What is Mitragynine (MIT)?
Mitragynine is an indole-based alkaloid and the most prevalent active compound found in the leaves of the kratom tree (Mitragyna speciosa), which is native to Southeast Asia. First isolated in 1921, mitragynine has since been the focus of extensive scientific study to understand its complex pharmacology. The term "MIT" is widely adopted by users and vendors as an abbreviation for mitragynine, streamlining communication and product labeling. As the dominant alkaloid, mitragynine's concentration significantly impacts a kratom product's potency and the nature of its effects. The percentage of mitragynine can vary depending on the specific kratom strain, the plant's geographical origin, harvest season, and processing methods.
How mitragynine affects the body and brain
Mitragynine's pharmacological profile is complex and multifaceted, contributing to kratom's varying effects based on the quantity used. Its primary mechanism of action involves interacting with opioid receptors, particularly acting as a partial agonist at the mu-opioid receptors. This unique interaction is a key factor distinguishing its effects from conventional opioid drugs.
Mitragynine's pharmacological actions:
- Opioid receptor interaction: Mitragynine binds to and activates mu-opioid, delta, and kappa opioid receptors, influencing pain relief, sedation, and euphoria. Unlike conventional opioids, its action at mu-opioid receptors is a "biased agonism," potentially avoiding the beta-arrestin pathway linked to severe respiratory depression.
- Central nervous system modulation: Mitragynine also affects other neurotransmitter systems like serotonin, dopamine, and norepinephrine, contributing to its varied effects, including stimulant properties when smaller quantities are used.
- Active metabolite: Mitragynine is metabolized by liver enzymes into compounds, notably 7-hydroxymitragynine (7-OH). While naturally occurring in trace amounts, 7-OH is significantly more potent at mu-opioid receptors than mitragynine and contributes significantly to kratom's stronger narcotic effects, particularly with the use of larger quantities. Some products are enhanced to contain higher levels of 7-OH.
The effects of mitragynine based on quantity used
Kratom's effects are biphasic, meaning they vary based on the quantity used, largely due to mitragynine content.
Typical effects when smaller quantities are used:
- Increased energy and alertness
- Improved focus and concentration
- Enhanced sociability
- Mild mood boost
Typical effects when larger quantities are used:
- Relaxation and calmness
- Sedative and pain-relieving effects
- Feelings of euphoria
Mitragynine vs. 7-Hydroxymitragynine: A comparison
It's important to distinguish between mitragynine and its metabolite, 7-hydroxymitragynine (7-OH), due to their differing potencies and concentrations.
| Feature | Mitragynine (MIT) | 7-Hydroxymitragynine (7-OH) |
|---|---|---|
| Potency at Opioid Receptors | Moderate; acts as a partial agonist. | Highly potent, with much greater affinity for mu-opioid receptors. |
| Natural Occurrence | Most abundant alkaloid in kratom leaves, making up a high percentage of total alkaloid content. | Occurs naturally in only trace amounts, typically less than 2%. |
| Metabolism | Serves as the precursor that the body converts into 7-OH. | Is the active metabolite of mitragynine, responsible for many of kratom's potent opioid-like effects. |
| Addiction Potential | Possesses abuse potential, potentially lower risk than classic opioids in some contexts. | High concentrations may increase the potential for addiction, tolerance, and withdrawal. |
Risks, safety concerns, and regulation
The lack of federal regulation in the U.S. and many other regions means kratom product quality and safety are not guaranteed by agencies like the FDA. This leads to several safety concerns:
- Contamination: Unregulated products may contain heavy metals or harmful bacteria such as Salmonella.
- Adulteration: Some products, particularly extracts, have been found to contain adulterants or enhanced levels of potent synthetic alkaloids, increasing toxicity and addiction risk.
- Side Effects: Adverse effects include nausea, vomiting, dizziness, constipation, and potential liver toxicity. Chronic use can cause dependence and withdrawal symptoms.
- Drug Interactions: Mitragynine can interact with other medications by inhibiting liver enzymes.
- Legal Status: While not federally scheduled in the U.S., kratom's legality varies by state and locality; some areas have banned or regulated it.
Conclusion
In summary, MIT refers to mitragynine, kratom's primary active alkaloid, which dictates its effects based on the quantity used. These effects range from stimulant when using smaller quantities to sedative when using larger quantities, mediated by interactions with opioid and other brain receptors, and metabolism into the more potent 7-hydroxymitragynine. Due to the unregulated market, risks like contamination, adulteration, and dependence exist. Consumers should prioritize products from reputable sources with lab testing where legal and consult healthcare professionals.
For more information on the pharmacology of kratom, see the review on mitragynine on ScienceDirect.
