Kratom Alkaloids

The following is a list of Alkaloids and the percentages that are found within the kratom leaf. 

Mitragynine is the main alkaloid found in kratom, with concentrations of up to 66%. Other alkaloids present in kratom include speciogynine, speciociliatine, paynantheine, raubasine, and mitraphylline. In addition, a small amount of corynantheidine and other alkaloids are also present.

Alkaloids in Kratom

1. Ajmalicine (Raubasine): Cerebrocirculant, antiaggregant, anti-adrenergic (at alpha 1), sedative, anticonvulsant, smooth muscle relaxer. Also found in Rauwolfia serpentina. Cerebrocirculant, antiaggregant, anti-adrenergic (at alpha 1), sedative, anticonvulsant, smooth muscle relaxer.
2. It is structurally related to alkaloids from yohimbe. Ajmalicine is an α1-adrenergic receptor antagonist with preferential actions over α2-adrenergic receptors, which is the reason for its hypotensive effects. According to ‘Alkaloids: Biochemistry, Ecology, and Medical Applications‘, ajmalicine “depletes peripheral noradrenaline stores, resulting in a decrease of peripheral resistance and blood pressure. It also causes depletion of catecholamine and serotonin stores in the brain, heart, and many other organs.”
3. Akuammigine: An indole alkaloid associated with the seeds of Picralima nitida(akaumma). It is structurally like yohimbine and mitragynine. Like yohimbine, it is known to have antimalarial activity.
4. Ciliaphylline: antitussive, analgesic. < 1% of total content found in Kratom leaf.
5. Corynantheidine: μ -opioid antagonist, also found in Yohimbe. < 1% of total content found in Kratom leaf.
6. μ -opioid antagonist, also found in Yohimbe. It is related to ajmalicine and is a diastereomer of yohimbine.
7. Like ajmalicine, it is an α1-adrenergic and α2-adrenergic receptor antagonistwith 10x greater affinity for the α1-adrenergic receptor. This contrasts with yohimbine and its other diastereomer, rauwolscine, which have a 30x higher affinity for the α2-adrenergic receptor over the α1-adrenergic (opposite affinities).
8. Corynoxeine: Calcium channel blocker. < 1% of total alkaloid content found in Kratom leaf.
9. Corynoxine A and B: Dopamine mediating anti-locomotives. < 1% of total content found in Kratom leaf.
10. Dopamine mediating anti-locomotives, meaning that they act as somewhat of a sedative. They are also found in Chinese Cat’s Claw (Uncaria tomentosa). There is also some research that suggeststhey may help with Parkinson’s.
11. Epicatechin: Antioxidant, antiaggregant, antibacterial, antidiabetic, antihepatitic, anti-inflammatory, anti-leukemic, antimutagenic, antiperoxidant, antiviral, potential cancer preventative, alpha amylase inhibitor. It is also found in dark chocolate, green tea, and grapes.
12. 9-Hydroxycorynantheidine: Partial opioid agonist. One study found that “9-Hydroxycorynantheidine inhibited electrically stimulated guinea-pig ileum contraction, but its maximum inhibition was weaker than that of mitragynine and its effect was antagonized by naloxone, suggesting that 9-hydroxycorynantheidine possesses partial agonist properties on opioid receptors.”
13. 7-hydroxymitragynine: Analgesic, antitussive, antidiarrheal; total content found in Kratom leaf is minimal and believed to be extinct within the kratom leaf itself.
14. Isomitraphylline: Immunostimulant, anti-leukemic. < 1% of total content found in Kratom leaf.
15. Isomitrafoline: < 1% of total content found in Kratom leaf.
16. Isopteropodine: Immunostimulant, antimicrobial.
17. Isorhynchophylline: Immunostimulant. < 1% of total alkaloid content found in Kratom leaf.
18. Isospeciofoline: < 1% of total alkaloid content found in Kratom leaf.
19. Mitraciliatine: < 1% of total alkaloid content found in Kratom leaf.
20. Mitragynine: Indole alkaloid. Analgesic, antitussive, antidiarrheal, adrenergic, antimalarial, possible psychedelic (5-HT2A) antagonist. Roughly 66% of total alkaloid content is found in Kratom leaf.
21. Mitragynine oxindole B. < 1% of total alkaloid content found in Kratom leaf.
22. Mitrafoline: < 1% of total alkaloid content found in Kratom leaf.
23. Mitraphylline: Oxindole alkaloid. Vasodilator, antihypertensive, muscle relaxer, diuretic, antiamnesic, anti-leukemic, possible immunostimulant. <1% of total alkaloid contents in Kratom leaf.
24. Mitraversine Found in Mitragyna parvifolia and may also be in Mitragyna speciosa.
25. Paynantheine: Indole alkaloid. Appears to be a smooth muscle relaxer, but there is limited research available and more needs to be done. 8.6% to 9% of total alkaloid contents in Kratom leaf. Second most abundant alkaloid.
26. Rhynchophylline: Vasodilator, antihypertensive, calcium channel blocker, antiaggregant, anti-inflammatory, antipyretic (fever reducing), antiarrhythmic, and anthelmintic (treatment of parasitic worms). It is also a non-competitive NMDA antagonist and appears to also have effects on dopamine and 5-HT receptors. Chinese Cat’s claw (Uncaria tomentosa) has also been found to contain Rhynchophylline. It has a similar chemical structure to mitragynine and represents < 1% of total alkaloid content found in kratom leaf.
27. Speciociliatine: Weak opioid agonist. 0.8% to 1% of total content of Kratom leaf, unique to Kratom.
28. Speciofoline: Potential analgesic and antitussive. Patented (US3324111) by Smith Kline (of Glaxo Smith Kline) in 1964. Also patented (US20100209542) by the University of Massachusetts Medical School and University of Mississippi in 2009 to treat opiate withdrawal. As of February 18, 2019, the patent is listed as abandoned.
29. Speciogynine: Diastereomer of mitragynine. Possible smooth muscle relaxer. 6.6% to 7% of total alkaloid contents of kratom leaf, representing the third most abundant alkaloid.
30. Speciophylline: Indole alkaloid. Anti-leukemic. <1% of total alkaloid contents of Kratom leaf.
31. Stipulatine: More research needed.
32. Tetrahydroalstonine: Hypoglycemic, anti-adrenergic (at alpha 2).

Mitragynine

Typically, trees that were harvested during the first growth spurt after a long dry season have the highest mitragynine content. This is especially true for frequently harvested trees. This is due to a combination of reasons.

During the dry season, the leaves’ growth is limited. As a result, mitragynine and other alkaloids accumulate in the leaf buds. After the first rain, the leaves experience a growth spurt, and these are then deposited into the leaves. These leaves can often have a red-ish appearance.

The frequency of harvesting also affects the concentration, particularly mitragynine. It is thought that Mitragyna speciosa produces substances called alkaloids, including mitragynine, as a defense mechanism.

This is to prevent animals from eating the leaves. If the leaves are not being harvested, the plant does not waste energy producing the alkaloids. However, if the leaves are frequently being removed, then Mitragyna speciosa produces more to prevent this.

CHELSEA COLLEGE: Department of Pharmacy/King’s College London Department of Pharmacy

Between 1961 and 1970, they collected thirty samples of Kratom from Thailand, Malaysia, and Papua New Guinea. All contained mitragynine, but also proved to have considerable variation in the makeup. The most common profile for red and green / white leaved plants of Thailand was mitragynine, speciogynine, speciociliatine, and paynantheine. Additionally, there were traces of ajmalicine, (C9) methoxy-oxindoles, and other indoles.

Yet other Thai plants contained distinct profiles, some with many more alkaloids. In the Malay specimens, one contained mitragynine, Speciofoline, and other indoles and oxindoles.

The other specimens contained mitragynine, ajmalicine, speciogynine, speciociliatine, paynantheine, traces of indoles, and (C9) methoxy-oxindoles. Specimens from Papua New Guinea contained mitragynine, speciogynine, speciociliatine, paynantheine, specionoxeine, and isospecionoxeine.

Before the late 1990s, most chemical studies of Kratom focused on mitragynine. It was assumed that mitragynine was the main active indole alkaloid. 7-hydroxymitragynine has been identified as the main psychoactive alkaloid in Kratom. Therefore, many elements of these studies must be revised.

Hiromitsu Takayama also found that Thai and Malay Kratom had the alkaloids mitragynine, speciogynine, speciociliatine, paynantheine and 7-hydroxymitragynine in common. Mitragynine was the most abundant alkaloid in both Thai and Malay samples.

In the Thai Kratom sample, it made up 66% of the total alkaloids. However, in the Malaysian sample, it only made up 12%. The Malay Kratom sample had mitragynaline and pinoresinol as major components, as well as mitralactonal, mitrasulgynine and 3,4,5,6-tetradehydromitragynine.

In 1986, Peter Houghton and Ikram Said discovered four new indole alkaloids. These alkaloids were corynantheidaline, corynantheidalinic acid, mitragynaline, and mitragynalinic acid. They were found in the young leaves of Malay Mitragyna Kratom plants.

These new alkaloids were found to be more abundant in the Malay Kratom sample than in the Thai sample. In the Malay sample, they made up 30% of the total alkaloids, while in the Thai sample they only made up 12%.

The Malay Kratom sample contained new alkaloids. This may explain why it had different effects than the Thai Kratom. Further research on these new alkaloids is needed to determine their potential therapeutic effects.

Edward Joseph Shellard 1914–2010

In the 1960s, Professor Shellard achieved global recognition for his work on alkaloids in Mitragyna plants. He was a great supporter of young scientists, and his laboratory provided an environment for those who would later become influential pharmacognosists in places such as Ghana and Thailand.

Shellard’s studies revealed the presence of several alkaloids in Mitragyna Kratom plants, including mitragynine, 7-hydroxymitragynine, mitraphylline, and speciogynine. He also identified several other alkaloids, such as Rhynchophylline, Corynoxeine, Corynoxine, and epicatechin. In addition, he identified several new alkaloids, such as Mitrafoline, Mitrafoline, mitrafolinic acid, and mitragynaline.

Shellard’s work provided a foundation for further research into the pharmacology of Kratom plants. Today, Kratom is widely used for its medicinal properties and is gaining traction as an effective alternative to conventional treatments for a variety of ailments.

Researchers have discovered a variety of alkaloids in various Kratom samples. Further studies and experimentation are needed to investigate the activity, effects, and potential applications of these alkaloids.

Conclusion

Through its makeup and tradition of use, it is clear Mitragyna speciosa Kratom is much more than a simple opioid-like narcotic and mild stimulant. Many secondary chemicals are present in Mitragyna speciosa, but in tiny amounts. Their role in the pharmacology of the plant is not fully understood yet. This is because research has only just begun.

Concentration percentages given come from different studies of alkaloid concentrations in Mitragyna speciosa (Kratom) leaf. Some of the alkaloids given in this list still need to be studied more specifically to determine their potential activity. Further studies are needed to gain insight into the activity, effects, and applications of these alkaloids.

It is evident that Mitragyna speciosa Kratom is much more than a mere opioid-like narcotic and mild stimulant. While there are many secondary chemicals present in Mitragyna speciosa, their exact role in the pharmacology of the plant has yet to be fully understood, as current research is still in its infancy. To gain a better understanding of the alkaloids present in Mitragyna speciosa, further experimentation is necessary to determine the concentrations and potential activity of each alkaloid.