Kava (Piper methysticum)

James Meschino DC, MS, ROHP

General Features
Natives of the South Pacific have used a nonalcoholic drink made from Kava root as a ceremonial and social drink for centuries. Kava was valued for its mellowing effects and to encourage socializing by these native groups.  It has been cultivated over the years for such purposes by Pacific Islanders as first reported by Captain James Cook on his historic voyages through the South Seas. The Kava beverage first causes a numbing and astringent effect in the mouth, followed by a relaxed sociable state where fatigue and anxiety are lessened.  Eventually a deep restful sleep ensues from which one is said to awaken the next morning refreshed and without symptoms of a hangover.  Excess intake can produce a stupor and dizziness, a condition described as Kava abuse.  ²⁶

In 1966, European scientists interested in Kava’s sedative and intoxicant effects isolated its kavalactone constituents, which have been found to produce sedative, pain-killing, and anticonvulsant properties.  Kava is a member of the pepper family and its rootstock or rhizome (underground stem) is used for medicinal purposes.  Its most well defined application is in regards to its ability to reduce feelings of anxiety and as a natural sedative.  ^{1, 9,10, 11}

Principle Active Constituents

Kava-lactones, also known as Kava-pyrones – these consist of fat soluble resins such as dihydrokavain, which have been found to produce sedative, painkilling and anticonvulsant effects.  Other Kava-lactones include kavain, methysticin, and dihydromethysticin.  ^{1, 9, 12,13,14.}

Clinical Application and Mechanism of Action

1. Anxiety

Kava-lactones have been shown to have natural sedative properties by influencing GABA (gamma amino benzoic acid) receptors, in a similar fashion as does benzodiazepines (e.g, valium), but appears to modulate the limbic system emotional processes rather than affect parts of the brain affected by benzodiazepines.  ^{15, 16}The limbic system is the primitive part of the brain that controls our emotions and survival instincts.  ¹⁰

At least six, well-designed, clinical studies have provided evidence that Kava extract can be an effective intervention in the management of anxiety, from non organic causes (e.g., not appropriate for anxiety secondary to hyperthyroidism). These studies have tested Kava extract against placebo, against hormone replacement therapy in the treatment of anxiety associated with menopausal symptoms, and against common drugs used to treat anxiety, such as oxazepam, bromazepam, and other standard benzodiazepines.  In one of the smaller trials, involving 52 anxiety patients, 81% of the subjects treated with Kava extract rated the treatment as very good or good.  In the study of menopausal women, the Kava group reported better overall relief from anxiety than did the groups given hormone replacement therapy or placebo.  When tested head-to-head against anti-anxiety drugs from the class of benzodiazepines, the Kava group reported the same level of improvement as provided by these proven medications.  In total, these studies have followed more than 400 patients and suggest that Kava is an effective intervention for the treatment of anxiety from non-organic causes.  However, Kava’s anti-anxiety effects may not manifest themselves until the eight week of continuous supplementation, although some studies indicate a benefit along these lines within the first week of treatment.  The German Commission E states that Kava is useful for relieving “states of nervous anxiety, tension, and agitation”.  ^{17,18,19,20,21,22,23,24,11}    

Of special note is the fact that unlike benzodiazepines, Kava does not seem to impair reaction time or alertness when taken in divided doses throughout the day for the treatment of anxiety, at recommended intake levels.

2. Insomnia

Kava is known to have sedative effects at specific levels of intake, which have prompted its use as a natural treatment for insomnia.  This effect is also considered to be mediated through its influence of the limbic system. ¹⁰ In one placebo-controlled study of 12 healthy volunteers Kava extract was shown to improve the ability to fall asleep at a dose of 300 mg per day (yielding 210 mg of Kava-lactone content).  It also lengthened the deep sleep phase and shortened the wakeful phases in sleep, according to EEG recordings (electro-encephalogram).  These effects are looked upon favorably compared to effects on sleep induced by benzodiazepines and barbituate drugs.  Kava administration also increased the density of sleep spindles, an effect, which is comparable to medical sedative drugs.  ²⁶

Dosage and Standardized Grade
Kava extract should be standardized to contain a set percentage of Kava-lactone content.  High-yielding products contain 70% Kava-lactone content as a rule

1. Anxiety (mild to moderate cases) – 45-70 mg Kava-lactones, three times daily.  Up to 240 mg per day of Kava-lactone intake has been used for this purpose. The total daily dose should not exceed 300 mg.  ^9,10,11,26
2. Insomnia – 180—210 mgs of Kava-lactones one hour before bed time.^1,2,3

According to the German Commission E monograph Kava should not be taken for more than three months without the advice of a physician.  ²⁷

Adverse Side Effects, Toxicity and Contraindications

1. Liver Damage: Over the years there has been some suggestion that Kava use may induce liver damage in long-term users, as evidenced by the yellowing of the skin that occurs in some Kava users. ²⁸   However, this was considered to be a skin reaction by many authorities and concern about liver injury was not strongly considered. As such, Kava was generally regarded as a safe supplement until recently. ²⁷ However, in November 2001, German authorities reported 24 cases of liver damage associated with the use of Kava in Germany.  Liver problems included hepatitis, liver failure, and cirrhosis.  Of these, one person died and three required a liver transplant.  ²⁹ The 1998 edition of the German Commission E Monographs does not mention liver disease in its discussion of Kava’s side effects. ²⁷   Since that publication date, four case reports of Kava-induced liver toxicity have appeared in medical journals.  In two of these cases, severe liver failure resulted in the need for a liver transplant.  ^30,31,32,33   Of interest is the fact that in most, but not all of these cases, patients were taking other medications, which are known to cause liver damage as an established side effect.  This may imply that Kava potentiated the liver-damaging effects of these drugs in these cases and that the use of Kava in the absence of such medications may not pose the same degree of risk of liver injury. ³⁴   However, some of the cases of Kava-related liver disease cannot be explained by the concomitant use of other drugs.  ⁹

Other investigations have implicated Kava as an agent that can produce liver injury.  A survey of the aboriginal community in Australia revealed that heavy Kava users were at higher risk of developing liver damage, as evidenced by laboratory studies, than were non- users and occasional users of Kava.  Risk of liver injury was directly related to the amount of Kava consumed.  ³⁵

In Germany, Canada and the United States, governments are have considered banning the use of Kava, due to reports from Europe indicating that taking Kava at recommended intake levels can induce severe liver injury, even in occasional users.  At this time, Kava is still available without a prescription in many parts of the world, but experts suggest that individuals seek appropriate monitoring of liver enzymes by their physician if they intend to use this herbal agent on any level of frequency.  Anyone with pre-existing liver disease or taking other drugs known to cause liver damage, or consuming alcohol on a regular basis, should avoid the use of Kava altogether. ¹¹

On December, 18, 2001 the Food and Drug Administration (FDA) in the United States informed health care practitioners that it was launching an investigation to determine if Kava supplementation poses a health threat to human health.  The agency noted that German and Swiss health authorities had reported approximately 25 cases of serious liver toxicity, related to Kava consumption. This initial communication was to serve as a data-gathering tool and was not issued as a warning or alert.  “ Although there are currently no published reports of liver toxicity in the U.S., the FDA has indicated that it has received adverse event reports through its MEDWATCH system that potentially links Kava to liver damage.”  ⁴¹

2. Other Side Effects: Long-term use (few months to a year) can produce Kava dermopathy (scali skin eruptions) on the palms, soles, forearms, back and shins. High doses (7310 gms per week) may decrease serum albumin, protein, urea, bilirubin, platelet count and lymphocyte count.^1,2,3,4  Kava may temporarily turn skin yellow, create mild gastrointestinal disturbances, induce an allergic skin reaction, such as a rash and/or produce pupil enlargement in long-term users.  ^28,36,37   Short-term Kava studies (4 –7 weeks) at usual intake doses have not shown any significant side effects other than the occasional report of gastrointestinal upset or skin rash.   ³⁸
3. Acute Dystonic Reactions: Kava should not be use by individuals who have had acute dystonic reactions, which consist of spasms in the muscles of the neck and movements of the eyes. These problems are related to the neurotransmitter dopamine, according to popular beliefs, and are typically caused by antipsychotic drugs, which affect dopamine.  Kava may trigger these reactions in patients with a known history of dystonic reactions.  ⁴⁰

Drug-Nutrient Interactions

Kava supplementation is reported to potentiate the effects of the following medications leading to excess sedation and thus, should not be taken concurrently:

1. Sedative medications ( benzodiazepines)^{42, 43}
2. Alprazolam – a reported case possibly lead to coma in a patient combining Kava with this drug. ⁴⁴
3. Antidepressant drugs ⁴²
4. Diphenydramine – an over-the-counter drug that induces sedation ^41,42
5. Alcohol – some reports suggest that Kava can increase alcohol’s damaging effects to the heart, nervous system, liver, immune system, kidneys and other organs. It is advisable not to combine Kava intake with the consumption of alcohol.  ^48,49,50
6. Antipsychotic drugs – Kava may increase risk of dystonic reactions if combined with these drugs. ¹¹
7. Levodopa – patients with Parkinson’s disease taking levodopa should avoid Kava as Kava’s effects on the dopamine system may reduce the effectiveness of levodopa. ¹¹

1. Singh Y, Kava: An Overview, J Ethnopharmacol 37, 1992, 13-45.
2. Holm E, et.al., Studies on the Profile of the Neurophysiological Effects of D.L.-kavain: Cerebral Sites of Action and Sleep-Wakefulness-Rhythm in Animals, Arzneimittel-Forsch 41, 1991, 673-683.
3. Lindenberg D and Pitule-Schodel H, D, L-kavain in Comparison with Oxazepam in Anxiety Disorders. A Double-blind Study of Clinical Effectiveness, Forschr Med 108, 1990, 49-50, 53-54.
4. Kinzler E, Kromer J, and Lehmann E, Clinical Efficacy of a Kava Extract in Patients with Anxiety Syndrome: Double-blind Placebo Controlled Study Over 4 Weeks, Arzneimittel-Forsch 41, 1991, 584-588.
5. Warnecke G, Neurovegetative Dystonia in the Female Climacteric. Studies on the Clinical Efficacy and Tolerance of Kava Extract WS 1490, Forschr Med 109, 1991, 120-122.
6. Norton SA and Ruze P, Kava Dermopathy, J Am Acac Dermatol 31, 1994, 89-97.
7. Ruze P, Kava-induced Dermopathy: A Niacin Deficiency, Lancet 336, 1990, 1442-1445.
8. Mathews JD, et.al., Effects of the Heavy Usage of Kava on Physical Health: Summary of a Pilot Survey in an Aboricinal Community, Med J Aust 148, 1988, 548-555.
9. Healthnotes, Inc. 2001. healthnotes.com: Kava
10. Dietary Supplement Information Bureau. content.intramedicine.com: Kava
11. Natural Product Encyclopedia. consumerslab.com: Kava
12. 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;44:902-3
13. 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
14. Bruggemann VF, Meyer HJ. Studies on the analagesic efficacy of the kava constituents dihydrokavain (DHK) and dihydromethysticin (DHM) [in German; English abstract]. Arzneimittelforschung 1963;13:407-9
15. 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;116:469-74
16. Boonen G, Haberlein H. Influence of genuine kavapyrone enantiomers on the GABA_A binding site. Planta Med 1998;64:504-6
17. 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
18. Kinsler E, Kromer J, Lehmann E. Effect of a special kava extract in patientw with anxiety-,tension-, and excitation states of non-psychotic genesis. Double blind study with placebos over 4 weeks [translated from German]. Arzneimittelforschung 1991;41:584-8
19. 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;11:81-6
20. Warnecke G. Psychosomatic disorders in the female climacterium, clinical efficacy and tolerance of kava extract WS 1490 [translated from German]. Fortschr Med 1991;109:119-22
21. 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. Available at:http://www.escop.com/issue_1. Accessed May 10, 2001
22. Woelk H, Kapoula O, Lehri S et Al. The treatment of patients with anxiety. A double blind study: dava extract WS 1490 versus benzodiazepine [translated from German]. Z Allg Med 1993;69:271-7
23. Cropley M, Cave Z. Effect of kava and valerian on physiological responses to psychological stress assessed under laboratory conditions [abstract]. FACT 2001;6:76
24. 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;39:185-8
25. Munte 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-recognicition task. Pharmacoelctroencephalog 1993;27:46-53
26. Principles and Practice of Phytotherapy. Mills S and Bone K. Churchill Livingstone. 2000: 456-58
27. Blumenthal M, Busse WR, Goldberg A et al. (eds.) The Complete Commission E Monographs: Therapeutic Guide to Herbal Medicines. Boston MA: Integrative Medicine Communications 1998:156-7
28. Jappe U, Franke I, Reinhold D, Golinick HPM. Sebotropic drug reaction resulting from kava-kava extract therapy: A new entity? J Amer Acad Dermatol 1998:38:104-6
29. Stafford, Ned. Germany may ban kava kava herbal supplement. Reuters Nov.19 2001
30. Escher M, Desmeules J, Giostra E, Mentha G. Hepatitis associated with kava, a herbal remedy for anxiety. BMJ 2001;322:p139
31. Kraft M, Spahn TW, Menzel J et al. [Fulminant liver failure after administration of the herbal antidepressant Kava-Kava.] Dtsch Med Wochenschr 2001;126:970-2 [in German].
32. Strahl S, Ehret V, Dahm HH, Maier KP. [Necrotizing hepatitis after taking herbal remedies.] Dtsch Med Wochenschr 1998;123:1410-4 [in German]
33. Russmann S, Lauterburg BH, Helbling A. Kava hepatotoxicity. Ann Intern Med 2001;135:68-9 [letter]
34. Information provided by the German Federal Institute for Drugs and Medical Devices.
35. Mathews JD, Riley MD, Fejo L et al. Effects of the heavy usage of kava on physical health: summary of a pilot survey in an aboriginal community. Med J Aust 1988;148:548-55
36. Schmidt P, Boehncke WH. Delayed-type hypersensitivity reaction to kava-kava extract. Contact Derm 2000;42:363-4
37. Blumenthal M, Busse WR, Goldberg A et al (eds.) The Complete Commission E Monographs: Therapeutic Guide to Herbal Medicines. Boston MA: Integrative Medicine Communications 1998:156-7
38. Schulz V, Hansel R, Tyler VE. Rational Phytotherapy: A Physician’ Guide to Herbal Medicine. 3^rd Berlin, Germany: Springer-Verlag;1998:p71
39. Schelosky L, Raffauf C, Jendroska K et al. Kava and dopamine antoginism [letter]. J Neurol Neurosurg Psychiatry 1995;58:639-40
40. National Nutritional Foods Association Update. December 21, 2001. Kava safety concerns raised.
41. Jussofie A et al. Kavapyrone enriched extract from piper methysticum as modulator of the GABA binding site in different regions of rat brain. Psychopharmacology (Berl). Dec 1994;116(4):469-74
42. Klohs MW. Chemistry of Kava. Psychopharmacol Bull 1967;4(3):p10
43. Almeida JC et al. Coma from the health food store: Interaction between Kava and Alprazolam. Ann Intern Med Dec1996;125(11):940-1
44. Jamieson DD et al. Positive interaction of ethanol and kava resin in mice. Clin Exp Pharmacol Physiol Jul1990;17(7):509-14
45. Cantor C. Kava and alcohol. Med J Aust Nov1997;167(10):p560
46. Herberg KW. Effect of Kava-special extract WS 1490 combined with ethyl alcohol on safety-relevant performance parameters. Blutalkohol Mar1993;30(2):96-105