New Kratom Research Aims to Bridge Gaps in Understanding and Promote Responsible Use

In a recent discussion on his podcast, Hamilton Morris sat down with pharmacologist Dr. Oliver Grundmann from the University of Florida and Soren Shade, a producer on Morris’s Pharmacopoeia series and co-founder of the kratom tea company TopTree. The conversation delved deep into the complexities surrounding kratom, from its pharmacology and varied consumption methods to the societal biases and regulatory challenges it faces.

A central theme of the discussion was the launch of a new kratom consumer study, a collaboration between Dr. Grundmann’s research team and TopTree. This survey marks a significant step forward as it’s designed to gather data on a defined amount of kratom delivered in a tea bag form, allowing for a more precise understanding of dosing and effects compared to the often undefined loose powders or extracts available on the market.

Shedding Light on User Patterns

Dr. Grundmann, who has previously conducted the largest kratom consumer study in 2017 and subsequent international surveys, emphasized the importance of these studies in gathering basic, yet crucial, information about kratom users. “It’s bizarre to think that we know so much about the chemistry and molecular neuropharmacology of kratom alkaloids and very simple questions like what’s the average age of an American kratom user are more difficult to answer,” Morris noted.

The survey, distributed online via a secure Qualtrics platform and linked via QR codes on TopTree products, aims to uncover:

• Primary reasons for kratom use (e.g., pain, anxiety, opioid withdrawal).

• Demographic data and how users first learned about kratom.

• Specific benefits and adverse effects experienced.

• Concomitant use of other substances and diagnosed health conditions.
  

Both Grundmann and Morris acknowledged the inherent bias in self-reported survey data, as respondents are often more self-aware or invested in the topic. However, Grundmann highlighted that insights from less biased sources, like Reddit user forums analyzed by his collaborator Kirsten Smith, often align with survey findings, particularly regarding adverse effects and dependence development.

Navigating the “Kratom Conundrum”

A significant portion of the interview addressed what Morris termed the “kratom conundrum”—the challenge of disentangling political dimensions from basic pharmacological truths. He pointed out that users, fearing prohibition, sometimes perpetuate a “false narrative” by downplaying any negative aspects of the plant.

Dr. Grundmann strongly agreed, stating, “It would be irresponsible for anybody who does research on kratom to say that kratom is just innocuous.” He stressed the dose-response relationship for adverse effects and dependence, advocating for responsible labeling and quality standards for kratom products, aligning with initiatives like the Kratom Consumer Protection Act.

Pharmacology and Safety: A Deeper Look

The conversation turned to kratom’s unique pharmacology, particularly its main alkaloid, mitragynine, and its metabolite, 7-hydroxy-mitragynine. Morris questioned why kratom appears significantly safer than classical opioids like morphine or fentanyl, despite acting on opioid receptors.

Dr. Grundmann explained that mitragynine acts as a partial agonist at mu-opioid receptors, meaning it doesn’t fully activate them like morphine (a full agonist). Furthermore, kratom alkaloids exhibit biased signaling, meaning they preferentially activate certain intracellular pathways while avoiding others (like the beta-arrestin 2 pathway, which is associated with severe respiratory depression and constipation in classical opioids). While some opioid-like effects like constipation and dependence potential are present, the critical life-threatening respiratory depression is notably absent at typical doses.

The researchers also discussed 7-hydroxy-mitragynine, a more potent metabolite, and the possibility that its presence might vary depending on whether the leaf is fresh or dried—a distinction crucial when comparing traditional use (chewing fresh leaves) to modern consumption of dried products.

The Power of Preparation

Soren Shade emphasized how the method of preparation can significantly impact the user experience and potential for negative effects. He drew a parallel to coffee, noting its historical stigmatization and how its preparation has evolved from simple grinding to complex brewing methods.

Morris, recalling an anecdote about coca tea being as effective as psychosurgery for cocaine addiction, highlighted how simply changing the route and frequency of administration can profoundly alter a substance’s effects and abuse potential. Dr. Grundmann concurred, stating that consuming a “slurry” of powder is unpredictable, whereas a hot water extraction from a tea bag provides a much more controlled and defined absorption profile.

Confronting Opiophobia

Morris posited that “opiophobia”—the pervasive fear and stigma associated with anything labeled an opioid—might be hindering research into potentially beneficial opioids that lack the severe adverse effects of traditional ones. Dr. Grundmann passionately agreed, asserting that “substances no matter if it’s a drug or whatever it is inherently are neither good nor bad. It is what we attribute to them.” He criticized the “war on drugs” mentality, arguing that it misdirects blame from problematic drug use to the drugs themselves. He also underscored the critical role opioids play in pain management, particularly in palliative care, and the need for a more educated and nuanced societal approach.

A Glimpse into the Future

The new survey promises to yield invaluable data on the effects of precisely dosed kratom in a tea format. Dr. Grundmann is eager to analyze correlations between consumption patterns, overall health, and pain status. The researchers expressed optimism that such studies, combined with advancements in understanding the complex pharmacology of all the alkaloids present in kratom, will contribute to a more informed public discourse and potentially pave the way for safer, more effective therapeutic applications of the plant in the future. https://youtu.be/npVkYGk1dJo?si=5VN2rvGAJek8cw03