Mitragynine is an indole alkaloid with the molecular formula C23H30N2O4. It is the most abundant active alkaloid in the plant Kratom plant Mitragyna speciosa, and was therefore first thought to be responsible for the plant’s activity, before 7-hydroxymitragynine was looked into, and proved to be much more potent.
According to available studies the average alkaloid content of common red-veined leaves of Mitragyna speciosa is said to be about 0.5%, about half of which would be mitragynine. Dry Mitragyna speciosa Kratom leaf roughly contains about 0.25% mitragynine.
Knowing that an average Kratom leaf weighs about 1.7 grams fresh or 0.43 grams dried, twenty leaves contain approximately 17mg of mitragynine. Yet such precise alkaloid measurements should be taken cautiously, since Mitragyna speciosa Kratom is known to change in alkaloid makeup according to geographical factors and environmental conditions such as the harvest season (which is possibly behind the differences between red-vein/white green-vein Kratom), factors that have not always been taken into account.
Mitragynine was isolated in 1907 by D. Hooper, a process repeated in 1921 by E. Field who gave the alkaloid its name. Its structure was first fully determined in 1964 by D. Zacharias, R. Rosenstein and E. Jeffrey.
Mitragynine is orally active, a typical dose ranging from 10 mg to 65 mg.
Mitragynine is structurally related to some Yohimbe alkaloids, and has been shown to be similarly adrenergic (like some related alkaloids from Yohimbe), sharing some adrenergic receptor activity similar to that of yohimbine, yet with
different effects. Mitragynine also enacts a yohimbine-like binding to alpha-adrenergic receptors.
Stimulation of postsynaptic alpha-2-adrenoceptors, blockade of 5-HT2A receptors, or both, are involved in mitragynine's suppression of 5-HT2A mediated head-twitch response in mice test subjects. There has been some speculation that mitragynine's activity on 5-HT2A receptors may actually suppress the activity of psychedelic drugs, which are agonists at these receptor sites. More distantly, mitragynine is also structurally related to voacangine, an ibogaine precursor found predominantly in the rootbark of Voacanga africana.
It is even more distantly related to other tryptamine psychedelic substances such as psilocybin or L.S.D., but develops no real psychedelic effect, even in higher doses. With increased dosages, its action is increasingly sedative, much closer to that of opiates.
Other sources, mostly based on animal studies, give results that are to some extent inconclusive and sometimes even contradictory. According to such sources, 50mg of pure mitragynine produced motor excitement, giddiness, rombergism (a swaying of the body or falling when standing with the feet close together and the eyes closed; the result of loss of joint position sense), and tremors to the face, member extremities and tongue.
Yet researcher E. Macko, for instance, found no evidence of toxicity such as tremors or convulsions at doses as high as 920mg/kg in dogs. In cats, E. Macko found that such high doses had stimulating effects unlike those from opiates. There was increased exploratory behaviour, yet without the "fear and rage complex" opiates produce at similar doses.
Other effects of mitragynine are a reduction in smooth muscle tone, local anaesthesia, and central nervous system depression. Heavy use can result in a prolonged sleep, although many experiments show that most users find it stimulating, making sleep difficult.
More severe side effects of mitragynine may include dry mouth, increased urination, loss of appetite, and constipation, with small, blackish stools. As with other morphine or other opiates, mitragynine decreases 2-deoxy-D-glucose-stimulated gastric acid secretion, which may have an anorexic effect and potentially be involved in the weight loss reported by some Thai users.
Unlike opiates, mitragynine does not appear to cause systematic nausea or vomiting, yet this is dosage relative. One specific study has found mitragynine has some anti-malarial activity.
Mitragynine has a specific mode of action on μ opioid receptors, which are responsible for the enjoyable effects of the opiates, analgesia, and physical dependence. By suppressing opiate withdrawal without fully replacing the addiction mechanism by another (its effects are not reversed by the opiate antagonist nalorphine), mitragynine has a good potential for the treatment of drug addiction/easing of withdrawal symptoms from opiates. However, the equilibrium and mechanisms of Mitragyna speciosa Kratom’s full alkaloid spectrum is not fully studied or understood yet.
Physically, Mitragynine freebase is a white to yellow, amorphous powder, soluble in alcohol, chloroform and acetic acid.
Tinctures of mitragynine, high purity isolated alkaloid dissolved in ethanol, were made commercially available, and some experimenting has been done, though the purity and precision of the manufacturing process used (which requires advanced laboratory equipment and procedures such as column chromatography) is always a question in such cases.
Most bio-assays of mitragynine were attempted through oral or intranasal intake, after drying out the tincture on a glass. Mitragynine apparently burns before it vaporises, and thus cannot be taken this way.
Reports of experiences with pure (90%) mitragynine tincture state that:
This indicates that the synergy and balance between the different alkaloids of Mitragyna speciosaKratom plays an important role in defining the nature of Kratom’s effects, and stresses the fact that although it clearly does play a significant role mitragynine psychoactivity alone does not accurately represent the basis of the Kratom experience.
- A dosage of 10-30mg induces stimulant effects, slight excitation similar to a couple cups of coffee, and no opiate-like effects.
- A dosage of 30-50mg induced stronger stimulant effects, caffeine like excitation, with a decreased appetite and sense of well-being, and numbed the mouth. Another report describes this as much less enjoyable than a 15g dose of Mitragyna speciosa Kratom leaves, even though the mitragynine level should have been equal to more than in this dose.
Recently, an analog of mitragynine has been made available: 7-Acetoxy mitragynine. While derived from mitragynine, this alkaloid is not found in Mitragyna speciosa Kratom however. Reports state oral doses of 8.30mg as inducing little effects.
15-20mg as inducing a slight sense of well-being, clear headedness yet inebriated, with strong cotton mouth- slightly similar to dose of 10g of Kratom. Effects last roughly 2-3 hours.
20-30mg induced an alteration of consciousness, with energy to be productive yet no motivation to partake in activities. Effects are said to mild (the acetoxy group probably diminishing potency of effects). lasting roughly 4 hours with 1 hour of "after glow".