Constituents The general structure of the<unk> lactones, without the R1-R2 -O-CH2-O- bridge and with all possible C=C double bonds shown. A total of 18 different<unk> lactones (or<unk> pyrones) have been identified to date, at least 15 of which are active. However, six of them, including<unk> in, dihydrokavain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin, have been determined to be responsible for about 96% of the plant's pharmacological activity. Some minor constituents, including three chalcones, flavokavain A, flavokavain B, and flavokavain C, have also been identified, as well as a toxic alkaloid (not present in the consumable parts of the plant), pipermethystine. Alkaloids are present in the roots and leaves. Pharmacodynamics The following pharmacological actions have been reported for<unk>  and/or its major active constituents: * Potentiation of GABAA receptor activity (by<unk> in, dihydrokavain, methysticin, dihydromethysticin, and yangonin). * Inhibition of the reuptake of norepinephrine (by<unk> in and methysticin) and possibly also of dopamine (by<unk> in and desmethoxyyangonin). * Binding to the CB1 receptor (by yangonin). * Inhibition of voltage-gated sodium channels and voltage-gated calcium channels (by<unk> in and methysticin). * Monoamine oxidase B reversible inhibition (by all six of the major<unk> lactones). Receptor binding assays with botanical extracts have revealed direct interactions of leaf extracts of<unk>  (which appear to be more active than root extracts) with the GABA (i.e., main) binding site of the GABAA receptor, the D2 receptor, the μ- and δ-opioid receptors, and the H1 and H2 receptors. Weak interaction with the 5-HT6 and 5-HT7 receptors and the benzodiazepine site of the GABAA receptor was also observed. Potentiation of GABAA receptor activity may underlie the anxiolytic effects of<unk> , while elevation of dopamine levels in the nucleus accumbens likely underlie the moderately psychotropic effects the plant can produce. Changes in the activity of 5-HT neurons could explain the sleep-inducing action However, failure of the GABAA receptor inhibitor flumazenil to reverse the anxiolytic effects of<unk>  in mice suggests that benzodiazepine-like effects are not contributing to the pharmacological profile of<unk>  extracts. Heavy, long-term use of<unk>  has been found to be free of association with reduced ability in saccade and cognitive tests, but has been associated with elevated liver enzymes. Detection Recent usage of<unk>  has been documented in forensic investigations by quantitation of<unk> in in blood specimens. The principal urinary metabolite, conjugated 4'-OH-kavain, is generally detectable for up to 48 hours.
Kava
Kuru 
Kuru
Samu
Wart
Riken
Uinyeo
Superbill