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Planta Med 2011; 77(2): 107-110
DOI: 10.1055/s-0030-1250290
Perspectives
© Georg Thieme Verlag KG Stuttgart · New York

Re-introduction of Kava (Piper methysticum) to the EU: Is There a Way Forward?

Jerome Sarris1 , 2 , Rolf Teschke3 , Con Stough2 , Andrew Scholey2 , Isaac Schweitzer1
  • 1Department of Psychiatry, Faculty of Medicine, The University of Melbourne, Melbourne, Australia
  • 2Brain Sciences Institute, Swinburne University of Technology, Melbourne, Australia
  • 3Department of Internal Medicine II, Section of Gastroenterology and Hepatology, Klinikum Hanau, Teaching Hospital of the Johann Wolfgang Goethe University of Frankfurt/Main, Germany
Further Information

Publication History

received March 16, 2010 revised June 28, 2010

accepted July 26, 2010

Publication Date:
02 September 2010 (online)

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Abstract

Kava (Piper methysticum) is an effective anxiolytic that has been withdrawn from various consumer markets in European countries due to concerns over its hepatotoxicity. It is plausible that the reported hepatotoxicity may be due in part to plant substitution, or an incorrect cultivar, or plant parts being used (such as leaves or bark); thus both the plant chemotype and the plant part used may be critical factors. If re-institution of kava in the EU is to occur, more evidence is required to determine its safety and efficacy. Furthermore, according to current evidence, the study of traditional water soluble rhizome extracts using a noble cultivar of kava may be advised. The Kava Anxiety-Lowering Medication (KALM) project is due to start in late 2010 to address these considerations. The KALM project uses an aqueous rhizome extract of a noble cultivar of kava in participants with generalised anxiety and Generalised Anxiety Disorder (GAD). The project comprises of 1) an acute RCT, kava (180 mg of kavalactones) versus oxazepam and placebo in 20 anxious people, testing effects on cognition, mood, anxiety, and driving; 2) an 8-week RCT comparing kava (120 mg kavalactones) versus placebo in 100 patients with GAD. To assess differences between dosages, non-responders at 3 weeks will be titrated to 240 mg of kavalactones. The project will also assess the effects of kava on liver function tests and its side effects profile. A novel component of the project is the pharmacogenomic exploration of phenotypical responses (GABA system and cytochrome P450 markers). The results of the study may be of benefit to sufferers of anxiety and the future economy of the Pacific islands, potentially providing an important step in the way forward with kava.

Key words

kava - Piper methysticum - Piperaceae - kava hepatotoxicity - anxiety - generalised anxiety disorder - pharmacogenomics

References

  • 1 Sarris J, Kavanagh D J. Kava and St John's wort: Current evidence for use in mood and anxiety disorders.  J Altern Complement Med. 2009;  15 827-836
    CrossrefPubMedGoogle Scholar
  • 2 Pittler M H, Ernst E. Efficacy of kava extract for treating anxiety: systematic review and meta-analysis.  J Clin Psychopharmacol. 2000;  20 84-89
    CrossrefPubMedGoogle Scholar
  • 3 Clouatre D L. Kava kava: examining new reports of toxicity.  Toxicol Lett. 2004;  150 85-96
    CrossrefPubMedGoogle Scholar
  • 4 Bauer R. Relevant hepatotoxicity effects of kava still need to be proven.  Planta Med. 2003;  69 971-972
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Coulter D. Assessment of the risk of hepatotoxicity with kava products. Geneva; WHO appointed committee 2007
    PubMedGoogle Scholar
  • 6 Teschke R, Genthner A, Wolff A. Kava hepatotoxicity: comparison of aqueous, ethanolic, acetonic kava extracts and kava-herbs mixtures.  J Ethnopharmacol. 2009;  123 378-384
    CrossrefPubMedGoogle Scholar
  • 7 Teschke R. Kava hepatotoxicity – a clinical review.  Ann Hepatol. 2010;  9 251-265
    PubMedGoogle Scholar
  • 8 Nerurkar P, Dragull K, Tang C. In vitro toxicity of kava alkaloid, pipermethysticine, in HepG2 cells compared to kavalactones.  Toxicol Sci. 2004;  79 106-111
    CrossrefPubMedGoogle Scholar
  • 9 Anke J, Ramzan I. Pharmacokinetic and pharmacodynamic drug interactions with Kava (Piper methysticum Forst. f.).  J Ethnopharmacol. 2004;  93 153-160
    CrossrefPubMedGoogle Scholar
  • 10 Mathews J M, Etheridge A S, Black S R. Inhibition of human cytochrome P450 activities by kava extract and kavalactones.  Drug Metab Dispos. 2002;  30 1153-1157
    CrossrefPubMedGoogle Scholar
  • 11 Guo L, Li Q, Xia Q, Dial S, Chan P C, Fu P. Analysis of gene expression changes of drug metabolizing enzymes in the livers of F344 rats following oral treatment with kava extract.  Food Chem Toxicol. 2009;  47 433-442
    PubMedGoogle Scholar
  • 12 Fu P P, Xia Q, Guo L, Yu H, Chan P C. Toxicity of kava kava.  J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2008;  26 89-112
    PubMedGoogle Scholar
  • 13 Lude S, Torok M, Dieterle S, Jäggi R, Berger Büter K, Krähenbühl S. Hepatocellular toxicity of kava leaf and root extracts.  Phytomedicine. 2008;  15 120-131
    CrossrefPubMedGoogle Scholar
  • 14 Jhoo J, Freeman J, Heinze T, Moody J D, Schnackenberg L K, Beger R D, Dragull K, Tang C S, Ang C Y. In vitro cytotoxicity of nonpolar constituents from different parts of kava plant (Piper methysticum).  J Agric Food Chem. 2006;  54 3157-3162
    CrossrefPubMedGoogle Scholar
  • 15 Wu D, Yu L, Nair M, DeWitt D, Ramsewak R. Cyclooxygenase enzyme inhibitory compounds with antioxidant activities from Piper methysticum (kava kava) roots.  Phytomedicine. 2002;  9 41-47
    CrossrefPubMedGoogle Scholar
  • 16 Lechtenberg M, Quandt B, Schmidt M, Nahrstedt A. Is the alkaloid pipermethystine connected with the claimed liver toxicity of Kava products?.  Pharmazie. 2008;  63 71-74
    PubMedGoogle Scholar
  • 17 Duffield A M, Jamieson D D, Lidgard R O, Duffield P H, Bourne D J. Identification of some human urinary metabolites of the intoxicating beverage kava.  J Chromatogr. 1989;  475 273-281
    CrossrefPubMedGoogle Scholar
  • 18 Li X Z, Ramzan I. Role of ethanol in kava hepatotoxicity.  Phytother Res. 2010;  24 475-480
    PubMedGoogle Scholar
  • 19 Whitton P A, Lau A, Salisbury A, Whitehouse J, Evans C S. Kava lactones and the kava-kava controversy.  Phytochemistry. 2003;  64 673-679
    CrossrefPubMedGoogle Scholar
  • 20 Loew D, Franz G. Quality aspects of traditional and industrial kava-extracts.  Phytomedicine. 2003;  10 610-612
    CrossrefPubMedGoogle Scholar
  • 21 Simeoni P, Lebot V. Identification of factors determining kavalactone content and chemotype in Kava (Piper methysticum Forst. f.).  Biochem Syst Ecol. 2002;  30 413-414
    CrossrefPubMedGoogle Scholar
  • 22 Lebot V, Levesque J. Evidence for conspecificity of Piper methysticum Forst f. and Piper witchmannii C. DC.  Biochem Syst Ecol. 1996;  24 775-782
    CrossrefPubMedGoogle Scholar
  • 23 Lasme P, Davrieux F, Montet D, Lebot V. Quantification of kavalactones and determination of kava (Piper methysticum) chemotypes using near-infrared reflectance spectroscopy for quality control in Vanuatu.  J Agric Food Chem. 2008;  56 4976-4981
    CrossrefPubMedGoogle Scholar
  • 24 Lebot V. The quality of kava consumed in the South Pacific.  Herbal Gram. 2006;  71 34-37
    PubMedGoogle Scholar
  • 25 Connor K M, Payne V, Davidson J R. Kava in generalized anxiety disorder: three placebo-controlled trials.  Int Clin Psychopharmacol. 2006;  21 249-253
    CrossrefPubMedGoogle Scholar
  • 26 Sarris J, Kavanagh D, Byrne G, Bone K M, Adams J, Deed G. The Kava Anxiety Depression Spectrum Study (KADSS): A randomized, placebo-controlled, cross-over trial using an aqueous extract of Piper methysticum.  Psychopharmacology (Berl). 2009;  205 399-407
    CrossrefPubMedGoogle Scholar
  • 27 Vanuatu Kava Act, No. 7. Vanuatu; Republic of Vanuatu 2002
    Google Scholar
  • 28 Schweitzer I, Maguire K, Ng C. Sexual side-effects of contemporary antidepressants: review.  Aust N Z J Psychiatry. 2009;  43 795-808
    CrossrefPubMedGoogle Scholar
  • 29 Schosser A, Kasper S. The role of pharmacogenetics in the treatment of depression and anxiety disorders.  Int Clin Psychopharmacol. 2009;  24 277-288
    CrossrefPubMedGoogle Scholar
  • 30 Hirunsatit R, Ilomaki R, Malison R, Räsänen P, Ilomäki E, Kranzler H R, Kosten T, Sughondhabirom A, Thavichachart N, Tangwongchai S, Listman J, Mutirangura A, Gelernter J, Lappalainen J. Sequence variation and linkage disequilibrium in the GABA transporter-1 gene (SLC6A1) in five populations: implications for pharmacogenetic research.  BMC Genet. 2007;  8 71
    CrossrefPubMedGoogle Scholar
  • 31 Ulrich-Merzenich G, Panek D, Zeitler H, Wagner H, Vetter H. New perspectives for synergy research with the “omic”-technologies.  Phytomedicine. 2009;  16 495-508
    CrossrefPubMedGoogle Scholar
  • 32 Teschke R, Schwarzenboeck A, Akinci A. Kava hepatotoxicity: a European view.  N Z Med J. 2008;  121 90-98
    PubMedGoogle Scholar

Dr. Jerome Sarris

Department of Psychiatry
The University of Melbourne
The Melbourne Clinic

130 Church Street, Richmond

Victoria 3121 Melbourne

Australia

Phone: + 61 3 94 20 93 50

Fax: + 61 3 94 27 75 58

Email: j.sarris@uq.edu.au

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