Kratom Alkaloids: How They Interact Enzymes & Receptors

Self-reports, preclinical, and early clinical research provide abundant evidence of the therapeutic effects of kratom's alkaloids, particularly for relieving pain, managing substance use disorder, and coping with emotional or mental health disorders. On the other hand, there are also reports about kratom use and possible health risks. Reviews of kratom often talk about these two things. Here, we want to focus on a few key areas that are important for understanding how kratom alkaloids work in the body. This includes how they interact with enzymes that break down drugs and predictions of clinical drug-drug interactions, how they bind to receptors, how they interact with cellular barriers in terms of barrier permeability, how they involve membrane transporters, and how they change the way barriers work when they are exposed to alkaloids.

The Use of Kratom

Kratom (Mitragyna speciosa Korth.) has been used in Southeast Asian countries, especially Malaysia and Thailand, since the 1930s to treat minor illnesses and make people more able to work. Its use has spread to the West, especially the United States, where it is used to self-treat pain, cut down on the use of opioids that don't need a prescription, and deal with mental health problems. The scientific community is becoming more and more interested in looking into the plant's health benefits and risks. About 45 alkaloids have been found in kratom, and studies done before it was used in people have shown that it reduces pain. For a better understanding of how kratom alkaloids work, more research needs to be done at the cellular and molecular levels.

This picture shows how kratom alkaloids interact with enzymes, receptors, and cellular barriers. These are new areas of research into kratom alkaloids that are very important for figuring out whether they could be used as medicines.

Related Link: Best Kratom for Pain Relief Strain Guide

Interactions With Enzymes 

Metabolism of Kratom Alkaloids

The alkaloids in kratom are broken down in two steps: phase I and phase II. Phase I is made up of hydrolysis, oxidation, and reduction reactions. Phase II is made up of glucuronidation and sulfation conjugation reactions. We don't know much about how kratom alkaloids are broken down and what role different enzymes that break down drugs play in getting rid of them. Rat and human studies have shown that kratom alkaloids are broken down into many different phase I and phase II metabolites by hydrolysis, O-demethylation, oxidation, and reduction. Some metabolites then go through a process called phase II metabolism, which makes glucuronides and sulfate conjugates. Table 1 lists the proposed metabolic pathways and a separate figure shows the metabolites that are made.

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Possible Drug Interactions

Mitragynine and similar alkaloids are being studied to see how they interact with enzymes, especially those that are important in medicine. Drug metabolism enzymes (DMEs) are very important for getting rid of drugs in the body. Other chemicals can change the activity of these enzymes, which can lead to drug-drug interactions (DDIs) that can cause harmful side effects or lessen the effectiveness of a drug. DDI is a big problem that makes it hard to find and make new drugs, and it has caused some drugs to be taken off the market. During the preclinical phase, the U.S. Food and Drug Administration and the European Medicines Agency have guidelines for recognizing DDI. Mitragynine and related alkaloids have also been shown to interact with enzymes other than DMEs. 

Central Nervous System Receptors

Kratom alkaloids interact with different receptors in the central nervous system (CNS), such as opioid κ, μ, δ  subtypes, D1, and D2, alpha-1A, alpha-2A, 5-HT2A,  5-HT1A, receptors. According to research, kratom alkaloids interact with these receptors. In vivo research has shown that kratom alkaloids have central analgesic, anti-drug addiction, anti-anxiety, and antipsychotic effects, principally by activating the central opioidergic, adrenergic, serotonergic, and dopaminergic neurotransmission systems. In the central nervous system (CNS), the pharmacological targets of kratom alkaloids are further split into non-opioid and opioid receptors such as adrenergic, dopamine, and serotonin receptors.

Related Link: What are the Benefits of Kratom? Buyer's Guide

Kratom Alkaloids With Cellular Barriers

Cellular barriers are essential for maintaining homeostasis and safeguarding the microenvironment of tissues. The barriers regulate the movement of chemicals across tissue compartments by acting as a gatekeeper. The limiting nature of cellular barriers poses a considerable obstacle to medication development and discovery. In pathophysiology, the functions of cellular barriers are disrupted. Interactions between kratom alkaloids and cellular barriers are examined in terms of barrier permeability, transporter involvement, and impacts on barrier function.

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Understanding Kratom Alkaloids

Kratom alkaloids are a powerful and mostly untapped source of natural energy and potential medicinal value. Thanks to the advances in receptor technology and research into enzyme interactions, scientists are beginning to understand how alkaloids interact with bodies on an individual level. The effects can vary greatly depending on dosage, alkaloid concentration, delivery method, and body chemistry. Despite this apparent variability, many long-term users can attest to the energizing effects of kratom for natural stimulation in place of coffee or energy drinks. At the same time, it should be noted that more research is needed to understand how differences in alkaloid profiles affect various receptor sites and enzymes. For anyone looking for a safe alternative to caffeinated or sugary energy drinks and other artificial stimulants, why not try the Shot of Joy’s Kratom & Kava Shot? This all-natural blend provides a great way to naturally boost energy. 

Related Link: Best Kratom Brands for Quality and Safety

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