So what is it in kratom that gives the leaf its effects? If you’ve been a kratom consumer for long enough, you have most likely heard of special plant chemicals called alkaloids. The most popular of kratom’s alkaloids are mitragynine and 7-hydroxymitragynine.

In all, there are over 50 of these special chemicals that are responsible for the wide range of effects felt by kratom users. Read on for a little background on kratom’s alkaloids and, how they contribute to your experience, and how they may help in terms of overall health.

Important – this article covers special things that have been discovered about the chemicals inside the kratom leaf, not the kratom leaf itself. Not enough research has been done to determine how, if at all, these data could relate to traditional kratom products.

What are Alkaloids?

Alkaloids are a class of naturally occurring organic compounds that contain at least one nitrogen atom. This broad definition covers a wide range of chemicals, as alkaloids can be found in an array of plant families across the world. Many popular drugs come from plant alkaloids, including nicotine, cocaine, and morphine.

These substances tend to be bitter to the taste and can have physiological effects on humans and animals. In kratom, two of the most well-known alkaloids are mitragynine and 7-hydroxymitragynine, but there have been more than 50 discovered altogether in the kratom leaf.

Kratom’s Alkaloids

Mitragynine

Mitragynine is the most abundant of kratom’s alkaloids and is responsible for much of the plant’s effects. It is found in especially high concentrations in Green Maeng Da and Super Green kratom. This substance was first isolated in 1907 by a Dutch colonial botanist working in Malaysia.

At low doses, mitragynine provides stimulant-like effects, increased energy and alertness. At higher doses, it produces sedative effects. It is these sedative effects that make kratom an effective tool for managing pain.

Mitragynine is found at concentrations of anywhere from 0.5% to >2% in natural kratom leaf. For example, a gram of kratom powder that contains 1.5% mitragynine will yield 15 mg of the alkaloid. It makes up roughly 66% of all the alkaloids found in the leaf overall.

7-hydroxymitragynine

The other primary alkaloid in kratom, 7-hydroxymitragynine, is responsible for kratom’s more potent effects. It is found in very small concentrations in organic kratom leaf but it provides significant effects.

Although the numbers vary widely between studies, one study found that 7-hydroxymitragynine is about 99% as effective in terms of receptor activation and 10.71x more potent than morphine. The same study found mitragynine to be 95% as effective and about 1/4 as potent as morphine.

7-hydroxymitragynine is present in kratom at concentrations of roughly zero to 0.05% with anything higher being considered rare. In fact, many of the pieces of legislation related to regulating kratom include a requirement that 7-hydroxymitragynine be limited to less than 2% of total weight. This is because it has shown a notably higher propensity for abuse and greater side effects.

Paynantheine

Paynantheine is another alkaloid found in kratom that has received attention for its potential effects. Paynantheine is an smooth muscle relaxant and a selective inhibitor of the neuronal uptake of dopamine.

In vitro clinical trials have shown that paynantheine produces similar effects to drugs like baclofen and diazepam. Paynantheine has also been shown to increase the effects of other kratom alkaloids, including mitragynine and especially, seven-hydroxymitragynine.

Paynantheine is found in kratom at concentrations of around 9% of total alkaloid content and about 0.25% in comparison to the weight of the whole leaf. This means that a gram of it contains roughly 2.5 mg of paynantheine, though this amount can vary between batches due to the variability in nature and how the leaf is processed or cured.

Speciogynine

Another one of kratom’s alkaloids is is speciogynine. Speciogynine is structurally similar to mitragynine and other yohimbe alkaloids and it acts as a smooth muscle relaxant.

Speciogynine has been shown to produce relaxing and sedative effects in animal studies. These effects are likely mediated by the speciogynine’s ability to act as an agonist at kappa-opioid receptors.

Speciogynine is found in kratom at concentrations of about 7% of total alkaloids. In relation to the total weight of the leaf, its concentration is aroud 0.20% to 0.25%. This means a gram of pure kratom leaf contains in the neighborhood of 2.2 mg of speciogynine.

While speciogynine’s effects have not been studied as extensively as other of kratom’s alkaloids, the available evidence suggests that it may play a role in kratom’s relaxation and sedative effects.

Speciociliatine

Speciociliatine is one of kratom’s alkaloids that is structurally similar to speciogynine and other yohimbine alkaloids. It is found in kratom at concentrations of around 0.80% to 0.99% of total alkaloids, which ends up being about 0.2% to 0.25% relative to the weight of the ground leaf. This means a gram of kratom contains 2.0 to 2.5 mg of the substance.

Just like several of kratom’s alkaloids, it acts on the opioid receptors. However, it shows mild activity at the µ-opioid receptors and negligible efficacy at κ-opioid receptors.

It is about 2% as effective as morphine in its ability to bind to the opioid receptors, which makes it approximiately 13x less potent than morphine. Its oral bioavailability, which is a measure of how well the body absorbs a substance, is around 21% compared to mitragynine’s 17%. To put that into perspective, morphine’s bioavailability is a bit over 20%.

Mitraphylline

Mitraphylline is another one of kratom’s alkaloids that has received attention for its potential effects but is lacking in study data. Mitraphylline is structurally similar to yohimbine and other alkaloids in the class of indolealkylamines.

It acts as a smooth muscle relaxant and a selective inhibitor of the neuronal uptake of dopamine. It may also act as a vasodilator, diuretic, and a potential-anti-cancer agent.

Its ability to potentially stimulate the immune system, particularly by regulating lymphocyte production, have been documented. Also, studies have shown that mitraphylline inhibits the growth of certain cancer cells.

In vitro clinical trials have shown that mitraphylline produces similar effects to drugs like baclofen and diazepam. Mitraphylline has also been shown to increase the effects of other kratom alkaloids, including paynantheine and, especially, seven-hydroxymitragynine.

Mitraphylline is found in kratom at concentrations of around 0.50% to 0.70% of total alkaloids. Again, the concentration in wild kratom leaves can vary wildly based on plant genealogy, time of year, climate, soil conditions, and the drying process.

Ajmalicine

Ajmalicine, also known as raubasine or by its chemical name, cis-trans-isoajmalicine, is yet another one of kratom’s alkaloids with a long history of use in traditional medicine. It is an alpha-adrenergic receptor antagonist.

It has a wide range of potential effects and uses including treatment for anxiety, depression, hypertension (high blood pressure), and as an anti-inflammatory agent.

Ajmalicine is structurally similar to yohimbine and other alkaloids in the class of indolealkylamines. This may explain much of its blood pressure regulating effects. In fact, it has been marketed worldwide as the main ingredient in many prescription drugs such as Duxil, Lamuran, and Sarpan.

Ajmalicine is found in kratom at concentrations of around 0.03% to 0.09%. This means that a gram of kratom contains about 30 to 90 micrograms (mcg) of ajmalicine.

Corynantheidine

Unlike a handful of kratom’s alkaloids that have only agonistic actions at the opioid receptors, corynantheidine shows some antagonist action. It is an antagonist at the delta-opioid receptor.

Nevertheless, the alkaloid showed potent antinociception (pain relief) properties in live rats. Its presence in kratom leaves is less than 1% of total alkaloid content. Aside from the kratom leaf, it is also found in yohimbe.

In a study performed on rats, it was shown to block the blood pressure increasing effects of adrenaline at certain dosages, which is a strong attestation to its anti-hypertensive effects. It also inhibits the growth of some strains of the flu virus. Additionally, studies show that corynantheidine is toxic to five different types of human cancel cells.

Corynoxine A and B

Corynoxine A and B are two more of kratom’s alkaloids that have received a good deal of attention for their potential effects and how understudied they are. They are found in the kratom leaf at concentrations of around 0.09% to 0.14%. This means that a gram of kratom contains about 90 to 140 mcg of corynoxine A and B.

Corynoxine A has also been shown to increase dopamine release in the striatum while corynoxine B has been shown to decrease dopamine release in the striatum. This mediation of dopamine helps explain some of its effects.

The corynoxines have also been shown to induce autophagy and diminish neuroinflammation in rotenone-induced animal models of Parkinson’s disease. This suggests that they may have neuroprotective effects and could be potential treatments for neurodegenerative diseases like Parkinson’s.

The corynoxines are also known to have vasodilatory effects. This means that they can widen blood vessels and increase blood flow. This is a positive thing for those who seek to modulate their blood pressure.

Epicatechin

Epicatechin is a catechin, which is a type of flavonoid. It is found in kratom at concentrations of around 0.02% to 0.03%. This means that a gram of kratom contains about 20 to 30 mcg of epicatechin.

Most famous for being found in dark chocolate, epicatechin is also found in notable quantities in green tea. It is a powerful antioxidant and is capable of protecting against oxidation due to the radicals hydroxyl, peroxyl, superoxide, and DPPH radicals.

Protection against oxidation means less damage to cells and this can make you appear to age less, improve your brain health, reduce your chances of cancer, improve your mood, and improve the appearance of your eyes and skin.

It has also shown promise in the areas of building lean muscle mass through myostatin inhibition, increasing nitric oxide production, regulating blood sugar, and lowering cholesterol.

Rhynchophylline and Isorhynchophylline

The last of kratom’s alkaloids which will be covered here are rhynchophylline and isorhynchophylline. These are tetracyclic oxindole alkaloids found in relatively low concentrations in the kratom leaf – under 1% of total alkaloids.

They are neuroprotective, meaning they protect neurons from damage and thus support healthy brain function. One study done with isorhynchophylline showed improved cognition in rats after they were treated with a compound that is toxic to neuronal cells.

Both alkaloids have shown potential to treat vascular dementia, cerebral ischemia, arrhythmia, and epileptic seizures. This is due to they protect neurological cells and regulate the metabolism of neurotransmitters.

As another benefit, these two alkaloids block the calcium channel of cells while simultaneously opening the potassium channels. This stops calcium from getting into the cells of the heart and arteries, allowing the heart to beat more easily. This causes blood vessels to dilate and effectively reduces blood pressure.

Conclusion

Alkaloids are chemicals found in various plant species throughout the world. Kratom’s alkaloids are what gives it its effects and provides its health benefits.

Mitragynine and 7-hydroxymitragynine are the most common of over 50 alkaloids and provide most of the pain relieving and stimulatory effects of kratom. These two of kratom’s alkaloids, and the many others, have also been associated with health benefits ranging from blood pressure maintenance to anti-cancer properties.

What are Alkaloids?