The Mitragyna species are very rich in active compounds, and over 40 alkaloids have already been isolated in the leaves of its various species. Mitragyna speciosavar. Korthals has over 25 reported active alkaloids.
The alkaloid content of the Kratom tree’s leaves varies from place to place, and at different times of the year. Within each location, there is a quantitative variation in alkaloid content from month to month, the indole content seemingly the most stable, while the oxindole content shows tremendous variation.
Over 25 active alkaloids have been identified/isolated in the Mitragyna speciosa Kratom tree specifically, yet it is important to remember the fore mentioned variations in alkaloid content from location and period of harvest, as with other Mitragyna species.
Such variations were noted in a study analysing collected Thai Kratom material: some variation being clearly based upon different geographic origins of the leaves (though unfortunately the precise places of collection are unknown), yet within each geographical region there was also a quantitative variation from month to month, which transformed itself into a qualitative variation, certainly as far as the oxindole alkaloids were concerned.
The most abundant alkaloids of Mitragyna speciosa Kratom leaves consist of three indoles and two oxindoles. The main indole alkaloidal content is fairly stable and it seems that mitragynine, speciogynine, paynantheine with small amounts of speciociliatine are present in all leaves.
Mitragynine is the dominant alkaloid in quantity and is thought to be exclusive to Mitragyna speciosa. Paynantheine and speciociliatine also appear to be specific to the Mitragyna speciosa species. Speciogynine, mitraciliatine on the other hand have also been isolated from other Mitragyna species such as Mitragyna inermis.
In this complex alkaloid makeup, 3 Kratom alkaloids stand out as the main psychoactive chemicals: mitragynine (first thought to be the primary active principle), mitraphylline, and 7-hydroxymitragynine (which is currently the most likely candidate for the primary active chemical in the plant).
The effects of mitragynine are clearly stimulating in small doses and narcotic in larger doses, while 7-hydroxymitragynine appears to have a more sedating effect and is actually many times more potent per weight than mitragynine.
Bio-assays experiments seem to point that 7-hydroxymitragynine also acts strongly on μ opioid receptors (hinted by euphoria, respiratory depression, analgesia, and potential nausea) and maybe also sigma opioid receptors (hinted by cardiac stimulation, visual distortion).
Research indicates that the stimulant-sedative effects of mitragynine are probably linked to its action on the delta-opiate receptor site, to which it binds at higher concentrations, and which is closely related to the μ-opiate receptor
site. This is significant, as one of the mechanics of heroin/opiate addiction is due to over stimulation of the μ-opiate receptors.
Although mitragynine does not attach directly to the appropriate receptor site, its attraction to the neighbouring site and the spill over effect onto the μ-site is said to produce a similar effect in the opiate user, thus satisfying the craving
for opiates. This indirect action is one of the key elements in the theories of using Kratom as a potential way of treating opiate addiction and its cravings without replacing one addiction for another, as it is done so frequently in
modern treatments such as methadone.