Class Modules:
Kratom Pharmacodynamics
How Kratom
Works in the Body
This page features educational content from Dr. Erin Berthold.
Introduction to Kratom as a Plant
Leaf kratom is a plant that contains a wide variety of phytochemicals including terpenoid saponins, glycosides, polyphenols, flavonoids, and alkaloids. What makes leaf kratom particularly fascinating is that its reported effects tend to be contradictory, and how it works for one individual doesn’t seem to be the way it works for all individuals.
What Are Alkaloids?
An alkaloid is a naturally occurring compound that contains at least one nitrogen. Alkaloids are not unique to leaf kratom – they are found in other plants, bacteria, fungi, and even animals. A common and widely used example of an alkaloid is caffeine.
Interacting with Your Body
When you ingest a substance, it interacts with your body in two distinct ways:
Pharmacodynamics
This is what the substance does to the body – like how coffee wakes you up.
Pharmacokinetics
This is what the body does to the substance – like how the liver breaks down the caffeine from coffee into paraxanthine.
Understanding Receptors
This content focuses on pharmacodynamics, specifically what receptors kratom alkaloids interact with
What Are Receptors?
There are hundreds of different receptor types in the human body, modulating neurotransmission, hormone regulation, sensory perception, and immune function. Estimates suggest between 200-300 distinct receptor classes.
Think of receptors as little padlocks on your body’s cells. Each has a unique shape, so only the right key can fit. The keys for receptors are compounds.
Types of Compounds
Endogenous Compounds: “Originating from within the body.” These are like custom-made keys, perfectly designed to fit those locks (receptors). Examples include neurotransmitters (like dopamine or serotonin) and hormones (like insulin or adrenaline).
Exogenous Compounds: From outside your body, from sources like food, medicine, or supplements.
How Compounds
Interact with Receptors
Not every compound that binds to a receptor produces the same effect:
1. Full Agonists
Fit into the lock and fully open the door, fully activating the receptor and producing all expected effects.
2. Partial Agonists
Unlock the receptor but only partially activate it, like a door that doesn’t fully open, producing some but not all expected effects.
3. Antagonists
Fit into the lock but prevent it from opening, blocking the receptor’s function entirely.
This distinction is essential when discussing kratom’s pharmacology, as its alkaloids interact with receptors in diverse ways, influencing their effects and safety profile.
Adrenergic Receptor Interactions
Activated by adrenaline and noradrenaline, these receptors regulate autonomic functions:
- Mitragynine interacts with adrenergic receptors as both an agonist and antagonist, depending on the receptor subtype
- Corynantheidine acts as a full agonist at alpha-1D receptors and a partial agonist at alpha-2A receptors
- Paynantheine and speciogynine engage with alpha-2 receptors
Opioid Receptor Interactions
- Mitragynine, mitraciliatine, and speciociliatine act as partial agonists at the mu opioid receptor
- Corynantheidine plays the role of an antagonist
Serotonergic System Interactions
Alkaloids such as mitragynine, paynantheine, and speciogynine bind to 5-HT1A receptors.
Kratom Alkaloids
and Receptor Systems
The most abundant and well-studied kratom alkaloids include:
- Mitragynine
- Speciociliatine
- Speciogynine
- Paynantheine
- Mitraciliatine
- Isopaynantheine
- Corynantheidine
These alkaloids interact with various neurotransmitter systems in the brain, including opioidergic, serotonergic, and adrenergic systems. These neurotransmitter systems are involved in physiological and psychological processes that affect mood, perception, well-being, and reactions to stress or arousal.
The Complex Picture
Kratom’s alkaloids interact with different receptors, each shaping the biological response in a distinct yet interconnected way. Ongoing research continues to uncover the depth of these interactions, providing greater insight into their roles within the body’s vast neural network.
Next Steps in Understanding
Now that we know where the compounds from kratom will act in your body, we need to know how much of each compound is available in your body after kratom consumption and for how long.
For more scientific
resources and research on kratom
Your Comprehensive Resource Library
Navigate effortlessly between General, Scientific, Legal and Regulatory and Product Safety resources— with just a single click. Join the fight against misinformation by sharing fascinating facts you discover. Simply hit ‘Download’ to receive the knowledge and invite others to explore our rich repository of information!
-
2024 Kratom Consumer Survey
This survey review offers key insights into the kratom user base, revealing who they are, why they use kratom, and their perspectives on its health effects. -
The Evolution of Kratom: A Historical Timeline
An infographic tracing kratom’s journey from its traditional origins in Southeast Asia to its current complex legal and political landscape in the United States. -
Not All Kratom Is Equal
An infographic of clear visual guide comparing the potency, history, alkaloid sources, and common product forms of leaf kratom, kratom extract, and synthetic 7. -
The Differences Between Kratom Products
A detailed diagram visual comparison of leaf kratom, extracts, and synthetic “kratom,” highlighting distinctions in their market entry, alkaloid profiles, and appropriate regulatory approaches. -
Kratom Safety, Taxonomy, and Regulation
Provides a general overview of kratom, addressing common confusion between product types and outlining the GKC’s goals for a safe and regulated marketplace.
-
2024 FDA Study: Kratom Dosing & Safety Results
A summary of an FDA-commissioned study that found controlled servings of dried leaf kratom were generally well-tolerated and resulted in no serious adverse events. -
FDA Pilot Study: Updates on Kratom Alkaloid Research
A presentation from the FDA detailing updates on its pilot dose-finding study of kratom alkaloids, including study design, preliminary observations, and next steps. -
Scientists’ Statement on 7-OH and MGPI Products
A statement from leading scientists clarifying that products with high amounts of 7-OH and MGPI are synthetic and do not constitute natural kratom. -
Scientific Statement on Kratom Products
An overview by scientists covering the history of kratom use, its current regulatory status, and the scientific understanding of its effects in the United States. -
Comprehensive Report on Substance Use Disorders
A detailed analysis comparing the prevalence, severity, and symptoms of Substance Use Disorders (SUDs) associated with kratom, caffeine, alcohol, opioids, and other substances. -
The Science of Leaf Kratom: Psychoactive Effects
This document reviews scientific evidence on leaf kratom’s effects, refuting claims about cognitive impairment and abuse potential while clarifying its atypical opioid profile. -
2024 FDA Pilot Study on Kratom Dose Response
Details of the FDA’s pilot study evaluating the effects, safety, and pharmacokinetics of orally administered botanical kratom in non-dependent, recreational polydrug users. - Show more
-
Congressional Letter to the FDA on Kratom
A letter from members of Congress to the FDA expressing concerns about mislabeled kratom products and requesting information on consumer protection measures. -
GKC Letter to FDA on Public Safety Guidance
A letter from the Global Kratom Coalition to the FDA, expressing a desire to collaborate on public safety guidance for kratom products and regulatory approaches. -
Louisiana Voter Poll on Kratom Regulation
This poll assesses public opinion in Louisiana regarding kratom’s legality and regulation, including support for banning synthetic drugs while keeping leaf kratom accessible. -
List of Banned Zip Codes: USA
A data file listing zip codes across the country where the sale, possession, or distribution of kratom is currently illegal. -
-
KCAC Position: Registration of Kratom Products
This statement advocates for a public registry of kratom vendors and products to ensure transparency, accountability, and a safer market for consumers. -
GKC Statement on Synthetic 7-OH Products
The GKC clarifies its opposition to synthetic 7-hydroxymitragynine (7-OH) products, arguing they are not kratom and should be regulated as new drugs, not supplements. -
KCAC Position: Status and Legality of 7-OH Products
This KCAC statement discusses the legal and regulatory status of 7-OH products, arguing they are not “kratom” and require a distinct regulatory approach. - Show more
-
The Severity and Prevalence of Addictive Substances
This infographic visually compares Substance Use Disorder (SUD) severity and prevalence across various substances, including kratom, heroin, alcohol, tobacco, and caffeine. -
Comparative Safety Analysis of Kratom
This document provides a comparative risk analysis of kratom versus other legal and illicit substances, using data from the FDA and poison control centers. -
Contaminants in 7-Hydroxy Mitragynine Products Report
A detailed report identifying synthetic alkaloid contaminants found in 7-Hydroxymitragynine products and discussing the serious implications for regulatory oversight and consumer safety. -
Botanical Safety Handbook: Kratom Entry
An entry for Mitragyna speciosa from the American Herbal Products Association’s handbook, providing safety classifications, contraindications, and potential drug interactions for kratom leaf. -
Debunking Myths About “7”: The Facts
A fact sheet refuting misleading claims about “7” (a synthetic substance), arguing that it is not natural kratom, is not safe, and is deceptively marketed. -
In-Depth: Debunking Myths About “7”
A more detailed version of the fact sheet refuting claims about “7,” providing comprehensive evidence that it is a dangerous, unapproved, and illegal synthetic drug. -
KCAC Position: Proper Labeling of Kratom
This statement advocates for the importance of clear, comprehensive labeling on kratom products to ensure consumer safety and outlines essential information that should be included. -
KCAC Position: Kratom Use in Children
This statement outlines concerns about kratom use by minors, highlighting potential adverse events and the issue of products being marketed in ways that appeal to children. -
UCONN Continuing Education: Kratom Course for Pharmacists
An educational program from the UCONN School of Pharmacy designed to inform pharmacists about natural kratom, its effects, and key points for patient education. -
The Fourth Wave of the Opioid Epidemic
This presentation warns of a potential “fourth wave” of the opioid crisis driven by dangerous and addictive synthetic opioid stimulators, arguing they must be banned. -
Fact Check: “Synthetic 7” and the Opioid Crisis
This KCAC statement fact-checks and refutes misleading claims that the sale of “synthetic 7” products has reduced opioid-related deaths, citing a lack of evidence. -
GKC Perfect Label – Kratom Product Label Guidelines
This document from the Global Kratom Coalition provides comprehensive guidelines for labeling kratom products to ensure consumer safety and regulatory compliance. - Show more
