Desmethoxyyangonin (DMY) #1
Most of the effects of kava can be attributed to its six major kavalactones, including desmethoxyyangonin (DMY). DMY is the first kavalactone on the chemotype list and is not commonly found in high amounts. It obtains its number from the time taken to travel through the HPLC column. Although DMY may play a role in regulating dopamine levels in the brain, there is currently no direct evidence to support this claim. To date, no study has specifically targeted DMYs psychological effects.
Desmethoxyyangonin (DMY) may have monoamine oxidase inhibition properties. This is similar to the mechanism of first-generation antidepressants, which can prevent the breakdown of neurotransmitters such as dopamine, allowing more of them to be available in the brain. In a study, DMY was found to be one of the most potent inhibitors of MAO-B, along with methysticin [3]. These findings may provide some evidence for kava’s uplifting and antidepressant effects and its potential role in reverse tolerance. However, further research is necessary to establish a direct correlation.
Another effect caused by desmethoxyyangonin is the induction of CYP3A23. Induction in this regard indicates an increased amount and activity of relevant drug-metabolizing CYPs, which may lead to enhanced metabolism of co-medicated drugs [4]. In short, kavalactones may accelerate the metabolism of drugs that use the same metabolization pathway. This may lend evidence toward an herb-drug (where a pharmaceutical drug was added when taking kava) model of toxicology. Inductive activity is synergistically enhanced by other kavalactones that have no or less inductive activity [5], suggesting an entourage-type effect.
It is important to note, however, that these studies likely employed levels of kavalactones that are significantly higher than those that would normally be consumed by humans. Consequently, the real-world implications of these findings might not be as dramatic as they appear in the laboratory setting, suggesting that the toxicity risk could be overstated.
[1] Lebot, V. and J. Levesque. “The origin and distribution of kava piper methysticum forst. f. piperaceae a phytochemical approach.” (1989).
[2] Baum SS, Hill R, Rommelspacher H. Effect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of rats. Prog Neuropsychopharmacol Biol Psychiatry. 1998 Oct;22(7):1105-20. doi: 10.1016/s0278-5846(98)00062-1. PMID: 9829291.
[3] Uebelhack, R., Franke, L., & Schewe, H. (1998). Inhibition of Platelet MAO-B by Kava Pyrone-Enriched Extract from Piper Methysticum Forster (Kava-Kava). Pharmacopsychiatry, 31(05), 187-192. doi:10.1055/s-2007-979325
[4] CYP Induction. (n.d.). Retrieved January 04, 2021, from https://www.admescope.com/drug-interactions/cyp-induction.html
[5] Yuzhong Ma, Karuna Sachdeva, Jirong Liu, Michael Ford, Dongfang Yang, Ikhlas A. Khan, Clinton O. Chichester and Bingfang Yan. “Desmethoxyyangonin and dihydromethysticin are two major pharmacological kavalactones with marked activity on the induction of CYP3A23”. Drug Metabolism and Disposition. November 1, 2004, 32 (11) 1317-1324