Uncovering the Risks and Regulations of Kratom in the Community.

Introduction

Kratom is a plant-based drug derived from the leaves of a botanical species Mitragyna speciosa, a tree indigenous to Southeast Asia. Kratom is becoming increasingly popular, with more businesses offering various dosages of the drug for purchase. This is commonly used for pain treatment and opioid withdrawal. In native countries, such as Thailand, kratom was not considered a drug of abuse, but a way of life. Many individuals would use kratom to not only enhance physical endurance and productivity but also to elicit euphoric effects.1  Even with this status quo, the Thai government made kratom illegal in 1943, and further strengthened its anti-kratom position by classifying kratom as a schedule 5 drug in the Narcotics Drug Act of 1979 due to the lethal side effects of Kratom. 2 Despite the native areas banning the plant, there is a growing interest in kratom within the USA and Europe. Within the USA, the Drug Enforcement Administration has attempted to classify kratom as a Schedule I drug but have withdrawn its efforts due to public backlash.3

Kratom Pharmacology

Regarding the physiological reactions of kratom in humans, the pharmacology of the drug can be studied. The active ingredients in this species are alkaloids, which are known to cause physiological actions in humans (https://www.britannica.com/science/alkaloid). The primary active ingredients are mitragynine and 7-hydroxy mitragynine, which should also be referred to when looking at the dosage of kratom. These alkaloids also contain a partial agonist of the mu-opioid receptor.4 The mu opioid receptor is the one in the body to which morphine and codeine bind to.5 While the exact effects and dosage of kratom are unknown, understanding that they can partially bind to these same receptors raises some flags amongst the scientific community. In lower dosages, individuals report having more energy, more focus, and pain relief. Yet, in higher dosages, individuals begin to report opioid-like effects, such as euphoria and sedation.6 Furthermore, long-time kratom users also report withdrawal symptoms such as anxiety, depression, vomiting, and pain.6 While the basic chemical structures of kratom have been isolated, the major pharmacokinetics of the drug have not been fully comprehended yet.

This is an image of how a partial agonist works. Since mitragynine is a partial agonist of the mu-opioid receptor, one can see how it can elicit the same effects as morphine on the receptor, yet at a smaller scale.13

Dosage/Lethality

In each kratom sample I have obtained, there have been no specified dosages on the packaging. A kratom extract purchased had a suggested serving size, but no formal dosage instructions. When looking at how to determine the dosage for a drug, or its lethality of it, one must look at the active ingredients and how they interact within the body. For kratom, the active ingredients to look at are mitragynine and 7-hydroxy mitragynine. To determine what the lethal dosage is, scientists, refer to the drug “LD50,” or the amount of the substance that will be a lethal dosage to 50% of the test subjects, this is expressed in milligrams of substance/ kilograms of subject body weight (mg/kg BW). There are many factors to additionally consider when testing this, including the method by which the substance enters the body. For kratom, varying studies have shown vast differences in the LD50 of the drug depending on how the kratom is entered into the body.

This is an example of an LD50 curve. Here, you can see how the LD50 value corresponds to the dosage and percentage dead. 14

In 2018, research led by Lauren Smith of the Scripps Research Institute, in investigating kratom lethality, administered mitragynine and 7-hydroxy mitragynine intravenously and orally to mice and calculated the LD50 levels of the drug.7 As a baseline to consider, the LD50 of heroin is 23.7 mg/kg BW. When injected intravenously, the LD50 of mitragynine was 27.8 mg/kg BW and the LD50 of 7-hydroxy mitragynine was 24.7 mg/kg BW. Both levels are extremely alarming, especially considering how close in value they are to heroin, which is currently classified as a Schedule 1 drug. When administered orally, however, the LD50 increased considerably. For mitragynine, the LD50 was found to be 547.7 mg/kg BW. For the 7-hydroxy mitragynine, there was no LD50 determined to kill the mice, yet the ones who were given large doses had side effects such as seizures and depressed breathing.8 While the 7-hydroxy mitragynine did not display lethal dosages on its own, since kratom also contains mitragynine, it must be the mitragynine LD50 dosages that are adhered to in order to prevent overdosages.

Marketing of The Drug

From the research that I have gathered, there are a few specific markets I see kratom being advertised toward. The first group is those who would use kratom for over-the-counter “medicinal” purposes/ mental health, i.e., anxiety, depression, and pain relief. Some individuals/ companies claim that in lower dosages (~2g/day) that kratom helps with “natural energy” and “focus.” The other market, the one I would argue is the primary one, is the market of individuals seeking opioid-dependence treatment. Consumers against the Deas’s attempt to classify kratom as a Schedule I drug utilized this as their main argument, claiming that kratom was far less fatal than other opioids, and in making kratom a Schedule I drug they were further advancing the usages of other, more fatal opioids.

Distribution of Kratom / Processing

The distribution of kratom is not limited to one main form of consumption. It is sold as capsules, powders, extracts, gums, leaves, and teas. Regarding processing, kratom is generally processed by the kratom plant being cultivated and harvested in Southwest Asia, where it is then dried and fermented to be imported into the USA.9 Some companies send their imported kratom products to a “third-party laboratory” where the product is tested for subjects such as alkaloid levels, label transparency, mold, or other pathogens.9

This image is a visual representation of how kratom is processed.15

Regulation of the Drug

Federally, kratom is not regulated. In 2016, the Drug Enforcement Administration (DEA) announced its intent to make kratom a Schedule I drug, alongside heroin and marijuana, but with the public backlash, decided to withdraw its intent to move forward with the decision.3 In order for the DEA to classify a drug as Schedule I, they will refer to the Eight Factor Test, which analyzes the substance’s actual or relative potential for abuse; scientific evidence of the pharmacological effects and general pharmacology; the state of current scientific knowledge regarding the drug or other substance; its history and current pattern of abuse; the scope, duration, and significance of abuse; what, if any, risk there is to the public health; its psychic or physiological dependence liability; and whether the substance is an immediate precursor of a substance already controlled.10 The DEA must consider three of the eight factors and for kratom, the intent to classify this drug was considered via the substance’s history and current pattern of abuse; the scope, duration, and significance of abuse; and what, if any, risk there is to the public health.3 Critiques claimed that kratom does not possess the harm that the DEA states it does and that creating a “hasty” ban on kratom would lead to further harm than benefit. The DEA withdrew its intent after the public backlash and has not intervened since. Similarly, the FDA has made statements warning about the harmfulness of kratom but has not set any federal guidelines.

This is an image of kratom advocates protesting to keep kratom legal.16

While there are no federal laws banning kratom, certain state and local governments have taken action. The states of Alabama, Arkansas, Indiana, Rhode Island, Vermont, and Wisconsin have banned kratom; while the states of Arizona, Georgia, Nevada, and Utah have passed laws protecting kratom. Local governments in California, Colorado, Florida, Illinois, Mississippi, and New Hampshire have stepped in making county-wide bans on kratom, but the state government has yet to intervene.17

This is a visual representation of states that have made statewide laws protecting or banning kratom.17

Chemical Testing of Kratom

Regarding labs to have this chemically tested, there is a myriad of options. Locally, Quality Analytical Laboratories could potentially do a chemical analysis of the supplements. They have a specialty in plant tissue testing, so this could be a viable option (Quality Analytical Labs Website).
Additional labs to consider could be larger ones, though farther away. Intertek has a North American chemical testing lab that compares products’ compliance with state, federal, and global chemical regulations and standards (Intertek Website). Labcorp is another company that is capable of testing products for human safety, environmental safety, regulatory standards, and toxicology (Labcorp Website).

Experience

To obtain kratom, I went to different gas stations and vape shops. I started at the Citgo gas station, located at 2521 Thomas Dr, Panama City, FL 32408, and purchased “Red Maeng Da Kratom” from the Earth Kratom Organic brand for $14.98 in cash (referred to as K1 for the remainder of this paper). This product is contained in capsules and regarding dosage, the only claim is to “consult your healthcare professional.” The packaging claims that due to mitragynine (the active ingredient) not being an approved dietary supplement, the manufacturers cannot advise on its usage. Other claims on the packaging claim it is “Third-Party Tested”, “100% Chemical Free”, “Highest Quality Kratom”, and “Not for use by those under the age of 18.” When purchasing, I was not asked to provide any form of identification. They did not push any additional products.
This is the K1 kratom obtained.

The next location I obtained Kratom from was the Exxon gas station, located at 11100 Panama City Beach Pkwy, Panama City Beach, FL 32407. I purchased “Thai Kratom” from the brand Remarkable Herbs (referred to as K2 for the remainder of this paper) and “Gold Full Spectrum Kratom Extract” from the brand Hush Kratom (referred to as K3 for the remainder of this paper). The former came in the form of powder (8oz) and the latter in capsule form. Together, these products cost $62.64. The former packaging contains claims such as “100% Guaranteed Quality- Non-GMO, Natural, Organic” and “Not for use by those under the age of 18.” Regarding dosage, the K2 package also states to “consult your healthcare professional.” The latter packaging claims to be “Made in the USA” and has “Good Manufacturing Practices.” Regarding dosage, the K3 packaging does contain a “Suggested Use” section that states individuals should not take more than 1 serving (1 capsule) at a time. When purchasing, I was not asked to provide any form of identification. They did not push any additional products.

This is the K2 kratom obtained.

This is the K3 kratom obtained.

For the K1 and K2 packaging, there are blanket statements from the manufacturers claiming that by opening the package/ ingesting the product, the consumer is liable for any actions. It claims that manufacturers and resellers assume no responsibility or liability for the uses or misuse of the product. K1 is distributed by Fire Wholesale, K2 by RH Natural Products, and K3 by Hush Worldwide, LLC.

Additionally, the Busy Bee gas station, located at 14100 Panama City Beach Pkwy, Panama City Beach, FL 32413, was also visited and did not contain any kratom products.