Mitragyna speciosa, more commonly known as kratom, is a plant native to Southeast Asia, the leaves of which have been used traditionally as a stimulant, analgesic, and treatment for opioid addiction (1,2):
- major active alkaloid found in kratom, mitragynine, has been reported to have opioid agonist and analgesic activity in vitro and in animal models, consistent with the purported effects of kratom leaf in humans
- in its native regions, leaves of the kratom tree are typically consumed as a tea or chewed directly, and are purported to induce stimulant and opioid-like analgesic effects in the user in a dose- and time-dependent manner
- contains a number of indole alkaloids that are believed to be the primary contributors to its psychoactive effects
- mitragynine typically constitutes 1–2% of the dry leaf mass and up to approximately two-thirds of the total alkaloid content
- 7-hydroxymitragynine constitutes typically less than 0.05% of the dried leaf mass
- mitragynine is converted in vitro in both mouse and human liver preparations to the much more potent mu-opioid receptor agonist 7-hydroxymitragynine and that this conversion is mediated by cytochrome P450 3A isoforms
- compared to morphine, 7-OH-mitragynine has about 13 times the affinity for opioid receptors. 7-OH-mitragynine has about 46 times the affinity for opioid receptors compared to mitragynine (2)
- produces a mild stimulant effect in small doses, opioid-like effects in moderate to high doses, and sedative properties in very high dose
- studies have found a range of toxicities and adverse events associated with kratom use, including hepatotoxicity, seizure and coma, lung injury, kidney injury, and cardiotoxicity (2)
Reference:
- Kruguel AC et al. 7-Hydroxymitragynine Is an Active Metabolite of Mitragynine and a Key Mediator of Its Analgesic Effects. ACS Cent Sci. 2019 Jun 26;5(6):992-1001.
- Jentsch MJ, Pippin MM. Kratom. 2023 Aug 28. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. PMID: 36256767