What is the pharmacology of kratom?
Kratom is a plant that originated from Southeast Asia and Thailand. It has been used to treat opioid withdrawal, cough, diarrhea, and pain in Asia. It is due to these benefits that kratom is becoming popular especially in the field of medicine. This Wiki page is replete with info on Mitragyna Speciosa.
The primary active substances in kratom are mitraphylline, mitragynine, and 7-hydroxymitragynine. Others less active chemicals include: raubasine, corynanthidine, rhynchophylline, and many others. The location of the kratom trees determines the composition of the active chemicals. For instance, the level of active compounds is very high in trees grown in Southeast Asia. The levels are low in trees grown in other areas, greenhouses included.
The mode of action of kratom is similar to that of an opioid receptor agonist. When compared to the traditional opiates, its effects and pharmacological actions tend to differ significantly. On the mu receptors, mitragynine and 7-hydroxymitragynine bind as partial agonists. On the kappa and delta receptors, they act as an antagonist. Their binding affinities are high in mu and kappa receptors. Kratom also has an affinity for norepinephrine, serotonin, and kappa, unlike the other opioids. The kratom’s stimulating properties are as a result of activation of serotonin and norepinephrine.
It is the most abundant active alkaloid in the Mitragyna speciosa. 1.2% to 2.1% of the compound is contained in the dried kratom’s leaves. It is involved in the improvement of mood and has analgesic effects. It also promotes relaxation and stimulation. It acts on mu-opioid receptors. When oxidized, a product called mitragynine pseudoindoxyl is formed. This product works as a selective mu-opioid agonist and has reduced affinity for both kappa and delta receptors. In chronic users, mitragynine has been put under extensive studies. Its metabolism takes place in the liver. it has linear kinetics, and its half-life is long.
Mitragynine has a molecular weight of 398.503g/mol. Its molecular formula is C23H30N204.
It exists as a white amorphous powder. At 235 degrees Celsius and 5 mm of mercury, the compound boils. It has a melting point of 104 degrees Celsius. The substance is soluble in organic compounds such as chloroform, alcohol, acetic acids, and many others.
Body fluids detection
The method of detection is referred to as liquid chromatography-mass spectrometry. People using kratom for recreational purposes have a mitragynine concentration of between 10 and 50 micrograms per liter in their blood.
Absorption, distribution, and excretion
On rats, a study was conducted. An oral dose of 20mg/kg of mitragynine was administered to each rat. At the end of the study period, it was observed that the mean plasma concentration was 424ng/ml. The time needed to reach the maximum plasma concentration was found to be 1.26 hours. The elimination half-life was 3.85 hours. 6.35l/hr./kg was the apparent total clearance. Finally, the apparent volume of distribution was 37.90l/kg.
Metabolism and its metabolites
Using Liquid Chromatography-Tandem Mass Spectrometry, mitragynine, paynantheine and speciogynine were found present in rats and human’s urine. Apart from mitragynine and speciogynine, other isomeric substances were detected. The urine of the kratom users was further screened to determine the phase I and II of the speciogynine. It was found that due to its retention times and mass spectra, the speciogynine and its metabolites were hard to identify in human urine. In phase I, seven metabolites were identified. They suggested that mitragynine underwent metabolism through hydrolysis of the methyl ester occupying position 16, O-demethylation of the 9-methoxy group and 17-methoxy group via the intermediate aldehydes by decreasing to alcohols or oxidation to carboxylic acids.
7-hydroxymitragynine is a terpenoid indole alkaloid extracted from Mitragyna speciosa. On the mu receptors, 7-hydroxymitragynine acts as an agonist. It has a potency that is thirty-fold high as compared to mitragynine. Morphine has a strength that is 17-fold lower than that 7-hydroxymitragynine. The compound is associated with fewer side effects as compared to morphine.
- It is an opioid agonist. An opiate effect is felt when it reacts with the opioid receptors. The effect is essential in relieving pain.
- It possesses a relaxing effect. When in high doses, 7-hydroxymitragynine provides a sedative and relaxing effects.
- It brings about euphoria. Euphoria is felt when kratom is used in low doses. The euphoric effect makes kratom an alternative recreational drug.
Its molecular formula is C23H30N2O5. It has a molecular weight of 414.502g/mol.
Factors such as health, age, body size and others determine the required dose. There is no specific dosage provided thus one should follow the directions on the product label. One can consult a healthcare provider. For safety purposes, it is recommended that one should avoid taking kratom regularly and in high amounts. No standardization and quality control in regulating the production and sale of kratom, therefore coming up with a standard dosage is quite challenging.
Kratom’s drug interaction
Combination of kratom with other drugs results in adverse drug interactions. The interaction is because some drugs share the same pharmacological properties with kratom. For instance, combining opiates and kratom is not recommended. This is to avoid synergy due to drug interaction, leading to over-sedation and respiratory depression.
Kratom is extensively being used for both recreational and medical purposes. This due to the many benefits that it is associated with. A variety of active compounds are abundantly found in kratom as research suggest. These compounds are associated with the production of significant pharmacological effects at the opioid receptors. Kratom also has similar pharmacology as compared to other prescription opiates.
They are partial agonists and thus are associated with few side effects unlike other opiates, which are full agonists. Kratom just like other drugs is metabolized in the liver. Due to similar pharmacology, kratom tends to interact with other medications. Therefore, one should avoid combining it with other medicines. On the hand, one can seek the advice from a medical officer on the effectiveness and safety of combining kratom with other drugs. As a general rule, always avoid taking kratom in large doses. To reduce the chances of developing the side effects Kratom should not be used frequently.