Mitragynine is an indole-based alkaloid and is one of the main psychoactive constituents in the Southeast Asian plant Mitragyna speciosa, commonly known as kratom.

Such preparations are orally consumed and typically involve dried kratom leaves which are brewed into tea[4][5] or ground and placed into capsules.

[7][8] As of 2018[update], the FDA had noted, in particular, that there had been no clinical trials to study safety and efficacy of kratom in the treatment of opioid addiction.

[9] Mitragynine-containing kratom extracts, with their accompanying array of alkaloids and other natural products, have been used for their perceived pain-mitigation properties for at least a century.

[12][4] In one laboratory study in a rat model in 2016, alkaloid-containing extracts of kratom gave evidence of inducing naloxone-reversible antinociceptive effects in hotplate and tail-flick tests to a level comparable to oxycodone.

[5][10][4] The concentration of mitragynine and other alkaloids in kratom have been found to vary between particular "strains" of the plant, thus indicating "strain-specific" effects from consumption, as well.

[5] Kratom extracts are often mixed with other easily attainable psychoactive compounds—such are found in over-the-counter cough medicines—to potentiate the effects of the concentrated levels of mitragynine.

[13] Due at least in part to the activity on opioid receptors, mitragynine can result in dependence and lead to withdrawal symptoms when discontinued.

[20] The solubility of mitragynine in acidic water is higher (3.5 mg/ml at pH 4), however, this alkaloid can become unstable, so certain products, such as low-pH beverages, have a very short shelf life.

[22][5] Additionally, several reports of mitragynine pharmacology indicate potential biased agonism activity favoring G protein signaling pathways independent of beta arrestin recruitment,[22][11][10] which was originally thought to be a primary component in reducing opioid-induced respiratory depression.

[22] However, recent evidence suggests that low intrinsic efficacy at the mu-opioid receptor is responsible for the improved side effect profile of mitragynine, as opposed to G protein bias.

[22][4] Mitragynine consumption for medicinal and recreational purposes dates back centuries, although early use was primarily limited to Southeast Asian countries such as Indonesia and Thailand, where the plant grows indigenously.

[26][27][28] This opposition led the DEA to withdraw its report of intent in October 2016, allowing for unencumbered research into the potential benefits and health risks associated with mitragynine and other alkaloids in the kratom plant.

Conversely, animal studies control for such variability, but offer limited translatable information relevant to humans.