Kratom contains many alkaloids including 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).[1] Although 7-hydroxymitragynine and mitragynine are structurally related to yohimbine and other tryptamines, their pharmacology is quite different, acting primarily as mu-opioid receptoragonists. Other active chemicals in kratom include raubasine (best known from Rauwolfia serpentina) and some yohimbe alkaloids such as corynantheidine.
Kratom's primary pharmacology is mediated by the alkaloids 7-hydroxymitragynine and mitragynine. While these molecules share structural similarities to the psychedelics, there is no psychedelic activity or similarities in effects to such substances. Instead these alkaloids primarily interact with the opioid receptors. Accordingly, kratom is known to prevent or delay withdrawal symptoms in an opiate dependent individual, and it is often used for this purpose. It can also be used for other medicinal purposes and is sometimes used recreationally.
Kratom has been traditionally used in regions such as Malaysia, Thailand, and Indonesia, but was discovered by Western civilization during the 19th century. Besides kratom (or krathom), in Southeast Asia and the Pacific Islands it also goes by the names ithang, biak biak, ketum, kakuam, and in southern regions, thom. In these areas kratom has a history of use by laborers and in folk medicine for opium dependence and diarrhea.
Of the two main active constituents, mitragynine has been studied more thoroughly than 7-hydroxymitragynine. At lower doses, Mitragynine exhibits a yohimbine-like binding to alpha-adrenergic receptors, as well as some binding to the delta opioid receptors. As doses increase, binding to delta receptors increases, and in yet higher doses, crossover to mu receptors occurs.
7-hydroxymitragynine was only recently understood to be the main active ingredient. Limited animal research suggests it is a potent opiate agonist, but with a ceiling effect that limits the potential for respiratory depression and euphoria. No fatal overdose of kratom is known to have occurred.
While one study of Thai users reported that kratom has sedative effects in low doses, changing over to stimulation in higher doses, this seems to be incorrect. Most other sources say that it is a stimulant in lower doses, becoming sedative in higher doses, which is consistent with mitragynine's receptor binding profile. However, recent publications indicate that different alkaloids may be at work to achieve stimulation versus sedation: whereas higher concentrations of mitragynine are attributed to act as a stimulant, 7-hydroxymitragynine is the most significant alkaloid for sedation with more potent analgesic activity than that of morphine.[1] Effects come on within five to ten minutes after use, and last for several hours. The feeling has been described as happy, strong, and active, with a strong desire to do work. The mind is described as calm.
Side effects, although rare, may include dry mouth, increased or decreased urination, loss of appetite, and nausea or vomiting. Heavy use can result in a prolonged sleep. Possible side effects from long term use include anorexia and weight loss, insomnia, and dependence. Comprehensive scientific and clinical studies have yet to be conducted to establish the potential health risks associated with consistent long term consumption of kratom.
Kratom has recently become more known and used in Europe and North America where it has been prized for its applications to many conditions and ailments, primarily pain, depression, anxiety, and opiate withdrawal. While an unknown number of Americans use kratom for various conditions, the large number of internet vendors that sell kratom indicate there is a significant demand in the United States.
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