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The [[root]] of the plant is used to produce a drink with [[sedative]], [[anesthetic]], and [[euphoria]]nt properties. Its active ingredients are called [[kavalactone]]s.<ref name="wang">{{cite journal|pmc=4325077|year=2013|last1=Wang|first1=J|title=Kavalactone content and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of kavalactones using different solvents|journal=Journal of Food Science and Technology|volume=52|issue=2|pages=1164–1169|last2=Qu|first2=W|last3=Bittenbender|first3=H. C|last4=Li|first4=Q. X|doi=10.1007/s13197-013-1047-2|pmid=25694734}}</ref> A 2003 [[systematic review]] concluded it had a small effect for treating short-term [[Anxiety disorder|anxiety]].<ref name="pittler">{{Cite journal|author=Pittler MH, Ernst E |title=Kava extract for treating anxiety |journal=Cochrane Database of Systematic Reviews |issue=1 |pages=CD003383 |year=2003 |volume=2003 |pmid=12535473 |doi=10.1002/14651858.CD003383 |url=http://www.cochrane.org/CD003383/DEPRESSN_kava-extract-for-treating-anxiety|editor1-last=Pittler|editor1-first=Max H|pmc=6999799 }}</ref> Moderate consumption of kava in its traditional form, i.e., as a water-based suspension of kava roots, has been deemed to present an "acceptably low level of health risk" by the [[World Health Organization]].<ref name="fao-who">{{cite web|title=Kava: a review of the safety of traditional and recreational beverage consumption|date=2016|publisher=Food and Agriculture Organization of the United Nations and World Health Organization, Rome, Italy|url=http://www.fao.org/3/a-i5770e.pdf}}</ref> However, consumption of kava [[extract]]s produced with [[organic solvents]], or excessive amounts of poor-quality kava products, may be linked to an increased risk of adverse health outcomes, including potential [[Hepatotoxicity|liver injury]].<ref name="fao-who" /><ref name="Kuchta 1647–1653">{{Cite journal|last1=Kuchta|first1=Kenny|last2=Schmidt|first2=Mathias|last3=Nahrstedt|first3=Adolf|date=2015-12-01|title=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|journal=Planta Medica|volume=81|issue=18|pages=1647–1653|doi=10.1055/s-0035-1558295|issn=1439-0221|pmid=26695707|s2cid=23708406 }}</ref><ref name=":0">{{cite journal|pmid=25464054|year=2015|last1=Showman|first1=A. F.|title=Contemporary Pacific and Western perspectives on 'awa (Piper methysticum) toxicology|journal=Fitoterapia|volume=100|pages=56–67|last2=Baker|first2=J. D.|last3=Linares|first3=C|last4=Naeole|first4=C. K.|last5=Borris|first5=R|last6=Johnston|first6=E|last7=Konanui|first7=J|last8=Turner|first8=H|doi=10.1016/j.fitote.2014.11.012}}</ref> {{TOC limit|3}} ==History and names== {{See also|Domesticated plants and animals of Austronesia}} Kava is conspecific with ''Piper wichmannii,'' indicating Kava was domesticated from ''Piper wichmannii'' (syn. ''Piper subbullatum'').<ref>{{cite journal |last1=Applequist |first1=Wendy L. |last2=Lebot |first2=Vincent |title=Validation of Piper Methysticum var. wichmannii (Piperaceae) |journal=Novon: A Journal for Botanical Nomenclature |date=25 April 2006 |volume=16 |issue=1 |pages=3–4 |doi=10.3417/1055-3177(2006)16[3:VOPMVW]2.0.CO;2|s2cid=86552278 |url=https://www.biodiversitylibrary.org/part/121786 }}</ref><ref name="Ross2008Lexicon">{{cite book|first1=Malcolm|last1=Ross|editor1-first=Malcolm|editor1-last=Ross|editor2-first=Andrew|editor2-last=Pawley|editor3-first=Meredith|editor3-last=Osmond|title =The lexicon of Proto Oceanic: The culture and environment of ancestral Oceanic society|chapter =Other cultivated plants|publisher =Pacific Linguistics|volume=3 |year =2008|pages=389–426|isbn =978-0-85883-589-4|chapter-url =https://openresearch-repository.anu.edu.au/handle/1885/106908}}</ref> Kava originated in Fiji and spread through the pacific by [[Polynesian navigation]]. It was spread by the [[Austronesian peoples|Austronesian]] [[Lapita culture]] after contact eastward into the rest of [[Polynesia]]. It is endemic to [[Oceania]] and is not found in other Austronesian groups. Kava reached [[Hawaii]], but it is absent in [[New Zealand]], where it cannot grow.<ref name="Ross2008Lexicon"/><ref name="Lebot1989">{{cite journal |last1=Lebot |first1=V. |last2=Lèvesque |first2=J. |title=The Origin and Distribution of Kava (''Piper methysticum'' Forst. F., Piperaceae): A Phytochemical Approach |journal=Allertonia |date=1989 |volume=5 |issue=2 |pages=223–281}}</ref><ref name="temarareoKava">{{cite web|url=http://www.temarareo.org/PPN-Kava.html|title=*Kava ~ *Kavakava |work=Te Mära Reo: The Language Garden|publisher=Benton Family Trust|access-date=15 January 2019}}</ref> Consumption of kava is also believed to be the reason why [[betel nut chewing]], ubiquitous elsewhere, was lost for Austronesians in Oceania.<ref name="blusttrusell">{{cite journal |last1=Blust |first1=Robert |last2=Trussel |first2=Stephen |title=The Austronesian Comparative Dictionary: A Work in Progress |journal=Oceanic Linguistics |date=2013 |volume=52 |issue=2 |pages=493–523 |doi=10.1353/ol.2013.0016 |s2cid=146739541 |url=https://www.researchgate.net/publication/265931196}}</ref> According to Lynch (2002), the reconstructed [[Proto-Polynesian language|Proto-Polynesian]] term for the plant, ''*kava'', was derived from the [[Proto-Oceanic language|Proto-Oceanic]] term ''*kawaR'' in the sense of a "bitter root" or "potent root [used as fish poison]". It may have been related to reconstructed ''*wakaR'' (in Proto-Oceanic and [[Proto-Malayo-Polynesian language|Proto-Malayo-Polynesian]]) via [[Metathesis (linguistics)|metathesis]]. It originally referred to ''[[Zingiber zerumbet]]'', used to make a similar mildly psychoactive bitter drink in Austronesian rituals. Cognates for ''*kava'' include [[Pohnpeian language|Pohnpeian]] ''sa-kau''; [[Tongan language|Tongan]], [[Niue language|Niue]], [[Rapa Nui language|Rapa Nui]], [[Tuamotuan language|Tuamotuan]], and [[Rarotongan language|Rarotongan]] ''kava''; [[Samoan language|Samoan]], [[Tahitian language|Tahitian]], and [[Marquesan language|Marquesan]] ''{{okina}}ava''; and [[Hawaiian language|Hawaiian]] ''{{okina}}awa''. In some languages, most notably [[Māori language|Māori]] ''kawa'', the cognates have come to mean "bitter", "sour", or "acrid" to the taste.<ref name="Ross2008Lexicon"/><ref name="Lynch2002">{{cite journal |last1=Lynch |first1=John |title=Potent Roots and the Origin of kava |journal=Oceanic Linguistics |date=2002 |volume=41 |issue=2 |pages=493–513 |doi=10.1353/ol.2002.0010|s2cid=145424062 }}</ref><ref name="Heathcote2012">{{cite journal |last1=Heathcote |first1=Gary M. |last2=Diego |first2=Vincent P. |last3=Ishida |first3=Hajime |last4=Sava |first4=Vincent J. |title=An osteobiography of a remarkable protohistoric Chamorro man from Taga, Tinian |journal=Micronesica |date=2012 |volume=43 |issue=2 |pages=131–213}}</ref><ref name="McLean2014">{{cite book|first1=Mervyn|last1=McLean|title =Music, Lapita, and the Problem of Polynesian Origins|publisher = Polynesian Origins|year =2014|isbn =978-0-473-28873-0|url =http://polynesianorigins.org/chapter-11-food-plants/}}</ref> In the [[Cook Islands]], the reduplicated forms of ''kawakawa'' or ''kavakava'' are also applied to the unrelated members of the genus ''[[Pittosporum]]''. In other languages, such as [[Futunan language|Futunan]], compound terms like ''kavakava atua'' refer to other species belonging to the genus ''[[Piper (genus)|Piper]]''. The [[reduplication]] of the base form is indicative of falsehood or likeness, in the sense of "false kava".<ref name="temarareoKawakawa">{{cite web|url=http://www.temarareo.org/TMR-Kawa.html|title=Kawa ~ Kawakawa |work=Te Mära Reo: The Language Garden|publisher=Benton Family Trust|access-date=15 January 2019}}</ref><ref name="temarareoKava"/> In [[New Zealand]], it was applied to the kawakawa (''[[Piper excelsum]]''), which is [[endemic]] to New Zealand and nearby [[Norfolk Island]] and [[Lord Howe Island]]. It was exploited by the Māori based on previous knowledge of the kava, as the latter could not survive in the colder climates of New Zealand. The [[Māori language|Māori]] name for the plant, ''kawakawa'', is derived from the same [[etymon]] as kava, but [[reduplicated]]. It is a sacred tree among the [[Māori people]]. It is seen as a symbol of death, corresponding to the rangiora (''[[Brachyglottis repanda]]''), which is the symbol of life. However, ''kawakawa'' has no psychoactive properties. Its connection to kava is linked to its similarity in appearance and bitter taste.<ref name="temarareoKawakawa"/> == Characteristics == Kava was historically grown only in the [[Hawaiian Islands|Pacific islands of Hawaii]], [[Federated States of Micronesia]], [[Vanuatu]], [[Fiji]], the [[Samoa]]s, and [[Tonga]]. An [[inventory]] of ''P. methysticum'' distribution showed it was cultivated on numerous islands of [[Micronesia]], [[Melanesia]], [[Polynesia]], and [[Hawaii]], whereas specimens of ''P. wichmannii'' were all from [[Papua New Guinea]], the [[Solomon Islands]], and Vanuatu.<ref>{{cite journal|author1=Vincent Lebot|author2=Patricia Siméoni|title=Is the Quality of Kava (Piper methysticum Forst. f.) Responsible for Different Geographical Patterns?|journal=Ethnobotany Research & Applications|date=2004|volume=2|pages=19–28|url=https://scholarspace.manoa.hawaii.edu/bitstream/10125/135/4/I1547-3465-02-019.pdf|doi=10.17348/era.2.0.19-28|doi-access=free}}</ref> Traditionally, plants are harvested around four years of age, as older plants have higher concentrations of kavalactones. After reaching about {{convert|2|m|ft}} in height, plants grow a wider stalk and additional stalks, but not much taller. The roots can reach a depth of {{convert|60|cm|ft}}. === Cultivars === [[File:John LaFarge - Young Girls Preparing Kava Outside of the Hut Whose Posts Are Decorated wih Flowers.jpg|thumb|Painting showing women preparing kava by [[John La Farge]] ({{Circa|1891}}).]] Kava consists of sterile cultivars cloned from its wild ancestor, ''Piper wichmanii''.<ref name=:1/> 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 its psychoactive properties.<ref name=:1/> ==== Noble and non-noble kava ==== 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'').<ref name=:1/><ref name="Teschke 2503–2516">{{Cite journal|last1=Teschke|first1=Rolf|last2=Lebot|first2=Vincent|date=2011-10-01|title=Proposal for a Kava Quality Standardization Code|journal=Food and Chemical Toxicology|volume=49|issue=10|pages=2503–2516|doi=10.1016/j.fct.2011.06.075|pmid=21756963}}</ref> Traditionally, only noble kavas have been used for regular consumption, due to their more favourable composition of kavalactones and other compounds that produce more pleasant effects and have lower potential for causing negative side effects, such as nausea, or "kava hangover".<ref name=:1/><ref name="Kuchta 1647–1653"/> The perceived benefits of noble cultivars explain why 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 originated.<ref name=":1" /> 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 products in Europe.<ref name="Kuchta 1647–1653"/> 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.<ref>{{Cite web|url=http://www.fijitimes.com/story.aspx?id=262207|title=Drink the right mix - Fiji Times Online|website=www.fijitimes.com|access-date=2016-05-29|archive-url=https://web.archive.org/web/20160630143526/http://www.fijitimes.com/story.aspx?id=262207|archive-date=30 June 2016|url-status=dead}}</ref> The tudei cultivars may be 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. The concerns about the adverse effects of non-noble varieties, produced by their undesirable composition of kavalactones and high concentrations of potentially harmful compounds ([[flavokavain]]s, which are not present in any significant concentration in the noble varieties), have led to legislation prohibiting exports from countries such as Vanuatu.<ref name="Kuchta 1647–1653"/> Likewise, efforts have been made to educate non-traditional customers about the difference between noble and non-noble varieties and that non-noble varieties do not offer the same results as noble cultivars.<ref>{{Cite web|url=http://www.radionz.co.nz/international/pacific-news/289424/vanuatu-hopes-for-kava-export-growth|title=Vanuatu hopes for kava export growth|date=2015-11-11|website=Radio New Zealand|access-date=2016-05-29}}</ref><ref>{{Cite web|url=http://www.radionz.co.nz/international/programmes/datelinepacific/audio/201778477/vanuatu-kava-cleared-for-european-market|title=Vanuatu kava cleared for European market|date=2015-11-12|website=Radio New Zealand|access-date=2016-05-29}}</ref> In recent years, government regulatory bodies and non-profit NGOs have been set up with the declared aim of monitoring kava quality; producing regular reports; certifying vendors selling proper, noble kava; and warning customers against products that may contain tudei varieties.<ref name="teschke2011">{{Cite journal|last1=Teschke|first1=Rolf|last2=Sarris|first2=Jerome|last3=Lebot|first3=Vincent|date=2011-01-15|title=Kava hepatotoxicity solution: A six-point plan for new kava standardization|journal=Phytomedicine|volume=18|issue=2–3|pages=96–103|doi=10.1016/j.phymed.2010.10.002|pmid=21112196|url=http://agritrop.cirad.fr/568311/}}</ref> ==== Growing regions ==== In Vanuatu, exportation of kava is strictly regulated. Only cultivars classified as noble are allowed to be exported. Only the most desirable cultivars for everyday drinking are classified as noble 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 cultivars are "Borogu" or "Borongoru" from [[Pentecost Island]], "Melomelo" from [[Aoba Island]] (called ''Sese'' in the north [[Pentecost Island]]), and "Palarasul" kava from [[Espiritu Santo]]. In Vanuatu, Tudei ("two-day") 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 cultivars of kava ({{langx|haw|ʻawa}}). Some of the most popular cultivars are ''Mahakea'', ''Moʻi'', ''Hiwa'', and ''Nene''. The ''[[Aliʻi]]'' (kings) of [[Ancient Hawaii|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": {{Blockquote|<poem> 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 god!<ref name=JohnstonRogers/></poem>}} Winter describes a [[hula]] prayer for inspiration that 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.<ref name=JohnstonRogers>{{Cite book |url=http://www.awadevelopment.org/wp-content/uploads/2014/01/awabook-web-part-1-of-2.pdf |title=Hawaiian ʻawa: views of an ethnobotanical treasure |last1=Johnston |first1=Ed |last2=Rogers |first2=Helen |last3=Association for Hawaiian ʻAwa|date=2006-01-01 |publisher=Association for Hawaiian ʻAwa |location=Hilo, Hawaii|page=34|language=en|oclc = 77501873}}</ref> More recently, specialized kava varieties have been introduced to [[South Florida]] which have been acclimated and adapted to grow well in South Florida's unique soil and climate and have significant resistance to pest and disease pressures. As of 2024, cultivation of these varieties is limited to a small number of commercial farms and backyard growers. ==== Relationship with kawakawa ==== [[File:Piper excelsum excelsum G.Forst. (AM AK347570-2).jpg|thumb|left|Kawakawa (''[[Piper excelsum]]'') plant may have been named by early [[Polynesian culture|Polynesian voyagers]] to [[New Zealand]] due to its similarities to kava.]] The Kawakawa (''[[Piper excelsum]]'') plant, known also as "Māori kava", may be confused with kava. While the two plants look similar and have similar names, they are different, but related, species. Kawakawa is a small tree endemic to New Zealand, having importance to traditional medicine and [[Māori culture]]. 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."<ref>{{Cite web|url=https://kavasociety.nz/blog/2018/2/5/kava-vs-kawakawa-and-the-maori-memories-of-kava|title=Kava vs Kawakawa {{!}} Kava use in New Zealand {{!}} Maori Memories of Kava|website=kavasociety.nz|access-date=2016-07-02}}</ref> Further, "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".<ref name=":1" /> Kawakawa is commonly used in Maori traditional medicine for the treatment of skin infections, wounds, and cuts, and (when prepared as a tea) for stomach upsets and other minor illnesses.<ref>{{Cite web|url=http://maoriplantuse.landcareresearch.co.nz/WebForms/PeoplePlantsDetails.aspx?firstcome=firstcome&PKey=DF6C4669-4A57-4473-8B3F-CE49593273A2|title=Māori Plant Use Database Plant Use Details of Macropiper excelsum|website=maoriplantuse.landcareresearch.co.nz|access-date=2016-07-02|url-status=dead|archive-url=https://web.archive.org/web/20160811031207/http://maoriplantuse.landcareresearch.co.nz/WebForms/PeoplePlantsDetails.aspx?firstcome=firstcome&PKey=DF6C4669-4A57-4473-8B3F-CE49593273A2|archive-date=11 August 2016}}</ref> === Composition === Fresh kava root contains on average 80% [[water]]. Dried root contains approximately 43% [[starch]], 20% [[dietary fibre|dietary fiber]], 15% [[kavalactone]]s,<ref name=wang/> 12% water, 3.2% [[sugar]]s, 3.6% [[protein (nutrient)|protein]], and 3.2% [[micronutrient|minerals]]. In general, kavalactone content is greatest in the roots and decreases higher up the plant into the stems and leaves.<ref name=wang/> Relative concentrations of 15%, 10%, and 5% have been observed in the root, stump, and basal stems, respectively.<ref name=Lebot1992/> The relative content of kavalactones depends not only on plant segment but also on the kava plant variety, plant maturity, geographic location, and time of harvest.<ref name=wang/> The kavalactones present are [[kavain]], [[demethoxyyangonin]], and [[yangonin]], which are higher in the roots than in the stems and leaves, with [[dihydrokavain]], [[methysticin]], and [[dihydromethysticin]] also present.<ref name=wang/> 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 {{convert|50|kg|lb|abbr=on}} 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 {{convert|1.5|to|5|in|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== ===Constituents=== [[File:Kavalactone General Structure.PNG|frame|right|The general structure of the [[kavalactone]]s, without the R<sub>1</sub>-R<sub>2</sub> -O-CH<sub>2</sub>-O- bridge and with all possible C=C double bonds shown.]] A total of 18 different [[kavalactone]]s (or kavapyrones) have been identified to date, at least 15 of which are active.<ref name="pmid21073405">{{cite journal | vauthors = Sarris J, LaPorte E, Schweitzer I | title = Kava: a comprehensive review of efficacy, safety, and psychopharmacology | journal = Aust N Z J Psychiatry | volume = 45 | issue = 1 | pages = 27–35 | year = 2011 | pmid = 21073405 | doi = 10.3109/00048674.2010.522554 | s2cid = 42935399 }}</ref> 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.<ref name="pmid21073405" /> Some minor constituents, including three [[chalcone]]s — [[flavokavain A]], [[flavokavain B]], and [[flavokavain C]] — have also been identified,<ref name="pmid21073405" /> as well as a toxic alkaloid (not present in the consumable parts of the plant<ref>{{Cite journal|last1=Bunchorntavakul|first1=C.|last2=Reddy|first2=K. R.|date=2013-01-01|title=Review article: herbal and dietary supplement hepatotoxicity|journal=Alimentary Pharmacology & Therapeutics|language=en|volume=37|issue=1|pages=3–17|doi=10.1111/apt.12109|pmid=23121117|s2cid=6949220|issn=1365-2036|doi-access=free}}</ref>), [[pipermethystine]].<ref name="pmid21506562">{{cite journal | vauthors = Olsen LR, Grillo MP, Skonberg C | title = Constituents in kava extracts potentially involved in hepatotoxicity: a review | journal = Chem. Res. Toxicol. | volume = 24 | issue = 7 | pages = 992–1002 | year = 2011 | pmid = 21506562 | doi = 10.1021/tx100412m }}</ref> [[Alkaloid]]s are present in the roots and leaves.<ref name="drugs">{{cite web|url=https://www.drugs.com/npp/kava.html|title=Kava|date=3 January 2018|publisher=Drugs.com|access-date=12 January 2018}}</ref> ===Pharmacodynamics=== The following [[pharmacology|pharmacological]] actions have been reported for kava and/or its major active constituents:<ref name="pmid12383029">{{cite journal | vauthors = Singh YN, Singh NN | title = Therapeutic potential of kava in the treatment of anxiety disorders | journal = CNS Drugs | volume = 16 | issue = 11 | pages = 731–43 | year = 2002 | pmid = 12383029 | doi = 10.2165/00023210-200216110-00002| s2cid = 34322458 }}</ref> * Potentiation of [[GABAA receptor|GABA<sub>A</sub> receptor]] activity (by kavain, dihydrokavain, methysticin, dihydromethysticin, and yangonin). * [[Reuptake inhibitor|Inhibition]] of the [[reuptake]] of [[norepinephrine]] (by kavain and methysticin) and possibly also of [[dopamine]] (by kavain and desmethoxyyangonin). * Binding to the [[CB1 receptor|CB<sub>1</sub> receptor]] (by yangonin).<ref name="pmid22525682">{{cite journal | vauthors = Ligresti A, Villano R, Allarà M, Ujváry I, Di Marzo V | title = Kavalactones and the endocannabinoid system: the plant-derived yangonin is a novel CB₁ receptor ligand | journal = Pharmacol. Res. | volume = 66 | issue = 2 | pages = 163–9 | year = 2012 | pmid = 22525682 | doi = 10.1016/j.phrs.2012.04.003 }}</ref> * Inhibition of [[voltage-gated sodium channel]]s and [[voltage-gated calcium channel]]s (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|GABA<sub>A</sub>]] receptor, the [[D2 receptor|D<sub>2</sub> receptor]], the [[μ-opioid receptor|μ-]] and [[δ-opioid receptor]]s, and the [[H1 receptor|H<sub>1</sub>]] and [[H2 receptor|H<sub>2</sub> receptors]].<ref name="pmid11458444">{{cite journal | vauthors = Dinh LD, Simmen U, Bueter KB, Bueter B, Lundstrom K, Schaffner W | title = Interaction of various Piper methysticum cultivars with CNS receptors in vitro | journal = Planta Med. | volume = 67 | issue = 4 | pages = 306–11 | year = 2001 | pmid = 11458444 | doi = 10.1055/s-2001-14334 | s2cid = 260281694 }}</ref><ref name="DasguptaHammett-Stabler2011">{{cite book|author1=Amitava Dasgupta|author2=Catherine A. Hammett-Stabler|title=Herbal Supplements: Efficacy, Toxicity, Interactions with Western Drugs, and Effects on Clinical Laboratory Tests|url=https://books.google.com/books?id=oNrIvxlFG1sC&pg=PA57|date=2011|publisher=John Wiley & Sons|isbn=978-0-470-92275-0|page=57}}</ref> Weak interaction with the [[5-HT6 receptor|5-HT<sub>6</sub>]] and [[5-HT7 receptor|5-HT<sub>7</sub> receptors]] and the [[benzodiazepine site]] of the GABA<sub>A</sub> receptor was also observed.<ref name="pmid11458444" /> Potentiation of GABA<sub>A</sub> 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.<ref name="pmid9829291">{{cite journal | vauthors = Baum SS, Hill R, Rommelspacher H | title = Effect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of rats | journal = Prog. Neuropsychopharmacol. Biol. Psychiatry | volume = 22 | issue = 7 | pages = 1105–20 | year = 1998 | pmid = 9829291 | doi = 10.1016/s0278-5846(98)00062-1| s2cid = 24377397 }}</ref> However, failure of the GABA<sub>A</sub> 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.<ref name="pmid12845414">{{cite journal | vauthors = Garrett KM, Basmadjian G, Khan IA, Schaneberg BT, Seale TW | title = Extracts of kava (Piper methysticum) induce acute anxiolytic-like behavioral changes in mice | journal = Psychopharmacology | volume = 170 | issue = 1 | pages = 33–41 | year = 2003 | pmid = 12845414 | doi = 10.1007/s00213-003-1520-0 | s2cid = 10805207 }}</ref> Heavy, long-term use of kava has been found to be free of association with reduced ability in [[saccade]] and [[cognitive test]]s, but has been associated with elevated liver enzymes.<ref name="pmid12589393">{{cite journal | vauthors = Cairney S, Clough AR, Maruff P, Collie A, Currie BJ, Currie J | title = Saccade and cognitive function in chronic kava users | journal = Neuropsychopharmacology | volume = 28 | issue = 2 | pages = 389–96 | year = 2003 | pmid = 12589393 | doi = 10.1038/sj.npp.1300052 | doi-access = free }}</ref> ===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.<ref>R. Baselt, ''Disposition of Toxic Drugs and Chemicals in Man'', 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 803–804.</ref> == Preparations== [[File:Kava fiji.jpg|thumb|right|Kava root drying in [[Lovoni]] village, [[Ovalau (Fiji)|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 pestle|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. 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 that the [[psychoactive]]s 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). [[File:Fijian kava ceremony.jpg|thumb|right|upright=1.2|Fijian kava ceremony being performed for tourists (2015). Traditionally, kava grog is drunk from the shorn half-shell of a coconut, called a ''bilo''.<ref>{{cite web|title=Fiji -> In depth -> Food and Drink|url=http://www.frommers.com/destinations/fiji/252193#sthash.jQFrK6a6.dpbs|website=www.frommers.com|publisher=Frommers|access-date=7 August 2014}}</ref>]] {{anchor|Grog}}[[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''. [[File:Kava vanuatu.jpg|thumb|right|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]],<ref>{{cite journal|last=Viorica|first=Lopez-Aila|title=Supercritical fluid extraction of kava lactones from Piper methysticum (kava) herb|doi=10.1002/jhrc.1240201007|volume=20|issue=10|year=1997|journal=Journal of High Resolution Chromatography|pages=555–559}}</ref> [[acetone]], and [[ethanol]] to produce pills standardized with between 30% and 90% kavalactones.<ref name=teschke2011/> ==== Concerns ==== Numerous scholars<ref name="teschke16" /> and regulatory bodies<ref name=":2">{{Cite journal|date=2016-05-25|title=Kava: A Human Health Risk Assessment|url=http://www.foodstandards.govt.nz/publications/documents/30_Kava1.pdf|journal=Technical Report Series No 30|access-date=25 May 2016|archive-date=11 February 2016|archive-url=https://web.archive.org/web/20160211001359/http://www.foodstandards.govt.nz/publications/documents/30_Kava1.pdf|url-status=dead}}</ref><ref name=":7" /> 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 are consequently largely absent from kava prepared with water.<ref name=":5">{{Cite journal|last1=Kraft|first1=M|last2=Spahn|first2=T W|last3=Menzel|first3=J|last4=Senninger|first4=N|last5=Dietl|first5=K.-H|last6=Herbst|first6=H|last7=Domschke|first7=W|last8=Lerch|first8=M M|date=2001|title=Fulminantes Leberversagen nach Einnahme des pflanzlichen Antidepressivums Kava-Kava|journal=Deutsche Medizinische Wochenschrift|language=en|volume=126|issue=36|pages=970–972|doi=10.1055/s-2001-16966|pmid=11544547|s2cid=260067545|issn=0012-0472}}</ref> 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.<ref>{{Cite journal|last1=Zhou|first1=Ping|last2=Gross|first2=Shimon|last3=Liu|first3=Ji-Hua|last4=Yu|first4=Bo-Yang|last5=Feng|first5=Ling-Ling|last6=Nolta|first6=Jan|last7=Sharma|first7=Vijay|last8=Piwnica-Worms|first8=David|last9=Qiu|first9=Samuel X.|date=December 2010|title=Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive oxidative stress through modulation of IKK/NF-κB and MAPK signaling pathways|journal=The FASEB Journal|volume=24|issue=12|pages=4722–4732|doi=10.1096/fj.10-163311|doi-access=free |issn=0892-6638|pmc=2992378|pmid=20696856}}</ref><ref name="Kuchta 1647–1653" /> 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".<ref name=":5" /> 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.<ref name=":6">{{Cite journal|date=2003-10-01|title=Kava lactones and the kava-kava controversy|journal=Phytochemistry|language=en|volume=64|issue=3|pages=673–679|doi=10.1016/S0031-9422(03)00381-9|issn=0031-9422|last1=Whitton|first1=Peter A|last2=Lau|first2=Andrew|last3=Salisbury|first3=Alicia|last4=Whitehouse|first4=Julie|last5=Evans|first5=Christine S|pmid=13679089|bibcode=2003PChem..64..673W }}</ref> 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".<ref name=":6" /> 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 that contain the hepatotoxic alkaloid [[Pipermethystine]], 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".<ref name=":7">{{Cite book|url=https://books.google.com/books?id=2KXWY6kPESUC&q=%22products+should+be+developed+from+water-based+suspensions+of+kava%22+WHO&pg=PA25|title=Assessment of the Risk of Hepatotoxicity with Kava Products|last=Organization|first=World Health|date=2007|publisher=WHO Regional Office Europe|isbn=978-92-4-159526-1|language=en}}</ref> The government of Australia prohibits the sales of such kavalactone extracts, and only permits the sale of kava products in their natural form or produced with cold water.<ref>{{Cite web|url=https://www.legislation.gov.au/Details/F2011C00587|title=Australia New Zealand Food Standards Code - Standard 2.6.3 - Kava|last=Health|website=www.legislation.gov.au|date=11 July 2011 |language=en|access-date=2018-09-02}}</ref> === Kava culture === [[File:Kava.JPG|thumb|A sign showing a "Kava licence area" at [[Yirrkala]], in the [[Northern Territory]] of [[Australia]].]] {{Main|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, or religious functions, usually involving a ritual presentation of the bundled roots as a ''sevusevu'' (gift) and drinking of the ''yaqona'' itself.<ref>{{cite book |last1=Biturogoiwasa |first1=Solomoni |first2=Anthony R. |last2=Walker |year=2001 |title=My Village, My World: Everyday Life in Nadoria, Fiji |location=Suva, Fiji |publisher=Institute of Pacific Studies, University of the South Pacific |pages=17–20 |isbn=978-982-02-0160-6}}</ref><ref>{{cite journal |last1=Tomlinson |first1=Matt |year=2007 |title=Everything and Its Opposite: Kava Drinking in Fiji |journal=Anthropological Quarterly |volume=80 |issue=4 |pages=1065–81 |doi=10.1353/anq.2007.0054|s2cid=144600224 }}{{synthesis inline|date=June 2013}}</ref> 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.<ref name=":1" /> === Kava bars === {{See also|Nakamal}} With kava's increasing popularity, bars serving the plant in its liquid state are beginning to open up outside of the South Pacific.<ref name="Kuchta 1647–1653" /><ref>{{cite news|url=https://www.nytimes.com/2017/12/22/nyregion/in-brooklyn-a-hare-krishna-reckoning.html|title=In Brooklyn, a Hare Krishna Reckoning|first=Kaya|last=Laterman|date=22 December 2017|access-date=22 December 2017|work=The New York Times}}</ref> 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 (drug)|alcohol]].<ref>{{Cite web|url=http://www.browardpalmbeach.com/news/south-florida-kava-bars-unworried-about-two-day-kava-6452978|title=South Florida Kava Bars Unworried about Two-Day Kava|last=Swanson|first=Jess|date=2014-03-20|access-date=2016-07-28}}</ref> == Effects of consumption == The nature of effects will largely depend on the cultivar of the kava plant and the form of its consumption.<ref name=":3" /> Traditionally, only noble kava cultivars have been consumed, as they are accepted as safe and produce desired effects.<ref name="Lebot 554–560">{{Cite journal|last1=Lebot|first1=V.|last2=Do|first2=T. K. T.|last3=Legendre|first3=L.|date=2014-05-15|title=Detection of flavokavins (A, B, C) in cultivars of kava (Piper methysticum) using high performance thin layer chromatography (HPTLC)|journal=Food Chemistry|volume=151|pages=554–560|doi=10.1016/j.foodchem.2013.11.120|issn=0308-8146|pmid=24423570}}</ref> 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 consumption.<ref name=":3">{{Cite book|url=https://books.google.com/books?id=783SJSFvoucC|title=Kava: Medicine Hunting in Paradise: The Pursuit of a Natural Alternative to Anti-Anxiety Drugs and Sleeping Pills|last=Kilham|first=Christopher|date=1996-06-01|publisher=Inner Traditions / Bear & Co|isbn=978-0-89281-640-8|language=en}}</ref> However, it can be stated that in general, noble kava produces a state of calmness, relaxation, and well-being without diminishing cognitive performance.<ref name=":1" /><ref>{{Cite journal|last1=Cairney|first1=Sheree|last2=Clough|first2=Alan R|last3=Maruff|first3=Paul|last4=Collie|first4=Alex|last5=Currie|first5=Bart J|last6=Currie|first6=Jon|date=2003-02-14|title=Saccade and Cognitive Function in Chronic Kava Users|journal=Neuropsychopharmacology|language=en|volume=28|issue=2|pages=389–396|doi=10.1038/sj.npp.1300052|issn=0893-133X|pmid=12589393|doi-access=free}}</ref><ref>{{Cite journal|last1=LaPorte|first1=E.|last2=Sarris|first2=J.|last3=Stough|first3=C.|last4=Scholey|first4=A.|date=2011-03-01|title=Neurocognitive effects of kava (Piper methysticum): a systematic review|journal=Human Psychopharmacology|volume=26|issue=2|pages=102–111|doi=10.1002/hup.1180|issn=1099-1077|pmid=21437989|s2cid=44657320}}</ref> Kava may produce an initial talkative period, followed by muscle relaxation and eventual sleepiness.<ref>{{Cite journal|last=Baker|first=Jonathan D.|date=2011-06-01|title=Tradition and toxicity: evidential cultures in the kava safety debate|journal=Social Studies of Science|volume=41|issue=3|pages=361–384|issn=0306-3127|pmid=21879526|doi=10.1177/0306312710395341|s2cid=33364504}}</ref> 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".<ref>{{Cite book|url=https://books.google.com/books?id=S2FnAwAAQBAJ&q=%22listening+to+kava%22&pg=PA63|title=Kava: Medicine Hunting in Paradise: The Pursuit of a Natural Alternative to Anti-Anxiety Drugs and Sleeping Pills|last=Kilham|first=Christopher S.|date=1996-06-01|publisher=Inner Traditions / Bear & Co|isbn=978-1-62055-034-2|language=en}}</ref> Despite its psychoactive effects, kava is not considered to be physically addictive and its use does not lead to dependency.<ref>{{Cite journal|last1=Lebot|first1=V.|last2=Lèvesque|first2=J.|date=1989-01-01|title=The origin and distribution of kava (Piper methysticum Forst. F., Piperaceae): A phytochemical approach|journal=Allertonia|volume=5|issue=2|pages=223–281|jstor=23187398}}</ref><ref>{{Cite journal|last1=Sarris|first1=J.|last2=Stough|first2=C.|last3=Teschke|first3=R.|last4=Wahid|first4=Z. T.|last5=Bousman|first5=C. A.|last6=Murray|first6=G.|last7=Savage|first7=K. M.|last8=Mouatt|first8=P.|last9=Ng|first9=C.|date=2013-11-01|title=Kava for the Treatment of Generalized Anxiety Disorder RCT: Analysis of Adverse Reactions, Liver Function, Addiction, and Sexual Effects|journal=Phytotherapy Research|language=en|volume=27|issue=11|pages=1723–1728|doi=10.1002/ptr.4916|pmid=23348842|s2cid=19526418|issn=1099-1573}}</ref> ==Toxicity, safety, and potential side effects== === General observations === There is limited safety information available on the effects of kava consumption, but in general, moderate consumption appears unlikely to be harmful, while there is evidence of harm from heavy use.<ref name="fao-who" /> === Effects on the liver === There is published evidence of the [[hepatotoxicity]] of kava extracts, and concerns about this led to kava being omitted from the [[US Pharmacopeia]].<ref>{{cite journal |vauthors=Brown AC |title=Liver toxicity related to herbs and dietary supplements: Online table of case reports. Part 2 of 5 series |journal=Food Chem Toxicol |volume=107 |issue=Pt A |pages=472–501 |date=September 2017 |pmid=27402097 |doi=10.1016/j.fct.2016.07.001 |type=Review}}</ref> === Other adverse reactions === Adverse reactions may result from the poor quality of kava raw material used in the manufacturing of various kava products.<ref name=teschke2011/><ref name=drugs/><ref name=":4">{{Cite journal|last1=Teschke|first1=Rolf|last2=Schulze|first2=Johannes|title=Risk of Kava Hepatotoxicity and the FDA Consumer Advisory|journal=JAMA|year=2010|volume=304|issue=19|pages=2174–5|doi=10.1001/jama.2010.1689|pmid=21081732|issn=0098-7484}}</ref><ref name="teschke16">{{Cite journal|last1=Teschke|first1=Rolf|last2=Sarris|first2=Jerome|last3=Glass|first3=Xaver|last4=Schulze|first4=Johannes|year=2016|title=Kava, the anxiolytic herb: back to basics to prevent liver injury?|journal=British Journal of Clinical Pharmacology|volume=71|issue=3|pages=445–448|doi=10.1111/j.1365-2125.2010.03775.x|issn=0306-5251|pmc=3045554|pmid=21284704}}</ref> In addition to the potential for hepatotoxicity, adverse reactions from chronic use may include visual impairment, rashes or dermatitis, seizures, weight loss, and malnutrition, but there is only limited high-quality research on these possible effects.<ref name=fao-who/><ref name=drugs/> On the basis of research findings and long history of safe use across the South Pacific, experts recommend using water-based extractions of high-quality peeled rhizome and roots of the noble kava cultivars to minimize the potential of adverse reactions to chronic use.<ref name=fao-who/><ref name=teschke2011/> === Potential interactions === Several adverse interactions with drugs have been documented, both prescription and nonprescription — including, but not limited to, [[anticonvulsants]], alcohol, [[anxiolytics]] (central nervous system depressants such as [[benzodiazepines]]), [[antipsychotics]], [[levodopa]], diuretics, and drugs metabolized by [[Cytochrome P450|CYP450]] in the liver.<ref name=drugs/> 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.<ref name=drugs/><ref>{{cite journal |author1=Cairney S. |author2=Maruff P. |author3=Clough A. R. |author4=Collie A. |author5=Currie J. |author6=Currie B. J. | year = 2003 | title = Saccade and cognitive impairment associated with kava intoxication | journal = Hum. Psychopharmacol. | volume = 18 | issue = 7| pages = 525–533 | doi=10.1002/hup.532|pmid=14533134 |s2cid=21555220 }}</ref> Regarding cognitive function, kava has been shown to have additive cognitive impairments while taken with alcohol when compared to taking placebo and alcohol alone.<ref name="ReferenceA">{{cite journal | author = Spinella M | year = 2002 | title = The importance of pharmacological synergy in psychoactive herbal medicines | journal = Altern Med Rev | volume = 7 | issue = 2| pages = 130–137 | pmid = 11991792 }}</ref> * 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]].<ref name=drugs/><ref name="ReferenceA"/> Kava taken in combination with [[alprazolam]] can cause a semicomatose state in humans.<ref>{{cite journal |last1=Hu |first1=Z |last2=Yang |first2=X |last3=Ho |first3=PC |last4=Chan |first4=SY |last5=Heng |first5=PW |last6=Chan |first6=E |last7=Duan |first7=W |last8=Koh |first8=HL |last9=Zhou |first9=S |date=2005 |title=Herb-drug interactions: a literature review. |journal=Drugs |volume=65 |issue=9 |pages=1239–82 |doi=10.2165/00003495-200565090-00005 |pmid=15916450 |s2cid=46963549}}</ref> * [[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.<ref>{{cite journal|author=Lees AJ|title=The on-off phenomenon|journal=J Neurol Neurosurg Psychiatry|year=1989|volume=Suppl|issue=9|pages=29–37|pmid=1033307|pmc=1033307 | doi=10.1136/jnnp.52.suppl.29|doi-access=free}}</ref> When taking levodopa and kava together, it has been shown that there is an increased frequency of this "on-off phenomenon".<ref>Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: a systematic review" ''Drugs'' 2001;61(15):2163-75.</ref> === Kava dermopathy === Long-term and heavy kava consumption is associated with a reversible [[cutaneous condition|skin condition]] known as "kava dermopathy", or ''kanikani'' (in the [[Fijian language]]), characterised by dry and scaly skin covering the palms of the hands, soles of the feet, and back.<ref name=drugs/><ref>{{Cite journal|last=Ruze|first=P.|date=1990-06-16|title=Originally published as Volume 1, Issue 8703Kava-induced dermopathy: a niacin deficiency?|journal=The Lancet|volume=335|issue=8703|pages=1442–1445|doi=10.1016/0140-6736(90)91458-M|pmid=1972218|s2cid=9737032|doi-access=free}}</ref><ref name="Norton 89–97">{{Cite journal|last1=Norton|first1=Scott A.|last2=Ruze|first2=Patricia|date=1994-07-01|title=Kava dermopathy|journal=Journal of the American Academy of Dermatology|volume=31|issue=1|pages=89–97|doi=10.1016/S0190-9622(94)70142-3|pmid=8021378}}</ref> The first symptom to appear is usually dry, peeling skin; some Pacific Islanders deliberately consume large quantities of kava for several weeks in order to get the peeling effect, resulting in a layer of new skin.<ref>{{cite web|title=Kava Side Effects|url=http://www.kavalibrary.com/side-effects.html|website=The Kava Library|access-date=8 September 2017}}</ref> These effects appeared at consumption levels between {{convert|31|g|oz}} to {{convert|440|g|lb}} a week of kava powder. Despite numerous studies, the mechanism that causes kava dermopathy is poorly understood "but may relate to interference with cholesterol metabolism".<ref name="Norton 89–97" /> 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.<ref name="Norton 89–97" /> Kava dermopathy should not be confused with rare instances of allergic reactions to kava that are usually characterised by itchy rash or puffy face.<ref>{{cite journal|title=Sebotropic drug reaction resulting from kava-kava extract therapy: A new entity?|journal=Journal of the American Academy of Dermatology|volume=38|issue=1|pages=104–6|doi=10.1016/S0190-9622(98)70547-X|pmid=9448214|year=1998|last1=Jappe|first1=Uta|last2=Franke|first2=Ingolf|last3=Reinhold|first3=Dirk|last4=Gollnick|first4=Harald P.M.}}</ref> ==Research== Kava is under preliminary research for its potential [[psychoactive]]<ref name=pmid21073405/> &mdash; primarily [[anxiolytic]] &mdash; sleep-inducing, and sleep-enhancing properties.<ref>{{Cite journal|last=Wheatley|first=David|date=2001-06-01|title=Stress-induced insomnia treated with kava and valerian: singly and in combination|journal=Human Psychopharmacology|volume=16|issue=4|pages=353–356|doi=10.1002/hup.299|issn=1099-1077|pmid=12404572|s2cid=37457833}}</ref> Preliminary analysis of kava effects in people with short-term [[anxiety disorder]]s indicated a small level of improvement.<ref name=pittler/> ==Traditional medicine== [[File:Yaqona-bundle-Fiji-2010.jpg|thumb|A traditional Fijian yaqona bundle of roots]] Over centuries, kava has been used in the [[traditional medicine]] of the South [[Pacific Islands]] for [[central nervous system]] and peripheral effects.<ref name="Showman 56–67">{{Cite journal|last1=Showman|first1=Angelique F.|last2=Baker|first2=Jonathan D.|last3=Linares|first3=Christina|last4=Naeole|first4=Chrystie K.|last5=Borris|first5=Robert|last6=Johnston|first6=Edward|last7=Konanui|first7=Jerry|last8=Turner|first8=Helen|date=2015-01-01|title=Contemporary Pacific and Western perspectives on 'awa (Piper methysticum) toxicology|journal=Fitoterapia|volume=100|pages=56–67|doi=10.1016/j.fitote.2014.11.012|issn=1873-6971|pmid=25464054}}</ref> As noted in one literature review: "Peripherally, kava is indicated in traditional Pacific medicine for urogenital conditions ([[gonorrhea]] infections, chronic [[Urinary tract infection|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) and preparative method to be used".<ref name="Showman 56–67"/> ==Regulation== Kava remains legal in most countries. Regulations often treat it as a food or [[dietary supplement]]. ===Australia=== In Australia, the supply of kava is regulated through the National Code of Kava Management.<ref name=ANZFSC>{{cite web |url=https://www.legislation.gov.au/Details/F2009C01242|title=Australia New Zealand Food Standards Code - Standard 2.6.3 - Kava|date=5 October 2006 |publisher=Federal Register of Legislation|access-date=22 October 2016}}</ref> Travellers to Australia are allowed to bring up to 4&nbsp;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. Initially, the import limit was 2&nbsp;kg per person; it was raised to 4&nbsp;kg in December 2019, and a pilot program allowing for commercial importation was implemented on 1 December 2021.<ref>{{cite news |url=http://www.xinhuanet.com/english/2019-12/17/c_138637423.htm |archive-url=https://web.archive.org/web/20191217110924/http://www.xinhuanet.com/english/2019-12/17/c_138637423.htm |url-status=dead |archive-date=17 December 2019 |title=Travelers from Fiji to Australia can now take more kava for social functions |date=17 December 2019 |access-date=21 January 2020 |publisher=[[Xinhua News Agency|Xinhua]]}}</ref><ref>{{cite web |url=https://www.odc.gov.au/import-requirements-kava|title=Import requirements: Kava|date=1 December 2021|website=The Office of Drug Control, Department of Health, Government of Australia|access-date=7 February 2022}}.</ref> The Australian [[Therapeutic Goods Administration]] has recommended no more than 250&nbsp;mg of kavalactones be taken in a 24‑hour period.<ref>{{cite web | url=http://www.tga.gov.au/cm/kavafs0504.htm | access-date=10 July 2006 | title=Kava fact sheet | publisher=Therapeutic Goods Administration, Government of Australia | date=April 2005 | url-status=dead | archive-url=https://web.archive.org/web/20060720200953/http://www.tga.gov.au/cm/kavafs0504.htm | archive-date=20 July 2006}} ([http://www.tga.gov.au/cm/kavafs0504.pdf Download PDF 44KB] {{webarchive|url=https://web.archive.org/web/20060820014802/http://www.tga.gov.au/cm/kavafs0504.pdf |date=20 August 2006 }}).</ref> Kava possession is limited to 2&nbsp;kg per adult in the [[Northern Territory]].<ref>{{cite web|url=https://nt.gov.au/law/crime/kava|title=Kava|publisher=Northern Territory Government|date=12 December 2016|access-date=14 February 2017}}</ref><ref>{{cite web|publisher=Special Broadcasting Service (SBS), Sydney|url=http://www.sbs.com.au/news/article/2015/02/18/islanders-shocked-australia-moves-ban-kava|title=Islanders shocked as Australia moves to ban kava|date=10 July 2015|author=Armbruster, Stefan|access-date=14 February 2017}}</ref> While it was previously banned in [[Western Australia]] in the 2000s, the Western Australian Health Department announced the lifting of the ban in February 2017, bringing Western Australia "into line with other States" where it has always remained legal, albeit closely regulated.<ref>{{Cite news|url=https://thewest.com.au/news/health/kava-legal-in-relaxation-of-was-drug-laws-ng-b88384684z|title=Kava legal in WA, marketed at troubled sleepers|date=2017-02-13|work=The West Australian|access-date=2017-02-13|language=en-AU}}</ref> ===Europe=== Following discussions on the safety of certain pharmaceutical products derived from kava and sold in Germany, the EU imposed a temporary ban on imports of kava-based pharmaceutical products in 2002. The sale of kava plant became regulated in [[Switzerland]], [[France]], and in prepared form in the [[Netherlands]].<ref>{{cite web | author=C.I.J.M. Ross-van Dorp | title=Besluit van 23 april 2003, houdende wijziging van het Warenwetbesluit Kruidenpreparaten (verbod op Kava kava in kruidenpreparaten) | publisher=Staatsblad van het Koninkrijk der Nederlanden | year=2003 | website=Sdu Uitgevers | url=http://www.ipfsaph.org/cds_upload/kopool_data/FAOLEX_0/unknown_net60412.pdf | access-date=7 February 2007 | archive-url=https://web.archive.org/web/20080227114537/http://www.ipfsaph.org/cds_upload/kopool_data/FAOLEX_0/unknown_net60412.pdf | archive-date=27 February 2008 | url-status=dead }}</ref> Some Pacific island states which 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.<ref>{{cite web|url=http://www.worldtradereview.com/news.asp?pType=N&iType=A&iID=113&siD=23&nID=22522|title=Fiji takes kava ban fight to WTO|date=August 2005|publisher=The World Trade Review|access-date=26 October 2013|url-status=dead|archive-url=https://web.archive.org/web/20131029190558/http://www.worldtradereview.com/news.asp?pType=N&iType=A&iID=113&siD=23&nID=22522|archive-date=29 October 2013}}</ref> The pressure prompted [[Germany]] to reconsider the evidence base for banning kava-based pharmaceutical products.<ref>{{cite web|url=http://www.wto.org/english/res_e/booksp_e/casestudies_e/case33_e.htm|title=The Pacific Island Nations: Towards Shared Representation|last=Bowman|first=Chakriya |publisher=[[WTO]]|access-date=26 October 2013}}</ref> 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.<ref>{{cite web |url=https://www.pharmazeutische-zeitung.de/ausgabe-162015/comeback-unter-strengen-auflagen/ |title=Comeback unter strengen Auflagen |publisher=Pharmazeutische Zeitung |date=16 August 2015 |language=de |access-date=25 July 2021}}</ref> These strict measures have been opposed by some of the leading kava scientists. In early 2016, a court case was 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.<ref>{{Cite web|url=https://www.dailypost.vu/news/new-kava-challenge/article_8e921a99-f924-54a9-b17c-891d55811f52.html |title=New Kava Challenge|website=Vanuatu Daily Post |access-date=12 June 2023 |date=17 February 2016 |last=Joshua |first=Jane }}</ref> In the [[United Kingdom]], it is a criminal offence to sell, supply, or import any medicinal product containing kava for human consumption.<ref>{{cite web|url=http://www.legislation.gov.uk/uksi/2002/3170/contents/made|title=The Medicines for Human Use (Kava-kava) (Prohibition) Order 2002|access-date=26 October 2013 |website=Legislation.gov.uk}}</ref> It is legal to possess kava for personal use or to import it for purposes other than human consumption (e.g., for animals). Until August 2018, Poland was the only EU country with an "outright ban on kava" and where the mere possession of kava was prohibited and may have resulted in a prison sentence.<ref>{{Cite news|url=http://dailypost.vu/news/kava-banned-in-poland/article_845575d3-6dd0-5c03-a1c4-e0720c868a7a.html|title=Kava banned in Poland |date=Dec 27, 2017 |last=Garae|first=Len|work=Vanuatu Daily Post|access-date=2018-09-02|language=en}}</ref> Under the new legislation, kava is no longer listed among prohibited substances and it is therefore legal to possess, import, and consume the plant,<ref>{{Cite web|url=https://isap.sejm.gov.pl/isap.nsf/DocDetails.xsp?id=WDU20180001591 |title=Rozporządzenie Ministra Zdrowia z dnia 17 sierpnia 2018 r. w sprawie wykazu substancji psychotropowych, środków odurzających oraz nowych substancji psychoaktywnych|website=prawo.sejm.gov.pl|language=pl|access-date=12 June 2023 }}</ref> but it remains illegal to sell it within Poland for the purpose of human consumption.<ref>{{Cite web|url=https://www.rp.pl/Zdrowie/309039965-Kava-zalegalizowana-Marihuana-bedzie-nastepna.html|title=Kava zalegalizowana. Marihuana będzie następna?|website=www.rp.pl|language=pl|access-date=2018-12-12}}</ref> In the Netherlands, for unknown reasons, the ban was never lifted, and it is still prohibited to prepare, manufacture, or trade kava or goods containing kava.<ref>{{Cite web|url=https://wetten.overheid.nl/BWBR0012174/2022-07-01/0#Artikel4|title=Warenwetbesluit Kruidenpreparaten|first=Ministerie van Binnenlandse Zaken en|last=Koninkrijksrelaties|website=wetten.overheid.nl}}</ref> ===New Zealand=== When used traditionally, kava is regulated as a food under the Food Standards Code. Kava may also be used as an herbal remedy, where it 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, water extractions prepared from these roots) can legally be sold as food or dietary supplements in New Zealand. The aerial parts of the plant (growing up and out of the ground), unlike the roots, contain relatively small amounts of kavalactones; instead, they contain a mildly toxic alkaloid, pipermethysticine.<ref name=":2" /> While not normally consumed, the sale of aerial plant sections 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).<ref>{{Cite web|url=https://www.beehive.govt.nz/release/dunne-kava-unaffected-psychoactive-substances-bill|title=Dunne: Kava unaffected by Psychoactive Substances Bill|website=The Beehive|access-date=2016-10-24}}</ref><ref>{{Cite web|url=https://gazette.govt.nz/notice/id/2015-gs1906|title=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|website=gazette.govt.nz|access-date=2016-07-02}}</ref> ===North America=== In 2002, [[Health Canada]] issued an order prohibiting the sale of any product containing kava.<ref>{{cite journal|title=Marketed Health Products Directorate Heath Products and Foods Branch|journal=Canadian Adverse Reaction Newsletter|volume=12|issue=4|url=http://www.hc-sc.gc.ca/dhp-mps/medeff/bulletin/carn-bcei_v12n4-eng.php|year=2002}}</ref> While the restrictions on kava were lifted in 2012,<ref>{{cite web |url=http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/newdrug-drognouv/ndrugs_ndrogue-eng.php |title=Listing of Drugs Currently Regulated as New Drugs (The New Drugs List) |date=26 May 2016 |website=www.hc-sc.gc.ca |publisher=Health Canada |access-date=3 July 2017}}</ref> Health Canada lists five kava ingredients as of 2017.<ref>{{cite web|url=https://www.healthlinkbc.ca/health-topics/kava|title=Kava|publisher=HealthLink BC, Government of British Columbia|date=23 September 2021|access-date=3 March 2022}}</ref><ref>{{cite web|url=http://webprod.hc-sc.gc.ca/nhpid-bdipsn/ingredsReq.do?srchRchTxt=kava&srchRchRole=-1&mthd=Search&lang=eng|title=Ingredients - Kava|publisher=Health Canada|date=2017|access-date=1 July 2017|archive-date=11 August 2022|archive-url=https://web.archive.org/web/20220811202841/http://webprod.hc-sc.gc.ca/nhpid-bdipsn/ingredsReq.do?srchRchTxt=kava&srchRchRole=-1&mthd=Search&lang=eng|url-status=dead}}</ref> In 2002, the U.S. [[regulation of food and dietary supplements by the U.S. Food and Drug Administration|Food and Drug Administration]] issued a Consumer Advisory: "Kava-Containing Dietary Supplements May be Associated with Severe Liver Injury". No legal action was taken, and this advisory has since been archived.<ref>{{cite web|url=https://www.fda.gov/Food/ResourcesForYou/Consumers/ucm085482.htm|title=Consumer Advisory: Kava-Containing Dietary Supplements May be Associated with Severe Liver Injury|publisher=US Food and Drug Administration|archive-url=https://web.archive.org/web/20090603082809/https://www.fda.gov/Food/ResourcesForYou/Consumers/ucm085482.htm|archive-date=2009-06-03|access-date=2020-06-28|url-status=dead|date=25 March 2002}}</ref> ===Vanuatu=== 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).<ref>{{Cite web|url=http://faolex.fao.org/docs/html/van38473.htm|title=Vanuatu - Legislation - Kava Act 2002|website=faolex.fao.org|access-date=2016-07-02}}</ref> == See also == * [[List of herbs with known adverse effects]] * [[Alcohol and Drugs History Society]] * [[Betel]] * [[Domesticated plants and animals of Austronesia]] * [[Kava culture]] * [[Nakamal]] * [[Paan]] * [[Samoa 'ava ceremony]] * [[Samoan plant names]] == References == {{Reflist}} == External links == {{Wikispecies|Piper methysticum}} {{EB1911 poster|Kava}} * {{cite web|url=http://www.unodc.org/unodc/en/data-and-analysis/bulletin/bulletin_1973-01-01_2_page008.html|title=UNODC - Bulletin on Narcotics: The narcotic pepper - The chemistry and pharmacology of Piper methysticum and related species|year=1973|publisher=United Nations Office on Drugs and Crime|pages=Issue 2|access-date=19 February 2014}} * [https://web.archive.org/web/20030901220234/http://www.spc.int/cis/kava.htm Kava ban documents] * [http://www.hear.org/species/piper_methysticum/ ''Piper methysticum'' information] from the Hawaiian Ecosystems at Risk project ([http://www.hear.org/ HEAR]) * {{Cite EB9|wstitle=Kava|volume=14 |short=x}} {{Kava}} {{Herbal Sedatives}} {{Culture of Oceania}} {{Cannabinoidergics}} {{Channelergics}} {{GABAAR PAMs}} {{Opioidergics}} {{Taxonbar|from=Q161067}} {{Authority control}} [[Category:Kava| ]] [[Category:Anxiolytics]] [[Category:Drinks]] [[Category:Entheogens]] [[Category:Culture of Fiji]] [[Category:Medicinal plants]] [[Category:Oceanian drinks]] [[Category:Piper (plant)]] [[Category:Culture of Samoa]] [[Category:Culture of Tonga]] [[Category:Drugs in Tonga]] [[Category:Culture of Vanuatu]] [[Category:Ceremonial food and drink]] [[Category:GABAA receptor positive allosteric modulators]] [[Category:Sodium channel blockers]] 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