are active. however, six of them, including kavain, 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 kava and/or its major active constituents: potentiation of gabaa receptor activity (by kavain, dihydrokavain, methysticin, dihydromethysticin, and yangonin). inhibition of the reuptake of norepinephrine (by kavain and methysticin) and possibly also of dopamine (by kavain and desmethoxyyangonin). binding to the cb1 receptor (by yangonin). inhibition of voltage-gated sodium channels and voltage-gated calcium channels (by kavain and methysticin). monoamine oxidase b reversible inhibition (by all six of the major kavalactones). receptor binding assays with botanical extracts have revealed direct interactions of leaf extracts of kava (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 kava, 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 kava in mice suggests that benzodiazepine-like effects are not contributing to the pharmacological profile of kava extracts. heavy, long-term use of kava 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 kava has been documented in forensic investigations by quantitation of kavain in blood specimens. the principal urinary metabolite, conjugated 4'-oh-kavain, is generally detectable for up to 48 hours. preparations kava root drying in lovoni village, ovalau, fiji (2005) traditional preparation kava is consumed in various ways throughout the pacific ocean cultures of polynesia, vanuatu, melanesia and some parts of micronesia and australia. traditionally, it is prepared by either chewing, grinding or pounding the roots of the kava plant. grinding is done by hand against a cone-shaped block of dead coral; the hand forms a mortar and the coral a pestle. the ground root/bark is combined with only a little water, as the fresh root releases moisture during grinding. pounding is done in a large stone with a small log. the product is then added to cold water and consumed as quickly as possible. the extract is an emulsion of kavalactone droplets in starch and buttermilk. the taste is slightly pungent, while the distinctive aroma depends on whether it was prepared from dry or fresh plant, and on the variety. the colour is grey to tan to opaque greenish. kava prepared as described above is much more potent than processed kava. chewing produces the strongest effect because it produces the finest particles. fresh, undried kava produces a stronger beverage than dry kava. the strength also depends on the species and techniques of cultivation. in vanuatu, a strong kava drink is normally followed by a hot meal or tea. the meal traditionally follows some time after the drink so the psychoactives are absorbed into the bloodstream more quickly. traditionally, no flavoring is added. in papua new guinea, the locals in madang province refer to their kava as waild koniak ("wild cognac" in english). fijian kava ceremony being performed for tourists (2015). traditionally, kava grog is drunk from the shorn half-shell of a coconut, called a bilo. fijians commonly share a drink called grog made by pounding sun-dried kava root into a fine powder, straining and mixing it with cold water. traditionally, grog is drunk from the shorn half-shell of a coconut, called a bilo. grog is very popular in fiji, especially among young men, and often brings people together for storytelling and socializing. drinking grog for a few hours brings a numbing and relaxing effect to the drinker; grog also numbs the tongue and grog drinking typically is followed by a "chaser" or sweet or spicy snack to follow a bilo. kava root being prepared for consumption in asanvari village on maewo island, vanuatu (2006) supplements and pharmaceutical preparations water extraction is the traditional method for preparation of the plant. pharmaceutical and herbal supplement companies extract kavalactones from the kava plant using solvents such as supercritical carbon dioxide, acetone, and ethanol to produce pills standardized with between 30% and 90% kavalactones. concerns numerous scholars and regulatory bodies have raised concerns over the safety profile of such products. one group of scholars say that organic solvents introduce compounds that may affect the liver into the standardized product; these compounds are not extracted by water and consequently largely absent from kava prepared with water. for instance, when compared with water extraction, organic solvents extract vastly larger amounts of flavokavains, compounds associated with adverse reactions to kava that are present in very low concentrations in noble kava, but significant in non-noble. also "chemical solvents used do not extract the same compounds as the natural water extracts in traditional use. the extraction process may exclude important modifying constituents soluble only in water". in particular, it has been noted that, unlike traditional, water-based preparations, products obtained with the use of organic solvents do not contain glutathione, an important liver-protecting compound. another group of researchers noted: "the extraction process (aqueous vs. acetone in the two types of preparations) is responsible for the difference in toxicity as extraction of glutathione in addition to the kava lactones is important to provide protection against hepatotoxicity". it has also been argued that kavalactone extracts have often been made from low-quality plant material, including the toxic aerial parts of the plant, non-noble kava varieties, or plants affected by mold, which, in light of the chemical solvents' ability to extract far greater amounts of the potentially toxic compounds than water, makes them particularly problematic. in the context of these concerns, the world health organization advises against the consumption of ethanolic and acetonic kavalactone extracts, and says that "products should be developed from water-based suspensions of kava". the government of australia prohibit the sales of such kavalactone extracts, and only permit the sale of kava products in their natural form or produced with cold water. kava culture a sign showing a "kava licence area" at yirrkala, in the northern territory of australia kava is used for medicinal, religious, political, cultural, and social purposes throughout the pacific. these cultures have a great respect for the plant and place a high importance on it. in fiji, for example, a formal yaqona (kava) ceremony will often accompany important social, political, or religious functions, usually involving a ritual presentation of the bundled roots as a sevusevu (gift), and drinking of the yaqona itself. due to the importance of kava in religious rituals and the seemingly (from the western point of view) unhygienic preparation method, its consumption was discouraged or even banned by christian missionaries. kava bars with kava's increasing popularity, bars serving the plant in its liquid state are beginning to open up outside of the south pacific. a 2010 review concluded that it's possible that ethanol combined with kava may be the cause of kava hepatotoxicity. while some bars have been committed to only serving the traditional forms and types of kava, other establishments have been accused of serving non-traditionally consumed non-noble kava varieties which are cheaper, but far more likely to cause unpleasant effects and adverse reactions, or of serving kava with other substances, including alcohol. effects of consumption the nature of effects will largely depend on the cultivar of the kava plant and the form of its consumption. traditionally, only noble kava cultivars have been consumed as they are accepted as safe and produce desired effects. the specific effects of various noble kavas depend on various factors, such as the cultivar used (and the related specific composition of kavalactones), age of the plant, and method of its consumption. however, it can be stated that in general noble kava produces a state of calmness, relaxation and well-being without diminishing cognitive performance. kava may produce an initial talkative period, followed by muscle relaxation and eventual sleepiness. as noted in one of the earliest western publications on kava (1886): "a well prepared kava potion drunk in small quantities produces only pleasant changes in behavior. it is therefore a slightly stimulating drink which helps relieve great fatigue. it relaxes the body after strenuous efforts, clarifies the mind and sharpens the mental faculties". according to contemporary descriptions: kava seizes one's mind. this is not a literal seizure, but something does change in the processes by which information enters, is retrieved, or leads to actions as a result. thinking is certainly affected by the kava experience, but not in the same ways as are found from caffeine, nicotine, alcohol, or marijuana. i would personally characterize the changes i experienced as going from lineal processing of information to a greater sense of "being" and contentment with being. memory seemed to be enhanced, whereas restriction of data inputs was strongly desired, especially with regard to disturbances of light, movements, noise and so on. peace and quiet were very important to maintain the inner sense of serenity. my senses seemed to be unusually sharpened, so that even whispers seemed to be loud while loud noises were extremely unpleasant. when the mixture is not too strong, the subject attains a state of happy unconcern, well-being and contentment, free of physical or psychological excitement. at the beginning conversation comes in a gentle, easy flow and hearing and sight are honed, becoming able to perceive subtle shades of sound and vision. kava soothes temperaments. the drinker never becomes angry, unpleasant, quarrelsome or noisy, as happens with alcohol. both natives and whites consider kava as a means of easing moral discomfort. the drinker remains master of his conscience and reason. ...in the late afternoon, a large museum crew would retire en masse to one of the many kava bars; kava, the national ritual drink, is a relaxing tonic of a cloudy green, which you drink from a miso-bowl "shell" in the solitude of a shadow. unlike traditional bars, which tend to become louder and more volatile as people drink, kava bars tend to get quieter and calmer as the evening fades to black – until practically the only sounds are the screech of the native fruit bat. despite its psychoactive effects, kava is not considered to be physically addictive and its use does not lead to dependency. adverse drug interactions alprazolam: semicomatose state. research a 2010 review concluded that it's possible that ethanol combined with kava may be the cause of kava hepatotoxicity. toxicity, safety, and potential side effects general observations a 2016 comprehensive review of kava safety conducted by the world health organization (who) and the food and agriculture organization (fao) concluded that: "on balance, the weight-of-evidence from both a long history of use of kava beverage and from the more recent research findings indicates that it is possible for kava beverage to be consumed with an acceptably low level of health risk". the authors of the review noted that: kava beverage has a long history of consumption in the south pacific and has an important role in traditional community ceremonies. in recent times, it has become more widely consumed as a recreational beverage in both the south pacific islander community as well as in the wider international community. within these communities, kava is considered to be a safe and enjoyable beverage, based on a long tradition of use and little evidence of harm. there is little documented evidence of adverse health effects associated with traditional moderate levels of consumption of kava beverage, with only anecdotal reports of general symptoms of lethargy and headaches. whether this reflects genuine low incidence or an under-reporting of adverse health effects is unclear. clinical trials examining the efficacy of aqueous extracts of kava in treating anxiety, although limited, have also not identified adverse health effects. at the same