What is Mitragynine? (KRATOM)

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Mitragynine is an alkaloid found in the Mitragyna Speciosa plant, otherwise known as Kratom.

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Mitragynine itself acts primarily via opioid receptors, though its oxidation product mitragynine pseudoindoxyl, acts as an even more potent and selective opioid agonist but with less affinity for δ or κ receptors. Another alkaloid with a major contribution to the opioid activity of the kratom plant is the related compound 7-hydroxymitragynine, which, while present in the plant in much smaller quantities than mitragynine, is a much more potent opioid agonist. The extent to which this minor but more potent agonist constituent of the plant contributes to the subjective effects of Kratom consumption is still unclear.

Dry kratom leaf contains roughly 1-6% mitragynine. A typical dose ranges from 15 mg to 65 mg. A notable distinction between mitragynine and traditional opioids is that mitragynine does not cause hypoventilation (respiratory depression) and therefore does not carry the primary safety risk associated with traditional opioids, most likely due to its agonism of the opioid receptor.

Mitragyna speciosa also known as ketum or kratom, is a tropical deciduous and evergreen tree in the coffee family (Rubiaceae) native to Southeast Asia in the Indochina and Malaysia floristic regions. M. speciosa is indigenous to Thailand and, despite growing naturally in the country, has been outlawed for 70 years because it was reducing the Thai government's tax revenue from opium distribution.

Its leaves are used for a variety of medicinal effects, but mainly to manage pain and/or anxiety. Though not an opiate itself, kratom is thought to behave similar to an μ-opioid receptor agonist like morphine and thus 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 insomnia, sweating, nausea, vomiting, chest pain, dizziness and confusion have also been reported, albeit rarely. Withdrawal symptoms have been described as light, on par with those of caffeine withdrawal.

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 known.