"The natural history of kratom use, including its clinical pharmacology and toxicology, are poorly understood," points out one of the few experts in the plant, Dr. Edward Boyer, in Addiction journal. Only a handful of scientific papers in English have been written about kratom, its effects, and its centuries-long history of use.
What we do know is over 25 alkaloids have been isolated from kratom and until recently mitragynine was believed to be the main one responsible for kratom’s effects, it being the most abundant alkaloid in the plant. Then in 2002, 7-hydroxymitragynine was discovered by a group of Japanese researchers to be the most significant substance. Despite being present in much smaller amounts, this minor alkaloid of kratom was found to be even more potent than morphine.
The Japanese researchers filed a patent for all possible medical uses of mitragynine with the hope of developing kratom derivatives as pharmaceutical drugs.
Later research has determined that both alkaloids act as partial opioid receptor agonists, activating supraspinal mu- and delta- opioid receptors. Hence the similar effects to morphine, and kratom’s use by chronic narcotics users to lessen opioid withdrawal symptoms.
A medical toxicologist at a Harvard Medical School teaching hospital, Dr. Boyer became interested in kratom after reading about it on mutual support websites for some of the 40 million Americans who manage their own chronic pain.
They had been buying their meds online until 2006, when the government began to shut down Internet pharmacies. All these self-medicators were left high and dry and looking for a way to deal with opioid withdrawal they stumbled across kratom.
Supply soon began to increase to meet the demand, and as its availability increased and word of its more recreational effects spread, so the inevitable media reports and demonization began. But this growing public attention, however ignorantly informed, also helped bring kratom to the notice of serious researchers.
Although the alkaloid structure of Kratom distantly resembles those of other psychedelic drugs such as psilocybin or LSD, but no psychedelic activity has ever been reported after ingestion of Kratom. Instead, Kratom induces effects ranging from increased focus and activity to serious drowsiness and prolonged sleep. But there are vastly unknown desirable side-effects of Kratom ... and way more chemicals involved than only the so far furthest researched active substances 7-Hydroxymitragynine and Mitragynine. During our research about the ingredients of Kratom we came across these chemical substances: Ajmalicin, 7-acetoxymitragynine, Corynantheidin, Corynoxein, Corinoxin, 3-Dehydromitragynin, (-)-Epicatechin, 3-Isocorynantheidin, 3-Isopaynanthein, Isomitraphyllin, Isospeciofolin, Isospecionoxein, Mitraciliatin, Mitrafolin, Mitragynalin , Mitraphylin, Mitraspecin, Mitraversin, Paynanthein, Speciociliatin, Speciofolin, Speciogynin, Specionoxein, Speciogynin, Speciofolin, Stipulatin, but we'll limit our excursus to the most interesting compounds 7-Hydroxymitragynine, Mitragynine and (-)-Epicatechin. Kratom actually contains over 40 chemicals, but we simply didn't find them all to list them here.
7-Hydroxymitragynine is the main ingredient in Kratom tinctures and has opioid agonistic activity. Recent research about the active substances in Kratom has shown that its potency is 30-fold higher than that of Mitragynine, which makes 7-Hydroxymitragynine the top candidate as main active substance in Kratom and puts Mitragynine, the previously assumed as main active chemical, in second place. 7-hydroxymitragynine interacts with the three major opiod sites Kappa, Delta and Mu, but it preferably binds to Mu receptors; these receptors are responsible for the enjoyable effects of opiates, analgesia and physical dependence.
Mitragynine is an indole alkaloid and already has been isolated for the first time in 1907 by D. Hooper, so it actually took almost 100 years until it found its way to recreational use. It has been thought to be the primary active substance in Kratom, but it turned out to be only the most abundant active alkaloid (about 0.1-0.3%, depending on the plant). A small dose of Mitragynine acts like a stimulant because it binds to the Delta receptors, but at higher doses it also binds to the Mu receptors and alleviates pain. Although the structure of Mitragynine is similar to LSD or Psilocybin it does not induce any psychedelic effects. Since Mitragynine was assumed to be the main active substance in Kratom, it is better researched than 7-Hydroxymitragynine.
Epicatechin is a real all-rounder with its versatile benefits for health. It reduces the effects of free radicals on the body, which reduces the cancer risk and helps prevent fat cells from oxidizing and blocking arteries. Moreover it helps with blood sugar levels and is beneficial to diabetics because it mimics endogenous insulin. On top of that it prevents growth of bacteria such as E-Coli and inhibits alpha-amylase.