HomeKratomWhat Is Mitragynine: An Overview Of Pharmacology And Toxicology

What Is Mitragynine: An Overview Of Pharmacology And Toxicology

The Mitragyna speciosa is a psychoactive plant. It is also known as kratom. It contains the naturally occurring indole alkaloid mitragynine. The Kratom tree is tropical and evergreen. It is native to Southeast Asia, particularly Thailand, Malaysia, and Indonesia.

Traditional communities in these regions have long used kratom for its medicinal properties. They utilized the plant’s aqueous decoction to address various health issues such as diarrhea, muscle pain, and hypertension.


Approximately 54 alkaloids have been isolated and identified from this plant species. These alkaloids contribute to the overall chemical composition of kratom and may play a role in its potential effects and properties. Mitragynine is primarily responsible for the psychoactive properties of kratom.

In Mitragyna speciosa leaves, the amount of mitragynine can differ based on climatic and geographical conditions. Studies have shown that Thai M. speciosa exhibits a significantly higher mitragynine content, reaching as high as 66%, compared to Malaysian-cultivated M. speciosa, which typically has approximately 12% mitragynine content.

Phytochemistry And Pharmacokinetics

Mitragynine is classified as a corynanthe-type alkaloid. It consists of an indole aromatic ring connected to two piperidine rings. It has a methoxy group (OCH3) at the C9 position of the indole ring. A carboxylic acid group (COOH) at the C17 position and a hydroxyl group (OH) at the C16 position. It has a bicyclic structure with a central indole ring fused with a dual-ring system. Mitragynine is classified as a corynanthe-type alkaloid.

Alkaloids of corynanthe-type, including mitragynine, are categorized into four different groups. These categories are standard, pseudo, allo, and epi-also, depending on their chemical structures. Mitragynine is part of the allo group. The diastereoisomers, speciogynine and speciociliatine, fall under regular and epi-allo groups. These structural differences are believed to play a significant role in the psychoactive effects of these alkaloids.

Mitragynine is also called 9-methoxy-corynantheidine. It has an empirical formula of C23H30N2O4 and a molecular weight of 398.50. Its pKa value is 8.1, indicating its basicity, and it has a melting point of 104°C.


The conformational studies have revealed free rotation in exocyclic groups. While Rings A and B are considered planar, contributing to their aromatic nature. Ring C is a piperidine derivative crucial for mitragynine binding to opioid receptors. The nitrogen atom plays an essential role in the binding.

Mitragynine exhibits analgesic and sedative effects by acting on opioid receptors in the brain. It also has stimulant properties when taken in lower doses. Thus, it promotes enhanced energy and focus. Despite this effect, it is essential to note that the U.S. Food and Drug Administration (FDA) has not approved kratom or mitragynine for any medical applications. According to the FDA, the safety, potential risks, and lack of comprehensive scientific data regarding kratom use have raised concerns.

The chemical composition of kratom is more complex. It contains many alkaloids in varying concentrations. In addition to mitragynine, other alkaloids in kratom include speciogynine, paynantheine, speciociliatine, and 7-hydroxy-7H-mitragynine. The concentration of these alkaloids contributes to kratom’s overall effects and potency. Research has indicated that mitragynine has a high affinity for mu (µ), delta (δ), and kappa (κ) opioid receptors, which are involved in pain perception, mood regulation, and addiction processes.

Administration And Use

Kratom is traditionally consumed by chewing leaves or brewing tea. Modern users also smoke or swallow capsules or use them in gum-like substances. It is used for various purposes, including pain relief, stimulation, treating opioid addiction, and as a recreational euphoric.

Advocates of kratom suggest that the mitragynine herb offers various health benefits. These include pain relief, mood enhancement, increased energy levels, and improved focus. Concerns about its dependence have led to scrutiny and caution regarding kratom use worldwide.

Forensic Toxicology

Kratom and its alkaloids have faced scrutiny and regulatory challenges in different parts of the world. The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) highlights concerns about adverse effects and the lack of comprehensive scientific data on long-term use. It is important to note that using mitragynine and kratom is an ongoing debate and regulation topic. The effects and risks of these substances can vary among individuals. Their legal status may also differ in different jurisdictions.

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Mitragynine can produce opium-like effects at higher doses. The local agricultural community has consumed kratom as a stimulant to enhance endurance and combat fatigue while working in hot conditions. In contrast, some studies suggest  that mitragynine can have effects similar to cocaine and opium on the human body.

Mitragynine is often likened to opioids due to its analgesic properties but is associated with milder withdrawal symptoms. Extensive preclinical and clinical studies have supported using this alkaloid as a potential candidate for analgesic treatment. The available data suggest that mitragynine binds to opioid receptors, particularly MOR, to exert its analgesic effects.

These findings highlight the potential of mitragynine as an alternative to traditional opioid-based pain medications. Its unique pharmacological profile offers the potential for effective pain relief with reduced risk of adverse effects and dependence. However, further research is necessary to fully understand the mechanisms of action, optimize dosage guidelines, and evaluate long-term safety and efficacy.

Kratom has shown potential as an effective pain reliever for chronic pain by binding to opioid receptors. Among the compounds found in kratom, 7-hydroxy mitragynine stands out for its potency, being reported as 13 times more potent than morphine.

Kratom similarly exhibits interactions with opioid receptors to morphine and codeine, classifying it as an atypical opioid. By selectively modulating specific signals, kratom potentially accounts for its comparatively more tolerable side effects when compared to conventional opioids.

While mitragynine shows potential as an alternative to traditional opioid-based pain medications, further research is needed to fully understand its mechanisms of action, establish optimal dosage guidelines, and evaluate long-term safety and efficacy. Responsible use of mitragynine and kratom requires consultation with healthcare professionals and adherence to local regulations.

Its interaction with opioid receptors provides kratom with its analgesic, sedative, and stimulant properties. Nevertheless, it is essential to exercise caution and remain informed regarding the latest research findings, regulations, and recommendations. Further scientific exploration and evidence are needed to understand mitragynine and its potential benefits and risks comprehensively.


As the scientific exploration of mitragynine and kratom continues, it addresses research gaps. Establishing standardized dosage guidelines for kratom is essential. The ongoing evidence of comprehensive clinical trials and in-depth pharmacological studies are crucial. Mitragynine, one of the most potent alkaloids in kratom, plays a significant role in its effects.

Reference Links

  1. Hassan Z, Muzaimi M, Navaratnam V, Yusoff NHM, Suhaimi FW, Vadivelu R, Vicknasingam BK, Amato D, von Hörsten S, Ismail NIW, Jayabalan N, Hazim AI, Mansor SM, Müller CP. From Kratom to mitragynine and its derivatives: Physiological and behavioral effects related to use, abuse, and addiction. Drug Alcohol Depend. 2013 Jan 1;129(1-2):1-23. doi: 10.1016/j.drugalcdep.2012.10.002.
  2. Raffa RB, editor. Kratom and Other Mitragynines: The Chemistry and Pharmacology of Opioids from a Non-Opium Source. 1st edition. Boca Raton, FL: CRC Press; 2014. 366 pages. ISBN: 9781482225181.
  3. Basiliere SP. Improved Detection of Kratom Alkaloids in Forensic Toxicology [dissertation]. Huntsville, TX: Sam Houston State University; December 2019.
  4. Boffa L, Ghè C, Barge A, Muccio G, Cravotto G. Alkaloid Profiles and Activity in Different Mitragyna speciosa Strains. Nat Prod Commun. 2018 Sep;13(9):1111-1116.
  5. Suhaimi FW, Yusoff NHM, Hassan R, Mansor SM, Navaratnam V, Müller CP, Hassan Z. Neurobiology of Kratom and its main alkaloid mitragynine. Brain Res Bull; 2016.
Christina Earle
Christina Earle is a licensed psychologist practicing in Oakland, California since 1999. She provides counseling to people who are struggling with managing stress, and anxiety related issues. In her free time, she often writes on mental health conditions that educate the individuals to explore ways of improving their health.

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