Generalized Anxiety Disorder and Kava

Often known as a popular (though controversial) treatment for depression, Kava is used in many countries as a treatment for anxiety. In fact, when Kava is thought to be used to treat "depression" it is often being used to calm the anxiety that can be present in depressed individuals.

Up until 2002, the herb kava was widely used in Europe as a medical treatment for anxiety, based on the evidence of a substantial body of double-blind, placebo-controlled studies. However, because of recent concerns involving its potential effects on the liver, it has been withdrawn from the market in many countries.

Read more details about Kava.

There have been at least 11 placebo-controlled studies of kava, involving a total of more than 700 people.^{13,16,18,38,39,41-43, 55} Most found kava helpful for anxiety symptoms.

One of the best of these was a 6-month, double-blind study that tested kava's effectiveness in 100 people with various forms of anxiety.¹³ Over the course of the trial, they were evaluated with a list of questions called the Hamilton Anxiety Scale (HAM-A). The HAM-A assigns a total score based on such symptoms as restlessness, nervousness, heart palpitations, stomach discomfort, dizziness, and chest pain. Lower scores indicate reduced anxiety. Participants who were given kava showed significantly improved scores beginning at 8 weeks and continuing throughout the duration of the treatment.

This study is notable for the long delay before kava was effective. Previous studies had shown a good response in one week.^14,15,16 The reason for this discrepancy is unclear.

Several double-blind, placebo-controlled studies have specifically tested kava for the treatment of the anxiety that often occurs during menopause.^{15,16, 38} In one study, 40 women were given either kava plus standard hormone therapy or hormone therapy alone for a period of 6 months. The results showed that women given kava experienced greater improvement in symptoms than those given hormone therapy alone.

However, not all studies have been positive. One double-blind, placebo-controlled study failed to find kava effective for people with generalized anxiety disorder (GAD).³⁹ Another study failed to find kava more effective than placebo for people with both anxiety and insomnia.⁵⁵

Besides these placebo-controlled studies, one 6-month, double-blind study compared kava against two standard anxiety drugs (oxazepam and bromazepam) in 174 people with anxiety symptoms.¹⁸ Improvement in HAM-A scores was about the same in all groups. Another study found kava equally effective as the drugs buspirone and opipramol.^44 ^

A 5-week, double-blind, placebo-controlled trial studied 40 people who had been taking standard anti-anxiety drugs (benzodiazepines) for an average duration of 20 months.17 Participants were gradually tapered off their medications and switched to kava or placebo. Individuals taking kava showed some improvement in anxiety symptoms. This would appear to indicate that kava can successfully be substituted for benzodiazepine drugs. However, participants who were switched from benzodiazepines to placebo showed little to no increase in anxiety, suggesting perhaps that they didn't really need medication after all! Thus, the results of this study are hard to interpret.

Note: This trial involved close medical supervision and very gradual tapering of benzodiazepine dosages. Do not discontinue anti-anxiety medications without supervision. Withdrawal symptoms can be life-threatening.

One study purported to find evidence that kava helps reduce reactions to stressful situations.¹⁹ Although, the results mean little because the study lacked a placebo group.

Safety Issues

Until recently, kava had been considered a safe herb. Animal studies have shown that kava dosages of up to 4 times the normal amount cause no health problems, and 13 times the normal dosage causes only mild problems in rats. ¹ A study of 4,049 people who took a rather low dose of kava (70 mg of kavalactones daily) for 7 weeks found side effects in 1.5% of cases. These were mostly mild gastrointestinal complaints and allergic rashes. ² A 4-week study of 3,029 people given 240 mg of kavalactones daily showed a 2.3% incidence of basically the same side effects. ³ One review of the literature concluded that "the data support the safety of kava in treating anxiety at 280 mg kava lactones daily for 4 weeks." ⁴ However, a growing number of case reports have raised serious concerns about kava’s safety. These reports suggest that, occasionally, even normal doses of kava can cause severe liver injury. ^{5 6} Based on these reports, regulatory agencies have taken action in numerous countries banning or restricting sale of kava. However, case reports are notorious for failing to show cause and effect, and some well-regarded experts who have reviewed the literature feel that kava has not been shown to be unsafe. ⁷ In a report examining 26 alleged liver toxicity cases in kava users, consuming the herb at the recommended daily dose (less than 120 mg) and duration (less than 3 months) was clearly linked with only one case. ⁸ In all other cases, kava was either not implicated, was taken inappropriately, or was combined with another drug.

At present, if you wish to use this herb, we recommend that you seek physician supervision to monitor for liver inflammation. People with liver problems, who drink alcohol excessively, or who take medications that can harm the liver, are probably at increased risk of harm by kava.

There are other safety concerns as well. For example, kava should not be used by individuals who have had "acute dystonic reactions." These consist of spasms in the muscles of the neck and movements of the eyes, which are believed to be related to effects on dopamine. They are typically caused by antipsychotic drugs , which affect dopamine. Kava might trigger such reactions, too. ⁹ At ordinary doses, kava does not appear to produce mental cloudiness. ¹⁰ However, high doses cause inebriation ¹¹ and can lead to charges of driving under the influence of drugs.

One study suggests that kava does not amplify the effects of alcohol. ¹² However, there is a case report indicating that kava can increase the effects of certain sedative drugs. ¹³ For this reason, kava probably should not be combined with any drugs that depress mental function. Kava should also not be combined with antipsychotic drugs or drugs used for Parkinson's disease , due to the potential for increased problems with movement. ¹⁴ The German Commission E monograph warns against the use of kava during pregnancy and nursing. Safety in young children and individuals with kidney disease has not been established.

Interactions You Should Know About

If you are taking:

• Medications for insomnia or anxiety such as benzodiazepines : Do not take kava in addition to them.
• Antipsychotic drugs : Kava might increase the risk of a particular side effect consisting of sudden abnormal movements, called a dystonic reaction.
• Levodopa for Parkinson's disease: Kava might reduce its effectiveness.
• Medications that can irritate the liver: Avoid kava. Numerous medications have this potential. Ask your physician to see if this concern applies to you.

1. Schulz V, Hansel R, Tyler VE. Rational Phytotherapy: A Physicians' Guide to Herbal Medicine. 3rd ed. Berlin, Germany: Springer-Verlag; 1998:68.
2. Schulz V, Hansel R, Tyler VE. Rational Phytotherapy: A Physicians' Guide to Herbal Medicine. 3rd ed. Berlin, Germany: Springer-Verlag; 1998:71.
3. Schulz V, Hansel R, Tyler VE. Rational Phytotherapy: A Physicians' Guide to Herbal Medicine. 3rd ed. Berlin, Germany: Springer-Verlag; 1998:71.
4. Connor KM, Davidson JR, Churchill LE. Adverse-effect profile of kava. CNS Spectr. 6(10):848, 850-3.
5. Escher M, Desmeules J, Giostra E, Mentha G. Hepatitis associated with Kava, a herbal remedy for anxiety. BMJ. 322(7279):139.
6. Strahl S, Ehret V, Dahm HH, et al. Necrotizing hepatitis after taking herbal remedies [translated from German]. Dtsch Med Wochenschr. 1998;123:1410-1414.
7. Schulze J, Raasch W, Siegers CP. Related Articles, Links Abstract Toxicity of kava pyrones, drug safety and precautions—a case study. Phytomedicine. 2003;10(suppl 4):68-73. Review.
8. Teschke R, Schwarzenboeck A, Hennermann KH. Kava hepatotoxicity: a clinical survey and critical analysis of 26 suspected cases. Eur J Gastroenterol Hepatol. 20(12):1182-93.
9. Schelosky L, Raffauf C, Jendroska K, et al. Kava and dopamine antagonism [letter]. J Neurol Neurosurg Psychiatry. 1995;58:639-640.
10. Munte TF, Heinze HJ, Matzke M, et al. Effects of oxazepam and an extract of kava roots ( Piper methysticum ) on event-related potentials in a word recognition task. Neuropsychobiology. 1993;27:46-53.
11. Cairney S, Maruff P, Clough AR, Collie A, Currie J, Currie BJ. Saccade and cognitive impairment associated with kava intoxication. Hum Psychopharmacol. 18(7):525-33.
12. Herberg KW. Effect of Kava-Special Extract WS 1490 combined with ethyl alcohol on safety-relevant performance parameters [in German, English abstract]. Blutalkohol. 1993;30:96-105.
13. Almeida JC, Grimsley EW. Coma from the health food store: interaction between kava and alprazolam [letter]. Ann Intern Med. 1996;125:940-941.
14. Schelosky L, Raffauf C, Jendroska K, et al. Kava and dopamine antagonism [letter]. J Neurol Neurosurg Psychiatry. 1995;58:639-640.

References for Research Evidence for Kava on Generalized Anxiety Disorder

1. Meyer HJ, Kretzschmar R. Kawa pyrone—a new kind of substance group of central muscle relaxants of the mephenesin type [translated from German]. Klin Wochenschr. 1966;44:902-903.

2. Klohs MW, Keller F, Williams RE, et al. A chemical and pharmacological investigation of Piper methysticum Forst. J Med Pharm Chem. 1959;1:95-103.

3. Bruggemann VF, Meyer HJ. Studies on the analagesic efficacy of the kava constituents dihydrokavain (DHK) and dihydromethysticin (DHM) [in German; English abstract]. Arzneimittelforschung. 1963;13:407-409.

4. Meyer HJ. Pharmacology of the active compounds of the kava rhizome ( Piper methysticum Forst) [translated from German]. Arch Int Pharmacodyn Ther. 1962;138:505-536.

5. Meyer HJ, May HU. Local anaesthetic properties of natural Kava pyrones [translated from German]. Klin Wochenschr. 1964;42:407.

6. Meyer HJ, Kretzschmar R. Kawa pyrone—a new kind of substance group of central muscle relaxants of the mephenesin type [translated from German]. Klin Wochenschr. 1966;44:902-903.

7. Singh YN. Effects of kava on neuromuscular transmission and muscle contractility. J Ethnopharmacol. 1983;7:267-276.

8. Davies LP, Drew CA, Duffield P, et al. Kava pyrones and resin: Studies on GABAA, GABAB and benzodiazepine binding sites in rodent brain. Pharmacol Toxicol. 1992;71:120-126.

9. 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;116:469-474.

10. Boonen G, Haberlein H. Influence of genuine kavapyrone enantiomers on the GABA A binding site. Planta Med. 1998;64:504-506.

11. Emser W, Bartylla K. Improvement in sleep quality. Effect of kava extract WS 1490 on the sleep pattern in healthy subjects [in German, English abstract]. Neurol Psychiatr. 1991;5:636-642.

12. Holm E, Staedt U, Heep J, et al. The action profile of D,L-kavain. Cerebral sites and sleep-wakefulness-rhythm in animals [in German]. Arzneimittelforschung. 1991;41:673-683.

13. Volz HP, Kieser M. Kava-kava extract WS 1490 versus placebo in anxiety disorders—a randomized placebo-controlled 25-week outpatient trial. Pharmacopsychiatry. 1997;30:1-5.

14. Kinzler E, Kromer J, Lehmann E. Effect of a special kava extract in patients with anxiety-, tension-, and excitation states of non-psychotic genesis. Double blind study with placebos over 4 weeks [translated from German]. Arzneimittelforschung. 1991;41:584-588.

15. Warnecke G, Pfaender H, Gerster G, et al. Efficacy of an extract of kava root in patients with climacteric syndrome. A double blind study with a new mono-preparation [translated from German]. Z Phytother. 1990;11:81-86.

16. Warnecke G. Psychosomatic disorders in the female climacterium, clinical efficacy and tolerance of kava extract WS 1490 [translated from German]. Fortschr Med. 1991;109:119-122.

17. Malsch U, Klement S. Randomized placebo-controlled double-blind clinical trial of a special extract of kava roots (WS 1490) in patients with anxiety disorders of non-psychotic origin [abstract]. Eur Phytojournal [serial online]. 2000(1). ESCOP website. Available at: http://www.escop.com/issue_1. Accessed May 10, 2001.

18. Woelk H, Kapoula O, Lehrl S, et al. The treatment of patients with anxiety. A double blind study: kava extract WS 1490 versus benzodiazepine [translated from German]. Z Allg Med. 1993;69:271-277.

19. Cropley M, Cave Z. Effect of kava and valerian on physiological responses to psychological stress assessed under laboratory conditions [abstract]. FACT. 2001;6:76.

20. Schulz V, Hansel R, Tyler VE. Rational Phytotherapy: A Physicians' Guide to Herbal Medicine. 3rd ed. Berlin, Germany: Springer-Verlag; 1998:68.

21. Schulz V, Hansel R, Tyler VE. Rational Phytotherapy: A Physicians' Guide to Herbal Medicine. 3rd ed. Berlin, Germany: Springer-Verlag; 1998:71.

22. Schulz V, Hansel R, Tyler VE. Rational Phytotherapy: A Physicians' Guide to Herbal Medicine. 3rd ed. Berlin, Germany: Springer-Verlag; 1998:71.

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

24. Schelosky L, Raffauf C, Jendroska K, et al. Kava and dopamine antagonism [letter]. J Neurol Neurosurg Psychiatry. 1995;58:639-640.

25. Escher M, Desmeules J, Giostra E, et al. Hepatitis associated with Kava, a herbal remedy for anxiety. BMJ. 2001;322:139.

26. Strahl S, Ehret V, Dahm HH, et al. Necrotizing hepatitis after taking herbal remedies [translated from German]. Dtsch Med Wochenschr. 1998;123:1410-1414.

27. Munte TF, Heinze HJ, Matzke M, et al. Effects of oxazepam and an extract of kava roots ( Piper methysticum) on event-related potentials in a word recognition task. Neuropsychobiology. 1993;27:46-53.

28. Heinze HJ, Munthe TF, Steitz J, et al. Pharmacopsychological effects of oxazepam and kava-extract in a visual search paradigm assessed with event-related potentials. Pharmacopsychiatry. 1994;27:224-230.

29. Munte TF, Heinze HJ, Matzke M, et al. Effects of oxazepam and an extract of kava roots ( Piper methysticum) on event-related potentials in a word recognition task. Neuropsychobiology. 1993;27:46-53.

30. Heinze HJ, Munthe TF, Steitz J, et al. Pharmacopsychological effects of oxazepam and kava-extract in a visual search paradigm assessed with event-related potentials. Pharmacopsychiatry. 1994;27:224-230.

31. Schulz V, Hansel R, Tyler VE. Rational Phytotherapy: A Physicians' Guide to Herbal Medicine. 3rd ed. Berlin, Germany: Springer-Verlag; 1998:72.

32. Herberg KW. Effect of Kava-Special Extract WS 1490 combined with ethyl alcohol on safety-relevant performance parameters [in German, English abstract]. Blutalkohol. 1993;30:96-105.

33. Almeida JC, Grimsley EW. Coma from the health food store: interaction between kava and alprazolam [letter]. Ann Intern Med. 1996;125:940-941.

34. Schelosky L, Raffauf C, Jendroska K, et al. Kava and dopamine antagonism [letter]. J Neurol Neurosurg Psychiatry. 1995;58:639-640.

35. Veh I, Chatterjee SS, Kiianmaa K, et al. Reduction of voluntary ethanol intake in alcohol-preferring AA-rats by kava extract. Presented at International Congress and 49th Meeting of the Society for Medicinal Plant Research; September 2-6, 2001; Erlangen, Germany.

36. Russmann S, Lauterburg BH, Helbling A. Kava hepatotoxicity [letter]. Ann Intern Med. 2001;135:68-69.

37. Kraft M, Spahn TW, Menzel J, et al. Fulminant liver failure after administration of the herbal antidepressant Kava-Kava [in German; English abstract]. Dtsch Med Wochenschr. 2001;126:970-972.

38. De Leo V, la Marca A, Morgante G, et al. Evaluation of combining kava extract with hormone replacement therapy in the treatment of postmenopausal anxiety. Maturitas. 2001;39:185-188.

39. Connor KM, Davidson JR. A placebo-controlled study of Kava kava in generalized anxiety disorder. Int Clin Psychopharmacol. 2002;17:185-188.

40. 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;78:101-110.

41. Gastpar M, Klimm HD. Treatment of anxiety, tension and restlessness states with Kava special extract WS 1490 in general practice: a randomized placebo-controlled double-blind multicenter trial. Phytomedicine. 2003;10:631-639.

42. Geier FP, Konstantinowicz T. Kava treatment in patients with anxiety. Phytother Res. 2004;18:297-300.

43. Lehrl S. Clinical efficacy of kava extract WS((R)) 1490 in sleep disturbances associated with anxiety disorders. Results of a multicenter, randomized, placebo-controlled, double-blind clinical trial. J Affect Disord. 2004;78:101-110.

44. Boerner RJ, Sommer H, Berger W, et al. 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. 2003;10(suppl 4):38-49.

45. Gastpar M, Klimm HD. Treatment of anxiety, tension and restlessness states with Kava special extract WS 1490 in general practice: a randomized placebo-controlled double-blind multicenter trial. Phytomedicine. 2003;10:631-639.

46. Geier FP, Konstantinowicz T. Kava treatment in patients with anxiety. Phytother Res. 2004;18:297-300.

47. Connor KM, Davidson JR, Churchill LE, et al. Adverse-effect profile of kava. CNS Spectr. 2004;6:848-853.

48. Russmann S, Barguil Y, Cabalion P, et al. Hepatic injury due to traditional aqueous extracts of kava root in New Caledonia. Eur J Gastroenterol Hepatol. 2003;15:1033-1036.

49. Anke J, Ramzan I. Abstract Kava Hepatotoxicity: are we any closer to the truth? Planta Med. 2004;70:193-196.

50. Teschke R, Gaus W, Loew D. Kava extracts: safety and risks including rare hepatotoxicity. Phytomedicine. 2003;10:440-446.

51. Schulze J, Raasch W, Siegers CP. Related Articles, Links Abstract Toxicity of kava pyrones, drug safety and precautions—a case study. Phytomedicine. 2003;10(suppl 4):68-73. Review.

52. Anke J, Ramzan I. Abstract Kava Hepatotoxicity: are we any closer to the truth? Planta Med. 2004;70:193-196.

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

54. Cairney S, Maruff P, Clough AR, et al. Saccade and cognitive impairment associated with kava intoxication. Hum Psychopharmacol. 2003;18:525-533.

55. Jacobs BP, Bent S, Tice JA, et al. An internet-based randomized, placebo-controlled trial of kava and valerian for anxiety and insomnia. Medicine. 2005;84:197-207.

56. Teschke R, Schwarzenboeck A, Hennermann KH. Kava hepatotoxicity: a clinical survey and critical analysis of 26 suspected cases. Eur J Gastroenterol Hepatol. 2008;20:1182-1193.