m) tall and 15 ft (4.6 m) wide, although some species can reach 40–70 ft (12–21 m) in height. Mitragyna speciosa can be either evergreen or deciduous depending on the climate and environment in which it is grown. The stem is erect and branching. The leaves of the kratom tree are a dark green colour and can grow to over 7 inches (180 mm) long and 4 inches (100 mm) wide, are ovate-acuminate in shape, and opposite in growth pattern. The flowers are yellow and round and tend to grow in clusters at the end of the branches. The leaves of M. speciosa are elliptic and are smaller at the end of the branchlets and are pointed at the tip. The leaves have a round and heart-shape at the base with the petioles between 2 to 4 centimeters long. The flowers are crowded in a round terminal inflorescences that are three to five centimeters long. The calyx-tube is short and cup-shaped, with round lobes. The corolla-tube is five millimeters long with three millimiter long lobes and smooth and revolute in between.

Chemistry

There are more than 40 compounds in M. speciosa leaves, including many alkaloids such as mitragynine (once thought to be the primary active constituent), mitraphylline, and 7-hydroxymitragynine (which is currently the most likely candidate for the primary active chemical in the plant), and mitragynine pseudoindoxyl. Other active chemicals in M. speciosa include raubasine (best known from Rauwolfia serpentina) and some yohimbe alkaloids such as corynantheidine.

Mitragyna speciosa also contains at least one alkaloid (rhynchophylline) that is a calcium channel blocker, and reduces NMDA-induced current. The amount of mitragynine within the leaves depends highly on many factors, one major factor is the location of the tree. When trees are grown in Southeast Asia, the levels tend to be higher but when grown elsewhere (even in greenhouses) the levels tend to be low or non-existent. One analysis of products marketed as kratom leaf found, using liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS), mitragynine at levels of 1–6% and 7-hydroxymirtrogynine at levels of 0.01–0.04%. The chemical structure of mitragynines incorporate the nucleus of the tryptamine, and these may be responsible for the molecules observed in the serotonin and adrenergic systems. In mitragynine, the phenolic methyl ether is considered to be stronger in analgesic paradigms according to some studies. Moreover, the pharmacokinetics of M. speciosa in humans has not been well studied and various aspects such as the half-life, protein binding properties and other properties such as the elimination or metabolism is not known.

Uses

Kratom was used in Southeast Asia and by Thai natives to substitute for opium when opium was not available. It has also been used to manage opioid withdrawal symptoms by chronic opioid users.

Opioid withdrawal

Kratom and its derivatives have been used as substitutes for opium as well as for the management of opium withdrawal. Data on the incidence and prevalence of its use are lacking, as physicians are generally unfamiliar with it, and its use is not detected by typical drug screening tests. Kratom metabolites can be detected by specialized mass spectrometry tests. Incidence of kratom use appears 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 use. As of 2011, there have been no formal clinical trials performed to study the efficacy or safety of kratom to treat opioid addiction.

The pharmacological effects of kratom on humans are not well studied. Its metabolic half-life, protein binding, and elimination characteristics are all unknown. Kratom behaves as a μ-opioid receptor agonist, similar to opiates like morphine, although its effects differ significantly from those of opiates. Kratom does not appear to have significant adverse effects, and in particular appears not to cause the hypoventilation typical of other opioids. Compulsive use has been reported among drug users who inject opioids, and those who use opioids to manage pain without direction from medical professionals.

Traditional use

Kratom leaves

Kratom has been traditionally chewed, in raw leaf form, by people in Thailand and especially in the southern peninsula. Kratom is often used by workers in laborious or monotonous professions to stave off exhaustion as well as a mood enhancer and/or painkiller. Kratom is also used in neighboring countries in Southeast Asia where it grows naturally. Kratom has been used in Thailand as a form of traditional medicine as an antidiarrhoeal, as a treatment for opioid dependence as well as premature ejaculation during coitus. As traditionally used, kratom is not seen as a drug and there is often no stigma associated with kratom use or discrimination against kratom users. In southern Thailand, kratom has been a part of traditional culture for thousands of years and is common in traditional cultural performances and in agriculture. In southern Thailand, kratom chewers generally start at around the age of 25 and many continue to chew the leaves for the rest of their lives. A fresh leaf weighs on average 2 grams. The average number of leaves consumed is between 10 and 60 leaves per day, but even more than this is common. In some areas of southern Thailand, where Kratom is often referred to by the street name P̄hī or 'Goblin', it is thought that upwards of 70% of the male population uses kratom on a daily basis.

Side effects

Side effects associated with chronic kratom use include loss of appetite and weight loss, delayed ejaculation, constipation, and darkening of the skin color of the face. Chronic use has been associated with bowel obstruction. Chronic users have also reported withdrawal symptoms including irritability, runny nose and diarrhea. Withdrawal is generally short-lived and mild, and it may be effectively treated with dihydrocodeine and loperamide. Three case reports document deaths involving kratom. Other drugs were used in all cases, and Kratom was not found to be the cause in each case. Several deaths in Sweden did occur from the use of a product that was at first believed to consist solely of kratom, called "Krypton Kratom", which was later found to contain O-Desmethyltramadol, the active metabolite of the prescription drug tramadol.

Detection in body fluids

Blood or plasma mitragynine concentrations are expected to be in a range of 10–50 μg/L in persons using the drug recreationally, >100 μg/L in intoxicated patients and >300 μg/L in victims of acute overdosage.

Regulation

Thailand

Prohibition

Possession of kratom leaves is illegal in Thailand. The Thai government passed the Kratom Act 2486, effective August 3, 1943, which made planting the tree illegal and required existing trees to be cut down. This law was not found effective, since the tree is indigenous to the country. A large aspect of Thai culture supports kratom; indeed, kratom leaves have been used for medicinal purposes by nomadic tribes throughout history. However, despite this fact the Thai government had initiated a program of destroying kratom trees by burning forests or chopping large sections of kratom forests down. Eradication campaigns often destroy not only the trees but also other trees and wildlife in these areas, which are often untouched rainforests with sensitive ecosystems. A general consensus exists in southern Thailand, where the use of kratom is endemic, among leaders, public health officials, academics and policymakers that kratom use and dependence causes little, if any, health risks.

Proposed decriminalization

In 2010, the Thai Office of the Narcotics Control Board proposed decriminalizing kratom and affirmed its use as an integral part of Thai culture. The ONCB concluded that decades of unproblematic use, and an absence of health and social harm, make prohibiting the leaf unnecessary and counterproductive. According to the ONCB's report, kratom was in fact banned for economic reasons, not for health or social concerns. According to the Transnational Institute:

In Thailand, kratom was first scheduled for control in 1943 under the Kratom Act. At the time, the government was levying taxes from users and shops involved in the opium trade. Because of the increasing opium costs, many users were switching to kratom to manage their withdrawal symptoms. However, the launch of the Greater East Asia War in 1942 and declining revenues from the opium trade pushed the Thai government into action to curb and suppress competition in the opium market by making kratom illegal.

As of October 2, 2013, the justice ministry of Thailand suggested removal of kratom from the narcotic drug list relating to Category 5 of the Narcotic Drug Law of 1979, though still recommended regulating kratom in other ways due to its effects on the nervous system. This recommendation will be made to the Ministry of Public Health, which can move forward with the removal from the list or not.

Malaysia

The use of kratom leaves, known locally as 'ketum', is prohibited in Malaysia under Section 30 (3) Poisons Act 1952 and the user may be penalized with a maximum compound of MYR 10,000 (USD 3,150) or up to 4 years imprisonment. Certain parties have urged the government to penalize the use of kratom under the Dangerous Drugs Act instead of the Poisons Act, which will carry heavier penalties.

United States

The U.S. Drug Enforcement Administration has issued a "Drugs of Abuse Resource Guide", which states "Kratom is not controlled under the Federal Controlled Substances Act; however, there may be some State regulations or prohibitions against the possession and use of kratom... In addition, DEA has listed kratom as a Drug and Chemical of Concern." There is no FDA-approved medical use for kratom in the United States.

On June 9, 2015, the Food and Drug Administration (FDA) announced an import alert for kratom, issuing guidance that shipments are to be seized without physical examination from several vendors listed due to concerns that there is no evidence that Kratom does not pose an unnecessary risk of illness or injury, further stating that "[C]onsumption of kratom can lead to a number of health impacts, including respiratory depression, nervousness, agitation, aggression, sleeplessness, hallucinations, delusions, tremors, loss of libido, constipation, skin hyperpigmentation, nausea, vomiting, and severe withdrawal signs and symptoms."

Some U.S. states have considered making kratom or its psychoactive constituents illegal. In response to increasing synthetic drug use, in 2012 the Indiana House of Representatives HB1196 made Indiana the first and only state to ban chemicals in kratom. Also in 2012, Iowa legislators grouped Mitragyna speciosa as a synthetic cannabinoid when a bill was proposed that would reclassify nearly all controlled substances in their state. The Louisiana legislature proposed an age limit of 18 to be able to legally purchase, possess and consume kratom. Violators would have been assessed a penalty of no more than $500 or sentenced to six months in jail, or both. Massachusetts Representative Daniel K. Webster sponsored legislation in 2011 that would have included compounds of Mitragyna speciosa in the state's controlled substance classification list.

Advocacy

The Transnational Institute has argued that while continued research is needed, the criminalization of kratom is unfounded and is based on economic control and disinformation. This group has argued that few records are available showing negative health or social consequences from kratom consumption, but despite this fact kratom is becoming increasingly subject to actions of law enforcement in numerous countries. The criminalization of kratom has created numerous barriers for research. In Thailand, the eradication campaigns have made it especially difficult for academics and researchers to adequately research the medicinal benefits of kratom. This group has concluded that the criminalization of kratom is unnecessary, problematic and counter-productive, and has summarily recommended that kratom be decriminalized. It also concluded that the evidence showing the health benefits of kratom, especially in treating drug and alcohol dependence, should serve as an important point to consider.

External links

• Mitragynine on ToxNet CASRN: 4098-40-2
• Kratom (Mitragyna speciosa), from the European Monitoring Centre for Drugs and Drug Addiction
• American Kratom Association