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 in order to determine their potential activity.
Mitragynine: Indole alkaloid. Analgesic, antitussive, antidiarrheal, adrenergic, antimalarial, possible psychedelic (5-HT2A) antagonist. Mitragynine is the primary alkaloid in kratom, and is believed to be responsible for the majority of its effects. Roughly 66% of total alkaloid content found in Kratom leaf.
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.
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.
7-hydroxymitragynine: Analgesic and potent mu-opioid agonist, antitussive, and antidiarrheal. Along with mitragynine, 7-hydroxymitragynine is responsible for the primary effects of Kratom. It represents roughly 2% of total alkaloid content found in Kratom leaf, though this is highly variable. Some leaves have undetectable levels.
Mitraphylline: Oxindole alkaloid. Vasodilator, antihypertensive, muscle relaxer, diuretic, antiamnesic, anti-leukemic, possible immunostimulant. <1% of total alkaloid contents in Kratom leaf.
Isomitraphylline: Immunostimulant, anti-leukemic. < 1% of total alkaloid content found in Kratom leaf.
Speciophylline: Indole alkaloid also found in Chinese Cat’s claw (Uncaria tomentosa). Possible anti-leukemic. <1% of total alkaloid contents of Kratom leaf.
Rhynchophylline: Vasodilator, antihypertensive, calcium channel blocker,
antiaggregant, anti-inflammatory, antipyretic (fever reducing), antiarrhythmic, and anthelmintic (treatment of parasitic worms). It is a also 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.
Isorhynchophylline: Immunostimulant, and possible antihypertensive and neuroprotective. < 1% of total alkaloid content found in Kratom leaf.
Ajmalicine (Raubasine): Cerebrocirculant, antiaggregant, anti-adrenergic (at alpha-1), sedative, anticonvulsant, smooth muscle relaxer. It’s 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”. Ajmalicine is also found in Rauwolfia serpentina.
Akuammigine – an indole alkaloid associated with the seeds of Picralima nitida (akaumma). It is structurally similar to yohimbine and mitragynine. Like yohimbine, it is known to have antimalarial activity.
Ciliaphylline: antitussive, analgesic. < 1% of total alkaloid content found in Kratom leaf.
Corynantheidine (rauhimbine): μ -opioid antagonist, also found in Yohimbe. It’s related to ajmalicine, and is a diastereomer of yohimbine. Like ajmalicine, it is an α1-adrenergic and α2-adrenergic receptor antagonist with 10x greater affinity for the α1-adrenergic receptor. This is in contrast to yohimbine and its other diastereomer, rauwolscine, which have a 30x higher affinity for the α2-adrenergic receptor over the α1-adrenergic (opposite affinities). < 1% of total alkaloid content found in Kratom leaf.
Corynoxeine: Calcium channel blocker. < 1% of total alkaloid content found in Kratom leaf.
Corynoxine A and B: 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 suggests they may help with Parkinson’s. < 1% of total alkaloid content found in Kratom leaf.
Epicatechin: A flavonoid that’s an antioxidant, antiaggregant, antibacterial, antidiabetic, antihepatitic, anti-inflammatory, anti-leukemic, antimutagenic, antiperoxidant, antiviral, potential cancer preventative, alpha-amylase inhibitor. One preliminary study even claims that it may reduce myostatin, which would result in muscle growth and improved strength. It’s also found in dark chocolate, green tea, and grapes.
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”
Isomitrafoline: < 1% of total alkaloid content found in Kratom leaf.
Isopteropodine: Immunostimulant, antimicrobial.
Isospeciofoline: < 1% of total alkaloid content found in Kratom leaf.
Mitraciliatine: < 1% of total alkaloid content found in Kratom leaf.
Mitragynine oxindole B. < 1% of total alkaloid content found in Kratom leaf.
Mitrafoline: < 1% of total alkaloid content found in Kratom leaf.
Mitraversine: Found in Mitragyna parvifolia, and may also be in Mitragyna speciosa
Speciociliatine: Diastereomer (C3 stereoisomer) of mitragynine. Weak opioid agonist. May inhibit acetylcholine release from presynaptic nerve through means other than opioid receptor stimulation. 0.8% to 1% of total alkaloid content of kratom leaf. Unique to Kratom.
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.
Stipulatine: More research needed
Tetrahydroalstonine: Hypoglycemic, anti-adrenergic (at alpha-2).
Mitragyna speciosa (kratom) alkaloid content varies quantitatively from geographical location, and from month to month, at different leaf harvest times, which has lead some teams (Shellard et al. in the 1970s) to conclude that there may be different geographical variants within the same species. Alkaloid content can vary even from the same trees due to a variety of environmental and human factors, such as when the length of the rainy or dry season, the amount of time elapsed since the last rain, when the leaves were harvested in relation to the dry season, and the period of time between harvests.
Typically the highest mitragynine content is present in leaves from frequently harvested trees, especially those that were harvested during the first growth spurt when the rains return after a long dry season. This is due to a combination of reasons. During the dry season, the leaves do not grow as much, so mitragynine and other alkaloids build up in the leaf buds. After the first rain, the leaves experience a growth spurt, and these alkaloids are then deposited into the leaves. These leaves can often have a red-ish appearance.
The frequency of harvesting also affects the alkaloid concentration, particularly mitragynine. It is thought that Mitragyna speciosa produces mitragynine and other alkaloids as a defense mechanism to deter animals from eating the leaves. If the leaves are not being harvested, the plant doesn’t waste energy producing the alkaloids. However if the leaves are frequently being removed, then Mitragyna speciosa produces more in an attempt to prevent this.
The Chelsea College Pharmacognosy Research Laboratories collected thirty samples of Kratom from Thailand, Malaysia, and Papua New Guinea between 1961 and 1970. All contained mitragynine, but also proved to have considerable variation in the alkaloid makeup. For red and green / white leaved plants of Thailand, the most common alkaloidal profile was mitragynine, speciogynine, speciociliatine, paynantheine, traces of ajmalicine, traces of (C9) methoxy-oxindoles, and traces of other indoles.
Yet other Thai plants contained distinct alkaloidal profiles, some with many more alkaloids. In the Malay specimens, one contained mitragynine, speciofoline, and other indoles and oxindoles, while others 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.
Prior to the late 1990’s, nearly all chemical studies of Kratom activity focused on mitragynine with the assumption that mitragynine was the main active alkaloid. With 7-hydroxymitragynine now clearly identified out as the principal psychoactive alkaloid in Kratom, many elements of these studies need to be revised.
Takayama et al. also found that Thai and Malay Kratom had the alkaloids mitragynine, speciogynine, speciociliatine, paynantheine and 7-hydroxymitragynine in common. In both Thai and Malay samples, mitragynine was the most abundant alkaloid, yet it made up 66% of the total alkaloid in the Thai Kratom sample, while it made up only 12% of the alkaloids from the Malaysian sample. The Malay Kratom sample had mitragynaline and pinoresinol as major components, as well as mitralactonal, mitrasulgynine and 3,4,5,6-tetradehydromitragynine.
In 1986, researchers Peter Houghton and Ikram Said found 4 new types of indole alkaloids (corynantheidaline, corynantheidalinic acid, mitragynaline, and mitragynalinic acid), in very young leaves of Malay Mitragyna Kratom plants.
The variety of alkaloids discovered in diverse Kratom samples to this day still calls for further studies and experimentation, investigating their specific activity, effects, and potential applications.
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 of the secondary chemicals found in Mitragyna speciosa are present in small, yet appreciable, quantities, and their synergetic role and activity in the general pharmacology of Mitragyna speciosa is not yet fully understood, as thorough research has only just begun.