What is Mitragynine?
The most prevalent active alkaloid in the Southeast Asian plant Mitragyna speciosa, also referred to as kratom, is mitragynine, an indole-based alkaloid. Dried leaves have a total alkaloid content of 0.5% to 1.5%. In Thai variants, 7-hydroxymitragynine makes up only 2% of the overall alkaloid content, but mitragynine is the most common component, accounting for up to 66% of the total alkaloids. Mitragynine is found at a lesser quantity in Malaysian kratom variants (12% of total alkaloids). These oral formulations usually consist of dried kratom leaves that are powdered and put into capsules or made into tea.* Although mitragynine has been used for millennia for both medicinal and recreational purposes, its early use were mainly restricted to Southeast Asian nations where the plant is naturally found, such as Indonesia and Thailand. The usage of mitragynine as a medication and recreational substance has recently expanded throughout Europe and the Americas. Studies on the effects of kratom are starting to appear, but there aren’t as many on the main ingredient mitragynine.
The US Food and Drug Administration (FDA) declared in April 2019 that there were no clinical applications for kratom that were authorized and that there was no proof kratom was safe or effective for treating any illness. In a previous report, the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) had said as follows: In 2015, there was no approved medical use for kratom. In particular, the FDA had reported in 2018 that no clinical trials had been conducted to examine the safety and effectiveness of kratom in treating drug addiction. “There is no legitimate medical use for kratom,” the US Drug Enforcement Administration had also said as of 2013.
It is believed that the effects of kratom are due to mitragynine and its metabolite, 7-hydroxymitragynine. The effects of consuming dry kratom leaves vary based on the amount ingested. The plant is said to have a little stimulating effect at low doses and to generate the normal opioid drowsiness and antinociception at bigger doses. There are strain-specific effects from kratom intake, as evidenced by the variation in mitragynine and other alkaloids concentrations observed in different strains of the plant. Kratom extracts are frequently combined with other readily available psychoactive substances, such as those in over-the-counter cough remedies, in order to enhance the effects of mitragynine’s concentrated concentrations. However, the potential for abuse of mitragynine and related alkaloids has been documented in animal studies, including through the use of the conditioned place preference (CPP) test, which indicated a distinct reward-effect for 7-hydroxymitragynine. Adverse effects associated with the consumption of mitragynine-containing preparations from M. speciosa include a negative impact on cognition.
Reliance and disengagement
Mitragynine itself can cause dependence and withdrawal symptoms when stopped because of its action on opioid receptors. After stopping kratom, regular users report experiencing withdrawal symptoms similar to those of other drugs. When trying to stop using kratom, over half of the frequent users (67% of the total subjects) suffered withdrawal symptoms, which included pain, muscle spasms, and insomnia, according to a 2014 study that included 1118 male kratom users. In a research involving 239 male Malaysian kratom users who used between 40 and 240 mg of mitragynine daily, 89% of the participants reported having tried to quit kratom use in the past, with withdrawal symptoms ranging from mild (65% of subjects) to moderate/severe (35% of subjects). The majority of subjects in the same study experienced withdrawal symptoms for fewer than three days, ranging from psychological symptoms like restlessness, anxiety, and rage to physical symptoms like nausea, diarrhea, and muscular spasms. The occasional addition of additional ingredients, such as dextromethorphan and benzodiazepines, to the mitragynine mixture, however, may obscure the study’s findings and exacerbate the withdrawal symptoms. In a study involving animals, mice given intraperitoneal injections of mitragynine for 14 days experienced mitragynine withdrawal symptoms, which included anxiety, chattering teeth, and piloerection. These symptoms are similar to those of morphine withdrawal in mice and are indicative of drug withdrawal.
For at least a century, mitragynine-containing kratom extracts have been utilized for their supposed pain-mitigation (i.e., antinociception) effects, along with a variety of alkaloids and other natural compounds. Workers in Southeast Asia who report using the mild stimulant and perceived antinociceptive qualities of kratom to boost endurance and reduce discomfort while working are known to take mitragynine from whole leaf kratom preparations. Alkaloid-containing kratom extracts were shown to induce naloxone-reversible antinociceptive effects in hotplate and tail-flick tests at a level equivalent to oxycodone in a 2016 laboratory study using a rat model.
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