Kava (Piper methysticum)Published on Diagnostic Imaging (http://www.diagnosticimaging.com)

Kava (Piper methysticum)April 15, 2011By Barrie R. Cassileth, MS, PhD [1]

Kava is a plant indigenous to the Pacific Rim and the Hawaiian Islands whose root and rhizome areused to prepare a non-fermented beverage with relaxant effects that is used for social andrecreational purposes.

ALSO KNOWN AS: Kava-kava, kawa,kavain, rauschpfeffer, intoxicating long pepper, tonga, yagona, yaqona.

BACKGROUND: Kava is a plant indigenous to the Pacific Rim and the Hawaiian Islands whose rootand rhizome are used to prepare a non-fermented beverage with relaxant effects that is used forsocial and recreational purposes. Kava roots are chewed or ground into a pulp and added to coldwater, and the resulting brew—reported to mimic the effects of an alcoholic beverage—has beenused as a ceremonial drink in the Pacific Islands for hundreds of years.While kava is considered a sacred plant in the South Pacific and is used in a variety of ceremonies, itis also used in traditional medicine to relieve anxiety, stress, fatigue, and insomnia, and to treaturinary tract infections and menopausal symptoms.It is believed that kava was introduced to the West by Captain James Cook in 1768. Over the pasttwo decades, kava has gained popularity in Western countries, where it is promoted in supplementalform for anxiety, insomnia, and stress. It is available in health food stores and on the Internet in theform of tablets, capsules, liquid extracts, and tinctures.RESEARCH: Kavalactones, the compounds thought to be responsible for kava's activity, produceskeletal muscle relaxation, non-narcotic anesthestic effects, and local anesthetic effects. In vitro andin vivo studies suggest that these compounds induce mitochondrial dysfunction, oxidative stress,and apoptosis of human hepatocytes (Hep2G).[1,2] Animal studies suggest that kava'svasodepressor activity is mediated by a GABA receptor–sensitive pathway.[3] Kavapyrones alsodemonstrated additive effects with the serotonin 1A agonist, ipsapirone; these effects contribute tokava's sleep-inducing and anxiolytic properties.[4]Kava consumption has been associated with low cancer incidence,[5] but one of its constituents hasbeen shown to stimulate the growth of melanoma cells.[6]Several clinical trials indicate that kava is superior to placebo for reducing anxiety.[7,8] However,reports of hepatotoxicity have led to restrictions on the use of kava-containing products.[9,10]

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Kava (Piper methysticum)Published on Diagnostic Imaging (http://www.diagnosticimaging.com)

Possible mechanisms for kava's hepatotoxicity include inhibition of cytochrome P450, reduction inliver glutathione content, and inhibition of cyclooxygenase (COX) activity.[10,11]Nonetheless, recent studies using aqueous extracts of kava suggest that it is a safe and efficaciousanxiolytic agent.[12,13] Further, case analyses of 14 patients with hepatic injury resulting from kavause revealed low quality products, overdose, prolonged use,and co-medication as the causative factors.[14] Additional studies are needed.ADVERSE REACTIONS: As mentioned above, hepatotoxicity has occurred with kava use.[15]Urticaria has been reported following consumption of kava.[16] Kava overdose resulted in alteredmental status and ataxia.[17] Reversible kava dermopathy characterized by a scaly eruption hasbeen reported in heavy kava drinkers.[18]HERB-DRUG INTERACTIONS: Kava may have additive effects when administered concurrently withbenzodiazepines.[19] Kava inhibits cytochrome P450 2E1, 1A2, and 2D6, and can affect themetabolism of drugs that are metabolized by these enzymes.[20-22] Kava may potentiate thesedative effects of anesthetics.[23]TAKE HOME POINTS

• Existing data indicate kava's effectiveness as ananxiolytic agent.

• Several cases of hepatotoxicity have beenreported with use of kava.

• Kava can interact with some prescriptionmedications, such as benzodiazepines (eg,diazepam [Valium], alprazolam [Xanax]).

For additional information, visit the Memorial Sloan-Kettering Cancer Center Integrative Medicine Service website, "About Herbs," at http://www.mskcc.org/AboutHerbs.

COMMENTS: Current data support kava's efficacy against anxiety. It is also considered by some asan alternative to benzodiazepines and antidepressants, the current treatments for anxiety. However,kava and kava-containing products were withdrawn from Canadian, French, and British markets dueto concerns about hepatotoxicity.The FDA also issued an advisory about the potential risks of liver injury associated with consumptionof kava. Despite this warning, kava continues to be promoted as a relaxant and as an anxiolytic. Itshould be noted that initial research results stemming from a World Health Organization (WHO)recommendation to study aqueous extracts of kava support the benefits of this herb. Further studiesare needed to confirm these findings. References: REFERENCES

1. Lim ST, Dragull K, Tang CS, et al. Effects of kava alkaloid, pipermethystine, and kavalactones onoxidative stress and cytochrome P450 in F-344 rats. Toxicol Sci. 2007;97 214-21.

2. Lude S, Torok M, Dieterle S, et al. Hepatocellular toxicity of kava leaf and root extracts.Phytomedicine. 2008;15:120-31.

3. Hoover JM, Kaye AD, Ibrahim IN, et al. Analysis of responses to kava kava in the feline pulmonaryvascular bed. J Med Food. 2006;9:62-71.

4. Grunze H, Langosch J, Schirrmacher K, et al. Kava pyrones exert effects on neuronal transmissionand transmembraneous cation currents similar to established mood stabilizers—a review. ProgNeuropsychopharmacol Biol Psychiatry. 2001;25:1555-70.

5. Steiner GG. The correlation between cancer incidence and kava consumption. Hawaii Med J.2000;59:420-2.

6. Matsuda H, Hirata N, Kawaguchi Y, et al. Melanogenesis stimulation in murine B16 melanoma cellsby Kava (Piper methysticum) rhizome extract and kavalactones. Biol Pharm Bull. 2006;2:834-7.

7. Ernst E. Herbal remedies for anxiety—a systematic review of controlled clinical trials.

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Kava (Piper methysticum)Published on Diagnostic Imaging (http://www.diagnosticimaging.com)

Phytomedicine. 2006;13:205-8.

8. Witte S, Loew D, Gaus W. Meta-analysis of the efficacy of the acetonic kava-kava extract WS1490in patients with non-psychotic anxiety disorders. Phytother Res. 2005;19:183-8.

9. Escher M, Desmeules J, Giostra E, Mentha G. Hepatitis associated with Kava, a herbal remedy foranxiety. BMJ. Jan 20 2001;322:139.

10. Clouatre DL.Kava kava: examining new reports of toxicity. Toxicol Lett. 2004; 150:85-96.

11. Raman P, Dewitt DL, Nair MG. Lipid peroxidation and cyclooxygenase enzyme inhibitoryactivities of acidic aqueous extracts of some dietary supplements. Phytother Res. Feb2008;22:204-212.

12. Sarris J, Kavanagh DJ, Byrne G, et al. The Kava Anxiety Depression Spectrum Study (KADSS): arandomized, placebo-controlled crossover trial using an aqueous extract of Piper methysticum.Psychopharmacology (Berl). 2009;205:399-407.

13. Singh YN, Devkota AK. Aqueous kava extracts do not affect liver function tests in rats. PlantaMed. 2003;69:496-9.

14. Teschke R. Kava hepatotoxicity: pathogenetic aspects and prospective considerations. Liver Int.2010;30:1270-9.

15. Christl SU, Seifert A, Seeler D. Toxic hepatitis after consumption of traditional kava preparation. JTravel Med. 2009;16:55-6.

16. Grace R. Kava-induced urticaria. J Am Acad Dermatol. 2005;53:906.

17. Perez J, Holmes JF. Altered mental status and ataxia secondary to acute Kava ingestion. J EmergMed. 2005;28:49-51.

18. Norton SA, Ruze P. Kava dermopathy. J Am Acad Dermatol. 1994;31:89-97.

19. Almeida JC, Grimsley EW. Coma from the health food store: interaction between kava andalprazolam. Ann Intern Med. 1996;125:940-1.

20. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh,and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin PharmacolTher. 2005;77:415-26.

21. Russmann S, Lauterburg BH, Barguil Y, et al. Traditional aqueous kava extracts inhibitcytochrome P450 1A2 in humans: protective effect against environmental carcinogens? ClinPharmacol Ther. 2005;77:453-4.

22. Russmann S, Lauterburg BH, Helbling A. Kava hepatotoxicity. Ann Intern Med. 2001;135:68-9.

23. Ang-Lee MK, Moss J, Yuan CS. Herbal medicines and perioperative care. JAMA. 2001;286:208-16. Source URL: http://www.diagnosticimaging.com/integrative-oncology/kava-piper-methysticum

Links:[1] http://www.diagnosticimaging.com/authors/barrie-r-cassileth-ms-phd

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