What is Mitragynine? Everything You Need to Know About Kratom’s Primary Alkaloid

There are more than 16 active alkaloids in kratom, but up to 67% of the alkaloid profile comes down to just one compound — mitragynine. Here’s how it works. 

Dan Simms Last Updated: July 14, 2022 Print

With kratom becoming increasingly popular in the western hemisphere, its primary alkaloid — mitragynine — has been getting more and more attention. Scientists are still carrying out research on this active ingredient, but we already know a lot about it from the past 50 years of examination on kratom and its active ingredients. 

In this article, we’ll discuss exactly what mitragynine is, where it comes from, and how it interacts with the body. We’ll also explore what the research says so far about this controversial compound.

What is Mitragynine?

Mitragynine is one of the active alkaloids found naturally in the kratom tree (Mitragyna speciosa). This tree grows in the tropical forests around Southeast Asia, predominantly in places like Indonesia, Bali, Thailand, Vietnam, and Malaysia. 

Mitragynine is one of the dozens of alkaloids found in this plant, but it’s the one that appears in the highest concentrations and is believed to have the most significant impact on dopamine, opiate, serotonin, and norepinephrine receptors. 

What Does Mitragynine Do?

Mitragynine plays several roles in the human body and is responsible for a few of the primary effects you can expect when consuming kratom powder. We’ll briefly discuss the major effects of consuming mitragynine below and how they work.

1. Pain Relief (Opiate-Like Activity)

Kratom is quite commonly used to dull pain and delay the onset of fatigue. It’s been used for these purposes for hundreds — or perhaps, thousands — of years in traditional medicine. The primary pain-relieving effects of kratom are attributed to another alkaloid — 7-hydroxymitragynine — but mitragynine is still largely responsible for this benefit.

Specifically, mitragynine has been shown through scientific research to bind with μ-opioid receptors [1]. These receptors are specifically responsible for managing the body’s response to pain [2]. When compounds like mitragynine bind to these receptors, they prevent them from sending pain signals to the brain. As such, pain stimuli can be intercepted by alkaloids like mitragynine, which reduces the intensity of pain signals reaching the brain and, therefore, the overall perception of pain.

Mitragynine affects the body much like prescription opiates, such as oxycodone and hydrocodone. These prescription medications bind to opioid receptors and prevent pain signals from traveling to the brain, which leads to the perception of pain. The primary difference is the side effects that are attributed to opiate use, including depression of the respiratory system [3].

Kratom is considered to be far less addictive than opiates, which is an important distinction for those who need pain relief but have a history of addiction.

Mitragynine has also been shown to bind to δ-opioid receptors, which is another type of receptor responsible for managing pain [4]. The same research study suggests that mitragynine can block intracellular calcium channels that are required for the perception of pain.

Finally, mitragynine has been proven to be an alpha-2 agonist, which means it inhibits the release of norepinephrine, causing a cessation of neuropathic-specific pain [5,6,7].

2. Euphoria (Dopaminergic Effects)

Many strains of kratom produce a sense of euphoria for users. As mentioned above, mitragynine interacts with μ-opioid receptors. These receptors are responsible for sending negative signals to the brain, which are usually related to pain. However, these receptors are also involved with the regulation of dopamine and feelings of euphoria [4].

Research shows that mitragynine can also improve the user’s mood and outlook on life, possibly because it increases dopamine levels in the brain by binding to dopamine receptors [8]. Increased dopamine levels can lead to arousal, feelings of motivation, and increased energy and focus [9]. All of these natural responses combine to create a feeling of euphoria in kratom users that can be quite pleasant, especially if combined with relief of chronic or intense pain.

3. Sedation (GABAergic Activity)

Finally, mitragynine is responsible for feelings of relaxation and a general cessation of anxiety and stress in kratom users. Both μ-opioid and δ-opioid receptors play a role in feelings of stress and relaxation [10]. Since mitragynine binds to both, it causes the user to feel less anxious. Mitragynine is, evidently, one of the primary alkaloids responsible for the sedation that most kratom users experience.

Mitragynine is also a central nervous system suppressant overall, so it can reduce anxiety and pain signals that keep individuals up at night. As such, it’s unsurprising that kratom — because of its mitragynine content — is commonly used as a sleep aid and overall relaxant.

Is Mitragynine Safe?

Mitragynine is generally considered to be a safe compound [11], but it certainly comes with its fair share of problems. Most of these problems can be avoided by practicing responsible consumption. 

Kratom and its alkaloids are also important harm-reduction tools for keeping off more dangerous and addictive substances such as heroin, fentanyl, prescription painkillers, and benzodiazepines.

With that being said, any chemical or compound that interacts with the human body can potentially be dangerous, and mitragynine is no exception. We’ll explain some of the side effects of regular kratom use below.

Risk of Addiction

The most serious and most commonly cited risk of using mitragynine — via kratom — is dependency. Any chemical that interacts with neurotransmitters and the body’s opioid receptors comes with the risk of dependency. Chemicals that affect your brain chemistry can become physiologically addictive, especially if you’re using them to treat deep-seated issues like anxiety or depression.

Kratom can be an addicting compound, but it’s relatively easy to avoid this side effect. For most people, it suffices to take a week or two-week break from kratom once a month and to limit weekly intake to four to five days a week.

Kratom is generally considered to be far less addictive than opioids, and it’s even used as a tool to wean people off of opiate addiction. Still, it’s important to understand the risks so that you can avoid addiction entirely.

Kratom Wobbles

The kratom wobbles refer to a syndrome users experience after taking too much kratom. It involves a loss of coordination, nausea, and dizziness. 

Kratom can cause your blood pressure to drop or rise, depending on the strain and dosage. If you take a strain and volume that leads to a drop in blood pressure, you could experience dizziness, especially when moving from a lying down or sitting position to standing. Staying hydrated can help mitigate this symptom.

Lethargy

Any drug or compound that interacts with your dopamine levels and causes changes to hormone levels can cause lethargy. In the case of mitragynine, the compound can cause an increase in adrenaline levels, which, over time, raises your baseline level of bodily excitement and stimulation. This can lead to feelings of lethargy and exhaustion, especially once the kratom wears off and your adrenaline levels drop below that baseline.

Anxiety

Kratom’s effects on adrenaline can lead to anxiety, especially shortly after kratom use. Adrenaline levels can spike, and this hormone is primarily responsible for the body’s fight-or-flight mechanism. With increased levels of adrenaline, it’s common for users to feel stressed or anxious, similar to what you’d expect after drinking several cups of coffee.

Is Mitragynine an Opiate?

Mitragynine acts like an opiate, but it is not considered to be one. It can bind to opioid receptors and produce pain-relieving and sedative effects, much like prescription opiates. However, mitragynine is considered to be far less addictive than opioids, and they don’t cause the same bodily effects that conventional opiate drugs do. 

Specifically, kratom does not slow down your respiratory system. The euphoria experienced by opioid users is also less intense than is experienced by kratom users, making kratom less addictive overall.

Where Does Mitragynine Come From?

Mitragynine is naturally found in kratom, which is made from the leaves of the Mitragyna speciosa tree. Kratom is currently the only known natural source of mitragynine and many other alkaloids, including 7-hydroxymitragynine and 9-hydroxycorynantheidine.

Some of the other alkaloids in kratom can be found in plants like Pausinystalia johimbe or Uncaria rhynchophylla

What Kratom Strains Contain the Most Mitragynine?

If you’re looking to use mitragynine for pain relief, sedation, or relieving stress and anxiety, you’re most interested in kratom strains that contain high levels of this psychoactive alkaloid.

Kratom comes in three primary categories depending on how it was processed after harvest: white vein, green vein, and red vein. 

White kratom strains tend to be highest in mitragynine content. Furthermore, strains originating in Thailand are usually the most mitragynine-dense, while strains from Malaysia tend to have some of the lowest mitragynine concentrations.

Some specific strain suggestions for high mitragynine content include White Bali, White Elephant, and White Thai.

Mitragynine Dosage Guidelines

Mitragynine is very rarely available in its raw form, and most users take this alkaloid via kratom powder, kratom leaves, or kratom extracts. In fact, isolated kratom extracts have proven time and time again to be less effective and more dangerous than the raw plant. The effects of kratom alkaloids are complicated and likely rely on a synergistic cation between numerous compounds rather than the effects of just one. 

As such, it’s more or less useless to have a recommended dosage of pure mitragynine.

Instead, dosing mitragynine via kratom is more practical. For users looking for the pain relief and sedation provided by this alkaloid, high doses of kratom are recommended. For mitragynine-rich strains, a dose of raw powder between 5 and 6 grams is typically recommended. 

Beginners should start with a lower dose — between 2 and 5 grams — to avoid unwanted side effects.

Mitragynine is a somewhat unique compound in that the effects you experience will vary based on how much you consume. For users looking for euphoria or mild stimulation, a smaller dose of between 1 and 3 grams of kratom powder will likely do the trick. 

It’s also important to choose a strain that contains high levels of mitragynine and relatively low levels of 7-hydroxymitragynine, which include most white-vein kratom strains.

Final Thoughts: MItragynine and Its Uses

Mitragynine is one of the primary alkaloids contained within kratom, which refers to crushed leaves from the Mitragyna speciosa tree. Mitragynine is rarely available as a concentrated alkaloid and is instead consumed via kratom powder. In low doses, mitragynine can cause euphoria and stimulation, and sedation, anxiety relief, and pain relief are typically reported with higher doses.

Mitragynine is considered to be safer than prescription opioids, whose effects are commonly compared to those of kratom. However, there are some side effects — including dependency, nausea, dizziness, and lethargy — that you should be on the lookout for. Overall, mitragynine is a great option for those looking to reduce pain, induce relaxation, or increase motivation, and it’s safer and more natural than other prescription drugs that provide the same effects.


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