Desmethoxyyangonin (DMY)
This one took a bit more research than I was expecting. 95% of kava’s pharmacological activity can be traced back to the 6 major kavalactones. Of these 6, today we’ll be focusing on desmethoxyyangonin (DMY). DMY is the number 1 on the chemotype list, and is a rarer kavalactone to see towards the front of a kava’s chemotype. It is thought that DMY plays a part in the increase and decrease in dopamine in various parts of the brain [1], however the science in this area is a bit fuzzy. To date there doesn’t seem to be a study specifically targeted towards DMYs psychological effects.
Monoamine oxidase inhibition could possibly be one of the effects that this kavalactone produces. Similarly, to first generation anti-depressants, they can decrease the ability for neurotransmitters such as dopamine to be metabolized. This leaves more of the neurotransmitter available to be used in the brain cell. One study found the two most potent inhibitors of MAO-B were DMY and methysticin [2]. This could possibly lend evidence to kava’s uplifting and anti-depressant effect, as well as maybe speaking a bit to reverse tolerance, however more studies are needed to directly make this correlation.
Another effect found caused by desmethoxyyangonin is the induction of CYP3A23. Induction in this regard means the increased amount and activity of relevant drug metabolizing CYPs, which may lead to enhanced metabolism of co-medicated drugs [3]. In short, this kavalactone may speed up the metabolism of drugs that use the same pathway to metabolize. This may lend evidence towards an herb-drug (where a pharmaceutical drug was added when taking kava) model of toxicology. The inductive activity is synergistically enhanced by other kavalactones that have no or less inductive activity [4], once again suggesting an entourage type effect.
[1] 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.
[2] 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
[3] CYP Induction. (n.d.). Retrieved January 04, 2021, from https://www.admescope.com/drug-interactions/cyp-induction.html
[4] 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
This one took a bit more research than I was expecting. 95% of kava’s pharmacological activity can be traced back to the 6 major kavalactones. Of these 6, today we’ll be focusing on desmethoxyyangonin (DMY). DMY is the number 1 on the chemotype list, and is a rarer kavalactone to see towards the front of a kava’s chemotype. It is thought that DMY plays a part in the increase and decrease in dopamine in various parts of the brain [1], however the science in this area is a bit fuzzy. To date there doesn’t seem to be a study specifically targeted towards DMYs psychological effects.
Monoamine oxidase inhibition could possibly be one of the effects that this kavalactone produces. Similarly, to first generation anti-depressants, they can decrease the ability for neurotransmitters such as dopamine to be metabolized. This leaves more of the neurotransmitter available to be used in the brain cell. One study found the two most potent inhibitors of MAO-B were DMY and methysticin [2]. This could possibly lend evidence to kava’s uplifting and anti-depressant effect, as well as maybe speaking a bit to reverse tolerance, however more studies are needed to directly make this correlation.
Another effect found caused by desmethoxyyangonin is the induction of CYP3A23. Induction in this regard means the increased amount and activity of relevant drug metabolizing CYPs, which may lead to enhanced metabolism of co-medicated drugs [3]. In short, this kavalactone may speed up the metabolism of drugs that use the same pathway to metabolize. This may lend evidence towards an herb-drug (where a pharmaceutical drug was added when taking kava) model of toxicology. The inductive activity is synergistically enhanced by other kavalactones that have no or less inductive activity [4], once again suggesting an entourage type effect.
[1] 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.
[2] 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
[3] CYP Induction. (n.d.). Retrieved January 04, 2021, from https://www.admescope.com/drug-interactions/cyp-induction.html
[4] 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
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