Does the word kratom [kra-tm] mean anything to you? Well, if you were me a few months ago, the word kratom was abstract and had very little meaning. I had no idea how popular kratom was in both Southeast Asia and (more recently) Western countries as a medicinal remedy for many ailments. However, after doing some personal research, I have a newfound appreciation for kratom and its use as an alternative pain-relieving substance. I hope that once you finish reading this post, you will too.
What exactly is kratom? Well, for starters, it is a plant, but more specifically it is a tall tropical tree (standing anywhere between 4-16 meters tall) that is genetically close to the coffee plant in the Rubiaceae family. When people mention kratom, they can either be referring to mitragyna speciosa, which is the plant itself, or to the botanical products derived from its broad leaves.
The Kratom plant is indigenous to regions in Southeast Asia such as Thailand, Malaysia, and Papua New Guinea. Depending on where you might find yourself, kratom may also be referred to as ketum, ithang, or thom. For centuries people have chopped kratom leaves from its tree to chew, smoke, or boil to treat a wide variety of things. Some of the most common uses are to combat fatigue, curb pain, help with one’s anxiety and/or depression, induce euphoria, mitigate opioid and alcohol dependence, and to serve as an opiate substitute. There are also numerous accounts of kratom being used to help with intestinal infections and diarrhea.
Just by reading the previous list of treatment applications for kratom, it is pretty clear that this plant has quite the therapeutic range! On one end kratom can behave as a stimulant, whereas on the other end of the spectrum it can behave as a sedative or narcotic. But before we get into the fun pharmacology of kratom, we must first understand the chemical makeup of the plant!
Similar to Cannabis, which is the plant that synthesizes phytocannabinoids such as Δ9-THC and CBD, (if you are unfamiliar with the Cannabis plant and its phytocannabinoids, click on this link: Cannaba-what!?: Cannabinoids in their various forms – IU Blogs, to find out more!) kratom does not denote a single, specific compound. Rather, a cocktail of psychoactive (alkaloid) compounds occurs naturally in the plant. More than 40 of these compounds have been identified to date, although only two kratom compounds have been primarily studied: mitragynine and 7-hydroxymitragynine (7-OH-mitragynine).
Starting with mitragynine, which is the most prevalent compound of the kratom plant, scientists suggest it accounts for up to 66% of the total alkaloid content from leaf extracts. A more minor constituent of the plant is 7-OH-mitragynine, which only accounts for a modest 2% of the alkaloid content. Though it is found within the plant at much lower levels, following ingestion of kratom preparations levels of 7-OH-mitragynine in the blood spike. This result occurs from the high levels of mitragynine found in the kratom preparation being converted to 7-OH-mitragynine during a metabolic oxidation event in the liver. Though there are many different compounds found in kratom leaves, it’s mitragynine and 7-OH-mitragynine that scientists believe primarily contribute to kratom’s therapeutic effects (remember our extensive list above!). However, it is extremely important to acknowledge that the remaining compounds found within the leaves of kratom could very well be synergistically contributing to the overall effect of kratom, albeit in an unknown manner.
I briefly touched on kratom’s wide therapeutic spectrum. On one end it can be used as a simple remedy to stave fatigue. On the other it can be used as an opiate substitute, and elicit analgesia, euphoria, and feelings of being high, with many other purposes for use in between.
The effects of kratom will vary based on the dose. In other words, it has a dose dependent effect. Specifically, lower doses (1-5g) elicit stimulant-like effects, and higher doses (5-15g) have opioid-like effects. A common effect of kratom at higher doses is analgesia (or pain relief), which is an attractive quality of the natural substance, especially for those who may have been prescribed side effect-ridden avenues to treat their ailments (i.e., opioids).
Thanks to competitive binding assays, which are experiments that allow scientists to determine binding information (i.e., how well different molecular entities interact), as well as affinities for molecules to a target receptor, we know that both of primarily studied compounds of kratom (i.e., mitragynine and 7-OH-mitragynine) target each of the body’s opioid receptor subtypes (mu, delta, and kappa). Receptors are specialized proteins that can induce a cellular response following the binding of a molecule. When a molecule binds to (i.e., physically interacting with) a receptor, it changes the shape of the receptor, which dictates the following type of cellular response. Upon the activation of the body’s opioid receptor subtypes, the subsequent cellular response can result in the inhibition of pain perception and/or euphoria.
Though these compounds target each of the opioid receptor subtypes, their specific affinity for (i.e., ability to bind to) the mu opioid receptor plays a huge role in kratom’s overall analgesic properties. Recently, there are additional avenues being explored to fully elucidate mitragynine and 7-OH-mitragynine’s ability to curb pain (If interested in this topic, click here to learn more: Pharmacology of Kratom: An emerging botanical agent with stimulant analgesic and opioid-like effects). However, those will not be discussed here.
It is no secret that kratom has great therapeutic benefits, which is why it has been used for centuries in regions such as Malaysia and Thailand for its pain curbing and euphoria-inducing properties. Because of this, the natural substance has gained popularity in Western countries. Though naturally derived kratom preparations have great therapeutic properties, kratom can have unfavorable qualities as well.
Since kratom is not native to the US, access to the substance would primarily come through individuals selling and buying it online. A downfall of this is that sellers can manipulate these preparations and add additional substances that, upon ingestion, could cause lethal outcomes.
In addition to this, the lack of knowledge on the lethality of concurrently using various drugs and kratom, as well as kratom’s addictive qualities (when taken at high doses), resulted in a push to regulate the substance in 2016 by the FDA. Though nothing of great magnitude at the federal level resulted from this initial attempt to regulate kratom in the US, individual states, including Wisconsin, Indiana, Arkansas, Vermont, and Rhode Island, have recently passed bills to make kratom possession illegal. Outside of these US states, kratom is for the most part unregulated and people can purchase it with ease.
Though there are adverse effects of kratom that people should be aware of and educated on, when used appropriately, the substance has great therapeutic promise. Now I really enjoyed my mini personal research project on kratom, and I could go on for days about the pharmacokinetics, metabolism, toxicity, molecular/cellular targets, and additional uses for kratom, but I feel like this is a great place to stop…can’t take all the fun away from independent research! If you already knew what kratom was, I hope this post helped you learn more about it. If kratom was a new subject to you, I hope you enjoyed learning something new. Overall, I hope this post ignites an interest in kratom and maybe motivates you to do your own personal research on the substance as well.