Kava

<h3>Pills</h3>

<p><a href="http://en.wikipedia.org/wiki/Pharmaceutical" title="Pharmaceutical" class="mw-redirect">Pharmaceutical</a> and <a href="http://en.wikipedia.org/wiki/Herbal_supplement" title="Herbal supplement" class="mw-redirect">herbal supplement</a> companies extract kavalactones from the kava plant using solvents such as <a href="http://en.wikipedia.org/wiki/Supercritical_carbon_dioxide" title="Supercritical carbon dioxide">supercritical carbon dioxide</a>,<sup id="cite_ref-15" class="reference"><a href="http://en.wikipedia.org/wiki/Kava#cite_note-15">[15]</a></sup> <a href="http://en.wikipedia.org/wiki/Acetone" title="Acetone">acetone</a> and <a href="http://en.wikipedia.org/wiki/Ethanol" title="Ethanol">ethanol</a> to produce pills standardized with between 30% and 90% kavalactones. Some kava herbal supplements have been accused of contributing to very rare but severe hepatotoxic reactions (see <a href="http://en.wikipedia.org/wiki/Kava#Side_effects_and_safety" title="Kava">section on safety</a>) such may have been due to the use of plant parts other than the root, such as stems or peelings that are known to have been exported to European manufacturers. A kava pill usually has anywhere from 60 mg to 150 mg of kavalactones. By comparison the typical bowl of traditionally prepared kava beverage has around 250 mg of kavalactones.<sup class="Template-Fact" >[<i><a href="http://en.wikipedia.org/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed">citation needed</a></i>]</sup></p>

<h3>Herbal medicine</h3>

<p>Kava is chewed by some to relieve symptoms of throat pain, as it produces a "numbing" effect on the tongue and throat. The kava is first chewed in the back of the mouth for five to 10 minutes while swallowing the saliva and kavalactones released from the process. It produces an effect similar to that of <a href="http://en.wikipedia.org/wiki/Chloraseptic" title="Chloraseptic">Chloraseptic</a> spray (an over-the-counter medicine to alleviate sore throat by numbing it, via pump-spraying it into the mouth).</p>

<h2>Pharmacology</h2>

<p>Kava's active principal ingredients are the <a href="http://en.wikipedia.org/wiki/Kavalactone" title="Kavalactone">kavalactones</a>, of which at least 15 have been identified and are all considered psychoactive. Only six of them produce noticeable effects, and their concentrations in kava plants vary.<sup class="Template-Fact" >[<i><a href="http://en.wikipedia.org/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed">citation needed</a></i>]</sup> Different ratios can produce different effects.<sup class="Template-Fact" >[<i><a href="http://en.wikipedia.org/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed">citation needed</a></i>]</sup></p>

<div class="thumbcaption">The general structure of the <a href="http://en.wikipedia.org/wiki/Kavalactones" title="Kavalactones" class="mw-redirect">kavalactones</a>, without the R<sub>1</sub>-R<sub>2</sub> -O-CH<sub>2</sub>-O- bridge and with all possible C=C double bonds shown.</div>

</div>

<h3>Pharmacodynamics</h3>

<p>Effects of kavalactones include mild <a href="http://en.wikipedia.org/wiki/Sedation" title="Sedation">sedation</a>, a slight <a href="http://en.wikipedia.org/wiki/Paresthesia" title="Paresthesia">numbing</a> of the gums and mouth, and vivid dreams. Kava has been reported to improve cognitive performance and promote a cheerful mood.<sup id="cite_ref-16" class="reference"><a href="http://en.wikipedia.org/wiki/Kava#cite_note-16">[16]</a></sup> </p>

<p>

Kava has similar effects to <a href="http://en.wikipedia.org/wiki/Benzodiazepine" title="Benzodiazepine">benzodiazepine</a> medications, including <a href="http://en.wikipedia.org/wiki/Muscle_relaxant" title="Muscle relaxant">muscle relaxant</a>, <a href="http://en.wikipedia.org/wiki/Anaesthetic" title="Anaesthetic" class="mw-redirect">anaesthetic</a>, <a href="http://en.wikipedia.org/wiki/Anticonvulsant" title="Anticonvulsant">anticonvulsive</a> and <a href="http://en.wikipedia.org/wiki/Anxiolytic" title="Anxiolytic">anxiolytic</a> effects. </p>

<p>

They are thought to result from direct interactions of kavalactones with <a href="http://en.wikipedia.org/wiki/Voltage-gated_ion_channel" title="Voltage-gated ion channel">voltage-gated ion channels</a>.<sup id="cite_ref-17" class="reference"><a href="http://en.wikipedia.org/wiki/Kava#cite_note-17">[17]</a></sup> </p>

<p>

Research currently suggests kavalactones potentiate <a href="http://en.wikipedia.org/wiki/GABAA_receptor" title="GABAA receptor">GABA<sub>A</sub></a> activity, but do not alter levels of <a href="http://en.wikipedia.org/wiki/Dopamine" title="Dopamine">dopamine</a> and <a href="http://en.wikipedia.org/wiki/Serotonin" title="Serotonin">serotonin</a> in the <a href="http://en.wikipedia.org/wiki/Central_nervous_system" title="Central nervous system">CNS</a>.<sup id="cite_ref-18" class="reference"><a href="http://en.wikipedia.org/wiki/Kava#cite_note-18">[18]</a></sup> </p>

<p>

It is thought to do this via modulating GABA activity via altering the lipid membrane structure and sodium channel function.<sup id="cite_ref-19" class="reference"><a href="http://en.wikipedia.org/wiki/Kava#cite_note-19">[19]</a></sup> However, it has also been shown that administration of the GABA antagonist <a href="http://en.wikipedia.org/wiki/Flumazenil" title="Flumazenil">Flumazenil</a> does not have an antagonistic effect on kavalactones, suggesting that an alternative pathway may be involved.<sup id="cite_ref-20" class="reference"><a href="http://en.wikipedia.org/wiki/Kava#cite_note-20">[20]</a></sup> Heavy, long-term kava use does not cause any reduction of ability in <a href="http://en.wikipedia.org/wiki/Saccade" title="Saccade">saccade</a> and cognitive tests, but is associated with elevated liver enzymes.<sup id="cite_ref-21" class="reference"><a href="http://en.wikipedia.org/wiki/Kava#cite_note-21">[21]</a></sup>

<a href="http://en.wikipedia.org/wiki/Desmethoxyyangonin" title="Desmethoxyyangonin">Desmethoxyyangonin</a>, one of the six major kavalactones, is a reversible <a href="http://en.wikipedia.org/wiki/MAO_inhibitor" title="MAO inhibitor" class="mw-redirect">MAO-B inhibitor</a> (<a href="http://en.wikipedia.org/wiki/Binding_affinity" title="Binding affinity" class="mw-redirect">Ki</a> 280 <a href="http://en.wikipedia.org/wiki/Nano-" title="Nano-">n</a><a href="http://en.wikipedia.org/wiki/Mole_%28unit%29" title="Mole (unit)">M</a>)<sup id="cite_ref-22" class="reference"><a href="http://en.wikipedia.org/wiki/Kava#cite_note-22">[22]</a></sup> and is able to increase <a href="http://en.wikipedia.org/wiki/Dopamine" title="Dopamine">dopamine</a> levels in the <a href="http://en.wikipedia.org/wiki/Nucleus_accumbens" title="Nucleus accumbens">nucleus accumbens</a>. This finding might correspond to the slightly euphoric action of kava.<sup id="cite_ref-23" class="reference"><a href="http://en.wikipedia.org/wiki/Kava#cite_note-23">[23]</a></sup>

<a href="http://en.wikipedia.org/wiki/Kavain" title="Kavain">Kavain</a>, in both <a href="http://en.wikipedia.org/wiki/Enantiomer" title="Enantiomer">enantiomeric</a> forms, inhibits the <a href="http://en.wikipedia.org/wiki/Reuptake" title="Reuptake">reuptake</a> of <a href="http://en.wikipedia.org/wiki/Noradrenalin" title="Noradrenalin" class="mw-redirect">noradrenalin</a> at the transporter (<a href="http://en.wikipedia.org/wiki/Norepinephrine_transporter" title="Norepinephrine transporter">NAT</a>), but not of <a href="http://en.wikipedia.org/wiki/Serotonin" title="Serotonin">serotonin</a> (<a href="http://en.wikipedia.org/wiki/Serotonin_transporter" title="Serotonin transporter">SERT</a>).<sup id="cite_ref-24" class="reference"><a href="http://en.wikipedia.org/wiki/Kava#cite_note-24">[24]</a></sup> </p>

<p>

An elevated <a href="http://en.wikipedia.org/wiki/Extracellular" title="Extracellular">extracellular</a> noradrenalin level in the brain may account for the reported enhancement of <a href="http://en.wikipedia.org/wiki/Attention" title="Attention">attention</a> and focus.</p>

Kava

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