The kavalactones contained in kava root are a group of bioactive compounds responsible for its effects. The most notable kavalactones include kavain, dihydrokavain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin.[1][2][3] In animal studies, kavalactones have demonstrated the ability to cross the blood-brain barrier, which helps explain why kava has a psycho-emotional effect.[4] When taken orally at a dosage of 120 mg of kava per kg of body weight, effects have been seen within an hour as kavalactones begin to accumulate in the brain.[5][6]
Kavalactones may impart their psycho-emotional effects via glutaminergic, GABAergic, dopaminergic, and/or serotonergic signaling. It has so far proved difficult to establish the effects of individual kavalactones for two reasons: first, the effects of any individual kavalactone may be dose-dependent in ways we don’t understand; and second, when kavalactones are combined, they may not only have interactions, but those interactions could potentially vary depending on the ratio of the kavalactones in combination. In addition, both of these factors may affect humans and animal models differently, making it even harder to tease out these complex relationships. For example, case studies have reported seeing clinical signs of dopamine receptor blockage as a result of kava consumption,[7] but animal studies have not always supported the existence of an antidopaminergic effect.[8][9][10] Similarly, while a rodent trial found that mixed kavalactones did not affect serotonin levels, isolated dihydromethysticin increased serotonin in rats, while isolated desmethoxyyagonin produced reductions in it.[8]
While kavain damaged cultured rat neurons in vitro at concentrations of 300 µM or greater (i.e., greater than or equal to 300 micromoles of kavain per liter),[11] the kavalactones dihydromethysticin and methysticin may hold neuroprotective effects.[12] Animal and nonclinical studies suggest that dihydromethysticin and methysticin may also impart sedative effects through indirect GABAergic signaling.[8][4][13][14][15]
As with any plant or herbal preparation, factors such as plant part, growth conditions, and extraction methods may affect kavalactone content. Kava preparations with a standardized kavalactone concentration are more likely to produce consistent effects.