Kava

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This article is about the kava plant. For the class of pharmacological derivatives, see Kavalactone. For other uses, see Kava (disambiguation).
Kava
Starr 040318-0058 Piper methysticum.jpg
Young Piper methysticum
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) (Piper: Latin for "pepper", methysticum: Latinized Greek for "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), ava (Samoa), yaqona (Fiji), and sakau (Pohnpei).

The roots of the plant are used to produce a drink with sedative and anesthetic 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 Cochrane Collaboration systematic review of its evidence concluded it was likely to be more effective than placebo at treating short-term social anxiety.[2]

People taking certain kava-based drugs and dietary products have suffered liver damage or liver failure as a result of hepatotoxicity.[3] Consequently, kava is regulated in a number of countries.[4] In the EU it is strictly prohibited only in Poland.

Characteristics[edit]

The several cultivars of kava vary in concentrations of primary and secondary psychoactive substances. 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.

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.

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.

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 and origins[edit]

A painting showing women preparing kava

One of the most potent strains is called "Isa" in Papua New Guinea, and also called "Tuday" in Hawaii. In Vanuatu, it is considered a type of "Tudei" kava, pronounced as "two-day" because it is said to have effects lasting two days due to its chemical profile being high in the kavalactone dihydromethysticin. The plant itself is a strong, very hardy, fast-growing variety with multiple light to dark green stems covered with raised dark spots.

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 Ambae island (called sese in North Pentecost), and "Palarasul" kava from Espiritu Santo Island. 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. Some of the most popular strains are the "Mahakea," "Mo'i," "Hiwa" and "Nene" varieties. The Ali'i (kings) of old Hawaii coveted the special kava they called "Mo'i" that 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 Hawai‘i is evident in this portion of a chant recorded by N.B. Emerson and quoted by Handy and Handy. "This refers to the cup of sacramental‘awa brewed from the strong, black ‘awa root (‘awa 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 ‘awa,
A vision like that of a sacred god!

Winter describes a hula prayer for inspiration which contains the line, He ‘ike pū ‘awa hiwa. Pukui and Elbert translated this as "a knowledge from kava offerings". Winter explains that ‘awa, especially of the Hiwa variety, was offered to hula deities in return for knowledge and inspiration. [pg. 34, Hawaiian 'Awa, Views of an Ethnobotanical Treasure, 2006].

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

Composition[edit]

Fresh kava root contains on average 80% water. Dried root contains approximately 43% starch, 20% dietary fiber, 15% kavalactones,[5] 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]

Kava's active principal ingredients are the kavalactones, 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.[citation needed] Different ratios can produce different effects.[citation needed]

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

Research has suggested that kavalactones potentiate GABAA activity, but do not alter levels of dopamine and serotonin in the CNS.[6] It is thought to do this via modulating GABA activity via altering the lipid membrane structure and sodium channel function.[7] However, it has also been shown that administration of the GABA antagonist Flumazenil does not have an antagonistic effect on kavalactones, suggesting that an alternative pathway may be involved.[8] Heavy, long-term kava use does not cause any reduction of ability in saccade and cognitive tests, but is associated with elevated liver enzymes.[9]

Desmethoxyyangonin, one of the six major kavalactones, is a reversible MAO-B inhibitor (Ki 280 nM)[10] and is able to increase dopamine levels in the nucleus accumbens. This finding might correspond to the slightly euphoric action of kava.[11]

Kavain, in both enantiomeric forms, inhibits the reuptake of norepinephrine at the transporter (NAT), but not of serotonin (SERT).[12] An elevated extracellular norepinephrine level in the brain may account for the reported enhancement of attention and focus.

Yangonin, another major kavalactone, has been demonstrated to act as a CB1 agonist. This mechanism is also responsible for the effects of THC and likely contributes to the psychoactive effects of kava.[13]

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.[14]

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. 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.[15]

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

Pills[edit]

Pharmaceutical and herbal supplement companies extract kavalactones from the kava plant using solvents such as supercritical carbon dioxide,[16] acetone and ethanol to produce pills standardized with between 30% and 90% kavalactones.

Kava culture[edit]

A sign showing a "Kava license 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.[17]

A traditional Fijian yaqona bundle of roots

Effects of consumption[edit]

The effects of a kava drink vary widely with the particular selection of kava plant(s) and amount. A potent drink results in a faster onset with a lack of stimulation; the user's eyes become more sensitive, the person soon becomes somnolent and then has deep, dreamless sleep within 30 minutes. Sleep is often restful and pronounced periods of sleepiness correlate to the amount and potency of kava consumed. Kava drinkers are often perceived as having lazy days after consumption of kava the night before, which can be expected as many active kavalactones have half lives of approximately 9 hours.[18]

Efficacy[edit]

A few studies have shown that kava extracts possessed efficacious anxiolytic activity compared to placebo for the symptomatic treatment for anxiety. [19] As well, kava extracts may be an effective alternative to tricyclic antidepressants and benzodiazepines for the treatment of anxiety disorders. [20]

One study showed that 150mg/day of the standardized WS 1490 Kava extract in divided doses for 4 weeks was effective at decreasing anxiety symptoms but was not superior to the alternative dose of 300mg/day in divided doses used in other studies. [21]

Most of these studies used a standardized WS 1490 Kava extract formulation, which is composed of 70% kavalactones. [22]

Toxicity and safety[edit]

In 2001, concerns were raised about the safety of kava, which led to restrictions and regulations in many countries,[4] as well as reports by the United States CDC [23] and FDA.[24] A 2010 review of Kava's hepatotoxicity concluded that if kava and kava products were ever to return to the market, greater quality control would be needed during production, and the products would need to be used with care.[3]

Various components of the plant have been labelled responsible, particularly pipermethystine and flavokavain B. Yet, based on a retrospective study in Germany, the alkaloid pipermethystine is an unlikely cause for the observed hepatotoxicity, as, although it occurs in qualities up to 0.2% of the leaves, it is found in quantities a hundred-fold less in Western extracts.[25] Another suggested culprit, Flavokavain B, is also found in various preparations in the plant, although not in ethanol extracts of noble cultivars, and never in large enough amounts to cause any liver damage.[26] Kava hepatotoxicity may be due to contamination with aflatoxins or other mold hepatotoxins, but this requires further study.[27]

Other data suggests intrinsic metabolic cause. Three possible mechanisms for kavalactone hepatotoxicity have been theorized: inhibition of cytochrome P450, possible reduction in liver glutathione content and, more remotely, inhibition of cyclooxygenase enzyme activity. The direct toxicity of kava extracts is relatively small under any analysis, yet the potential for drug interactions and/or the potentiation of the toxicity of other compounds is large.[28]

In line with this reasoning, 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.[29]

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.[30] Although, this additive effect has not been studied in humans. But separately kava has been shown to induce sedation.[31] Regarding cognitive function, kava has been shown to have additive cognitive impairments while taken with alcohol when compared to taking placebo and alcohol alone.[32]
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.[33]
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.[34] When taking levodopa and kava together it has been shown that there is an increased frequency of this “on-off phenomenon”. [35]

The Australian studies that drove this debate focused on populations with heavy concomitant consumption of alcohol and overall poor health. In these studies, heavy kava use in an Aboriginal community in Arnhem Land was associated with overall poor health, a puffy face, scaly rash, and a slight increase in patellar reflexes.[36][37][38] A 2012 analysis of cases worldwide proposed that mold was the primary cause of hepatotoxicity in kava products.[39]

Regulation[edit]

In 2002 the EU imposed a ban on imports of kava-based pharmaceutical products.[40] The sale of kava plant is regulated in Switzerland, France, and the Netherlands.[41] 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.[42] The pressure prompted Germany to reconsider the evidence base for banning kava-based pharmaceutical products.[43]

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.[40]

In the United Kingdom it is a criminal offence to sell, supply or import any medicinal product containing kava.[44]

In 2002 Health Canada issued an order prohibiting the sale of any product containing kava,[45] however the restrictions on kava were lifted in 2012.[46]

In Australia, the supply of kava is regulated through the National Code of Kava Management. The importation and licensing of kava is prohibited in Western Australia.[47][48] In the Northern Territory, the police say that "the sale and, in majority of circumstances, possession of kava [...] is illegal".[49] The Australian Therapeutic Goods Administration has recommended no more than 250 mg of kavalactones be taken in a 24‑hour period.[50]

Legislation has been proposed to require that kava products be derived only from noble cultivars, which may be less toxic.[51][52] Other acts have been passed based on the assumption that aqueous solutions are less harmful.[26][52] Exclusion of certain aerial parts of the plant are also often required by law or convention, which contain less pipermethystine and other toxic compounds.[52]

See also[edit]

References[edit]

  1. ^ kava. (2010). In Merriam–Webster Online Dictionary.
  2. ^ 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. 
  3. ^ a b Teschke, R (2010). "Kava hepatotoxicity—a clinical review". Annals of hepatology 9 (3): 251–65. PMID 20720265. 
  4. ^ a b 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. 
  5. ^ 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.
  6. ^ Hunter, A (2006). "Kava (Piper methysticum) back in circulation". Australian Centre for Complementary Medicine 25 (7): 529. 
  7. ^ Teschke, Rolf; Qiu SX; Lebot V (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. 
  8. ^ Garrett, KM et al. (2003). "Extracts of kava (Piper methysticum) induce acute anxiolytic-like behavioral changes in mice.". Psychopharmacology 170 (1): 389–396. doi:10.1007/s00213-003-1520-0. PMID 12845414. 
  9. ^ Cairney, S et al. (2003). "Saccade and cognitive function in chronic kava users". Neuropsychopharmacology 28 (2): 389–396. doi:10.1038/sj.npp.1300052. PMID 12589393. 
  10. ^ Uebelhack R, Franke L, Schewe HJ (September 1998). "Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava)". Pharmacopsychiatry 31 (5): 187–92. doi:10.1055/s-2007-979325. PMID 9832350. 
  11. ^ Baum SS, Hill R, Rommelspacher H (October 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. 
  12. ^ Seitz U, Schüle A, Gleitz J (December 1997). "[3H]-monoamine uptake inhibition properties of kava pyrones". Planta Med. 63 (6): 548–9. doi:10.1055/s-2006-957761. PMID 9434608. 
  13. ^ Ligresti, A.; Villano, R.; Allarà, M.; Ujváry, I. N.; Di Marzo, V. (2012). "Kavalactones and the endocannabinoid system: The plant-derived yangonin is a novel CB1 receptor ligand". Pharmacological Research 66 (2): 163–169. doi:10.1016/j.phrs.2012.04.003. PMID 22525682.  edit
  14. ^ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 803–804.
  15. ^ Kevin Cassell (2005). "Fiji: A Visitor's Guide". Retrieved 25 April 2007. 
  16. ^ Viorica, Lopez-Aila. "Supercritical fluid extraction of kava lactones from Piper methysticum (kava) herb". Hüthig GmbH. Retrieved 5 September 2012. 
  17. ^ 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?]
  18. ^ McDonald, D (2000). "Kava in the Pacific Islands: a contemporary drug of abuse?". DRUG ALCOHOL REV 19: 217–227. 
  19. ^ Pittler MH, Ernst E. Efficacy of kava extract for treating anxiety: systematic review and meta-analysis. J Clin Psychopharmacol 2000;20:84
  20. ^ Volz HP, Kieser M. Kava-kava extract WS 1490 versus placebo in anxiety disorders--a randomized placebo-controlled 25-week outpatient trial. Pharmacopsychiatry 1997;30:1-5.
  21. ^ Gastpar M, Klimm HD. Treatment of anxiety, tension and restlessness states with Kava special extract WS 1490 in general practice: a randomized placebo-controlled double-blind multicenter trial.. Phytomedicine. 2003: 10(8):631-9.
  22. ^ Malsch U, Kieser M. Efficacy of kava-kava in the treatment of non-psychotic anxiety, following pretreatment with benzodiazepines. Psychopharmacology (berl). (2001)
  23. ^ 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. 
  24. ^ Center for Food Safety and 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. 
  25. ^ Lechtenberg, M.; Quandt, B.; Schmidt, M.; Nahrstedt, A. (2008). "Is the alkaloid pipermethystine connected with the claimed liver toxicity of Kava products?". Die Pharmazie 63 (1): 71–74. PMID 18271308. 
  26. ^ a b 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. 
  27. ^ Teschke R., Qiu S.X., Lebot V. "Herbal hepatotoxicity by kava: Update on pipermethystine, flavokavain B, and mold hepatotoxins as primarily assumed culprits" [Article in Press] Digestive and Liver Disease 2011
  28. ^ Clouatre, D. L. (2004). "Kava kava: Examining new reports of toxicity". Toxicology Letters 150 (1): 85–96. doi:10.1016/j.toxlet.2003.07.005. PMID 15068826. 
  29. ^ University of Maryland Medical Center (2011). "Kava Kava". Retrieved 18 December 2011. 
  30. ^ 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
  31. ^ Cairney, S., Maruff, P., Clough, A. R., Collie, A., Currie, J., and Currie, B. J. Saccade and cognitive impairment associated with kava intoxication. Hum.Psychopharmacol. 2003;18(7):525-533.
  32. ^ Spinella, M. The importance of pharmacological synergy in psychoactive herbal medicines. Altern Med Rev 2002;7(2):130-137
  33. ^ Spinella, M. The importance of pharmacological synergy in psychoactive herbal medicines. Altern Med Rev 2002;7(2):130-137
  34. ^ Lees AJ. The on-off phenomenon. J Neurol Neurosurg Psychiatr. 1989;Suppl:29-37.
  35. ^ Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: a systematic review. Drugs. 2001;61(15):2163-75.
  36. ^ Clough A (2001). "Enough! or too much. What is 'excessive' kava use in Arnhem Land?". Drug Alcohol Rev 22 (1): 43–51. doi:10.1080/0959523021000059820. PMID 12745358. 
  37. ^ Mathews JD, Riley MD, Fejo L, et al. (June 1988). "Effects of the heavy usage of kava on physical health: summary of a pilot survey in an aboriginal community". Med. J. Aust. 148 (11): 548–55. PMID 3374423. 
  38. ^ Kava R (March 2001). "The adverse effects of kava". Pac Health Dialog 8 (1): 115–8. PMID 12017812. 
  39. ^ 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 3269575. PMID 21801196. 
  40. ^ a b "Europe Explains Its Stand on Kava from the Pacific". Radio Australia. March 2012. Retrieved 10 October 2013. 
  41. ^ 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. 
  42. ^ "Fiji takes kava ban fight to WTO". The World Trade Review. August 2005. Retrieved 26 October 2013. 
  43. ^ Bowman, Chakriya. "The Pacific Island Nations: Towards Shared Representation". WTO. Retrieved 26 October 2013. 
  44. ^ "The Medicines for Human Use (Kava-kava) (Prohibition) Order 2002". Retrieved 26 October 2013. 
  45. ^ "Marketed Health Products Directorate Heath Products and Foods Branch". Canadian Adverse Reaction Newsletter (Health Canada) 12 (4). 2002. 
  46. ^ "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. 
  47. ^ "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.
  48. ^ "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. 
  49. ^ "Kava in the Northern Territory". Northern Territory Police. Retrieved 26 October 2013. 
  50. ^ "Kava fact sheet". Therapeutic Goods Administration, Government of Australia. April 2005. Retrieved 10 July 2006.  (Download PDF 44KB).
  51. ^ Teschke R, Sarris J, Glass X, Schulze J (March 2011). "Kava, the anxiolytic herb: back to basics to prevent liver injury?". Br J Clin Pharmacol 71 (3): 445–8. doi:10.1111/j.1365-2125.2010.03775.x. PMC 3045554. PMID 21284704. This raises the question as to whether noble cultivars may be better and safer regarding hepatotoxic effects than the medicinal kava varieties. 
  52. ^ a b c Teschke, Rolf (March 2011). "Kava and the Risk of Liver Toxicity: Past, Current, and Future". AHPA Report. Retrieved 26 December 2013. 

Literature[edit]

  • Lindstrom, Lamont; Lebot, Vincent; Merlin, Mark David (1992). Kava: The Pacific Elixir – The Definitive Guide to its Ethnobotany, History and Chemistry. New Haven, Conn: Yale University Press. ISBN 0-300-05213-8. OCLC 231506209 25708300. 

External links[edit]