Kava

From Wikipedia, the free encyclopedia
Jump to: navigation, search
This article is about the kava plant. For the class of pharmacological derivatives, see Kavalactone. For other uses, see Kava (disambiguation).
Kava
Starr 070515-7054 Piper methysticum.jpg
Piper methysticum leaves
Scientific classification
Kingdom: Plantae
(unranked): Angiosperms
(unranked): Magnoliids
Order: Piperales
Family: Piperaceae
Genus: Piper
Species: P. methysticum
Binomial name
Piper methysticum
G.Forst.

Kava or kava-kava (Piper methysticum: Latin "pepper" + Latinized Greek "intoxicating") is a crop of the western Pacific.

The name kava(-kava) is from Tongan and Marquesan;[1] other names for kava include ʻawa (Hawaiʻi),[2] ʻava (Samoa),[3] yaqona (Fiji),[4] sakau (Pohnpei),[5] and malok or malogu (parts of Vanuatu).[6]

The roots of the plant are used to produce a drink with sedative, anesthetic, euphoriant, and entheogenic properties. Kava is consumed throughout the Pacific Ocean cultures of Polynesia, including Hawaii, Vanuatu, Melanesia and some parts of Micronesia. (See canoe plants.) Kava is sedating and is primarily consumed to relax without disrupting mental clarity. Its active ingredients are called kavalactones. A systematic review of its evidence by Cochrane concluded it was likely to be more effective than placebo at treating short-term social anxiety.[7]

Characteristics[edit]

The several cultivars of kava vary in concentrations of primary and secondary psychoactive alkaloids. The largest number are grown in the Republic of Vanuatu, and so it is recognised as the "home" of kava. Kava was historically grown only in the Pacific islands of Hawaii, Federated States of Micronesia, Vanuatu, Fiji, the Samoas and Tonga. Some is grown in the Solomon Islands since World War II, but most is imported. Kava is a cash crop in Vanuatu and Fiji.[citation needed]

The kava shrub thrives in loose, well-drained soils where plenty of air reaches the roots. It grows naturally where rainfall is plentiful (over 2,000 mm/yr). Ideal growing conditions are 70–95 °F (21–35 °C) and 70–100% relative humidity. Too much sunlight is harmful, especially in early growth, so kava is an understory crop.[citation needed]

Kava cannot reproduce sexually. Female flowers are especially rare and do not produce fruit even when hand-pollinated. Its cultivation is entirely by propagation from stem cuttings.[citation needed]

Traditionally, plants are harvested around four years of age, as older plants have higher concentrations of kavalactones. After reaching about 2 m height, plants grow a wider stalk and additional stalks, but not much taller. The roots can reach a depth of 60 cm.

Strains[edit]

A painting showing women preparing kava

Kava consists of sterile cultivars cloned from its wild ancestor, Piper wichmanii.[8] Today it comprises hundreds of different cultivars grown across the Pacific. Each cultivar has not only different requirements for successful cultivation, but also displays unique characteristics both in terms of its appearance, and in terms of its medicinal and psychoactive properties.[8]

Noble and Non-Noble Kava[edit]

Scholars make a distinction between the so-called "noble" and non-noble kava. The latter category comprises the so-called "tudei" (or "two-day") kavas, medicinal kavas and wild kava (Piper wichmanii, the ancestor of domesticated Piper methysticum).[8][9][10] Traditionally, only noble kavas have been used for regular consumption due to their more favourable composition of kavalactones and other compounds that produces significantly more pleasant effects and has much lower potential for causing such negative side-effects as nausea or "kava hangover".[8][10] The noble cultivars are in fact a result of centuries of conscious selection of mutations with the most desirable properties: growers have selected cultivars to improve the chemical composition responsible for the physiological effects.[6]

According to Dr Vincent Lebot, the far more pleasant and beneficial effects of noble cultivars explain the fact that only these cultivars were spread around the Pacific by Polynesian and Melanesian migrants with presence of non-noble cultivars limited to the islands of Vanuatu from which they originate.[6] More recently, it has been suggested that the widespread use of tudei cultivars in the manufacturing of several kava products might have been the key factor contributing to the rare reports of adverse reactions to kava observed among the consumers of kava-based pharmaceutical products in Europe.[10] This could explain why no significant adverse health effects are observed among kava drinkers in the South Pacific who very rarely, if ever, consume non-noble varieties, especially in countries that generally do not grow any tudei cultivars (i.e. Tonga, Samoa and French Polynesia).

Tudei varieties have traditionally not been grown in Hawaii and Fiji, but in recent years there have been reports of farmers attempting to grow "isa" or "palisi" non-noble cultivars in Hawaii and of imports of dried tudei kava into Fiji for further re-exporting.[11] The key reason why many farmers and distributors are interested in growing and selling tudei varieties is the fact that they appear to be significantly easier and cheaper to grow (while it takes up to 5 years for noble kava to mature, non-noble varieties can often be harvested just one year after being planted). Another factor that has allowed the spread of non-noble varieties is the fact that while traditional drinkers would immediately be able to detect the unpleasant characteristics of tudei, many new consumers from outside of the South Pacific lack any knowledge about kava and hence can be persuaded that tudei-based products offer a normal kava experience.

The concerns about the adverse effects of non-noble varieties produced by their undesirable composition of kavalactones and high concentrations of potentially harmful compounds not present in any significant concentration in the noble varieties, have led to the creation of legislation that prohibits their exports from such countries as Vanuatu.[10] Likewise, efforts have been made to educate the non-traditional customers about the difference between noble and non-noble varieties and that non-noble varieties do not offer the same benefits as noble ones and can potentially cause adverse reactions.[12][13] In recent years, government institutions and non-profit NGOs (such as the US-based True Kava Group Labs[14]) have been set up with the aim of monitoring kava quality, producing regular reports, certifying vendors selling proper, noble kava and warning customers against products that may contain tudei varieties.

Kava growing regions[edit]

In Vanuatu, exportation of kava is strictly regulated. Only strains they deem as "noble" varieties that are not too weak or too potent are allowed to be exported. Only the most desirable strains for everyday drinking are selected to be noble varieties to maintain quality control. In addition, their laws mandate that exported kava must be at least five years old and farmed organically. Their most popular noble strains are "Boroguu" or "Boronggoru" from Pentecost Island, "Melomelo" from Aoba Island (called sese in north Pentecost Island), and "Palarasul" kava from Espiritu Santo. In Vanuatu, Tudei ("two days") kava is reserved for special ceremonial occasions and exporting it is not allowed. "Palisi" is a popular Tudei variety.

In Hawaii, there are many other strains of kava (Hawaiian: ʻawa). Some of the most popular strains are the Mahakea, Moʻi, Hiwa and Nene varieties. The Aliʻi (kings) of precolonial Hawaii coveted the Moʻi variety, which had a strong cerebral effect due to a predominant amount of the kavalactone kavain. This sacred variety was so important to them that no one but royalty could ever experience it, "lest they suffer an untimely death". The reverence for Hiwa in old Hawaiʻi is evident in this portion of a chant recorded by Nathaniel Bright Emerson and quoted by E. S. Craighill and Elizabeth Green Handy. "This refers to the cup of sacramental ʻawa brewed from the strong, black ʻawa root (ʻawa hiwa) which was drunk sacramentally by the kumu hula":

The day of revealing shall see what it sees:
A seeing of facts, a sifting of rumors,
An insight won by the black sacred ʻawa,
A vision like that of a sacred god![citation needed]

Winter describes a hula prayer for inspiration which contains the line, He ʻike pū ʻawa hiwa. Pukui and Elbert translated this as "a knowledge from kava offerings". Winter explains that ʻawa, especially of the Hiwa variety, was offered to hula deities in return for knowledge and inspiration.[15]

Other strains are found in Fiji, Tonga, and Samoa.

Relationship with Kawakawa[edit]

Kawakawa (Piper excelsum) plant, known also as "Maori kava" is often confused with kava. While the two plants look similar and have similar names, they are different, albeit related, species. Kawakawa is a small tree endemic to New Zealand, which is of crucial importance to traditional, indigenous Māori culture and medicine. It is most likely not a coincidence that this plant has a similar name to kava (piper methysticum). As noted by the Kava Society of New Zealand "in all likelihood the kava plant was known to the first settlers of Aotearoa [New Zealand]. It is also possible that (just like the Polynesian migrants that settled in Hawaii) the Maori explorers brought some kava with them. Unfortunately, most of New Zealand is simply too cold for growing kava and hence the Maori settlers lost their connection to the sacred plant."[16] According to Lebot et al. (1997) "In New Zealand, where the climate is too cold for kava, the Maori gave the name kawa-kawa to another Piperaceae, M. excelsum, in memory of the kava plants they undoubtedly brought with them and unsuccessfully attempted to cultivate. The Maori word kawa also means "ceremonial protocol", recalling the stylized consumption of the drug typical of Polynesian societies".[6] Kawakawa doesn't have any of kava's relaxing psychoactive properties. It is however commonly used in Maori medicine for the treatment of skin infections, wounds and cuts, and (when prepared as a tea) for stomach upsets and other conditions.[17]

Composition[edit]

Fresh kava root contains on average 80% water. Dried root contains approximately 43% starch, 20% dietary fiber, 15% kavalactones,[18] 12% water, 3.2% sugars, 3.6% protein, and 3.2% minerals. Kavalactone content is greatest in the roots and decreases higher up the plant. Relative concentrations of 15%, 10% and 5% have been observed in the root, stump, and basal stems, respectively.

The mature roots of the kava plant are harvested after a minimum of four years (at least five years ideally) for peak kavalactone content. Most kava plants produce around 50 kg (110 lb) of root when they are harvested. Kava root is classified into two categories: crown root (or chips) and lateral root. Crown roots are the large-diameter pieces that look like (1.5 to 5 inches (38 to 127 mm) diameter) wooden poker chips. Most kava plants consist of approximately 80% crown root upon harvesting. Lateral roots are smaller-diameter roots that look more like a typical root. A mature kava plant is about 20% lateral roots. Kava lateral roots have the highest content of kavalactones in the kava plant. "Waka" grade kava is made of lateral roots only.

Pharmacology[edit]

Constituents[edit]

The general structure of the kavalactones, without the R1-R2 -O-CH2-O- bridge and with all possible C=C double bonds shown.

A total of 18 different kavalactones (or kavapyrones) have been identified to date, at least 15 of which are active.[19] 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.[19] Some minor constituents, including three chalcones, flavokavain A, flavokavain B, and flavokavain C, have also been identified,[19] as well as a toxic alkaloid (not present in the consumable parts of the plant[20]), pipermethystine.[21]

Pharmacodynamics[edit]

The following pharmacological actions have been reported for kava and/or its major active constituents:[22]

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.[24][25] Weak interaction with the 5-HT6 and 5-HT7 receptors and the benzodiazepine site of the GABAA receptor was also observed.[24]

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 [26] 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.[27]

Heavy, long-term use of kava has been found to not reduce ability in saccade and cognitive tests, but has been associated with elevated liver enzymes.[28]

Detection[edit]

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.[29]

Preparation and consumption[edit]

Kava root drying in Lovoni village, Ovalau, Fiji

Traditional preparation[edit]

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. Many find mixing powdered kava with hot water makes the drink stronger.

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 quicker. 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).

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.[30]

Kava root being prepared for consumption in Asanvari village on Maewo Island, Vanuatu

Supplements and pharmaceutical preparations[edit]

Pharmaceutical and herbal supplement companies extract kavalactones from the kava plant using solvents such as supercritical carbon dioxide,[31] acetone and ethanol to produce pills standardized with between 30% and 90% kavalactones. Many experts warn against using such extracts due to the unknown quantities and compositions of compounds extracted using these methods, as well as the difficulty of determining the quality of the plant material used in their manufacturing and instead recommend using traditional kava products (i.e. water extractions of dried or fresh noble roots).[32]

Kava culture[edit]

A sign showing a "Kava licence area" at Yirrkala, in the Northern Territory of Australia
Main article: Kava culture

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, religious, etc. functions, usually involving a ritual presentation of the bundled roots as a sevusevu (gift), and drinking of the yaqona itself.[33]

The use of kava is strongly linked with the cultures of numerous Pacific Islands. This practice remained unknown to the rest of the world until James Cook, an English naval captain and explorer, discovered the plant's use in 1777 during one of his voyages in the Pacific Islands. George Forster, a naturalist on Cook's voyage, wrote a description of the process in which the islanders prepared the kava.

"[Kava] is made in the most disgustful manner that can be imagined, from the juice contained in the roots of a species of pepper-tree. This root is cut small, and the pieces chewed by several people, who spit the macerated mass into a bowl, where some water (milk) of coconuts is poured upon it. They then strain it through a quantity of fibers of coconuts, squeezing the chips, till all their juices mix with the coconut-milk; and the whole liquor is decanted into another bowl. They swallow this nauseous stuff as fast as possible; and some old topers value themselves on being able to empty a great number of bowls."[34]

Due to kava's importance 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.[6] On some islands (most notably the Cook Islands and Niue) their efforts were successful. On other islands, the missionaries either failed to completely eradicate kava (e.g. Hawaii) or actually incorporated it into Christian practices (most notably in Samoa and Tonga). Kava continue to be used on most Pacific Islands for various ceremonies and gatherings. Hillary Clinton, Pope John Paul II, Queen Elizabeth II and numerous other leaders have participated in a Kava ceremony while visiting communities who continue this practice. Today, kava is a staple cash crop in the Pacific Islands and it is extracted by machinery which is later manufactured into various forms.[34]

Kava bars[edit]

With kava's increasing popularity, bars serving the plant in its liquid state are beginning to open up outside of the South Pacific.[10] Starting in the early 2000s, kava bars first opened within the beach communities of Florida, Hawaii, and California.[35] Since then, locations have spread to other regions. 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 (cheaper to obtain, but with a much higher potential for producing unpleasant effects and adverse reactions than noble kava varieties) or serving kava with other substances, including alcohol.[36]

A traditional Fijian yaqona bundle of roots

Effects of consumption[edit]

General effects[edit]

The nature of effects will largely depend on the strain of the kava plant and the form of its consumption. Traditionally only noble kava cultivars have been consumed as they are widely known not only as safe but also for their very pleasant physiological effects, potential medicinal properties and low risk of any adverse reactions[37] The specific effects of various noble kava depend on a number of factor such as the cultivar used (and the related specific composition of kavalactones), age of the plant and the form of its consumption.[38] However, it can be stated that in general noble kava produces a state of calmness, relaxation and well-being without diminishing cognitive performance[39] or influencing drinker's capacity to think clearly;[6] with an initial talkative period, followed by muscle relaxation and eventual sleepiness.[40]

According to one contemporary description:

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.[6]

Despite its psychoactive effects, kava is not considered to be physically addictive and its use does not lead to dependency.[41]

Medicinal use[edit]

Kava has been the key plant of the traditional medicine of the islands of the South Pacific for centuries. It has been used for a wide range of both Central Nervous System (CNS)-centered and peripheral effects.[42] While the former group of effects, most notably kava's potential for treating or managing anxiety, stress and depression, have received the most scientific and popular attention, much of the broad list of traditional medicinal uses is related to its peripheral effects.[42] As noted in one literature review: "Peripherally, [kava] is indicated in traditional Pacific medicine for urogenital conditions (gonorrhea infections, chronic cystitis, difficulty urinating), reproductive and women's health (...), gastrointestinal upsets, respiratory ailments (asthma, coughs, and tuberculosis), skin diseases and topical wounds, and as an analgesic, with significant subtlety and nuance attending the precise strain, plant component (leaf, stem, root, etc.) and preparative method to be used."[42]

Kava today is primarily known for its anxiolytic properties. According to one comprehensive review of literature and research findings: "The current weight of evidence supports the use of kava in treatment of anxiety with a significant result occurring in four out of six studies reviewed." [43]

According to numerous studies, including the recent placebo-controlled clinical trial undertaken at the University of Melbourne kava could be a safe, non-addictive and effective remedy in treating generalized anxiety disorder(GAD)[44][45] and a potentially safer and alternative to tricyclic antidepressants and benzodiazepines for the treatment of anxiety disorders.[46]

Kava is also known for having a sleep inducing and potential sleep quality-enhancement effects[47] and might be an effective remedy for common restlessness and more serious insomnia.[48][49]

Recent findings suggest that the consumption of kava might have potential benefits for preventing or treating various forms of cancer,[42][50] most notably bladder,[51] colon[52] and lung cancer.[53]

Toxicity, safety and potential side effects[edit]

General observations[edit]

In its latest (2016) comprehensive review of kava safety conducted by the World Health Organization (WHO) and the Food and Agriculture Organization (FAO):

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. On the other hand, there is strong evidence that high levels of consumption of kava beverage can result in scaly skin rash, weight loss, nausea, loss of appetite and indigestion. These adverse health effects, while significant, are considered to be reversible upon cessation of kava use. Other possible effects include sore red eyes, laziness, loss of sex drive and general poor health. No effect on cognition, which might be associated with the pharmacological activity of kava, has been identified. No information is available on the potential for kava beverage consumption to impact on the incidence of chronic disease. Moderate to high kava beverage consumption also produces a reversible increase in the liver enzyme gamma glutamyltransferase (GGT), which may be an early indicator of cholestasis. Clinical surveys in Aboriginal communities in northern Australia with a history of heavy kava use have not revealed any evidence of long-term liver damage associated with consumption of kava beverage.[54]

Effects on the liver[edit]

According to a 2010 discussion paper prepared for the Codex Alimentarius Comission: "kava has had at least a 1500-year history of relatively safe use, with liver side effects never having arisen in the ethnopharmacological data. (...) Clinical trials of kava have not revealed hepatotoxicty as a problem. This has been confirmed by further studies evaluating the toxicology of kava drink. Based on available scientific information it can be inferred that kava as a traditional beverage is safe for human consumption."[55]

In 2001, concerns were raised about the safety of kava, which led to restrictions and regulations in several countries,[56] as well as reports by the United States CDC [57] and FDA.[58] Most of the concerns were related to a small number of reports indicating potential cases of hepatotoxicity caused by consumption of various commercial products derived from kava. A number of scientists and medical practitioners criticized the poor quality of the reports by pointing out that most of the reported rare cases of hepatotoxicity involved patients with a history of alcohol or prescription drugs abuse or concomitant use of medicines known as potentially hepatotoxic.[59] Likewise, the Australian studies from the late 1990s suggesting an association between health problems and heavy kava use[60] that contributed towards the rise of concerns about kava were found to be focused on populations with very heavy concomitant consumption of alcohol and overall poor health. More rigorous clinical research has found no evidence of any significant negative health issues (including any irreversible liver damage) that could be linked to kava.[61] In light of this information and subsequent research[10] on 10 June 2014, the German Administrative Court overturned the 2002 ban reinstating the regulatory requirements of 2001. The court stated that risk from kava exposure had not been clearly demonstrated, nor does it appear unusually high, an opinion presumably driven by the very small number of cases of reported toxicity (n ~ 3) with even a certain degree of causality linked to kava in a global kava-consuming community that may number in the millions of doses consumed daily.[62]

According to a comprehensive review of the relevant literature by Showman et al. (2014): "Despite the link to kava and liver toxicity demonstrated in vivo and in vitro, in the history of Western kava use, toxicity is still considered relatively rare. Only a fraction of the handful of cases reviewed for liver toxicity could be, with any certainty, linked to kava consumption and most of those involved the co-ingestion of other medications/supplements. That means that the incident rate of liver toxicity due to kava is one in 60-125 million patients."[62] According to an in-depth human health risk assessment commissioned by the New Zealand and Australian governments, while consumption of kava may result in such minor and reversible side effects as kava dermopathy (see below), "there is no evidence that occasional use of kava beverage is associated with any long-term adverse effects, including effects on the liver."[63]

Recent publications also confirm that kava appears to be safe and that the previously reported extremely rare cases of hepatotoxicity were in most cases likely related to rare idiosyncratic allergic reactions.[10][64] The only remaining area of potential concern is the use of the so-called "two-day" (known also as "tudei", "isa", "palisi") and wild (piper wichmanii) cultivars (traditionally not consumed) in the manufacturing of kava-based pharmaceutical products due to their very different phytochemistry and relatively high concentrations of potentially harmful compounds (flavokavains). While other ("noble") cultivars also contain these compounds "toxicity seems to be triggered only at relatively high concentrations, too high to be of relevance with the use of noble kava or its corresponding extract preparations".[10] In line with these findings, consumption of "two day" varieties is not recommended. Such cultivars mainly grow in Vanuatu which outlawed their exports in 2004.[9]

A 2012 analysis of cases worldwide proposed that mold could have also contributed to the very rare cases hepatotoxicity induced by kava-based pharmaceutical products.[65]

Potential interactions[edit]

Several adverse interactions with drugs have been documented, both prescription and nonprescription – including, but not limited to, anticonvulsants, alcohol, anxiolytics (CNS depressants such as benzodiazepines), antipsychotics, levodopa, diuretics, and drugs metabolized by CYP450 in the liver.[48]

A few notable potential drug interactions are, but are not limited to:

  • Alcohol It has been reported that combined use of alcohol and kava extract can have additive sedative effects in mice.[66] However, this additive effect has not been studied in humans. But separately kava has been shown to induce sedation.[67] Regarding cognitive function, kava has been shown to have additive cognitive impairments while taken with alcohol when compared to taking placebo and alcohol alone.[68]
  • Anxiolytics (CNS depressants such as benzodiazepines and barbiturates) Kava may have potential additive CNS depressant effects (such as sedation and anxiolytic effects) with benzodiazepines and barbiturates.[68]
  • Dopamine Agonist - Levodopa One of levodopa’s chronic side effects that Parkinson’s patients experience is the "on-off phenomenon" of motor fluctuations where there will be periods of oscillations between "on" where the patient experiences symptomatic relief and "off" where the therapeutic effect wears off early.[69] When taking levodopa and kava together it has been shown that there is an increased frequency of this "on-off phenomenon".[70]

Kava dermopathy[edit]

Long term and heavy kava consumption is associated with a fully reversible skin condition known as "kava dermopathy" or kani kani (in Fiji) characterised by dry and scaly skin covering the palms of the hands, soles of the feet, and back.[71][72] Despite numerous studies, the mechanism that causes kava dermopathy is poorly understood "but may relate to interference with cholesterol metabolism".[72] The condition is easily treatable with abstinence or lowering of kava intake as the skin appears to be returning to its normal state within a couple of weeks of reduced or no kava use.[72] Kava dermopathy should not be confused with rare instances of allergic reactions to kava that are usually characterised by itchy rash or puffy face.[73]

Regulation[edit]

Kava remains legal in most countries. Regulations often treat it as a food or dietary supplement.

Medical researchers have proposed that laws be passed to require that kava products be derived only from noble cultivars, which may be less toxic.[74][75] They have also suggested that aqueous solutions are less harmful.[75][76] Exclusion of above-ground parts of the plant - which contain pipermethystine and other toxic compounds - is often required by law or convention.[75]

Australia[edit]

In Australia, the supply of kava is regulated through the National Code of Kava Management.[77]

Travellers to Australia are allowed to bring up to 2 kg of kava in their baggage; provided they are at least 18 years old, and the kava is in root or dried form. Commercial import of larger quantities is allowed, under licence, for medical or scientific purposes. These restrictions were introduced in 2007 after concern about abuse of kava in indigenous communities.[78]

In 2015, there were moves by the Australian Federal Government to ban kava after claims that Tongan gangs were smuggling kava into Aboriginal communities in the Northern Territory, where it was introduced in the 1980s by missionaries from the Pacific islands as an alternative to alcohol. [79]

The Australian Therapeutic Goods Administration has recommended no more than 250 mg of kavalactones be taken in a 24‑hour period.[80]

The importation and licensing of kava is prohibited in Western Australia.[citation needed][60][81] In the Northern Territory, the police say that "the sale and, in majority of circumstances, possession of kava [...] is illegal".[82]

Europe[edit]

Following the discussions on the safety of certain pharmaceutical products derived from kava and sold in Germany, in 2002 the EU imposed a temporary ban on imports of kava-based pharmaceutical products.[83] The sale of kava plant became regulated in Switzerland, France, and the Netherlands.[84] Some Pacific Island States who had been benefiting from the export of kava to the pharmaceutical companies have attempted to overturn the EU ban on kava-based pharmaceutical products by invoking international trade agreements at the WTO: Fiji, Samoa, Tonga and Vanuatu argued that the ban was imposed with insufficient evidence.[85] The pressure prompted Germany to reconsider the evidence base for banning kava-based pharmaceutical products.[86] On 10 June 2014, the German Administrative Court overturned the 2002 ban making selling kava as a medicine legal (personal possession of kava has never been illegal), albeit strictly regulated. In Germany, Kava-based pharmaceutical preparations are currently prescription drugs. Furthermore, patient and professional information brochures have been redesigned to warn about potential side effects.[87] These strict measures have been opposed by some of the leading kava scientists. In early 2016 a court case has been filed against the Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM/German Federal Institute for Drugs and Medical Devices) arguing that the new regulatory regime is too strict and not justified.[88]

Fijian kava ceremony being performed for tourists

Poland is the only EU country with an "outright ban on kava" and where the mere possession of kava is prohibited and may result in a prison sentence.[83]

In the United Kingdom it is a criminal offence to sell, supply or import any medicinal product containing kava for human consumption.[89] It is legal to possess kava for personal use, or to import it for purposes other than human consumption (e.g. for animals).

New Zealand[edit]

When used traditionally kava is regulated as a food under the Food Standards Code. Kava can also be used as a herbal remedy. When used in this way kava is currently regulated by the Dietary Supplements Regulations. Only traditionally consumed forms and parts of the kava plant (i.e. pure roots of the kava plant and water extractions prepared from these roots) can legally be sold as food or dietary supplements in New Zealand. The sale of never traditionally consumed above-ground parts of the plant (unlike the roots of the plant, the aerial parts contain very small amounts of kavalactones and instead contain a mildly toxic alkaloid pipermethysticin[63]) and non-water based extract (such as CO2, acetonic or ethanol extractions) is prohibited for the purpose of human consumption (but can be sold as an ingredient in cosmetics or other products not intended for human consumption).[90][91]

North America[edit]

In 2002 Health Canada issued an order prohibiting the sale of any product containing kava.[92] While the restrictions on kava were lifted in 2012,[93] Health Canada has not licensed any kava products for sale in Canada.[94]

Vanuatu[edit]

The Pacific island-state of Vanuatu has passed legislation to regulate the quality of its kava exports. Vanuatu prohibits the export or consumption of non-noble kava varieties or the parts of the plant that are unsuitable for consumption (such as leaves and stems).[95]

See also[edit]

References[edit]

  1. ^ kava. (2010). In Merriam–Webster Online Dictionary.
  2. ^ Hawaiian Dictionary
  3. ^ Fitisemanu, Jacob (2007) Samoan social drinking: perpetuation and adaptation of ʻAva ceremonies in Salt Lake County, Utah B. A. Thesis, Westminster College p. 2.
  4. ^ Yaqona, kava drinking ceremony
  5. ^ Balick, Michael J. and Leem, Roberta (2002) Traditional use of sakau (kava) in Pohnpei: lessons for integrative medicine Alternative Therapies, Vol. 8, No.4. p. 96
  6. ^ a b c d e f g Lebot, Vincent; Merlin, Mark; Lindstrom, Lamont (1997). Kava: The Pacific Elixir: The Definitive Guide to Its Ethnobotany, History, and Chemistry. Inner Traditions / Bear & Co. p. 37. ISBN 978-0-89281-726-9. 
  7. ^ Pittler MH, Ernst E (2003). Pittler, Max H, ed. "Kava extract for treating anxiety". Cochrane database of systematic reviews (Online) (1): CD003383. doi:10.1002/14651858.CD003383. PMID 12535473. 
  8. ^ a b c d Lebot, Vincent; Merlin, Mark; Lindstrom, Lamont (1997-02-01). Kava: The Pacific Elixir: The Definitive Guide to Its Ethnobotany, History, and Chemistry. Inner Traditions / Bear & Co. ISBN 9780892817269. 
  9. ^ a b Teschke, Rolf; Lebot, Vincent (2011-10-01). "Proposal for a Kava Quality Standardization Code". Food and Chemical Toxicology. 49 (10): 2503–2516. doi:10.1016/j.fct.2011.06.075. 
  10. ^ a b c d e f g h Kuchta, Kenny; Schmidt, Mathias; Nahrstedt, Adolf (2015-12-01). "German Kava Ban Lifted by Court: The Alleged Hepatotoxicity of Kava (Piper methysticum) as a Case of Ill-Defined Herbal Drug Identity, Lacking Quality Control, and Misguided Regulatory Politics". Planta Medica. 81 (18): 1647–1653. doi:10.1055/s-0035-1558295. ISSN 1439-0221. PMID 26695707. 
  11. ^ "Drink the right mix - Fiji Times Online". www.fijitimes.com. Retrieved 2016-05-29. 
  12. ^ "Vanuatu hopes for kava export growth". Radio New Zealand. 2015-11-11. Retrieved 2016-05-29. 
  13. ^ "Vanuatu kava cleared for European market". Radio New Zealand. 2015-11-12. Retrieved 2016-05-29. 
  14. ^ "True Kava Group Labs". 
  15. ^ Johnston, Ed; Rogers, Helen; Association for Hawaiian ʻAwa (2006-01-01). Hawaiian ʻawa: views of an ethnobotanical treasure. Hilo, Hawaii: Association for Hawaiian ʻAwa. p. 34. 
  16. ^ "Kava vs Kawakawa | Kava use in New Zealand | Maori Memories of Kava". kavasociety.nz. Retrieved 2016-07-02. 
  17. ^ "Māori Plant Use Database Plant Use Details of Macropiper excelsum". maoriplantuse.landcareresearch.co.nz. Retrieved 2016-07-02. 
  18. ^ Naumov, P., Dragull, K., Yoshioka, M., Tang, C.-S., Ng, S. W. Structural Characterization of Genuine (—)-Pipermethystine, (—)-Epoxypipermethystine, (+)-Dihydromethysticin and Yangonin from the Kava Plant (Piper methysticum), Natural Product Communications(2008), 3(8) 1333—1336.
  19. ^ a b c Sarris J, LaPorte E, Schweitzer I (2011). "Kava: a comprehensive review of efficacy, safety, and psychopharmacology". Aust N Z J Psychiatry. 45 (1): 27–35. doi:10.3109/00048674.2010.522554. PMID 21073405. 
  20. ^ Bunchorntavakul, C.; Reddy, K. R. (2013-01-01). "Review article: herbal and dietary supplement hepatotoxicity". Alimentary Pharmacology & Therapeutics. 37 (1): 3–17. doi:10.1111/apt.12109. ISSN 1365-2036. 
  21. ^ Olsen LR, Grillo MP, Skonberg C (2011). "Constituents in kava extracts potentially involved in hepatotoxicity: a review". Chem. Res. Toxicol. 24 (7): 992–1002. doi:10.1021/tx100412m. PMID 21506562. 
  22. ^ Singh YN, Singh NN (2002). "Therapeutic potential of kava in the treatment of anxiety disorders". CNS Drugs. 16 (11): 731–43. doi:10.2165/00023210-200216110-00002. PMID 12383029. 
  23. ^ Ligresti A, Villano R, Allarà M, Ujváry I, Di Marzo V (2012). "Kavalactones and the endocannabinoid system: the plant-derived yangonin is a novel CB₁ receptor ligand". Pharmacol. Res. 66 (2): 163–9. doi:10.1016/j.phrs.2012.04.003. PMID 22525682. 
  24. ^ a b Dinh LD, Simmen U, Bueter KB, Bueter B, Lundstrom K, Schaffner W (2001). "Interaction of various Piper methysticum cultivars with CNS receptors in vitro". Planta Med. 67 (4): 306–11. doi:10.1055/s-2001-14334. PMID 11458444. 
  25. ^ Amitava Dasgupta; Catherine A. Hammett-Stabler (21 March 2011). Herbal Supplements: Efficacy, Toxicity, Interactions with Western Drugs, and Effects on Clinical Laboratory Tests. John Wiley & Sons. pp. 57–. ISBN 978-0-470-92275-0. 
  26. ^ Baum SS, Hill R, Rommelspacher H (1998). "Effect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of rats". Prog. Neuropsychopharmacol. Biol. Psychiatry. 22 (7): 1105–20. doi:10.1016/s0278-5846(98)00062-1. PMID 9829291. 
  27. ^ Garrett KM, Basmadjian G, Khan IA, Schaneberg BT, Seale TW (2003). "Extracts of kava (Piper methysticum) induce acute anxiolytic-like behavioral changes in mice". Psychopharmacology (Berl.). 170 (1): 33–41. doi:10.1007/s00213-003-1520-0. PMID 12845414. 
  28. ^ Cairney S, Clough AR, Maruff P, Collie A, Currie BJ, Currie J (2003). "Saccade and cognitive function in chronic kava users". Neuropsychopharmacology. 28 (2): 389–96. doi:10.1038/sj.npp.1300052. PMID 12589393. 
  29. ^ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 803–804.
  30. ^ Kevin Cassell (2005). "Fiji: A Visitor's Guide". Retrieved 25 April 2007. 
  31. ^ Viorica, Lopez-Aila. "Supercritical fluid extraction of kava lactones from Piper methysticum (kava) herb". Hüthig GmbH. Retrieved 5 September 2012. 
  32. ^ Teschke, Rolf; Sarris, Jerome; Lebot, Vincent (2011-01-15). "Kava hepatotoxicity solution: A six-point plan for new kava standardization". Phytomedicine: International Journal of Phytotherapy and Phytopharmacology. 18 (2-3): 96–103. doi:10.1016/j.phymed.2010.10.002. ISSN 1618-095X. PMID 21112196. 
  33. ^ There are many variations to this ceremony; one of which is described in: Biturogoiwasa, Solomoni; Walker, Anthony R. (2001). My Village, My World: Everyday Life in Nadoria, Fiji. Suva, Fiji: Institute of Pacific Studies, University of the South Pacific. pp. 17–20. ISBN 978-982-02-0160-6.  There are numerous anthropological studies, one example being: Tomlinson, Matt (2007). "Everything and Its Opposite: Kava Drinking in Fiji". Anthropological Quarterly. 80 (4): 1065–81. doi:10.1353/anq.2007.0054. [improper synthesis?]
  34. ^ a b Legacy, Herbal. "History of Kava Kava". www.herballegacy.com. Retrieved 2016-08-02. 
  35. ^ Djavaweb (2015-10-25). "New Kava Bars Prove Kava is Growing". Retrieved 2016-07-28. 
  36. ^ Swanson, Jess (2014-03-20). "South Florida Kava Bars Unworried about Two-Day Kava". Retrieved 2016-07-28. 
  37. ^ Lebot, V.; Do, T. K. T.; Legendre, L. (2014-05-15). "Detection of flavokavins (A, B, C) in cultivars of kava (Piper methysticum) using high performance thin layer chromatography (HPTLC)". Food Chemistry. 151: 554–560. doi:10.1016/j.foodchem.2013.11.120. ISSN 0308-8146. PMID 24423570. 
  38. ^ Kilham, Christopher (1996-06-01). Kava: Medicine Hunting in Paradise: The Pursuit of a Natural Alternative to Anti-Anxiety Drugs and Sleeping Pills. Inner Traditions / Bear & Co. ISBN 9780892816408. 
  39. ^ Cairney, Sheree; Clough, Alan R; Maruff, Paul; Collie, Alex; Currie, Bart J; Currie, Jon (2003-02-14). "Saccade and Cognitive Function in Chronic Kava Users". Neuropsychopharmacology. 28 (2): 389–396. doi:10.1038/sj.npp.1300052. ISSN 0893-133X. 
  40. ^ Baker, Jonathan D. (2011-06-01). "Tradition and toxicity: evidential cultures in the kava safety debate". Social Studies of Science. 41 (3): 361–384. doi:10.1177/0306312710395341. ISSN 0306-3127. PMID 21879526. 
  41. ^ Lebot, Vincent; Levesque, Joël (1996-09-01). "Genetic control of kavalactone chemotypes in Piper methysticum cultivars". Phytochemistry. 43 (2): 397–403. doi:10.1016/0031-9422(96)00209-9. 
  42. ^ a b c d Showman, Angelique F.; Baker, Jonathan D.; Linares, Christina; Naeole, Chrystie K.; Borris, Robert; Johnston, Edward; Konanui, Jerry; Turner, Helen (2015-01-01). "Contemporary Pacific and Western perspectives on `awa (Piper methysticum) toxicology". Fitoterapia. 100: 56–67. doi:10.1016/j.fitote.2014.11.012. ISSN 1873-6971. PMID 25464054. 
  43. ^ Jerome, Sarris; et al. (2011). "Kava: A Comprehensive Review Of Efficacy, Safety, And Psychopharmacology". Australian and New Zealand Journal of Psychiatry. 45: 27–35. doi:10.3109/00048674.2010.522554. PMID 21073405. 
  44. ^ Sarris, Jerome; Stough, Con; Bousman, Chad A.; Wahid, Zahra T.; Murray, Greg; Teschke, Rolf; Savage, Karen M.; Dowell, Ashley; Ng, Chee (2013-10-01). "Kava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled study". Journal of Clinical Psychopharmacology. 33 (5): 643–648. doi:10.1097/JCP.0b013e318291be67. ISSN 1533-712X. PMID 23635869. 
  45. ^ Pittler MH, Ernst E (2000). "Efficacy of kava extract for treating anxiety: systematic review and meta-analysis". J Clin Psychopharmacol. 20: 84–89. doi:10.1097/00004714-200002000-00014. 
  46. ^ Volz HP, Kieser M (1997). "Kava-kava extract WS 1490 versus placebo in anxiety disorders--a randomized placebo-controlled 25-week outpatient trial". Pharmacopsychiatry. 30: 1–5. doi:10.1055/s-2007-979474. 
  47. ^ Shinomiya, Kazuaki; Inoue, Toshio; Utsu, Yoshiaki; Tokunaga, Shin; Masuoka, Takayoshi; Ohmori, Asae; Kamei, Chiaki (2005-07-01). "Effects of kava-kava extract on the sleep-wake cycle in sleep-disturbed rats". Psychopharmacology. 180 (3): 564–569. doi:10.1007/s00213-005-2196-4. ISSN 0033-3158. PMID 15700178. 
  48. ^ a b "Kava kava". Complementary and Alternative Medicine Guide. University of Maryland Medical Center. Retrieved 25 September 2016. 
  49. ^ "Hava". Annals of Psychotherapy & Integrative Health. 2011. 
  50. ^ Steiner, G. G. (2000-11-01). "The correlation between cancer incidence and kava consumption". Hawaii Medical Journal. 59 (11): 420–422. ISSN 0017-8594. PMID 11149250. 
  51. ^ Tang, Yaxiong; Simoneau, Anne R.; Xie, Jun; Shahandeh, Babbak; Zi, Xiaolin (2008-11-01). "Effects of the kava chalcone flavokawain A differ in bladder cancer cells with wild-type versus mutant p53". Cancer Prevention Research (Philadelphia, Pa.). 1 (6): 439–451. doi:10.1158/1940-6207.CAPR-08-0165. ISSN 1940-6215. PMC 2830727free to read. PMID 19138991. 
  52. ^ Triolet, Julie; Shaik, Ahmad Ali; Gallaher, Daniel D.; O'Sullivan, Michael G.; Xing, Chengguo (2012-08-01). "Reduction in colon cancer risk by consumption of kava or kava fractions in carcinogen-treated rats". Nutrition and Cancer. 64 (6): 838–846. doi:10.1080/01635581.2012.689917. ISSN 1532-7914. PMID 22693990. 
  53. ^ Johnson, Thomas E.; Hermanson, David; Wang, Lei; Kassie, Fekadu; Upadhyaya, Pramod; O'Sullivan, Michael G.; Hecht, Stephen S.; Lu, Junxuan; Xing, Chengguo (2011-01-01). "Lung tumorigenesis suppressing effects of a commercial kava extract and its selected compounds in A/J mice". The American Journal of Chinese Medicine. 39 (4): 727–742. doi:10.1142/S0192415X11009202. ISSN 0192-415X. PMID 21721153. 
  54. ^ Kava: a review of the safety of traditional and recreational beverage consumption (2016). WHO/FAO. http://www.fao.org/3/a-i5770e.pdf
  55. ^ DISCUSSION PAPER ON THE DEVELOPMENT OF A STANDARD FOR KAVA (2010) http://www.ikec.org/sites/default/files/Codex%20alimentarius%20kava_draft_0.pdf
  56. ^ Sarris, J; Laporte, E; Schweitzer, I (2011). "Kava: A comprehensive review of efficacy, safety, and psychopharmacology". The Australian and New Zealand Journal of Psychiatry. 45 (1): 27–35. doi:10.3109/00048674.2010.522554. PMID 21073405. 
  57. ^ United States Centers for Disease Control and Prevention (2002). "Hepatic Toxicity Possibly Associated with Kava-Containing Products – United States, Germany, and Switzerland, 1999 2002". Morbidity & Mortality Weekly Report. 51 (47): 1065–1067. Retrieved 16 September 2005. 
  58. ^ Center for Food Safety; Applied Nutrition (2002). "Kava-Containing Dietary Supplements May Be Associated with Severe Liver Injury". United States Food and Drug Administration. Archived from the original on 25 March 2008. Retrieved 16 June 2005. 
  59. ^ Baker, Jonathan (2011). "Tradition and toxicity: Evidential cultures in the kava safety debate". Social Studies of Science. 41: 361–384. doi:10.1177/0306312710395341. 
  60. ^ a b "National Drug Strategy - Aboriginal and Torres Strait Islander Peoples Complementary Action Plan 2003–2009 - Background Paper". Ministerial Council on Drug Strategy, Commonwealth of Australia, May 2006. ISBN 0 642 82328 6.[dead link]
  61. ^ Clough, Alan R.; Bailie, Ross S.; Currie, Bart (2003-01-01). "Liver Function Test Abnormalities in Users of Aqueous Kava Extracts". Journal of Toxicology: Clinical Toxicology. 41 (6): 821–829. doi:10.1081/CLT-120025347. ISSN 0731-3810. PMID 14677792. 
  62. ^ a b Showman; et al. (2014). "Contemporary Pacific and Western perspectives on `awa (Piper methysticum) toxicology.". Filoterapia. 100: 56–67. doi:10.1016/j.fitote.2014.11.012. PMID 25464054. 
  63. ^ a b "Kava: A Human Health Risk Assessment" (PDF). Technical Report Series No 30. Food Standards Australia New Zealand. 2016-05-25. 
  64. ^ Pantano, Flaminia; Tittarelli, Roberta; Mannocchi, Giulio; Zaami, Simona; Ricci, Serafino; Giorgetti, Raffaele; Terranova, Daniela; Busardò, Francesco P.; Marinelli, Enrico (2016-04-16). "Hepatotoxicity Induced by "the 3Ks": Kava, Kratom and Khat". International Journal of Molecular Sciences. 17 (4). doi:10.3390/ijms17040580. ISSN 1422-0067. PMC 4849036free to read. PMID 27092496. 
  65. ^ Teschke, Rolf; Sarris, Jerome; Schweitzer, Isaac (2012). "Kava hepatotoxicity in traditional and modern use: The presumed Pacific kava paradox hypothesis revisited". British Journal of Clinical Pharmacology. 73 (2): 170–4. doi:10.1111/j.1365-2125.2011.04070.x. PMC 3269575free to read. PMID 21801196. 
  66. ^ Jamieson, D. D. and Duffield, P. H. "Positive interaction of ethanol and kava resin in mice." Clin Exp Pharmacol Physiol 1990;17(7):509-514
  67. ^ Cairney S.; Maruff P.; Clough A. R.; Collie A.; Currie J.; Currie B. J. (2003). "Saccade and cognitive impairment associated with kava intoxication". Hum.Psychopharmacol. 18 (7): 525–533. doi:10.1002/hup.532. 
  68. ^ a b Spinella M (2002). "The importance of pharmacological synergy in psychoactive herbal medicines". Altern Med Rev. 7 (2): 130–137. 
  69. ^ Lees AJ. "The on-off phenomenon. J Neurol Neurosurg Psychiatr. 1989;Suppl:29-37.
  70. ^ Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: a systematic review" Drugs 2001;61(15):2163-75.
  71. ^ Ruze, P. (1990-06-16). "Originally published as Volume 1, Issue 8703Kava-induced dermopathy: a niacin deficiency?". The Lancet. 335 (8703): 1442–1445. doi:10.1016/0140-6736(90)91458-M. 
  72. ^ a b c Norton, Scott A.; Ruze, Patricia (1994-07-01). "Kava dermopathy". Journal of the American Academy of Dermatology. 31 (1): 89–97. doi:10.1016/S0190-9622(94)70142-3. 
  73. ^ "Sebotropic drug reaction resulting from kava-kava extract therapy: A new entity?". www.sciencedirect.com. Retrieved 2016-10-24. 
  74. ^ Teschke R, Sarris J, Glass X, Schulze J (March 2011). "Kava, the anxiolytic herb: back to basics to prevent liver injury?". British Journal of Clinical Pharmacology. 71 (3): 445–8. doi:10.1111/j.1365-2125.2010.03775.x. PMC 3045554free to read. PMID 21284704. This raises the question as to whether noble cultivars may be better and safer regarding hepatotoxic effects than the medicinal kava varieties. 
  75. ^ a b c Teschke, Rolf (March 2011). "Kava and the Risk of Liver Toxicity: Past, Current, and Future" (PDF). AHPA Report. Retrieved 26 December 2013. [dead link]
  76. ^ Teschke, Rolf; Samuel Qiu; Vincent Lebot (September 2011). "Herbal hepatotoxicity by kava: Update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culprits". Digestive and Liver Disease. 43 (9): 676–681. doi:10.1016/j.dld.2011.01.018. PMID 21377431. 
  77. ^ "Australia New Zealand Food Standards Code - Standard 2.6.3 - Kava". Federal Register of Legislation.  Text "https://www.legislation.gov.au/Details/F2009C01242" ignored (help); .
  78. ^ "Restrictions on the import of kava to Australia". Therapeutic Goods Administration, Department of Health, Australian Government. 14 April 2015.  Text "https://www.tga.gov.au/restrictions-import-kava-australia" ignored (help); .
  79. ^ Armbruster, Stefan (10 July 2015). "Islanders shocked as Australia moves to ban kava". Special Broadcasting Service.  Text "http://www.sbs.com.au/news/article/2015/02/18/islanders-shocked-australia-moves-ban-kava" ignored (help); .
  80. ^ "Kava fact sheet". Therapeutic Goods Administration, Government of Australia. April 2005. Retrieved 10 July 2006.  (Download PDF 44KB).
  81. ^ "Kava". Government of the Northern Territory of Australia. Archived from the original on 8 January 2013. In accordance with the Australian Government National Emergency Response in the Northern Territory the commercial importation and licensing of kava is prohibited. 
  82. ^ "Kava in the Northern Territory". Northern Territory Police. Retrieved 26 October 2013. 
  83. ^ a b "Europe Explains Its Stand on Kava from the Pacific". Radio Australia. March 2012. Retrieved 10 October 2013. 
  84. ^ C.I.J.M. Ross-van Dorp (2003). "Besluit van 23 april 2003, houdende wijziging van het Warenwetbesluit Kruidenpreparaten (verbod op Kava kava in kruidenpreparaten)" (PDF). Sdu Uitgevers. Staatsblad van het Koninkrijk der Nederlanden. Retrieved 7 February 2007. 
  85. ^ "Fiji takes kava ban fight to WTO". The World Trade Review. August 2005. Retrieved 26 October 2013. 
  86. ^ Bowman, Chakriya. "The Pacific Island Nations: Towards Shared Representation". WTO. Retrieved 26 October 2013. 
  87. ^ Comeback unter strengen Auflagen(in German). PHARMAZEUTISCHE ZEITUNG online 16/2015. Retrieved 28 February 2016.
  88. ^ "New Kava Challenge". Vanuatu Daily Post. Retrieved 2016-03-03. 
  89. ^ "The Medicines for Human Use (Kava-kava) (Prohibition) Order 2002". Retrieved 26 October 2013. 
  90. ^ "Dunne: Kava unaffected by Psychoactive Substances Bill". The Beehive. Retrieved 2016-10-24. 
  91. ^ "Standard 2.6.3 – Kava – Food Standards (Proposal P1025 – Code Revision) Variation—Australia New Zealand Food Standards Code – Amendment No. 154 - 2015-gs1906 - New Zealand Gazette". gazette.govt.nz. Retrieved 2016-07-02. 
  92. ^ "Marketed Health Products Directorate Heath Products and Foods Branch". Canadian Adverse Reaction Newsletter. Health Canada. 12 (4). 2002. 
  93. ^ "Listing of Drugs Currently Regulated as New Drugs (The New Drugs List)". www.hc-sc.gc.ca. Health Canada. 6 November 2012. Retrieved 19 March 2014. 
  94. ^ http://www.healthlinkbc.ca/healthtopics/content.asp?hwid=tn7356spec
  95. ^ "Vanuatu - Legislation - Kava Act 2002". faolex.fao.org. Retrieved 2016-07-02. 

Literature[edit]

External links[edit]

Retrieved from "https://en.wikipedia.org/w/index.php?title=Kava&oldid=746119722"