Dihydromethysticin (DHM) # 5

Dihydromethysticin (di-hydro-meth-this-ta-sin)

Dihydromethysticin, also known as DHM, gets its number 5 from being the 5th kavalactone to exit the HPLC column at 23–26 min [1]. DHM is similar to DHK in that it can induce CYP1A1 pathways, which are thought to play a role in carcinogenesis (cancer forming process) [2]. On the other hand, it has also been found to have cancer preventative effects by blocking the induction of lung tumors and DNA damage in mice [3]. Dihydromethysticin has pain-relieving properties. The analgesic effectiveness of dihydrokavain and dihydromethysticin at 120 mg/kg body weight was reported to be equivalent to that of aspirin at 200 mg/kg body weight [4]. It has also shown some ability to block poisoning, as methysticin and dihydromethysticin were particularly effective in providing protection against the lethal effects of strychnine [5].  DHM is typically thought of as a nauseating kavalactone. Kava with high levels of this kavalactone are known to have strong psychotropic effects, and they usually have side effects such as nausea [6]. Kava with 5 at the beginning of the chemotype are generally of the non-noble or non-beverage-grade variety, being overly sedative and long lasting. Kava with the least amount of this kavalactone are generally favored over ones with higher amounts.

[1] Lebot, V. and J. Levesque. “The origin and distribution of kava piper methysticum forst. f. piperaceae a phytochemical approach.” (1989).

[2] Yan Li, Hu Mei, Qiangen Wu, Suhui Zhang, Jia-Long Fang, Leming Shi, Lei Guo, Methysticin and 7,8-Dihydromethysticin are Two Major Kavalactones in Kava Extract to Induce CYP1A1, Toxicological Sciences, Volume 124, Issue 2, December 2011, Pages 388–399, https://doi.org/10.1093/toxsci/kfr235

[3] Narayanapillai SC, Balbo S, Leitzman P, Grill AE, Upadhyaya P, Shaik AA, Zhou B, O'Sullivan MG, Peterson LA, Lu J, Hecht SS, Xing C. Dihydromethysticin from kava blocks tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis and differentially reduces DNA damage in A/J mice. Carcinogenesis. 2014 Oct;35(10):2365-72. doi: 10.1093/carcin/bgu149. Epub 2014 Jul 22. PMID: 25053626; PMCID: PMC4178470.

[4] Wu D, Yu L, Nair MG, DeWitt DL, Ramsewak RS. Cyclooxygenase enzyme inhibitory compounds with antioxidant activities from Piper methysticum (kava kava) roots. Phytomedicine. 2002 Jan;9(1):41-7. doi: 10.1078/0944-7113-00068. PMID: 11924763.

[5] Mark Blumenthal, Yadhu N, Sing. Pharmacology of Kava and its Constituents. HerbalGram. 1997; No. 39:50 (http://cms.herbalgram.org/herbalgram/issue39/article496.html)

[6] Lebot, V., Merlin, M., Lindstrom, L., 1997. Kava, The Pacific Elixir. Yale University Press, New Haven.