KAVA-KAVA COMPOUNDS
Kava lactones (kava pyrones, 5-12%): chief components include (+)-kavain, dihydrokavain (marindinine), (+)-methysticin, dihydromethysticin, yangonine, desmethoxyyangonin
Chalcones: including flavokavin A and B
KAVA-KAVA EFFECTS
The kava pyrones in the drug have centrally muscle-relaxing, anticonvulsive and antispasmodic effects. The herb also contains hypnotic/sedative, analgesic and psychotropic properties contributing to its use for anxiety and insomnia.
The centrally muscle-relaxing, analgesic and anticonvulsive action of the kava pyrones, kavain, dihydrokavain, dihydromethysticin and (+/-) kavain (synthetic kava pyrone) is attributed to the interaction with ion channels. The interaction consists of fast and specific inhibition of voltagedependent sodium channels and reduction of currents through voltage-activated sodium and calcium channels (Friese, 1998; Gleitz, 1995; Gleitz, 1996; Schirrmacher, 1999). The paralysis effect of Kava on neuromuscular transmission and muscle contractility is similar to that of local anesthetics (Jameison, 1989; Singh, 1983). The lipid soluble extract (kava resin) decreases spontaneous motility and motor control (Jamieson, 1989).
The analgesic action of kavain, dihydrokavain, methysticin and dihydromethysticin is due to antinociceptive activities. Nalaxone (opiate antagonist) is ineffective in reversing the antinociceptive activities, thus indicating the analgesia produced from the compounds occurs via non-opiate pathways (Jameison, 1990; Jameison, 1989).
The lipid soluble components of kava do not interact with benzodiazepine binding sites, but do seem to potentiate the activity of GABA-A in the brain center for sedative effects (Davies, 1992; Jussofie, 1994). The psychotropic properties of Kava have been demonstrated by the inhibition of norepinephrine uptake by kavain, dihydromethysticin and the racemate (+/-) kavain (Seitz, 1997). One study did find that desmethoxyyangonin, methysticin, yangonin, dihydromethysticin, kihydrokavain and kavain reversibly inhibit MAO-B (Uebelhack, 1998). An increase of dopamine and serotonin by activation of neurons results in central nervous system effects (Fachinfo Antares 120(R), 1996).
A recent study investigated the antithrombotic activity of kava pyrones. Kavain exerts antithrombotic action on human platelets through the inhibition of cyclooxygenase (COX) as a primary target. This suppresses the generation of thromboxane (TXA2), which normally induces aggregation of platelets and exocytosis of ATP by its binding on TXA2 receptors (Gleitz, 1997).
KAVA-KAVA CLINICAL TRIALS
A randomized, double-blind, placebo-controlled study was conducted with 101 outpatients suffering from anxiety of non-psychotic origin who met DSM-IH-R criteria. Improvements in anxiety were seen after week 8 with a standardized Kava Kava extract (70% kava-pyrone). The study continued over a 25-week period with significant improvement based upon the Hamilton Anxiety Scale (HAMA), somatic and psychic anxiety, Clinical Global Impression, Self-Report Symptom Inventory and Adjective Mood Scale (Volz, 1997).
The anxiolytic effect of a special kava extract (70 mg of kava pyrones three times daily) was compared to two benzodiazepine preparations (oxazepam 15mg/day, bromazepam). The multi-center, double-blind study involved 172 patients. There was a therapeutically relevant reduction in the severity of anxiety according to the HAMA scale in all three groups. There wasn’t a statistically significant difference between the three types of treatment in terms of reducing anxiety (Woelk, 1993).
A standardized Kava extract give’n 100 mg three times daily was compared to placebo in a randomized, double-blind study. The study included 58 patients with anxiety syndromes not caused by mental disorders. The HAMA overall score of anxiety symptoms revealed significant reduction in the Kava treatment group compared to placebo after 1 week of therapy. After 4 weeks of therapy, an even greater reduction in anxiety symptoms was seen with the Kava treatment group, with no adverse reactions (Lehmann, 1996).
