Piper methysticum / Kawa / Kava Kava


`AWA`Awa is one of the plants brought in their sailing canoes by the earliest Polynesian voyagers arriving in Hawai`i. `Awa (Piper methysticum), a member of the pepper family, grows in the wild now and is also cultivated increasily throughout the Pacific Islands, where it is called Kava or Kava Kava. This plant grows well at low elevations where there is constant moisture and partial sun. More than a dozen varieties of `awa were known in old Hawai`i.

The sparingly branched, erect shrub is very hardy and grows up to 12 feet high. It has large, smooth, heart-shaped leaves and green or black jointed stems, with swellings at the joint. The black `awa is the rare one. The flower is an inconspicuous narrow yellow-green spike. The root is thick, soft wooded when fresh, hardening as it dries. It needs to grow for 2 to 3 years minimum to achieve usable potency. It is valued as an intoxicating drink and as a medicine. `Awa is also a sedative, used as a sacred plant for prayer, as well as appreciated for pleasure, especially in the south Pacific islands. It assists in opening communication channels with others and with the elements.

As a medicine, the roots - as well as the leaves, stems and bark - are used for the following: general debility, weary muscles, chills, colds, headaches, lung and other respiratory diseases such as asthma, displacement of the womb, diabetes, congestion of the urinary tract as well as for rheumatism.

To make feverish or restless young children go to sleep, the leaf buds are given to the child after being chewed by the mother. The plant is also used during teething and in rituals at the time of weaning.

`Awa is used principally as a sedative to induce relaxation and sleep, especially when combined with lomi lomi massage. It is also used as a tonic when people feel weak, as it is stimulating and refreshing, unless drunk in large quantities. Over indulgence in `awa use for a period of time can adversely (but temporarily) affect the skin and eyes. The word `awa means bitter.

In the old days, it is said that the chiefs and priests were the principal users of `awa, but in more recent times it has been taken to use by all the people. Those who perform strenuous work especially appreciate its properties as a relief for stiffness, tenseness and fatigue in the muscles. `Awa is a muscle relaxant to weary farmers, fishermen, hunters and paddlers. Spiritual leaders use `awa ceremonially at appointed times, such as at a ritual following a canoe race-meet. It is a social tradition and an offering of gratitude to the divine, both before and after events and festivals in the life of the people.

In a story about the daughters of Haumea, the eldest being Pele, and her family's travels from Tahiti to Hawai`i Nei, throughout the islands, ending in Hawai`i Island where she resides now, there is a chant given, which was chanted upon making an offering of pig and `awa to Laka, the goddess of hula, to receive instruction. The last lines of the translation are:

...Low
accessible is the day whereby knowledge is gained,
Knowledge from the source, knowledge by hearing,
Like the flourishing `awa plant is the knowledge of the gods,
O hear me.

While living in Western Samoa, I learned that the chiefs and talking chiefs use `awa ceremonially. These villagers on the island of Savaii met together periodically to decide the issues of the village. The meetings were preceded by an `awa ceremony, bringing the leaders into one accord and goodwill, as they sat in a decision making circle around the fale.
To prepare the 'awa root, it is sometimes used fresh, sometimes sun-dried. It is washed clean, chopped into small pieces, and then pounded — or in modern times, blended in a blender — with water to create a suspension of kavalactones, which are lipid-soluble. Traditionally, the root pieces were chewed, usually by a young maiden. Now powdered and packaged root is often available.

An `awa drink, good for migraines or P.M.S. can be prepared for one's personal use in the following way. Put a few small pieces of the clean root in the mouth and chew them. Add a few more, until a cud the size of the thumb is formed. When three of these are ready, put them in a bowl and mash with about a cup of fresh water. Strain the liquid through a cloth to remove woody material. This will provide you with a drink that can be used for headaches or cramps. Sugar cane juice or honey can be added to sweeten. Sometimes a spoonful of noni juice is added as a chaser, to counter any unpleasant effects.
In the traditional manner, the chewed `awa is mixed with water or with coconut water, sometimes warmed by putting it in a kanoa, calabash, with hot stones. It is then stirred and strained with a fibrous plant bundle and drunk when it is cool.

Special cups (`apu `awa), made from coconut shell cut lengthwise are often reserved for this brew, and for the ceremony of `awa drinking. Distinctive bowls are also made and set aside for `awa ceremonies throughout Polynesia. `Awa/kava seems to be more widely used outside these Hawai`i islands.
E hanai `awa a ikaika ka makani. 
Feed with `awa so that the spirit may gain strength. 
One offers `awa and prayers to the dead so that their spirit may grow strong and be a source of help to the family.

When `awa cups are filled, a prayer of gratitude is offered. `Awa is usually gulped rather than sipped, with some of the liquid being left in the container and poured upon the earth, with thanksgiving. A chaser or pupu is sometimes used to offset the bitter taste: a piece of sugar cane, a bite of sweet potato,banana or fish. A numbness in the mouth may be noticed after `awa ingestion.

It is best to harvest the `awa root when the ground is moist from rain, so that it can be easily removed. For propagation, the stalk can be cut into sections that include the top of one knob and the bottom of the next one down. These can be planted right side up, with most of the cane being beneath the moist earth, in a shady place. Another method of planting is to lay a long piece of stem within the earth, allowing several plants to sprout from the knobby sections laid down.





Uit Tyler's herbs of choice: The therapeutic use of phytomedicinals
KavaKava  is  the  dried  roots  of Piper  methysticum  Forst.,  family  Piperaceae. Known also as kava-kava, the plant is a large shrub widely cultivated in Oceania. Its underground parts have been extensively used by the indig-enous  people  of  these  Pacific  islands  in  the  preparation  of  an  intoxicat-ing beverage. Kava beverage drinking predates recorded history and has acquired important significance from a social and ceremonial standpoint among the various island cultures. An overview of kava preparation and ceremonial use as well as kava chemistry and pharmacology has been pre-sented in detail by Singh and Blumenthal.15 Kava was ritually prepared by young men or women who chewed cut pieces of the scraped root, spitting the pieces into a bowl to which coconut milk was added to make an infu-sion. However, for sanitary reasons, pressures by colonizing governments and  missionary  influence  have  led  to  the  abandonment  of  the  chewing technique in favor of pounding or grating the root.Kava  bars  offer  the  beverage  on  various  Pacific  islands,  where  the muddy-looking liquid is rapidly drunk (not sipped) from coconut shells. It first causes a numbing and astringent effect in the mouth, followed by a relaxed sociable state in which fatigue and anxiety are lessened. Eventually, a  deep  restful  sleep  ensues  from  which  the  user  awakes  refreshed  and without hangover. Excessive consumption can lead to dizziness and stu-pefaction,16  and  use  over  a  prolonged  period  (a  few  months)  can  lead  to kava  dermopathy,  which  is  characterized  by  a  reversible  ichthyosiform scaly skin.17

The  CNS  activity  of  kava  is  due  to  a  group  of  resinous  compounds called kavalactones, kavapyrones, or styrylpyrones. Roots of good quality contain between 5.5 and 8.3 percent of kavalactones, including the major components kawain, dihydrokawain, and methysticin, as well as the minor compounds yangonin, desmethoxyyangonin, and dihydromethysticin.18 Animal  studies  have  demonstrated  the  ability  of  kava  extracts  or purified  kavalactones  to  induce  sleep  and  produce  muscle  relaxation and  analgesia  as  well  as  anticonvulsive  protection  against  strychnine and electroshocks.19 At low doses, kavalactones resemble t he phar maco-logic action of benzodiazepines, although they apparently do not bind at either GABA or benzodiazepine binding sites in rat or mouse brain membranes.20 Because of the diverse range of pharmacological activities shown by kava, kavalactones may act nonselectively and remain in the lipid membranes to cause modifications to a variety of receptor domains rather than interacting with any specific receptor binding site. There is evidence  that  the  spasmolytic,  analgesic,  and  anticonvulsant  activity of kavalactones might be explained by inhibition of voltage-dependent Na+ chan nels in the brain21; however, the question remains whether this inhibition is also responsible for the anxiolytic and hypnotic action.

Several relatively short-term clinical studies have provided favorable evidence  that  kava  is  effective  in  treating  anxiety  and  insomnia22;  how-ever,  the  first  long-term  clinical  trial  investigating  safety  and  efficacy  of kava  in  anxiety  patients  was  only  recently  published.  In  this  study,  101 outpatients with anxiety of nonpsychotic origin, determined on the basis of  the  American  Psychiatric  Association  anxiety  disorder  classification, were  included  in  a  twenty-five-week  multicenter,  randomized,  placebo-controlled, double-blind trial using a lipophilic kava extract standardized to contain 70 percent kavalactones. Patients were administered either 100 mg of extract (70 mg kavalactones) or placebo three times daily, and the main outcome criterion utilized the Hamilton Anxiety Scale.Adverse  effects  were  rare  and  distributed  evenly  in  both  groups,  and there  were  no  problems  with  tolerance,  dependence,  or  withdrawal  symp-toms—adverse effects often associated with long-term benzodiazepine use. The long-term efficacy (after the eighth week of treatment) of the kava extract was superior to that of placebo. In addition, kava extract was not associated w i t h  d e p r e s s e d  c o g n i t i v e  f u n c t i o n ,  d r o w s i n e s s ,  o r  i m p a i r m e n t  i n  m e n t a l  r e a c-tion time, problems found in the side-effect profile of benzodiazepines.23

The German Commission E has approved kava for conditions of nervous anxiety, stress, and restlessness; the recommended dosage is 70 mg of kavalactones, usually in the form of a standardized extract two to three times daily.24 
As a sleep aid, 180–210 mg of kavalactones can be taken one hour before bedtime. It is important to note that ethanol and other CNS depressants can potentiate the effects of kava; therefore, they should not be  taken  concomitantly.  In  this  regard,  a  drug  interaction  between  kava and the benzodiazapine alprazolam that caused a semicomatose state in a patient has been reported.25
In  June  2002,  the  German  Federal  Institute  of  Drugs  and  Medical Devices decided to withdraw all drug registrations for all products con-taining  kava,  on  account  of  reports  of  liver  toxicity  associated  with  the herb. However, in May 2005, the German government repealed the ban on kava products, pending evaluation of new data. An article by Anke and Ramzan in 2004 reviewed the kava hapatotoxicity controversy and summarized the major theories advanced to explain the case reports of liver failure but reached no satisfactory conclusion.26 An intriguing hypothesis has been recently proposed implicating a kava metabolite with the potential for reacting with glutathione in the liver, supported by an adduct identified in urine.27 Nonetheless, German herbal medicine experts, including former members of Commission E and officials of the Society of Medicinal Plant Research, regard kava extracts and kavalactones as “quite safe.”



Water-Based Kava Extract for Generalized Anxiety Disorder Shows No Adverse Effects in Liver Function 
by Heather S. Oliff, PhD HerbalGram. 2013; American Botanical Council

Reviewed: Sarris J, Stough C, Teschke R, Wahid ZT, Bousman CA, Murray G, Savage KM, Mouatt P, Ng C, and Schweitzer I. Kava for the treatment of generalized anxiety disorder RCT: analysis of adverse reactions, liver function, addiction, and sexual effects. Phytother Res. January 2013; [epub ahead of print]. doi: 10.1002/ptr.4916.

Empirical observations and clinical trial evidence suggest that preparations made from the root of kava (Piper methysticum, Piperaceae) are efficacious in the treatment of anxiety; however, cases of hepatotoxicity associated with kava use have led to its withdrawal or restricted use in many Western countries. Considering that kava has anxiolytic effects, questions arise as to whether kava is addictive, has adverse sexual side effects, or has withdrawal effects that might be similar to pharmaceutical anxiolytic drugs such as the benzodiazepines (drugs with an anti-anxiety effect). Uncertainty regarding the cause of the liver toxicity centers on poor-quality raw material, plant cultivars, and extraction solvents. Hence the purpose of this randomized, double-blind, placebo-controlled study was to evaluate adverse events (AEs), withdrawal/addiction effects, and liver function effects associated with kava use in patients with generalized anxiety disorder (GAD). Also, genetic polymorphism (when more than one different phenotype exists in the same species) of the liver enzyme cytochrome P450 2D6 (CYP2D6), which metabolizes compounds in kava, was evaluated to determine whether subjects who were poor or extensive metabolizers have different AEs using water-extracted kava from noble cultivars (that is, kava cultivars with higher levels of kavain and lower levels of dihydromethysticin).1

Patients (n=58; aged 18-65 years) with DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) diagnosed with GAD were recruited from the Greater Melbourne area in Victoria, Australia, via mass media. Patients were excluded if they had any of the following conditions: major depressive disorder or elevated depressive symptomatology (greater than 17 on the Montgomery-Asberg Depression Rating Scale); a DSM-IV diagnosis of a psychotic or bipolar disorder; significant suicidal ideation in the previous six months; current use of antidepressants, mood stabilizers, antipsychotics, opioid analgesics, or St. John’s wort (Hypericum perforatum, Clusiaceae); diagnosed hepatobiliary disease/inflammation; substance abuse or dependency disorder in the previous six months; a previous adverse reaction to kava or benzodiazepines; kava or benzodiazepine use in the previous 12 months; or abnormal baseline liver function. The study began with a one-week run-in phase to identify placebo responders. Any subject who showed a 50% improvement on the Hamilton Anxiety Scale (HAM-A) score during this placebo phase was excluded from the study.

For six weeks, patients received placebo or an aqueous kava extract with the equivalent of 120 mg of kavalactones/day, which was titrated to 240 mg/day in patients showing no response at three weeks. The kava was formulated from pressed, dried, aqueous peeled rootstock of kava (Medi-Herb, Integria Healthcare; Eight Mile Plains, Queensland, Australia). The kava extract was independently analyzed at Southern Cross University at Lismore, Australia, and was determined to contain various kavalactones: dihydrokavain (15.5 mg, 26%), kavain (12.5 mg, 21%), dihydromethysticin (11 mg, 18%) methysticin (8.5 mg, 14%), yangonin (8 mg, 13%), and desmethoxygangonin (5mg, 8%); the alkaloid pipermethystine, which has been implicated in some kava extracts associated with cases of liver dysfunction, was not detected.

At weeks two and seven, AEs were assessed via questionnaire, and blood was drawn for liver function tests and to determine polymorphisms.

No significant AEs were reported. One case of dermatitis and one case of minor stomach upset were associated with kava intake. Withdrawal was assessed by treating all patients with placebo for one week at study end. There was no significant increase in AEs in either treatment group. Addiction was assessed by evaluating the number of patients who said that they wanted an increase in dose. Both treatment groups had the same number of patients who wanted to increase the dosage. There were no significant differences from baseline in liver function tests, and no patients developed clinical signs of hepatic abnormality. However, gamma-glutamyl transpeptidase (GGT) showed a trend toward elevation in kava-treated patients compared with those who took placebo at week seven (P=0.08). This finding may be due to an outlier; one patient (an extensive CYP2D6 metabolizer) had isolated increases in GGT and alanine aminotransferase (ALT) that both returned to baseline levels after the study. However, intermediate or extensive CYP2D6 metabolizer status had no significant impact on the type or frequency of AEs or abnormal liver function tests. Kava did not diminish sexual performance or enjoyment in men or women. However, there was a trend for kava-treated men to have more difficulty reaching orgasm (P=0.067). Kava-treated women had a significant increase in sex drive (P=0.04).

The authors conclude that water-extracted kava from noble cultivars has no deleterious effects on sexual function and pleasure, has no addictive qualities or withdrawal issues, and is safe for patients with GAD when taken for six weeks. The researchers also wrote that patients with GAD would require treatment for longer than six weeks, so a larger, longer-term study is needed to confirm the findings. Nonetheless, this study contributes to the growing body of evidence that water-soluble, standardized formulations of kava from noble cultivars are safe. The authors conclude that these data may assist in the reintroduction of kava in restricted markets. This study uses a medicinal dose of kava, and the results cannot be extrapolated to traditional recreational use with higher doses of kavalactones.

—Heather S. Oliff, PhD

Reference
1.         Sarris J, Stough C, Bousman CA, Wahid ZT, Murray G, Teschke R, Savage KM, Dowell A, Ng C, Schweitzer I. Kava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled study. J Clin Psychopharmacol. 2013;33(5):1-6.


Planta Med 2015; 81(18): 1647-1653
Georg Thieme Verlag KG Stuttgart · New York
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

Kava, the rhizome and roots of Piper methysticum, are one of the most important social pillars of Melanesian societies. They have been used for more than 1000 years in social gatherings for the preparation of beverages with relaxing effects. During the colonial period, extract preparations found their way into Western medicinal systems, with experience especially concerning the treatment of situational anxiety dating back more than 100 years. It therefore came as a surprise when the safety of kava was suddenly questioned based on the observation of a series of case reports of liver toxicity in 1999 and 2000. These case reports ultimately led to a ban of kava products in Europe – a ban that has been contested because of the poor evidence of risks related to kava. Only recently, two German administrative courts decided that the decision of the regulatory authority to ban kava as a measure to ensure consumer safety was inappropriate and even associated with an increased risk due to the higher risk inherent to the therapeutic alternatives. This ruling can be considered as final for at least the German market, as no further appeal has been pursued by the regulatory authorities. However, in order to prevent further misunderstandings, especially in other markets, the current situation calls for a comprehensive presentation of the cardinal facts and misconceptions concerning kava and related drug quality issues.

The current state of ethnopharmacological and phytochemical research still does not confirm a causal relationship between the consumption of kava preparations and the occurrence of adverse liver reactions. With the assumption of the (albeit very rare) existence of such a type of reaction, manufacturers should seek guidance for the quality of plant material known to be safe through centuries of traditional experience. The problem of possible hepatotoxicity of kava preparations was potentially caused by ill-defined herbal drug identity, a lack of appropriate quality control, and misguided regulatory politics.

Thus, in order to re-establish “noble” kava to its rightful place as an essential anxiolytic drug in the European market, its botanical and phytochemical differentiation from the “non-noble” kava varieties has to be established by pharmacopoeial regulations. This should be a minor problem, as there are already several plant drugs where the pharmacopoeia does already differentiate between closely related and easily misidentified species (e.g.,Illicium verum vs. Illicium anisatum). With the circumstantial evidence supporting a raw drug identity/quality issue at the base of the problem of hepatotoxicity, the definition of appropriate quality standards should, in any case, be helpful.

There is, however, not much time to act on the problem of drug identity of pharmaceutically suitable kava varieties. In the past 10 years, kava exports from the South Pacific islands have again multiplied, reaching the same level as at the time before the kava ban in 2001. The United States have especially evolved as a kava market, with currently more than 90 kava bars serving kava of frequently highly doubtful quality. Similarly, the market of New Caledonia has shifted to the import of large quantities of two-day kava roots and (mainly) peelings from Vanuatu, with the argument that the higher kavalactone concentrations and, at the same time, relatively low costs allow for the production of more kava drinks at lesser expenses. If the flavokavins or other as yet non-identified constituents of non-noble kava are truly responsible for liver toxicity, this could be playing with fire. There are already isolated reports of liver toxicity related to kava use from New Caledonia – cases that are now discussed in the context of potential mould-related toxicity [54], but even this aspect would have to be part of quality specifications.

With the revocation of the German kava “ban” by the Administrative Court of Cologne and the Upper Administrative Court of Münster, a major hurdle for a constructive discussion and a potential comeback of kava has been overcome. Therefore, now is the time to act to prevent the problem of kava-related hepatotoxicity from reoccurring by introducing appropriate regulatory standards concerning its drug quality and, even more so, drug identity.

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Kava

The use of Kava originated in the “Oceana” island communities encompassed by Polynesia, Melanesia, and Micronesia (Singh and Blumenthal, 1997). In these cultures “Kava” (also known as “Kava-Kava,” “Ava,” and “Awa”) refers to an intoxicating beverage used in rituals and ceremonies, which is produced from the mashed rhizome and roots of the woody shrub, Piper methysticum. However, Kava is now used as the common name forP. methysticum as well as the phytomedicine produced from root/rhizome extracts. Worldwide, Kava is receiving considerable attention for its use as a treatment for anxiety, nervous tension, agitation, and/or insomnia. Clinical studies have shown an effectiveness of Kava that is comparable with sedatives such as benzodiazapines but without the development of either physical or psychological dependency (Singh and Blumenthal, 1997; Schulz et al., 1998).

From intensive chemical and pharmacological studies conducted on Kava root/rhizome extracts over the past century, several key active constituents have been identified (Bruneton, 1995; Singh and Blumenthal, 1997). The pharmacological activity of this plant appears to be associated with a family of styrylpyrones called “kavapyrones” (or “kavalactones”) that have effects on several neurotransmitter systems including those involving Gln, GABA, dopamine, and serotonin (Schulz et al., 1998). Whereas the kavapyrones shown in Figure4represent the predominant pharmacologically active components in Kava root extracts, a total of 18 have been identified at present (He et al., 1997). These remaining kavapyrones appear to be derivatives of either kawain, yangonin, or dihydromethysticin (Bruneton, 1995; He et al., 1997). Although details regarding kavapyrone biosynthesis are still lacking, evidence from other systems such asEquisetum arvense gametophytes suggest that styrylpyrones may arise from a triketide produced by successive condensation of two malonyl-coenzyme A (CoA) molecules with a phenylpropanoid CoA-ester (Schröder, 1997 and references therein). This is similar to reactions catalyzed by chalcone synthase except that two, rather than three, successive condensations involving malonyl CoA are involved. Recent studies have shown that kavapyrone levels in Kava roots are influenced by environmental factors. In cultivated Kava plants, kavapyrone levels appear to increase with irrigation and mineral nutrient supplementation and decrease with shading (Lebot et al., 1999). Moreover, varietal differences in Kava also appear to have a role in determining the overall level of kavapyrone production (Lebot et al., 1999).


Fig. 4.

Examples of kavapyrones from P. methysticum (Kava) (adapted from Bruneton, 1995).

It is quite interesting that Kava plants are sterile and plantation production involves propagation from stem cuttings (Singh and Blumenthal, 1997). From genetic studies, it has been suggested that Kava likely represents a sterile relative of Piper wichmannii (native to New Guinea), which became distributed across the South Pacific islands with human migration and through somatic mutation became sterile (Lebot et al., 1999 and references therein). Kava's sterility combined with its limited growth habitat range (South Pacific Tropics), time required for growth before root harvest (approximately 8 years), and high world demand have raised concerns about potential over harvesting. Although attempts have been made to grow Kava in tissue culture for propagation and possible in vitro phytochemical production, little success has been achieved (Taylor and Taufa, 1998).











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