Skip to main content
Springer Nature Link
Log in

The Kava Anxiety Depression Spectrum Study (KADSS): a randomized, placebo-controlled crossover trial using an aqueous extract of Piper methysticum

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Piper methysticum (Kava) has been withdrawn in European, British, and Canadian markets due to concerns over hepatotoxic reactions. The WHO recently recommended research into “aqueous” extracts of Kava.

Objective

The objective of this study was to conduct the first documented human clinical trial assessing the anxiolytic and antidepressant efficacy of an aqueous extract of Kava.

Design and participants

The Kava Anxiety Depression Spectrum Study was a 3-week placebo-controlled, double-blind crossover trial that recruited 60 adult participants with 1 month or more of elevated generalized anxiety. Five Kava tablets per day were prescribed containing 250 mg of kavalactones/day.

Results

The aqueous extract of Kava reduced participants' Hamilton Anxiety Scale score in the first controlled phase by −9.9 (CI = 7.1, 12.7) vs. −0.8 (CI = −2.7, 4.3) for placebo and in the second controlled phase by −10.3 (CI = 5.8, 14.7) vs. +3.3 (CI = −6.8, 0.2). The pooled effect of Kava vs. placebo across phases was highly significant (p < 0.0001), with a substantial effect size (d = 2.24, \( \eta_{\text{p}}^2 = 0.428 \)). Pooled analyses also revealed highly significant relative reductions in Beck Anxiety Inventory and Montgomery–Asberg Depression Rating Scale scores. The aqueous extract was found to be safe, with no serious adverse effects and no clinical hepatotoxicity.

Conclusions

The aqueous Kava preparation produced significant anxiolytic and antidepressant activity and raised no safety concerns at the dose and duration studied. Kava appears equally effective in cases where anxiety is accompanied by depression. This should encourage further study and consideration of globally reintroducing aqueous rootstock extracts of Kava for the management of anxiety.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Alonso J, Angermeyer MC, Bernert S, Bruffaerts R, Brugha TS, Bryson H (2004) Prevalence of mental disorders in Europe: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project. Acta Psychiatr Scand Suppl 420:21–27

    PubMed  Google Scholar 

  • American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders, 4th 'text revision' edn. American Psychiatric Association

  • Beck AT, Ward C, Mendelson M (1961) Beck depression inventory (BDI). Arch Gen Psychiatry 4:561–571

    PubMed  CAS  Google Scholar 

  • Beck AT, Epstein N, Brown G, Steer RA (1988) An inventory for measuring clinical anxiety: psychometric properties. J Consult Clin Psychol 56:893–897

    Article  PubMed  CAS  Google Scholar 

  • Blumenthal (2004) The ABC clinical guide to herbs. American Botanical Council

  • Boerner RJ, Sommer H, Berger W, Kuhn U, Schmidt U, Mannel M (2003) Kava-Kava extract LI 150 is as effective as opipramol and buspirone in generalised anxiety disorder—an 8-week randomized, double-blind multi-centre clinical trial in 129 out-patients. Phytomedicine 10(Suppl 4):38–49

    Article  PubMed  Google Scholar 

  • Chouinard G (2004) Issues in the clinical use of benzodiazepines: potency, withdrawal, and rebound. J Clin Psychiatry 65(Suppl 5):7–12

    PubMed  CAS  Google Scholar 

  • Clouatre DL (2004) Kava kava: examining new reports of toxicity. Toxicol Lett 150:85–96

    Article  PubMed  CAS  Google Scholar 

  • Coulter D (2007) Assessment of the risk of hepatotoxicity with kava products. WHO Appointed Committee

  • Currie B, Clough A (2003) Kava hepatotoxicity with western herbal products: does it occur with traditional kava use? MJA 178:412–422

    Google Scholar 

  • Dundar Y, Dodd S, Strobl J, Boland A, Dickson R, Walley T (2004) Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: a systematic review and meta-analysis. Hum Psychopharmacol 19:305–322

    Article  PubMed  CAS  Google Scholar 

  • Hamilton M (1959) The assessment of anxiety states by rating. Br J Med Psychol 32:50–55

    PubMed  CAS  Google Scholar 

  • Kessler RC, Keller MB, Wittchen HU (2001) The epidemiology of generalized anxiety disorder. Psychiatr Clin North Am 24:19–39

    Article  PubMed  CAS  Google Scholar 

  • Lebot V (2006) The quality of Kava consumed in the South Pacific. HerbalGram 71:34–37

    Google Scholar 

  • Lecrubier Y (2007) Widespread underrecognition and undertreatment of anxiety and mood disorders: results from 3 European studies. J Clin Psychiatry 68(Suppl 2):36–41

    PubMed  Google Scholar 

  • Martin JL, Sainz-Pardo M, Furukawa TA, Martin-Sanchez E, Seoane T, Galan C (2007) Benzodiazepines in generalized anxiety disorder: heterogeneity of outcomes based on a systematic review and meta-analysis of clinical trials. J Psychopharmacol 21:774–782

    Article  PubMed  CAS  Google Scholar 

  • Mathews JM, Etheridge AS, Valentine JL, Black SR, Coleman DP, Patel P, So J, Burka LT (2005) Pharmacokinetics and disposition of the kavalactone kawain: interaction with kava extract and kavalactones in vivo and in vitro. Drug Metab Dispos 33:1555–1563

    Article  PubMed  CAS  Google Scholar 

  • Mitte K, Noack P, Steil R, Hautzinger M (2005) A meta-analytic review of the efficacy of drug treatment in generalized anxiety disorder. J Clin Psychopharmacol 25:141–150

    Article  PubMed  CAS  Google Scholar 

  • Montgomery S, Asberg M (1979) New depression scale designed to be sensitive to change. Br J Psychiatry Suppl 134:382–389

    Article  CAS  Google Scholar 

  • Morris S (2008) Estimating effect sizes from pretest–posttest–control group designs. Organ Res Methods 11:364–386

    Article  Google Scholar 

  • Nerurkar P, Dragull K, Tang C (2004) In vitro toxicity of Kava alkaloid, pipermethysticine, in HepG2 cells compared to kavalactones. Toxicol Sci 79:106–111

    Article  PubMed  CAS  Google Scholar 

  • Pittler MH, Ernst E (2000) Efficacy of kava extract for treating anxiety: systematic review and meta-analysis. J Clin Psychopharmacol 20:84–89

    Article  PubMed  CAS  Google Scholar 

  • Pittler MH, Ernst E (2006) Kava extract for treating anxiety. Cochrane Database Syst Rev: CD003383

  • Posternak MA, Zimmerman M (2005) Is there a delay in the antidepressant effect? A meta-analysis. J Clin Psychiatry 66:148–158

    Article  PubMed  CAS  Google Scholar 

  • Rickels K, Rynn M (2002) Pharmacotherapy of generalized anxiety disorder. J Clin Psychiatry 63(Suppl 14):9–16

    PubMed  CAS  Google Scholar 

  • Robins LN, Wing J, Wittchen HU, Helzer JE, Babor TF, Burke J, Farmer A, Jablensky A, Pickens R, Regier DA, Sartorius N, Towle LH (1989) The Composite International Diagnostic Interview: an epidemiologic instrument suitable for use in conjunction with different diagnostic systems and in different cultures. Arch Gen Psychiatry 45:1069–1077

    Google Scholar 

  • Sarris J, Kavanagh DJ, Deed G, Bone KM (2009) St. John’s wort and Kava in treating major depressive disorder with comorbid anxiety: a randomised double-blind placebo-controlled pilot trial. Hum Psychopharmacol 24:41–48

    Article  PubMed  CAS  Google Scholar 

  • Singh YN, Devkota AK (2003) Aqueous kava extracts do not affect liver function tests in rats. Planta Med 69:496–499

    Article  PubMed  CAS  Google Scholar 

  • Stevinson C, Huntley A, Ernst E (2002) A systematic review of the safety of kava extract in the treatment of anxiety. Drug Safety 25:251–261

    Article  PubMed  Google Scholar 

  • Thompson R, Ruch W, Hasenöhrl R (2004) Enhanced cognitive performance and cheerful mood by standardized extracts of Piper methysticum (Kava-kava). Hum Psychopharmacol 19:243–250

    Article  PubMed  CAS  Google Scholar 

  • Tyrer P, Baldwin D (2006) Generalised anxiety disorder. Lancet 368:2156–2166

    Article  PubMed  Google Scholar 

  • Vanuatu Kava Act (2002) Republic of Vanuatu No.7

  • Wittchen HU (2002) Generalized anxiety disorder: prevalence, burden, and cost to society. Depress Anxiety 16:162–171

    Article  PubMed  Google Scholar 

  • Witte S, Loew D, Gaus W (2005) Meta-analysis of the efficacy of the acetonic Kava-kava extract WS1490 in patients with non-psychotic anxiety disorders. Phytother Res 19:183–188

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

Thanks are extended to Peter O’Rourke and Kylie Mallitt for their assistance with analyzing the data and to Ashley Dowell and the Centre for Phytochemistry and Pharmacology at Southern Cross University (Lismore Australia) for providing HPLC analysis of the Kava tablets.

Conflicts of interest

Kerry Bone is a consultant to MediHerb Pty Ltd (supplier of the tablets). He was not involved in the conduct of the study or the analysis of the data.

Author information

Authors and Affiliations

  1. School of Medicine, The University of Queensland, Brisbane, Australia

    J. Sarris, G. Byrne & G. Deed

  2. Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia

    D. J. Kavanagh

  3. School of Health, University of New England, Armidale, Australia

    K. M. Bone

  4. School of Population Health, The University of Queensland, Brisbane, Australia

    J. Adams

Authors
  1. J. Sarris
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. D. J. Kavanagh
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. G. Byrne
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. K. M. Bone
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. J. Adams
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. G. Deed
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to J. Sarris.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sarris, J., Kavanagh, D.J., Byrne, G. et al. The Kava Anxiety Depression Spectrum Study (KADSS): a randomized, placebo-controlled crossover trial using an aqueous extract of Piper methysticum . Psychopharmacology 205, 399–407 (2009). https://doi.org/10.1007/s00213-009-1549-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-009-1549-9

Keywords