The Science of Kratom's Most Well KnownCompound: Mitragynine Explained

• What is Mitragynine?
• Mitragynine Molecular Structure
• Mitragynine Pharmacological Effects
• Therapeutic Uses of Mitragynine
• Mitragynine Potential Risks
• Mitragynine Legal Ambiguities
• Kratom's Full Spectrum Alkaloid Profile
• FAQ
• Bottom Line

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Mitragynine is the most well known and quantified psychoactive compound in kratom, a tropical tree native to Southeast Asia. This pivotal component is responsible for Kratom's various effects, ranging from pain relief to enhanced focus. 

This article explores mitragynine's uses, effects, and potential risks, shedding light on this fascinating kratom compound.

What is Mitragynine?

Mitragynine is a naturally occurring alkaloid (active compound) found in the leaves of Mitragyna speciosa, a psychoactive medicinal plant known as kratom. Kratom leaves produce more than 40 structurally related alkaloids. However, research shows mitragynine is chief among them, making up about two-thirds of the plant’s total active content. Another prominent alkaloid in kratom is 7-hydroxymitragynine (7-OH-mitragynine). 

Mitragynine's physiological effects stem from interacting with the body's opioid receptors, primarily in the central nervous system. This interaction triggers various responses, including pain relief and stimulation, akin to those produced by opioid drugs like morphine. However, what sets mitragynine apart is its tendency to exhibit these effects with a lower intensity, minimizing the risk of severe adverse reactions often associated with traditional opioids.

The compound's potential as a tool for managing pain and mitigating the symptoms of opioid withdrawal has garnered significant attention. In regions where kratom is prevalent, such as Southeast Asia, locals have long relied on mitragynine to alleviate conditions like diarrhea, muscle pain, and hypertension. Its stimulating properties have also made it it valuable for agricultural workers seeking increased endurance and alertness during demanding labor.

Mitragynine Molecular Structure

On a molecular level, mitragynine is a “corynanthe-type monoterpene indole alkaloid (MIA).” MIAs are metabolites containing a bicyclic structure of a benzene ring fused to a five-membered pyrrole ring. Their chemical complexity lends them to various therapeutic uses, including cancer, neurological, and cardiovascular treatments. 

Mitragynine Pharmacological Effects

Mitragynine’s pharmacological effects come mainly from its ability to bind to the body’s opioid receptors, distributed throughout the central nervous system.

• Preliminary research in animal studies shows mitragynine acts as an “atypical” opioid agonist. 
• Specifically, mitragynine is an agonist of the μ-subtype opioid receptor (MOR), which targets serotonin and dopamine signaling pathways and is the main target of synthetic opioid drugs.
• Induces analgesia (pain relief) like classical opioids but with a milder effect.

Mitragynine also has a wider therapeutic window as an “atypical” opioid. A wider therapeutic window means mitragynine can be used over a range of doses with a greater safety margin between the effective dose and the dose that causes adverse or harmful effects. In practical terms, Mitragynine can provide its desired therapeutic benefits (such as pain relief or withdrawal symptom reduction) at doses less likely to result in severe side effects or overdose than other substances.

For example, animal studies with kratom show that mitragynine doesn’t appear to cause respiratory depression resulting from classical opioids, in which users have slower breathing. This is a crucial benefit because opioid overdoses usually occur when a user’s respiratory system stops completely. 

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Dose-dependent effects

Mitragynine effects also appear dose- and time-dependent, with distinct differences between lower and higher quantities. 

• Low doses, such as in a few grams of dried kratom leaves, cause invigorating effects and euphoria. Users might report increased work capacity, alertness, and sociability. The effects often start within 10 minutes and last 1 to 1.5 hours. 

• Intermediate doses, such as 10-15 grams of dried leaves, produce the most pain relief and withdrawal assistance. Users might experience soothing, opium-like effects, such as calmness, euphoria, and a dream-like state. 

• Higher doses, such as in 15-25 grams of dried leaves, can result in sweating and dizziness. 

Therapeutic Uses of Mitragynine

Southeast Asia cultures have traditionally consumed kratom’s mitragynine-filled leaves to treat ailments, such as: 

• Diarrhea
• Muscle pain
• Hypertension

Kratom’s stimulating and analgesic effects have also made it popular among agricultural workers who use it to increase endurance and counteract fatigue.

In the United States, people use kratom for recreational and medicinal purposes. According to a CNN Health report, thousands claim kratom helped them quell addictions to painkillers.

• “Kratom saved my life by getting me through the hardest thing I’ve ever had to do.”
• “Hooked on Oxy, Hydro, and Adderall for over a year. Kratom helped me kick the habit.”

Kratom's multifaceted uses and success stories highlight mitograine’s growing significance in addressing diverse health needs and addiction challenges. At the same time, mitragynine opioid-like powers also come with risks.

Mitragynine Potential Risks

Abuse potential: Mitragynine’s central nervous system actions involving μ-opioid receptors give it the same traits as other addictive drugs. While therapeutic, the effects also suggest a strong abuse potential.

Lack of clinical studies: No clinical studies involving humans examine mitragynine’s alleged therapeutic effects or quantify any potential risks of kratom use. The FDA reports it is unaware of any evidence that would meet the agency’s standard for approval.

Unregulated sales: The kratom industry is an unregulated market, which means that brands are not legally obligated to conduct safety and purity tests. Consumers must seek third-party tested products to avoid contaminated or mislabeled products. 

‍Withdrawal: Kratom’s withdrawal symptoms aren’t as severe as classical opioids. However, regular use can lead to dependence and mild adverse effects, including:

• Cravings
• Weakness and lethargy
• Anxiety
• Restlessness 
• Nausea
• Sweating
• Muscle pain
• Jerky movements of the limbs
• Tremors
• Sleep disturbances, and hallucinations

Mitragynine can also bind to receptors in the brain that impair neurologic and cardiovascular function. Although rare, seizures and respiratory depression can occur. The FDA released reports of 36 kratom-related deaths. 

Mitragynine Legal Ambiguities

Mitragynine legality varies worldwide. Kratom is illegal in many countries, from Australia to Japan to Sweden. However, it remains legal in the US. 

The DEA intended to place mitragynine into Schedule I of the Controlled Substances Act, but the agency didn’t proceed due to a large public outcry. 

Today, consumers in the United States can readily buy kratom online and find it in smoke shops, health stores, and even farmers’ markets. However, brands must be careful about how they advertise these products. The FDA reports that no companies legally market kratom and can enforce these rules through several mechanisms:

• Warning letters
• Product seizures
• Injuctions
• Recalls
• Criminal prosecution
• Civil monetary penalties

Kratom legality also varies by state. Several states, like Alabama, Rhode Island, and Wisconsin, have banned kratom use, sales, and possession. Other states have made moves to protect the industry. 

The Kratom Consumer Protection Act (KCPA) is the most recent movement aimed at codifying the industry while allowing regulators to establish common-sense rules. Currently, Georgia, Arizona, Nevada, Utah, and Florida have passed versions of the KCPA. Florida’s version prohibits the sale of kratom to anyone under the age of 21.

Beyond Mitragynine: Understanding Kratom's Full Spectrum Alkaloid Profile

Mitragynine has garnered significant attention as a key component in kratom for good reason. However, a common misconception prevails regarding its sole significance in determining the quality of Kratom products.

The market has witnessed the emergence of extracts with over 70% Mitragynine concentration. However, this focus on high Mitragynine content overlooks the pharmacological importance of kratom's other alkaloids, which contribute to the plant's full spectrum entourage effect.

For instance, certain kratom alkaloids such as Speciogynine and Paynantheine possess serotonergic properties, instrumental in mood enhancement, contrasting with mitragynine's role as primarily a partial opioid agonist. Users opting for high-mitragynine products in the pursuit of superior quality might inadvertently face issues with tolerance, given Mitragynine's opioid-like activity, and the diminished presence of mood-enhancing secondary alkaloids.

Such consumers may increase their intake, mistakenly expecting enhanced mood effects, while negatively affecting their tolerance. These high mitragynine extracts often contain less than two percent of other mood-boosting alkaloids, in stark contrast to full-spectrum extracts that may comprise 10 to 20% or more.

Similarly, the cannabis industryinitially focused on THC as the most important compound. However, it is now expanding to explore over 144 cannabinoids. As with cannabis, kratom's diverse alkaloids continue to be a subject of growing scientific interest.

FAQ

What is mitragynine used for?

Mitragynine is a unique chemical found in the leaves of the Mitragyna speciosa plant (also known as kratom), a tree native to Southeast Asia. The compound works by activating opioid receptors, giving it pain-relieving and stimulating properties similar to other opioid drugs such as morphine. 

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Is mitragynine stronger than morphine?

Mitragynine is not stronger than morphine. However, some of its derivatives and related alkaloids have shown higher potency than morphine in animal studies. For instance, one study found that mitragynine pseudoindoxyl was three times more potent than morphine, and 7-hydroxymitragynine was 5-fold more potent than morphine in mice. Another study reported that 7-hydroxymitragynine exhibited 13- and 46-fold higher potency than morphine and mitragynine

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How does mitragynine affect the brain?

Mitragynine and related active compounds in kratom, like 7-OH-mitragynine, bind to the body’s opioid receptors distributed mainly throughout the central nervous system. This interaction affects body functions, such as causing sedation, pleasure, and pain relief. 

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What is mitragynine toxicity?

Reports indicate mitragynine displays fewer side effects than classical opioid drugs such as morphine. While rare, cases of mitragynine toxicity can occur, in which users experience adverse effects such as seizures, liver damage, and respiratory issues. Because mitragynine inhibits the P450 enzyme, combining mitragynine with other drugs can cause severe reactions. 

Bottom Line

Mitragynine is the most abundant alkaloid in kratom. It works as μ-opioid receptor (MOR) agonist, activating receptors in the central nervous system that increase pleasure and pain similar to classical opioids but with less pronounced adverse effects. Its similarities with opioids give mitragynine a high potential for therapeutic value, especially in helping users recover from withdrawal symptoms caused by other opioid drugs. However, mitragynine also shares similar abuse potential. The unregulated market adds uncertainty. Despite challenges, Mitragynine holds promise as a valuable tool for health and well-being. 

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