Hello:

I am a licensed pharmacist in the state of Virginia and a board certified psychiatric pharmacist. I am writing to express support for amending 18VAC110-20-322 to include mitragynine and 7-hydroxymytragynine, the active alkaloids found in kratom, in Schedule I.  

Kratom is a potentially dangerous drug with no well-established medical use and known harmful effects. Mitragynine and 7-hydroxymytragynine act as "weak opioids" (mu-opioid receptor partial agonists, analogous to the opioid buprenorphine, used for managing opioid addiction and treating pain), which explains why people use kratom for pain management and opioid addiction. Mitragynine is also an alpha-2 agonist (analogous to the FDA-approved drug clonidine, commonly used off-label for opioid withdrawal), which may also contribute to pain relief and relief of opioid withdrawal. People use kratom for many other reasons, including anxiety, difficulty sleeping, and depression. People often use other illicit opioids for these purposes as well, managing "emotional pain" in addition to physical pain. Kratom may also possess weak stimulatory properties and pro-arrhythmic potential. While some patients report successful use of kratom, there are no high-quality clinical trials supporting its efficacy for any indication. However, the literature is replete with evidence of harm. One case series noted seizures and neonatal abstinence syndrome (Cumpston et al. 2018). One poison center found several critical care admissions, including one in an infant that was unintentionally exposed (DeJonge et al. 2023). Older adults, who are more likely to have chronic pain, may be particularly susceptible to the toxic effects of kratom, with an analysis of U.S. poison centers finding a higher prevalence of neurologic, cardiovascular, gastrointestinal, and respiratory effects in people age 70 and above (Graves et al. 2021). Kratom-induced liver injury has also been reported (Ahmad et al. 2021), including by some commenters here (Comment ID: 225168, 224990). A full literature review is beyond the scope of this comment--suffice to say there are many published reports of serious adverse effects to kratom.

I empathize with the commenters struggling with addiction, chronic pain, depression, and anxiety. However, as a psychiatric pharmacist, I do not believe that kratom is safe, and strongly discourage its use. There are safer, FDA-approved treatments for all these conditions, as well as life-saving non-pharmacological treatments. While it's not implausible that kratom may be better studied in the future, leading to the discovery of a use and dose with a reasonable balance of benefits and risks, it is not in the interest of the public health to allow its unregulated use in the meantime. Therefore, I support placement of mitragynine and 7-hydroxymytragynine, the active alkaloids found in kratom, in Schedule I.

Sincerely,

Joseph Cusimano, PharmD, BCPP

References

Ahmad J, Odin JA, Hayashi PH, Fontana RJ, Conjeevaram H, Avula B, Khan IA, Barnhart H, Vuppalanchi R, Navarro VJ; Drug-Induced Liver Injury Network. Liver injury associated with kratom, a popular opioid-like product: Experience from the U.S. drug induced liver injury network and a review of the literature. Drug Alcohol Depend. 2021 Jan 1;218:108426. doi: 10.1016/j.drugalcdep.2020.108426. Epub 2020 Nov 23. PMID: 33257199; PMCID: PMC8113016.

Cumpston KL, Carter M, Wills BK. Clinical outcomes after Kratom exposures: A poison center case series. Am J Emerg Med. 2018 Jan;36(1):166-168. doi: 10.1016/j.ajem.2017.07.051. Epub 2017 Jul 15. PMID: 28751041.

DeJonge P, Gummin D, Titelbaum N, Meiman J. Description of Kratom Exposure Events in Wisconsin as Reported to the Wisconsin Poison Center, January 1, 2010 to September 1, 2022. WMJ. 2023 Jul;122(3):187-190. PMID: 37494649; PMCID: PMC10403292.

Graves JM, Dilley JA, Terpak L, Brooks-Russell A, Whitehill JM, Klein TA, Liebelt E. Kratom exposures among older adults reported to U.S. poison centers, 2014-2019. J Am Geriatr Soc. 2021 Aug;69(8):2176-2184. doi: 10.1111/jgs.17326. Epub 2021 Jun 18. PMID: 34143890.