Updated: May 24, 2019
Burgers, Jan Brady, NFL and Kratom... all in the same blog.
A holistic approach
After eleven years of managing my health and well-being with the botanical mitragyna speciosa ---- from countless sources, in every conceivable color/shade, by every preparation method imaginable ---- I have formed an opinion. And here it is:
Kratom is an herb of great complexity and nuance. The real story behind the magick of kratom's alkaloids is often obscured by broad, sweeping over-simplifications and a persistent tunnel-vision focus on mitragynine and its oxidized analog, 7hydroxymitragynine.
The fact is, there are more than 40 other compounds, including approximately 25 active alkaloids besides MG and 7ohMG in the plant material ---- and the profile of these alkaloids is highly variable under the influence of time, season, environmental factors and post-harvest processing methods.
The magick of this botanical doesn't necessarily distill down to a single compound (or two), and a holistic view of the overall composition and organic chemistry at work could help yield new perspectives that are integrated, comprehensive and meaningful.
The science for this already exists... it's just the media, the industry, the FDA and even well-meaning advocates are so focused on mitragynine that everyone just assumes that's all there is to it.
Mitragynine... the star athlete
According to the American Chemical Society, mitragynine is an indole alkaloid isolated in 1921 by Ellen Field, a medicinal chemist at the University of Edinburgh. A woman, if you didn't catch that already. However, sources indicate that someone named Dr. Hooper first isolated mitragynine in 1907, and Field then recreated the experiment 14 years later. For years thereafter, mitragynine was the focus of all kratom research. It wasn't until 1994 that 7-hydroxymitragynine was isolated, found to be much more potent, and determined to be the main psychoactive alkaloid.
Yes, mitragynine and 7hydroxymitragynine are points of commonality in kratom samples, and are responsible for a great portion of the herb's desirable effects. Mitragynine in particular tends to account for the bulk of the average alkaloid content ---- but this is only part of the picture.
MG and 7ohMG are like star NLF quarterbacks. They gets all the attention in the press, but if you take them out of the context of their teams, they're just two guys playing with their balls.
Context matters. The TEAM matters.
Time for an analogy:
You can have two burgers.... they both have a bun and a patty, but one has ketchup, bacon and perfectly ripe avocados, and the other has grilled mushrooms, caramelized onions and a thick heavenly sluice of melted Swiss cheese.
Would you really choose to define these burgers strictly by the weight of the patty and the condition of the bun, or would you take into consideration that the other ingredients might be just as --- or more --- important to the way you perceive the overall character of the dish?
What if, all this time, it wasn't just the bun and patty that did it for you, but rather the way everything worked together? Would the meal be as delicious if it weren't so lusciously coated in onions, mushrooms and Swiss cheese? In fact, if you removed a significant portion of either the bun or the patty from your favorite preparation, might you still like it more than if you kept the bun and patty intact but removed a considerable portion of the other ingredients?
So how important is mitragynine, really? Does it exist in a vacuum?
Mitragynine is important... there's just more to it than that, and here's why.
Mitragynine is common to all kratom, but its levels are not consistent. Kratom cultivated in Malaysia has been found to contain between 12-25% mitragynine, while the levels from leaves grown in Thailand can be as high as 66%.
When it comes to kratom grown outside the bounds of its indiginous geography, sometimes mitragynine isn’t even the primary alkaloid. We see this phenomenon expressed in experiments involving Dr. Christopher McCurdy and kratom plants grown at the University of Mississippi (published in 2009 by León et. al). From 18g of concentrated leaf extract several alkaloid fractions were obtained. Mitraphylline was the most abundant alkaloid (24 mg of pure substance). Mitragynine was isolated as well (8 mg) along with 7-hydroxymitragynine (1.2 mg; apparently formed from mitragynine).
Worth noting, there seems to be a fairly consistent level up to 2% of 7-OH MG in natural leaf (some commercial products appear to artificially inflate this number with chemical additives, but that's a subject for a different article all together).
So, in spite of this high variability in mitragynine levels, kratom still seems to possess proported medicinal benefits that do not necessarily coincide in an linear fashion with testable levels of MG. Some people say a Green Malay seems stronger to them ---- much more so than a Thai ---- even though on paper the Malay has a considerably lower concentration of mitragynine. The reverse is true as well, depending on the product and the person you ask. Even in my own experiments, a product with a higher level of mitragynine did not have nearly the same level of awesomeness (how's that for a scientific term?) than something with a markedly lower level of MG.
So what is actually going on here?
Simply put, there are more alkaloids, flavonoids and desirable compounds to consider than just good ol' mitragynine.
Remember the experiment referenced above where mitragynine made up 66% of the Thai samples but only 12% of the Malaysian samples? Scientists found that kratom growing in both locations had the common alkaloids mitragynine, speciogynine, speciociliatine, paynantheine and 7-hydroxymitragynine. The Malaysian sample had mitragynaline and pinoresinol as major components, as well as mitralactonal, mitrasulgynine and 3,4,5,6-tetradehydromitragynine. The plants grown at the University of Mississippi had mitraphylline has the primary alkaloid. Specimens from Papua New Guinea contained mitragynine, speciogynine, speciociliatine, paynantheine, specionoxeine, and isospecionoxeine. And 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 plants.
I don't think it's beyond the scope of reason to consider how much these variable alkaloid profiles are responsible for the differences in flavor, character and efficacy often observed between samples.
In 1974 a kratom researcher named Shellard isolated more than twenty kinds of Corynanthe-type alkaloids, including oxindole derivatives, in their investigation of the alkaloid constituents in various samples of Mitragyna speciosa from Thailand. They pointed out that the variation in the constituents among different batches of leaves may be an indication of the presence of geographical variants of the species within Thailand (Shellard, 1974).
The myth of strains
Some people incorrectly use the word "strain" to distinguish these variations, but we have learned that this variation does not equate to actual "strains" with genetically reproducible phenotypes like you would see with cannabis. We now credit environmental conditions (both before and after harvest) with a lot of this variation. If you move a plant to a different location, the alkaloid profile will change from the profile produced at the original location (visible changes in appearance may also result). Furthermore, on the same plant, leaves produced at different times under different conditions will yield different alkaloid profiles. If you move a Malaysian plant out of Malaysia and grow it somewhere else, for example, it will exhibit different characteristics and is therefore not a reproducible strain. The same plant's leaves, harvested a month apart may have vastly different alkaloidal constituents.
This is true of all kratom, and only goes to underscore why it is so important to consider the many other constituents besides mitragynine as vital components of the leaf. These complex profiles are unique to particular batches, harvested in particular locations at particular times, variable in every way, and they account for a great part of the product's character.
This is why many people notice inconsistencies between one farmer's "green malay" (for example) and another farmer's. Or between different batches of the same product bought from the same company at different times. First of all, the name is not indicative of an actual strain. "Green Malay" is just a style of curing applied to green leaf. Not even grown in Malaysia necessarily... just named after the green kratom that originally indigenously grew there (in comparison to the red kratom native, and once unique, to Thailand). And furthermore, so many factors contribute to the overall alkaloid profile of each particular batch, that even in controlled conditions, it doesn't (yet) seem possible to consistently reproduce results.
For this reason, looking at the complete alkaloid profile of every batch of powder (regardless of what strain it's labeled as) would yield a litany of different results. To me this is exciting!
Genetic diversity, the magick of nature
Adding further complexity to the seemingly infinite possible permutations of alkaloid profiles based on environmental factors and curing methods, we must also take into account genetic diversity. When farmers in Indonesia are harvesting kratom, they harvest from many different trees. Most of these so-called "strains" are blends to begin with. Open up a kilo of powder and who knows how many different trees contributed their genetic material to that particular product.
One thing is certain, though: order another bag with the same name... and you're getting different trees, different genetic profiles, and different overall alkaloid makeup.
So what else is in there?
This is what we've been leading up to. If you made it this far, congratulations. Send us a message and tell us you found the "easter egg" in the alkaloid composition blog. You'll win an entry into our current contest to win a free plant.
Beyond mitragynine... a nice list with references copied from scientific literature:
7-hydroxymitragynine: Analgesic and potent mu-opioid agonist, antitussive, and antidiarrheal. Along with mitragynine, 7-hydroxymitragynine is said to be 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. Mitragynine is a precursor to 7ohMG and self-oxidizes.
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.”
Corynantheidine: 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).
Mitraphylline: Oxindole alkaloid. Vasodilator, antihypertensive, muscle relaxer, diuretic, antiamnesic, anti-leukemic, possible immunostimulant.
Speciogynine: Diastereomer of mitragynine. Possible smooth muscle relaxer. Represents 6.6% to 7% of total alkaloid contents of some tested samples of kratom leaf, representing the third most abundant alkaloid in the average tested samples.
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.
Speciophylline: Indole alkaloid also found in Chinese Cat’s claw (Uncaria tomentosa). Possible anti-leukemic.
Speciociliatine: Diastereomer (C3 stereoisomer) of mitragynine. Weak opioid agonist. May inhibit acetylcholine release from presynaptic nerve through means other than opioid receptor stimulation.
Ajmalicine (Raubasine): Cerebrocirculant, antiaggregant, anti-adrenergic (at alpha-1), sedative, anticonvulsant, smooth muscle relaxer. Also found in Rauwolfia serpentina.
Isorhynchophylline: Immunostimulant, and possible antihypertensive and neuroprotective.
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 found in some samples of Kratom leaf. Second most abundant alkaloid in the average of the tested samples.
Mitragynine pseudoindoxyl is a rearrangement product of 7-hydroxymitragynine and also known as Corynoxine B. It is an analgesic being more potent than morphine and about as potent as enkephalin. (wiki)
Isomitraphylline: Immunostimulant, anti-leukemic.
Ciliaphylline: antitussive, analgesic.
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.
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.
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.
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.
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
Stipulatine: More research needed
Tetrahydroalstonine: Hypoglycemic, anti-adrenergic (at alpha-2).
NOTE: the list provided above was referenced from kratomscience.org and does not constitute medical advice.
In conclusion, the variety of alkaloids discovered in diverse Kratom samples warrants much further investigation and consideration. Many of the secondary constituents found in the leaf material of mitragyna speciosa appear in quantities that, when combined, becomes significant. The synergistic action of these constituents must be considered for a complete and integrated picture of the true magick of this botanical.