Context
Plant scientist Pieter Willem Korthals of the Netherlands provided the first scientific description of Kratom in the 1800s. Mitragyna speciosa, the scientific name for kratom, is a tree mostly found in South Asia, especially in Malaysia, Thailand, and Indonesia.
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Kratom grows to a maximum height of 25 centimeters (cm) at maturity, when it takes on the distinctive ovate-acuminate leaf morphology. This tree’s leaves have pinnate venation, which can be red, green, or white in hue.
Kratom is a member of the coffee family and has comparable stimulant qualities that are dose-dependent, although it is free of caffeine and theophylline.
Due to its opioid-like effects and dose-dependent stimulant qualities that are mediated by the indole alkaloids found in its leaves, kratom has become more and more popular over the past 20 years.
Applications for kratom
In several Southeast Asian nations, kratom has long been used for recreational and medicinal uses. It dates back hundreds of years. Usually, the common name given to kratom is unique to the area in which it is cultivated.
Fishermen, farmers, and other laborers chew only the young leaves of the kratom plant to experience its stimulating effects and lessen weariness from hard work. Kratom has also been utilized to treat drug use disorder symptoms, namely opium withdrawal symptoms. Seldom are the dried leaves used for smoking or for making a water infusion.
Malaysia and Indonesia have outlawed the use of kratom, however Thailand permits the plant’s lawful cultivation and consumption. Nevertheless, Indonesia exports kratom to the US and a number of other nations as a cash crop.
Alongside products containing cannabidiol, cannabis, and kava—all of which have both therapeutic and recreational uses—kratom is offered in Europe and the United States. In Western nations, the most common forms of kratom for sale are loose powder, tablets, and capsules.
These kratom products usually have a mitragynine content of about 2%. In contrast, kratom that has between 7% and 40% mitragynine in it is offered for sale as soft gels, candies, or semisolid resins.
Kratom has historically been utilized as an analgesic, antipyretic, anti-diabetic, anti-diarrhea, and muscle relaxant. Thai young adults have also been using kratom for the past ten years in a handmade mixture called “4 × 100.” This plant has also been cooked with caffeine-containing soft beverages for oral use and combined with cough syrups containing codeine or diphenhydramine.
Constipation, hyperpigmentation, dehydration, and weight loss are a few side effects of kratom usage. Increased dosages of kratom carry a higher risk of dependency and tolerance development in addition to fatigue and sluggishness. In Thailand, reports of infrequent overdose fatalities from 4 × 100 mixtures have also been made.
pharmacological
According to earlier studies, mitragynine and other kratom indole alkaloids may act as patentable opioid agonist precursors and eventually be turned into pharmaceuticals. Together with δ- and κ-opioid receptor antagonists, mitragynine has also been shown in a number of in vitro and in vivo investigations to be a biased partial agonist of the μ-opioid receptor. A few recent studies have also shown that certain cytochrome P450 (CYP) enzymes may convert mitragynine to 7-hydroxy mitragynine, which may account for part of the analgesic benefits of the compound.
It has also been shown that mitragynine binds α-adrenergic receptors; of these, the α1A receptor has the highest affinity, while the α2B receptor has the lowest affinity. Additionally, this molecule has poor affinity for serotonin receptors 5-HT 1A and 5-HT 2B, while two of its enantiomers have strong affinity for these receptors.
pharmacokinetics
The main active ingredient in kratom, mitragynine, makes up 66% of the plant and is quickly absorbed by the small intestine, having an effect in a matter of minutes. This compound’s concentration drops in about four hours, with a 23-hour terminal half-life.
Typically, mitragynine is converted into at least seven distinct phase I metabolites in the liver after being protein-bound in the blood. Lower amounts of twenty-five additional alkaloids, including mitragynine, have also been detected in kratom.
both preclinical and clinical results
The primary alkaloid ingredient in kratom extract that has been shown in prior in vitro research using rats to be able to lower electroencephalography (EEG) activity in the parietal and frontal cortexes is mitragynine. But a recent study showed that kratom alkaloids were necessary for the analgesic effects and pain processing of kratom, not just mitragynine.
Due to the fact that kratom is not categorized as a medication, food, or supplement, clinical trials for this product are currently limited in many countries. For instance, the Food and Drug Administration (FDA) of the United States has declared that kratom and its alkaloids are opioids. The FDA has issued a warning to the public not to use kratom and has prohibited its importation.
According to a number of self-reported polls, middle-aged, non-Hispanic white men who work full-time or as independent contractors and earn a middle-class salary constitute the majority of kratom users. Many of these people use kratom to alleviate chronic pain or mental health issues.
negative health consequences of kratom
Larger dosages of kratom can have a negative effect on health, whereas smaller amounts seldom have any effect at all. An acute overdose might include agitation, convulsions, vomiting, tachycardia, or symptoms similar to those of sedatives or opioids. 9% of cases to U.S. Poison Centers and 16–18% of cases to a Poison Center in Thailand have been recorded with seizures.
Ventricular dysrhythmias, either polymorphic or monomorphic, are also linked to the usage of Kratom. One possible explanation for polymorphic ventricular tachycardia is the effect of kratom on the QTc interval. Furthermore, after ingesting large amounts of mitragynine, there have been some documented fatalities from lung congestion brought on by respiratory depression.
There have also been several reports of liver damage linked to kratom. While severe instances necessitate the injection of ursodeoxycholic acid, N-acetylcysteine, or glucocorticoids to decrease inflammation and restore metabolic capability, the majority of patients recover within a year.
Heavy kratom users have also reported cases of Kratom use disorder (KUD), which can cause withdrawal symptoms akin to those of opiate withdrawal. Neonatals born to moms who used kratom excessively throughout their pregnancies have been known to suffer from Kratom Associated Neonatal Abstinence Syndrome (KANAS). There have also been reports of kratom’s alkaloids interfering with the metabolism of a number of pharmaceuticals and treatments.
Currently, symptomatic treatment and cessation are used to address the negative consequences of kratom usage. It has been shown that naloxone can reverse respiratory depression, and that stopping the usage of kratom can alleviate liver damage. There is no clinical evidence to support the idea that anti-dysrhythmic medications can be helpful in treating dysrhythmias.
advantages of using kratom
The most popular uses of kratom are for the self-treatment of acute or chronic pain, anxiety, or depression; it may also be used to increase focus and energy. This herb is also used to treat prescription medication withdrawal symptoms and illegal drug addictions. Nevertheless, further clinical research is required to ascertain the advantages of kratom and its alkaloids.