Scientific Name
Piper methysticum G.Forst.
Synonyms
Methysticum methysticum (G.Forst.) A.Lyons [1], Macropiper methysticum (G. Forster) Hooker & Arnott, Macropiper latifolium Miquel [2]
Vernacular Name
| English | Kava, kava-kava [3] |
| Indonesia | Bari, waghi, wati [3] |
| Papua New Guinea | Keu, koniak, oyo [3] |
| Hawaii | ‘awa, kava, pu’awa [3] |
Geographical Distributions
Piper methysticum probably originated in Vanuatu, since its greatest diversity occurs there. It is cultivated all over Melanesia and Polynesia, especially in Vanuatu, Fiji, Samoa, Tonga and Micronesia. In South-East Asia, P. methysticum occurs mainly in the southern part of New Guinea, both in the wild and in occasional cultivation. Its cultivation and use in New Guinea have declined considerably due to discouragement from former colonial and religious authorities. [2][4]
Botanical Description
P. methysticum is a member of Piperaceae family. It is a dioecious, woody, perennial shrub that measures of 2—4 m tall, with a massive base at or just below the ground (crown or short rootstock) from which several shoots arise, giving the plant an overall rosette appearance. [2]
The stem is erect, 1—3 cm in diameter, green, red-brown or dark purple and looks jointed due to the swollen nodes and prominent scars left by abscission of leaves and branches. [2]
The leaves are alternate, deciduous; stipules large, persistent; petiole 2—7 cm long; blade cordate, 10—30 cm x 8—23 cm, base cordate, margin entire, apex acute, glabrous to finely pubescent, palmately veined, principal veins 9—13, all except the 3 uppermost spreading from base. [2]
Inflorescence a spike, axillary or opposite the leaves but much smaller; peduncle 1.5 cm long; spike 3—9 cm long, with small unisexual flowers without sepals or petals; the male spike bears numerous flowers with 2 short stamens; the female spike bears flowers with a single basal ovule in an unilocular ovary topped by a stigma. The fruit is seldom produced; it is a berry, containing one seed. [2]
Cultivation
No documentation.
Chemical Constituent
P. methysticum extract has been reported to contain kavalactones/kavapyrones (e.g. dihydrokavain, kavain, methysticin, dihydromethysticin, yangonin). [5]
Plant Part Used
Roots and rhizomes [4]
Traditional Use
No documentation.
Preclinical Data
Sedative activity
Kavapyrones extracted from P. methysticum rhizome has been mediated sedative effect on GABA binding site in different regions of rodent brain. [6][7]
Kavalactones isolated from P. methysticum also appear to act on the limbic system, in particular the amygdala complex – the primitive part of the brain that is the centre of the emotional being and basic survival functions. It is thought that kava may promote relaxation, sleep, and rest by altering the way in which the limbic system modulates emotional processes. [8]
Results of one in vitro study reported that P. methysticum seems to produce a pyrone-specific non-stereo-selective inhibition of the [3H]-noradrenaline which may be responsible for, in part, the psychotropic properties of kava pyrones. [9]
Anti-inflammatory activity
P. methysticum has been reported in laboratory studies to have anti-inflammatory activity, inhibiting the inflammatory cytokines NF-ΚB and TNF-α. [10][11]
Skeletal muscle relaxation activity
The effect of P. methysticum on neuromuscular and muscle contractility have been examined in mouse phrenic nerve-hemidiaphragm and frog Sartorius muscle preparations using twitch tension and intracellular recoding techniques. Result showed that P. methysticum extracts have been produced skeletal muscle relaxation (comparable to mephenesin). [12]
Anticonvulsive activity
Kava pyrones isolated from P. methysticum has been demonstrated anticonvulsive activity by producing an interaction of (+/-)-kavain with voltage-dependent Na+ and Ca2+ channels, thereby suppressing the 4-aminopyridine-induced increase in [Na+]i, [Ca2+]i and the release of endogenous glutamate. [13]
Antinociceptive activity
Aqueous and lipid soluble extracts of P. methysticum has been demonstrated antinociceptive activity in mice. [14]
Neuroprotective activity
P. methysticum extract is claimed to help protect the brain against ischemic damage in mice and rat. The P. methysticum extract (150 mg/kg, 1 h before ischemia) diminished the infarct area (p < 0.05) in mouse brains and the infarct volume (p < 0.05) in rat brains. [15]
Hepatotoxicity activity
Methanolic extracts of P. methysticum root and leaf independently were reported in an in vitro study to produce mitochondrial toxicity, leading to inhibition of the respiratory chain, increased ROS production, a decrease in the mitochondrial membrane potential and eventually to apoptosis of exposed hepatic cells in rats. [16]
Toxicity
No documentation.
Clinical Data
Clinical findings
Sedative activity
P. methysticum extract has been given orally to 101 outpatients suffering from anxiety disorders in a 25-week multicenter randomized placebo-controlled double-blind trial. The result support that P. methysticum extract as a treatment alternative to tricyclic antidepressants and benzodiazepines in anxiety disorders, with proven long-term efficacy and none of the tolerance problems associated with tricyclics and benzodiazepines. [17]
Studies have reported that P. methysticum preparations compare favorably to benzodiazepines in controlling symptoms of anxiety and minor depression, while increasing vigilance, sociability, memory, and reaction time. [18]
Using the Hamilton-Anxiety Scale, a double-blind study reported that a standardized P. methysticum preparation had a statistically significant reduction in symptoms of anxiety including feelings of nervousness and somatic complaints such as heart palpitations, chest pains, headache, dizziness, and feelings of gastric irritation. [19]
Researchers suggest after a multicenter, randomized, placebo-controlled, double-blind clinical trial that P. methysticum may be effective and safe when used for sleep disturbances associated with anxiety disorders. [20]
In one study, fifty-two outpatients suffering from anxiety of nonpsychotic origin were under observation while taking a P. methysticum supplement. 81% of the individuals taking the P. methysticum preparation rated the treatment as “very good” or “good.” The authors concluded that the results supported this P. methysticum supplement as an effective and safe alternative to antidepressants and tranquilizers in anxiety disorder without the tolerance problems associated with benzodiazepines. [21]
A randomized, placebo-controlled double-blind study of two groups each containing 20 patients with climacteric-related symptomatology were treated for a period of 8 weeks with kava WS 1490 extract 3 X 100 mg/day or a placebo preparation. The target variable – the HAMA overall score of anxiety symptomatology – revealed a significant difference in the drug-receiving group vis-à-vis the placebo group already after 1 week of treatment. [22]
One study of P. methysticum supplementation in forty menopausal women taking hormonal replacement therapy (HRT; topical estrogen/progestin) or placebo and also presenting with anxiety was performed. The women were divided into groups – those with physiological or surgical menopause for the past 1 to 12 years. After 3-6 months of therapy, a significant reduction in the HAMA score in all four groups of women studied. A greater reduction in the anxiety scores was reported in the groups treated with the HRT and kava, than patients treated with the hormones alone or with hormones and placebo. [23]
Another placebo-controlled study of 20 women with acute anxiety while waiting for the results of their mammography reported that a kava preparation reduced the situational anxiety, along with a significant increase in alertness and a lessening of fatigue, introverted behaviour and excitability as well as a reduction in levels of depression. [24]
The aqueous P. methysticum preparation produced significant anxiolytic and antidepressant activity and raised no safety concerns at the dose and duration studied in 60 adult participants. P. methysticum appears equally effective in cases where anxiety is accompanied by depression. [25]
Hepatotoxicity activity
A review of P. emthysticum-induced hepatoxicity in 14 patients found that hepatic effects of P. methysticum products occurred independently whether aqueous, ethanolic and acetonic P. methysticum extracts or P. methysticum-herbs mixtures were used. [26]
A small human study in 31 heavy P. methysticum users of traditional P. methysticum beverage compared to non-P. methysticum users found that heavy P. methysticum beverage consumption was associated with significantly elevated GGT levels. [27]
Precautions
P. methysticum should not be recommended to people with Parkinson’s. [28] Also, P. methysticum should not be used in individuals with symptoms of gall bladder or liver problems including cirrhosis, hepatic viral infections, among other hepatobilliary diseases. [29] Use with caution in individuals taking prescription and non-prescription medications that may place stress on hepatic function.
Use with caution when driving an automobile or operating heavy machinery. [30] According to the German Commission E, it is recommended to use P. methysticum for no more than 3 months unless under the supervision of a physician.
Side effects
With large consumption (doses 10 times recommended), such as in tea form, the potential for P. methysticum dermopathy may result. [31] Symptoms disappear if discontinued or if dosages are reduced.
Pregnancy/Breast Feeding
Based on pharmacology, do not use in pregnancy. [32]
Age limitation
No documentation.
Adverse reaction
No documentation.
Interaction & Depletion
Interaction with drug
Studies report that P. methysticum may cause sedation, which may enhance the effects of these medications and possibly the dose needed for treatment. These drugs include fluoxetine, fluvoxamine, paroxetine, sertraline, amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, nortriptyline, trimipramine, maprotiline, mirtazapine, trazodone, bupropion, venlafaxine, nefazodone, citalopram, protriptyline, phenelzine, tranylcypromine, isocarboxazid. [5]
P. methysticum has been reported in laboratory studies to inhibit CYP2E1 hepatic enzyme system and P-glycoprotein, both involved in drug metabolism. [33]
Studies report that P. methysticum may cause sedation, which may enhance the effects of these medications and possibly the dose needed for treatment. These drugs include temazepam, triazolam, alprazolam, diazepam, zolpidem, lorazepam, estazolam, flurazepam, quazepam, clorazepate dipotassium, chlordiazepoxide, zaleplon, glutethimide, acetylcarbromal, dexmedetomidine, chloral hydrate, paraldehyde, phenobarbital, pentobarbital, secobarbital, amobarbital, mephobarbital, butabarbital. [5][34]
Studies report that P. methysticum may cause sedation, which may enhance the effects of these medications and possibly the dose needed for treatment. These drugs include diphenhydramine. [5][34]
A human case report described an increase in the sedative effects of alprazolam while taking P. methysticum. This interaction may have possibly led to a coma in this case report. [35]
Studies report that P. methysticum may cause sedation, which may enhance the effects of alcoholic beverages. These drugs include beer, wine, hard liquor, mixed drinks. [36][37]
There has been a case report of P. methysticum decreasing the effectiveness of levodopa, leading to an increase in symptoms of Parkinson’s disease. [38]
A case report of P. methysticum decreasing levels of the muscle relaxing agent chlorzoxazone has been reported. [39]
Interaction with other Herbs
No documentation.
Contraindications
No documentation.
Case Report
In a case report, a 50 year old man presented with jaundice and had noticed fatigue for a month and a “tanned” skin, and dark urine. He had been consuming three to four capsules of a P. methysticum daily for two months (maximum recommended dose three capsules) corresponding to a dose of 210-280 mg lactones. He took no other drugs and did not consume alcohol. Liver function tests showed a 60-fold and 70-fold increase in aspartate aminotransferase and alanine aminotransferase concentrations, respectively. Alkaline phosphatase, 7-glutamyltransferase, lactate dehydrogenase and total and conjugated bilirubin levels were also significantly elevated. After admission to a hospital, he developed stage IV encephalopathy, subsequently receiving a liver transplant two days later and recovered. Heavy consumption of kava has been associated with increased concentrations of 7-glutamyltransferase, along with a case of recurring necrotizing hepatitis being reported. [29]
Hepatotoxicity has been previously suspected by national regulatory agencies in 26 patients in causal relationship with the treatment by P. methysticum extracts commonly used as herbal anxiolytic drugs. From the assessment, it has been confirmed that P. methysticum taken as recommended is associated with rare hepatotoxicity, whereas overdose, prolonged treatment, and co-medication may carry an increased risk. [40]
A pilot survey in an oboriginal community showed that P. methysticum users were more likely to complain of poor health and a “puffy” face, and were more likely to have a typical scaly rash, and slightly-increased patellar reflexes. Very heavy users of P. methysticum were 20% underweight and their levels of gamma-glutamyl transferase were increased greatly. [41]
Dosage
Dosage Range
Take 100-3000 mg (standardized extract), 1-3 times a day for anxiety or single dose of 250-300 mg (standardized extract) of P. methysticum one hour before bedtime for insomnia. [42]
Tincture: 30 drops with water 3 times daily. [42]
Infusion: Use 5-10 g dried herb; steep in one cup hot water (240 mL) for 10-15 minutes; strain and drink ½ cup twice daily. [42]
Most Common Dosage
No documentation.
Standardisation
The most current available medical and scientific literature indicates that this dietary supplement should be standardized to 30-70% kavalactones. [43]
Poisonous Management
No documentation.
Line drawing
References
- The Plant List. Ver1.1. Piper methysticum G.Forst. [homepage on the Internet]. c2013 [updated 2012 Mar 23; cited 2016 May 04]. Available from: http://www.theplantlist.org/tpl1.1/record/kew-2569602
- Onwueme IC. Piper methysticum G. Forster In: van der Vossen, HAM, Wessel M, editors. Plant Resources of South-East Asia No. 16: Stimulants. Leiden, Netherlands: Backhuys Publisher, 2000; p. 106-108.
- Quattrocchi U. CRC world dictionary of medicinal and poisonous plants: Common names, scientific names, eponyms, synonyms, and etymology. Volume IV M-Q. Boca Raton, Florida: CRC Press, 2012; p. 591.
- Burkill IH. A dictionary of economic products of the Malay Peninsula. Volume 2. Kuala Lumpur: Ministry of Agriculture and Cooperatives of Malaysia, 1966; p. 1745-1746.
- Klohs MW. Chemistry of kava. Psychopharmacol Bull. 1967;4(3):10.
- Jussofie A, Schmiz A, Hiemke C. Kavapyrone enriched extract from Piper methysticum as modulator of the GABA binding site in different regions of rat brain. Psyhopharmacology (Berl.) 1994;116(4):469-474.
- Davies LP, Drew CA, Duffield P, Johnston GA, Jamieson DD. Kava pyrones and resin: Studies on GABAA, GABAB and benzodiazepine binding sites in rodent brain. Pharmacol Toxicol. 1992;71(2):120-126.
- Holm E, Staedt U, Heep J, et al. The action profile of D,L-kavain. Cerebral sites and sleep-wakefulness-rhythm in animals. Arzneimittelforschung. 1991;41(7):673-683. German.
- Seitz U, Schüle A, Gleitz J. [3H]-monoamine uptake inhibition properties of kava pyrones. Planta Med. 1997;63(6):548-549.
- Shaik AA, Hermanson DL, Xing C. Identification of methysticin as a potent and non-toxic NF-kB inhibitor from kava, potentially responsible for kava’s chemopreventive activity. Bioorg Med Chem Lett. 2009;19(19):5732-5736.
- Pollastri MP, Whitty A, Merrill JC, Tang X, Ashton TD, Amar S. Identification and characterization of kava-derived compounds mediating TNF-alpha suppression. Chem Biol Drug Des. 2009;74(2):121-128.
- Singh YN. Effects of kava on neuromuscular transmission and muscle contractility. J Ethnopharmacol. 1983;7(3):267-276.
- Gleitz J, Friese J, Beile A, Ameri A, Peters T. Anticonvulsive action of (+/-)-kavain estimated from its properties on stimulated synaptosomes and Na+ channel receptor sites. Eur J Pharmacol. 1996;315(1):89-97.
- Jamieson DD, Duffield PH. The antinociceptive actions of kava components in mice. Clin Exp Pharmacol Physiol. 1990;17(7):495-507
- Backhauss C, Krieglstein J. Extract of kava (Piper methysticum) and its methysticin constituents protect brain tissue against ischemic damage in rodents. Eur J Pharmacol. 1992;215(2-3):265-269.
- Lüde S, Török M, Dieterle S, Jäqqi R, Büter KB, Krähenbühl S. Hepatocellular toxicity of kava leaf and root extracts. Phytomedicine. 2008;15(1-2):120-131.
- Volz HP, Kieser M. Kava-kava extract WS 1490 versus placebo in anxiety disorders – a randomized placebo-controlled 25-week outpatient trial. Pharmacopsychiatry. 1997;30(1):1-5.
- Münte TF, Heinze HJ, Matzke M, Steitz J. Effects of oxazepam and an extract of kava roots (Piper methysticum) on event-related potentials in a word recognition task. Neuropsychobiology. 1993;27(1):46-53.
- Kinzler E, Krömer J, Lehmann E. Effect of special kava extract in patients with anxiety-, tension-, and excition states of non-psychotic genesis. Double blind study with placebos over 4 weeks. Arzneimittelforschung. 1991;41(6):584-588. German.
- Lehrl S. Clinical efficacy of kava extract WS 1490 in sleep disturbances associated with anxiety disorders. Results of a multicenter, randomized, placebo-controlled, double-blind clinical trial. J Affect Disord. 2004;78(2):101-110.
- Scherer J. Kava-kava extract in anxiety disorders: An outpatient observational study. Adv Ther. 1998;15(4):261-269.
- Warnecke G. Psychosomatic dysfunctions in the female climacteric. Clinical effectiveness and tolerance of kava extract WS 1490. Fortschr Med. 1991;109(4):119-122. German.
- De Leo V, La Marca A, Lanzetta D. Assessment of the association of kava-kava extract and hormone replacement therapy in the treatment of postmenopause anxiety. Minerva Ginecol. 2000;52(6):263-267. Italian.
- Neuhaus W, Ghaemi Y, Schmidt T, Lehmann E. Treatment of perioperative anxiety in suspected breast carcinoma with a phytogenic tranquilizer. Zentralbl Gynakol. 2000;122(11):561-565. German.
- Sarris J, Kavanaqh DJ, Byrne G, Bone KM, Adams J, Deed G. The kava anxiety depression spectrum study (KADSS): A randomized, placebo-controlled crossover trial using an aqueous extract of Piper methysticum. Psychopharmacology (Berl.) 2009;205(3):399-407.
- Teschke R, Genthner A, Wolff A. Kava hepatotoxicity: comparison of aqueous, ethanolic, acetonic kava extracts and kava-herbs mixtures. J Ethnopharmacol. 2009;123(3):378-384.
- Brown AC, Onopa J, Holck P, et al. Traditional kava beverage consumption and liver function tests in a predominantly Tongan population in Hawaii. Clin Toxicol (Phila). 2007;45(5):549-556.
- Schelosky L, Raffauf C, Jendroska K, Poewe W. Kava and dopamine antagonism. J Neurol Neurosurg Psychiatry. 1995;58(5):639-640.
- Escher M, Desmeules J, Giostra E, Mentha G. Hepatitis associated with kava, a herbal remedy for anxiety. BMJ. 2001;322(7279):139.
- PDR for herbal medicines. Cornell University: Thomson PDR, 2004; p. 444.
- Piper methysticum (kava kava). Altern Med Rev. 1998;3(6):458-460.
- Pelton R. Natural therapeutics pocket guide. In: Krinsky DL, Lavelle JB, editors. Lexi-comp’s clinical reference library natural medicine series. University of Michigan: Lexi-Comp; 2002.
- Weiss J, Sauer A, Frank A, Unger M. Extracts and kavalactones of Piper methysticum G. Forst (kava-kava) inhibit P-glycoprotein in vitro. Drug Metab Dispos. 2005;33(11):1580-1583.
- Jussofie A, Schmiz A, Hiemke C. Kavapyrone enriched extract from Piper methysticum as modulator of the GABA binding site in different regions of rat brain. Psychopharmacology (Berl). 1994;116(4):469-474.
- Almeida JC, Grimsley EW. Coma from the health food store: Interaction between Kava and alprazolam. Ann Intern Med. 1996;125(11):940-941.
- Jamieson DD, Duffield PH. Positive interaction of ethanol and Kava resin in mice. Clin Exp Pharmacol Physiol. 1990;17(7):509-514.
- Herberg KW. Effect of Kava-special extract WS 1490 combined with ethyl alcohol on safety-relevant performance parameters. Blutalkohol. 1993;30(2):96-105. German.
- Gurley BJ, Swain A, Hubbard MA et al. Clinical assessment of CYP2D6-mediated herb-drug interaction in humans: Effects of milk thistle, black cohosh, goldenseal, kava kava, St. John’s wort, and Echinacea. Mol Nutr Food Res. 2008;52(7):755-763.
- Izzo AA, Ernst E. Interaction between herbal medicines and prescribed drugs: An updated systematic review. Drugs. 2009;69(13):1777-1798.
- Teschke R, Schwarzenboeck A, Hennermann KH. Kava hepatotoxicity: A clinical survey and critical analysis of 26 suspected cases. Eur J Gastroenterol Hepatol. 2008;20(12):1182-1193.
- Mathews JD, Riley MD, Fejo L. Effects of the heavy usage of kava on physical health: Summary of a pilot survey in an oborginal community. Med J Aust. 1988;148(11):548-555.
- Chevallier A. Encyclopedia of medicinal plants. Natural care. New York: Dorling Kindersley; 2001.
- AHC Media. An overview of herbal medicine for the primary care provider: An evidence-based approach. Primary Care Reports [serial online]. c2015-2017 [updated 2001 June 25; cited 2016 May 12]. Available from: http://www.ahcmedia.com/articles/71879-an-overview-of-herbal-medicine-for-the-primary-care-provider-an-evidence-based-approach.
