Glaring Hole in the Kratom Consumer's Protection Act (Open Letter to Legislators)

[Data Contributor]

An Open Letter to Any Legislator Considering Ratifying the KCPA.​

AN EXTREMELY LARGE HOLE IN SAFETY​

Consider sending this to any of your state reps that may be considering voting for any version of the Kratom Consumer's Protection Act. They NEED to know this.

I am writing to highlight a crucial oversight in the current versions of the Kratom Consumer Protection Acts (KCPAs) at both the state and federal levels, whether ratified or not. This oversight relates to the absence of regulations and guidelines surrounding the fermentation process of kratom (Mitragyna speciosa) products and the lack of established limits for the metabolite compound Mitragynine pseudoindoxyl (MP).
MP naturally occurs in tiny amounts in the standard metabolization of mitragynine in human plasma (Kamble et al. 2020), and can also emerge through the biotransformation of mitragynine during specific fermentation processes in manufacturing. Unlike mitragynine, MP exhibits a different pharmacological profile with potentially much more potent opioid receptor activity, significantly altering the safety and efficacy of kratom products (Chakraborty et al. 2021).
Research indicates that MP binds with high affinity to opioid receptors, particularly the mu-opioid receptor, suggesting potential strong narcotic effects as well as risks associated with opioid-like activity (McCurdy et al. 2024). The current KCPAs have significant holes, as they only set limits on 7-hydroxymitragynine presence and not other bioactive metabolites like MP (Lee and [r-Ut] 2023).
The fermentation process can lead to the biotransformation of mitragynine into MP without the side production of 7-hydroxymitragynine (Zarembo et al. 1974). This oversight in the current legislative framework is significant for several reasons:

1. Consumer Safety: Lack of safeguards against unintended effects on consumers, and lack of testing ability for consumer grade products.
2. Manufacturing Practices: Unregulated fermentation processes may alter the product's safety and addictive profile.
3. Product Consistency: Inconsistencies in product composition and quality, undermining consumer protection and choice.

To address these concerns, I propose the following recommendations:

1. Reject the current version of the Kratom Consumer’s Protection Act in its entirety.
   1. The lack of these specific regulations, across the country as well as in federal efforts, indicates a deliberate exclusion of these particular components of the act regarding fermentation to increase the potency of kratom products.
2. Demand there be Included specific provisions in any subsequent KCPAs that address the fermentation process used in kratom production.
3. Require the establishment of strict standards and limits for the concentration of MP in kratom products.
4. Encourage and support research into the effects of fermentation on kratom and its alkaloids and subsequent metabolites.

The glaring absence of regulations surrounding the fermentation process and the lack of established limits for MP in all existing KCPAs across the nation create a perilous loophole that unethical manufacturers will undoubtedly exploit, exposing consumers to severe and imminent health risks. It is highly probable that this dangerous exploitation is already occurring, as the current regulatory landscape fails to provide any safeguards against the production and distribution of kratom products with alarmingly high levels of MP. Even proponents of kratom should be deeply concerned about this issue, as it allows dishonest vendors to adulterate pure leaf kratom by way of fermentation to significantly increase levels of MP, raising its addictive and harmful potential, while still claiming it to be “natural”. This adulteration not only threatens the well-being of consumers but also jeopardizes the reputation and legitimacy of the entire kratom industry. Failure to address these critical issues promptly completely render the accepted and submitted KCPAs ineffective in their purported goal of consumer protection, leaving individuals vulnerable to the harmful effects of unregulated and potentially hazardous kratom products. Swift action is not merely advisable but absolutely essential to close this loophole and ensure that the true spirit of consumer protection is fully embodied in the regulation of these products, safeguarding the consumer and conserving their choice.
Thank you for considering this urgent matter.
Sincerely,

Chakraborty, Soumen, Rajendra Uprety, Samuel T. Slocum, Takeshi Irie, Valerie Le Rouzic, Xiaohai Li, Lisa L. Wilson, et al. 2021. “Oxidative Metabolism as a Modulator of Kratom’s Biological Actions.” Journal of Medicinal Chemistry 64 (22): 16553–72. https://doi.org/10.1021/acs.jmedchem.1c01111.

Crowley, Morgan, Samuel Obeng, Avi Patel, Lea Gamez‐Jimenez, Luis Restrepo, Nicholas Ho, Manuel Alvarez, et al. 2021. “Assessment of Contribution of 7‐hydroxymitragynine and Mitragynine Pseudoindoxyl to the MU‐opioid Activity of Mitragynine.” FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology 35 (S1). https://doi.org/10.1096/fasebj.2021.35.s1.05475.

Kamble, Shyam H., Francisco León, Tamara I. King, Erin C. Berthold, Carolina Lopera-Londoño, Kanumuri Siva Rama Raju, Aidan J. Hampson, et al. 2020. “Metabolism of a Kratom Alkaloid Metabolite in Human Plasma Increases Its Opioid Potency and Efficacy.” ACS Pharmacology & Translational Science 3 (6): 1063–68. https://doi.org/10.1021/acsptsci.0c00075.

Lee, and Mike [r-Ut]. 2023. Federal Kratom Consumer Protection Act. https://www.congress.gov/.../118th.../senate-bill/3039/text.

McCurdy, Christopher R., Abhisheak Sharma, Kirsten E. Smith, Charles A. Veltri, Stephanie T. Weiss, Charles M. White, and Oliver Grundmann. 2024. “An Update on the Clinical Pharmacology of Kratom: Uses, Abuse Potential, and Future Considerations.” Expert Review of Clinical Pharmacology 17 (2): 131–42. https://doi.org/10.1080/17512433.2024.2305798.

Yamamoto, Leonardo T., Syunji Horie, Shingo Yano, Hiromitsu Takayama, Norio Aimi, Shin-Ichiro Sakai, Jie Shan, Peter K. T. Pang, Dhavadee Ponglux, and Kazuo Watanabe. 1997. “Evidence for Opioid Effect of Mitragynine and Mitragynine Pseudoindoxyl, Compounds with Analgesic Effects Related to a Thai Medicinal Plant, in the Guinea-Pig Ileum and in the Receptor Binding.” Japanese Journal of Pharmacology 73: 284. https://doi.org/10.1016/s0021-5198(19)45636-9.

Zarembo, J. E., B. Douglas, J. Valenta, and J. A. Weisbach. 1974. “Metabolites of Mitragynine.” Journal of Pharmaceutical Sciences 63 (9): 1407–15. https://doi.org/10.1002/jps.2600630916.