In an industry full of setbacks, cheers to some good news: Mitragyna speciosa (kratom) is one step closer to human clinical trials. Researchers have graduated from rodent examinations to canine clinical research.
Animal studies are vital to the scientific process. According to scientists at the University of Florida (UF), where the kratom-dog studies occurred, “Research and development of a drug [sic] must be demonstrated in more than one animal species in order to predict human pharmacokinetics.”
Dogs and kratom—studied with safety, efficacy, and due diligence in mind—can teach us a lot about the kratom plant and its potential uses. In addition, animal studies advance our knowledge of kratom’s primary alkaloids: hydroxymitragynine, and 7-hydroxymitragynine. Scientists believe these alkaloids are responsible for the plant’s vast therapeutic effects.
The UF study took a keen interest in mitragynine, specifically. “Mitragynine is the most abundant alkaloid,” making it a compound of interest because, as several studies suggest, “Mitragynine and products containing mitragynine have analgesic, anti-inflammatory, antipyretic, antidiarrheal, euphoric, antidepressant, and anxiolytic effects.”
IN LAYMAN’S TERMS:
- Pharmacokinetics is the study of drug absorption, distribution, metabolism, and excretion. In other words: how a compound is absorbed into the body, used, and subsequently expelled.
- Humans share about 85% of their DNA with dogs, signifying a connection between canine and human pharmacokinetics of kratom.
- UF researchers recorded substantial findings when studying the effects of kratom in canine trials.
Kratom Alkaloids & Receptor Activity
Our bodies are full of tiny receptors. Their job is to send signals throughout the body, carrying pertinent biological information from one place to another. Receptors can be activated (agonist) or deactivated (antagonist) depending on the pharmacokinetics of a particular compound.
According to the UF study on dogs and kratom, “Mitragynine binds to opioid [mu], alpha-adrenergic, adenosine, dopamine, and serotonin receptors.” However, mitragynine “displays a moderate affinity for mu receptors, specifically. The study also notes that 7-hydroxymitragynine displayed high mu receptor binding.
FDA-approved drugs with similar receptor activity (and more side effects) are currently prescribed to treat chronic pain (mild to severe), hypotension/hypertension, and opiate use disorder (OUD). According to the Centers for Disease Control and Prevention (CDC), a variety of these medications carry a high potential for abuse and addiction.
IN LAYMAN’S TERMS:
- Receptors send signals throughout your body, passing around vital biological info.
- In canine studies, it was observed that mitragynine and 7-hydroxymitragynine alkaloids bind to a variety of receptors, especially mu receptors.
- Many FDA-approved drugs also bind to mu receptors yet offer additional, unwanted side effects and high dependence.
What We Learned From Giving Kratom to Dogs
UF researchers performed two fundamental studies on dogs and kratom, (1) administering a single oral dose at 5mg mitragynine per kilogram body weight and (2) administering an intravenous dose at 0.1mg mitragynine per kilogram body weight. Results from both studies indicate the general pharmacokinetic properties of kratom.
In their own words, “These results provide the first detailed pharmacokinetic information for mitragynine in a non-rodent species (the dog) and therefore also provide significant information for allometric scaling [deciding dosage for humans] and dose predictions when designing clinical studies.”
This is monumental progress towards human clinical trials. When human clinical trials are designed for mitragynine and 7-hydroxymitragynine, this research will undoubtedly be considered.
IN LAYMAN’S TERMS:
- Canines were split into two groups. One group received a single oral dose of mitragynine, while the second group received a smaller intravenous dose of mitragynine.
- These are the first non-rodent animal studies using kratom or any of its alkaloids. They allow for dosage predictions to be made for human clinical trials, a monumental step forward in the scientific process.
The Bioavailability of Kratom Alkaloids in Dogs
“Mitragynine showed a large volume of distribution…and high clearance” after intravenous administration. In terms of pharmacokinetics, this is an ideal outcome. According to the UF study, mitragynine has the ability to permeate metabolic barriers, extending its usefulness once inside the canine body.
Clearance is key to the pharmacokinetic process because it examines how much of a substance the body can safely expel after use. Determining clearance allows for more accurate dosage recommendations when it comes to kratom products.
As for oral administration, the bioavailability of mitragynine was established at 69.9%. For comparison, the oral bioavailability of CBD oil (another natural product) is about 6%. And according to Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, “In many cases, most of the orally administered drug is metabolized and eliminated before reaching systemic blood circulation.
7-hydroxymitragynine concentrations were observed in the plasma of orally dosed dogs but not in the plasma of intravenously dosed pups. UF researchers theorize, in oral dosage only: “7-hydroxymitragynine could represent the lion’s share” of receptor activity. This has also been observed in mice.
IN LAYMAN’S TERMS:
- Bioavailability is the amount of a substance that enters your bloodstream after metabolism and other processes that break down compounds entering the body.
- Mitragynine and 7-hydroxymitragynine have high bioavailability for a natural product: 69.9%.
- The canine body can safely clear mitragynine after use. This allows for improved human dosage recommendations as well.
- In oral dosage, 7-hydroxymitragynine concentrations were observed. What this means: how we take kratom may influence its effects.
Behavior and Tolerance of Kratom in Dogs
According to UF researchers, the administration of mitragynine was “well tolerated” for both oral and intravenous administration routes. Following administration, dogs were observed for a variety of physiological changes.
“No major adverse events were noted,” researchers noted. “Mild sedation and anxiolytic effects were observed.” The sedation lasted approximately two to four hours after oral administration and up to one hour after intravenous administration.
On top of that, “Stress-related frenetic signs such as pacing, barking, jumping, and spinning were reduced.” Among the orally-dosed pups, two displayed lip-licking and excessive drooling. Researchers believe this is due to the poor palatability of the oral solution. If you’ve taken kratom orally, you may remember the distinct taste. Lucky for kratom users, there are many ways to overcome the bitter taste of kratom.
As for other potential side effects: “Nausea cannot be completely ruled out,” but excessive drooling did resolve within 30 minutes following administration. All dogs from both groups “ate readily when offered food two hours after dosing” as well. Panting also occurred “transiently” in one dog.
Overall, “No clinically significant changes in vital signs, physical examinations, or clinical laboratory tests were observed for both oral and intravenous pharmacokinetic studies.”
What this means: kratom is well tolerated in dogs, and there were no significant side effects that would detract from mitragynine’s use potential.
If we achieve the same results in human clinical trials, we will better understand kratom’s unique potential as a therapeutic agent. Kratom-health recommendations could be made, connecting the plant to patients in need. Furthermore, the kratom industry could adopt commonplace practices like third-party laboratory testing and other safety precautions, standardizing products industry-wide.
Who said animal studies aren’t significant?
IN LAYMAN’S TERMS:
- Kratom is well tolerated in canines.
- Side effects were few and far between.
- Stress-related behavioral signs were reduced.
- Physical examinations revealed normal vital signs and other biological info.
- If future human clinical trials have the same success, kratom will likely prosper.
Should Pet Owners Give Their Dogs Kratom?
Absolutely not! The successes of the UF study do NOT indicate that dog owners should give kratom to their four-legged companions. To say it clearly: DO NOT GIVE KRATOM TO YOUR PETS. The mitragynine administered to dogs during the UF study was isolated in a lab-controlled setting. While you can trust human-grade Kratom Spot products for your own ethnobotanical needs, four-legged friends may not respond well to plant materials like kratom powder. We don’t yet know if canines can safely digest this plant material, only pure concentrations of the alkaloids found within.
IN LAYMAN’S TERMS:
- Don’t do it.
In Conclusion: Dogs and Kratom
UF researchers note that only a limited number of mitragynine pharmacokinetic studies on metabolism have been conducted to date. One—count them, one!—human pharmacokinetic study was performed using kratom tea. However, the human-kratom study did not account for mitragynine in a dose-specific setting.
Instead, the UF study using dogs and kratom follows the FDA’s guidelines for the approval of clinical trials. “Such studies are an essential precursor to examination of [kratom’s] efficacy as a treatment” for a variety of common ailments.
Because this study established guidelines for canine dosage of mitragynine, we have a starting point for first-in-human doses. And according to UF researchers, “Estimation of a first-in-human dose is an essential element in the clinical development of a drug for approval by the FDA.”
Time will tell how far we are from human clinical trials of kratom. However, the kratom community has remained strong. These latest canine studies indicate a scientific change in the kratom space. Researchers are finally validating what kratom users have known forever: this plant has the potential to change lives.