Definition
The alkaloids of kratom form a group of more than 40 identified nitrogenous secondary metabolites that accumulate in the leaves of the Mitragyna speciosa tree. The total alkaloid content in the dry leaf ranges between 0.5 and 1.8 % by weight; the remaining more than 98 % consists of cellulose, hemicelluloses, lignin, water, flavonoids, polyphenols and other non-target components.
What alkaloids are
In plant biochemistry, alkaloids are defined as natural, low-molecular-weight, nitrogenous heterocyclic compounds biosynthesised from amino acids. In the plant they serve a defensive function against herbivores and pathogens. From a medical and pharmacological standpoint they are an important group of bioactive substances (from caffeine through morphine to quinine).
Kratom's alkaloids belong to the indole alkaloids derived from the amino acid tryptophan - they therefore share a biosynthetic origin with alkaloids from plants of the Apocynaceae, Rubiaceae and Loganiaceae families (yohimbine, ajmalicine, vincristine, reserpine).
Main groups in kratom
Mitragynine alkaloids (corynantheine skeleton)
The core of this group consists of mitragynine (60-66 % of the content), plus speciogynine (≈ 7 %), paynantheine (8-9 %) and speciociliatine (≈ 1 %). Structurally they differ in the configuration of the piperidine ring and the position of the methoxy/methyl-ester groups.
Oxindole alkaloids
These arise from oxidation of the indole nucleus to an oxindole (lactam form). They include mitraphylline (an analogue of uncarine from Uncaria tomentosa), isomitraphylline and speciophylline. The content is typically below 1 % of the alkaloid profile.
Hydroxylated derivatives
The key one is 7-hydroxymitragynine, which despite its low content (0.1-2 %) contributes to the pharmacological profile because of its high receptor affinity.
Other trace alkaloids
Corynantheidine, isocorynantheidine, mitragynaline, mitragynalinic acid and dozens of others, generally at concentrations below 0.5 % of the alkaloid profile. Some are specific to particular ecotypes.
Variability by origin
The ratios of alkaloids fluctuate depending on a number of factors:
- Geographic origin: Indonesian leaves tend to have a higher total alkaloid content than Malaysian or Thai ones.
- Leaf age: young leaves contain relatively less mitragynine and more paynantheine.
- Drying and fermentation: oxidative processes change the mitragynine/7-OH-MG ratio.
- Seasonality: the rainy versus dry season slightly changes the content of individual alkaloids.
For this reason no single "typical" alkaloid profile can be given - each sample must be determined analytically (HPLC or LC-MS).
Significance for analysis
From a laboratory standpoint, the standard is to determine three markers:
- mitragynine (a quantitative indicator of content),
- 7-hydroxymitragynine (an indicator of the oxidative age of the raw material),
- total alkaloid content (a summary gravimetric or HPLC determination).
These three figures are typically stated in the Certificate of Analysis (COA) and serve as an initial indicator of a sample's quality.
Frequently asked questions
How many alkaloids have been identified in kratom?
Over 40 different compounds; the most recent review (Brown 2017) lists 54 structurally characterised alkaloids. Most of them are present in trace amounts below 1 % of the alkaloid content.
Why are some alkaloids present only in traces?
They are intermediates of biosynthesis or oxidative derivatives of the main alkaloids. Their accumulation is regulated by the plant according to enzymatic equilibrium.
Does the alkaloid profile change with drying?
Yes. Oxidative processes increase the proportion of 7-OH-MG at the expense of mitragynine. Improperly stored raw material may have an entirely shifted profile.
Is there a "standard" alkaloid profile of kratom?
No. Phytoanalysis committees require the profile to be determined for a specific batch, not a reference to a general value.
References
- Brown P. N., Lund J. A., Murch S. J. (2017). A botanical, phytochemical and ethnomedicinal review of the genus Mitragyna. Journal of Ethnopharmacology, 202, 302-325.
- León F. et al. (2009). Phytochemical characterization of the leaves of Mitragyna speciosa. Phytochemistry Letters, 2(2), 71-76.
- Flores-Bocanegra L. et al. (2020). The chemistry of kratom: alkaloids and analogues. Journal of Natural Products, 83(7), 2165-2177.
