Kratom Survey: Entourage Effect and Biotransformation

Learn all about the kratom entourage effect! This blog is a recap of Dr. Oliver Grundmann’s and Hamilton Morris’s discussion surrounding the science behind the kratom entourage effect and it’s biotransformations. When possible, citations have been provided for the topics discussed.

DR. OLIVER GRUNDMANN

Dr. Oliver Grundmann is one of the most cited kratom researchers in the world. His work regarding kratom ranges from the largest population study of kratom consumers ever conducted, all the way to detailing its neuropharmacology. He has spoken at several American Kratom Association hosted advocacy events, and continues to correct sensationalism with science.

He currently serves as the Director and faculty advisor for the online Master of Science and graduate certificate programs in Pharmaceutical Chemistry and Clinical Toxicology at the College of Pharmacy of the University of Florida.

HAMILTON MORRIS

Hamilton Morris is a renowned science and culture journalist. He directed, wrote, and hosted three seasons of the hit television series “Hamilton’s Pharmacopeia,” and his written work has appeared in Harper’s Magazine and Vice Magazine, among others. He researches drug development and pharmacology at the University of the Sciences in Philadelphia with long-time colleague Dr. Jason Wallach.

In 2017 he released his widely acclaimed documentary Kratom: The Forbidden Leaf as part of season 2 of his television series.  He has returned to the subject of kratom through his role as Scientific Advisor to Top Tree Herbs.

What is 7-OH-Mitragynine?

7-OH Mitragynine is a big part of the ongoing kratom entourage effect conversation. In this clip, Hamilton asks Dr. Grundmann about the mystery of the potent kratom alkaloid 7-hydroxymitragynine, or 7-OH-Mitragynine (7-OH). In essence, 7-OH is a mysterious alkaloid. Little is know about how it finds its way into the kratom leaf.

As some background, 7-OH is more potent than mitragynine, and the second most studied alkaloid in kratom. To account for its strength, states which have passed the KCPA (Kratom Consumer Protection Act) require that kratom products contain no more than 2% 7-OH in relation to total alkaloidal composition.

How’s It Made

At this time, 7-OH is understood to be an oxidation byproduct of mitragynine. This means that 7-OH forms from mitragynine through contact with oxidizing agents. An obvious candidate for the production of 7-OH in the tree are enzymes. Since the other alkaloids within kratom, and much of nature, are formed with “intent” by the plant, it makes sense to assume 7-OH is as well.

Alternatively, a popular hypothesis suggests that mitragynine transforms into 7-OH outside of the tree’s natural processes. In both explanations, mitragynine is first produced by the tree, and 7-OH comes into being a step later. The implications for 7-OH’s formation occurring following picking is that the drying, storing, and shipping process can affect the alkaloid content. Not only this, but the brewing process may also affect which alkaloids make it into your tea.

Yet due to the lack of science directed toward studying this particular phenomenon, the jury is still out. Luckily, researchers are digging into this question at this very moment.

In humans, it does seem like 7-OH is formed enzymatically after consuming mitragynine. This happens in the liver by CYP450 enzymes, specifically CYP450 3A4. The liver alters, or biotransforms, molecules all the time. The technical name for this is first-pass metabolism. Therefore, in the case of kratom, even if you only consume mitragynine, you could still have 7-OH in your system.

Nuances of Active Metabolites

Hamilton brings up why this process makes it hard to lay a finger on the exact effects that will occur following the consumption of kratom.  Since everyone’s body is different, it is impossible to say what the biotransformational process will result in. (For more information regarding this phenomenon, listen to Hamilton’s discussion with Dr. Yearlink.) It is common for different people to have different quantities and types of liver enzymes.

Furthermore, Dr. Grundman cites a recent discovery concerning the biotransformation of 7-OH itself into an even stronger molecule: mitragynine-pseudoindoxyl. In a short number of steps, the body gradually transforms mitragynine into ever stronger alkaloids. That, at least, is the implication of this study. Scientists are just now beginning to research this phenomena. For example, this study was in vitro, and therefore does not guarantee that this occurs in the body.

The gradual but profound transformations that occur in your body may hint as to why kratom seems to have a number of effects of different people. As always, more research is necessary to better understand what kratom tea is doing in the body, and why.

The Kratom Entourage Effect

As interesting as all these metabolites are, Dr. Grundmann warns us of the possibility of getting lost in the weeds.  While mitragynine is the most abundant alkaloid in kratom, it is not the only by any stretch of the imagination.  To date, over 40 alkaloids, many with the same rough shape as mitragynine, have been elucidated. There is still a profound lack of understanding of kratom as a whole by the scientific community. Most of these alkaloids are simply known to exist, but their precise purpose is still a mystery. 

Recently, a groundbreaking analytical chemistry paper tracks the pharmacodynamics of 11 of these alkaloids from a traditional kratom tea. The act of characterizing these alkaloids is a phenomenal first step in laying a foundation for later research. We highly recommend listening to Brian Gallagher and Dr. Jonathan Cachat’s latest discussion concerning this study.

We are particularly excited that Dr. Grundmann’s survey will be taking into account the concentration of not just mitragynine and 7-OH, but four or five other alkaloids. In these early stages of kratom research, it is important to cast as large of a net as possible. This is done to avoid accidentally getting attached to any possible correlations which may result from putting too much emphasis on mitragynine alone. This can, and does, occur now since most studies track only mitragynine and 7-OH.

Furthermore, metabolism changes depending on what it is processing. This is why some medication requires you take it on an empty stomach or in the morning. It is easier to predict what the liver will do when it is not multitasking. This implies that some kratom alkaloids may change the metabolism other kratom alkaloids. The technical term for this is synergy. Also known as the kratom entourage effect.

SURVEY INFO

Ultimately, this discussion is to promote Dr. Grundmann’s incredibly important population survey of kratom tea drinkers. The data from this survey will be able to further our scientific understanding of this leaf, and its consumption via the traditional preparation.

These are the crucial, final innings in the story of kratom. At the moment, it has drawn the ire of federal regulatory agencies, for whatever reason. Nobody can protect kratom by themselves. Rigorous, scientific analysis of kratom, including its potential for both good and bad is necessary. However, given the politics surrounding kratom, the ability for scientists to experiment with it is limited

This survey will help elucidate the mystery surrounding the synergy of kratom alkaloids. It will also help determine how people use kratom in the US. From these use patterns, we will also be able to learn about the safety and toxicity of the tea. But because it is a survey, it will also point out promising directions for kratom researchers to take in the future.

YOU CAN HELP

To get around this, we need a grassroots commitment to discovering the truth regarding this leaf. As such, surveys are one of our best options. The current survey that Dr. Grundmann is conducting is one of the most rigorous and controlled population surveys on kratom every conducted. For the results to have any weight, it is up to you to participate.

If we fail to collect adequate data to make any meaningful conclusions, then the enemies of kratom will be able to continue to propagate their ill informed claims. In the grand scheme of things, we know surprisingly little about kratom.  That means that both the claims made by advocates and kratom-haters are founded on thin evidence. To collect a meaningful amount of data from this survey would allow for a more scientific discussion to be had.  In effect, all those committed to honesty above speculation will want for this survey to be widely responded to.

HOW TO HELP

If you would like to participate in this historical research project, you can purchase a discounted bag of our crushed leaf kratom tea bags. From there, it’s as simple, and pleasurable, as drinking tea!  After you’ve drunk some of the tea, simply scan the QR code on the bag and fill out the anonymous survey.  Or, you can go directly to the survey via https://tinyurl.com/Kratomteasurvey.

To clarify, only our unblended kratom tea bags are associated with the survey.