Kava: A Safe Herbal Treatment for Anxiety

Kava: A Safe Herbal Treatment for Anxiety

Captain James Cook, in the account of his voyage to the South Seas in 1768, first described for the western world the ceremonial use of an intoxicating drink prepared from Piper methysticum, better known as kava. The kava beverage first causes a numbing and astringent effect in the mouth. This is followed by a relaxed, sociable state where fatigue and anxiety are lessened. Eventually a deep restful sleep ensues from which the user awakens the next morning refreshed and without a hangover. Excessive consumption can lead to dizziness and stupefaction, and a syndrome of kava abuse has been described. For this reason some practitioners have been reluctant to use kava therapeutically. However recent clinical studies from Germany have demonstrated the important value of kava as a safe, non-addictive anxiolytic with an efficacy comparable to benzodiazepines (such as Valium).


Piper methysticum Forst is a robust, slightly succulent, coarsely branching, erect, perennial shrub belonging to the pepper family (Piperaceae). It is found and used in nearly all the Pacific islands except New Zealand, New Caledonia and most of the Solomon Islands. Use in Hawaii was once common but has now practically disappeared.( 1)

The main active constituents in the root and rhizome (rootstock) are a group of resinous compounds called the kava lactones (also known as the kava a -- pyrones). Good quality rhizome contains between 5.5 and 8.3% kava lactones comprising mainly kavain, dihydrokavain (DHK) and methysticin although several others are present in lower quantities.( 2, 8) The kava beverage is usually prepared by extracting the powdered root with cold water. More potent kava beverages were either prepared by first chewing the rootstock (saliva breaks down the starch in the root and facilitates the suspension of the resin)( 4) or by extracting with alcohol. Pharmaceutical preparations are prepared with ethanol or other solvents to ensure complete extraction of the kava lactones.


A. Sedative and Hypnotic Effects

Early studies demonstrated the ability of kava extracts or purified lactones to induce sleep in a variety of test animals.( 4, 5) Sedative activities were also found( 4), and in one study the total extract of the rhizome was more active than any of the isolated kava lactones.( 6)

Meyer found that DHK and dihydromethysticin (DHM) produced sedation and hypothermia in mice,( 7) and kava lactones given to rabbits produced EEG (electroencephalogram) changes similar to sedative drugs.( 8)

The effects of a lactone-free aqueous extract of kava were compared to kava resin in mice.( 9) The aqueous extract on injection reduced spontaneous activity but unlike the resin did not reduce motor control or induce sleep. The aqueous extract was devoid of oral activity. It was concluded that the major pharmacological effects of kava are due to the compounds in the resin.( 9) Other workers have also recorded sedative effects from the injection of the aqueous extract of kava.( 10)

Kava resin also significantly countered amphetamine-induced hypermotility in mice and reduced the number of conditioned avoidance responses.( 11) However its effect was mild compared to standard antipsychotic drugs such as chlorpromazine. Higher doses of kava resin caused marked ataxia and sedation.( 11)

In an important study, German scientists investigated the effect of kavain and kava extract on EEG patterns.( 12) It was concluded that the limbic structures of the brain, and in particular the amygdalar complex, represent the preferential site of action for both kavain and the kava extract. The EEG changes due to the extract were more extensive than for kavain alone. The effect on the limbic structures, given their participation in modulating emotional processes, may explain the promotion of sleep even in the absence of sedation. According to the authors, the effects of kava on the brain are quite different from benzodiazepines or the tricyclic antidepressants.( 12) Neither kava resin nor kava lactones have any significant interaction with GABA (gamma-aminobutyric acid) or benzodiazepine binding sites in the brain.( 13)

B. Muscle-Relaxing and Anticonvulsant Activities

One of the characteristic effects of the kava lactones on the central nervous system is their ability to produce a mephenesin-like relaxation of skeletal muscle.( 14) Higher doses cause ataxia and paralysis without loss of consciousness, followed by complete recovery. Kava extract demonstrated a direct skeletal muscle relaxing effect in vitro.( 15)

Like the drug mephenesin, kava also has anticonvulsant properties. In fact the kava lactones were up to ten times more effective than mephenesin against the convulsant effect of strychnine.( 16) A mixture of the lactones in the proportion which is found in the root revealed a synergistic effect against strychnine convulsions. The potency of the mixture was comparable to the most potent lactone (DHM), which was only 5% of the mixture.( 6) Kava lactones also show anticonvulsant activity in the electroshock and pentylenetetrazol pharmacological models.( 17) When injected intravenously the differences in the anticonvulsant activity of the lactones are only small.( 18) The marked differences on oral dosing are therefore probably due to different rates of absorption. Hence the synergistic effect described above may be explained by enhanced absorption of the lactone mixture.

C. Local Anaesthetic and Analgesic Activities

Kava lactones have potencies similar to cocaine and procaine as local anaesthetics.( 19) The analgesic activities of kava resin and kava lactones have been demonstrated in several studies.( 9, 20, 21) As an analgesic, DHK was superior to aspirin, but considerably less potent than morphine.( 20) Combined administration of DHK with aspirin indicated an additive synergism between the two compounds. Caffeine diminished the duration, but not the intensity, of the analgesic effects of DHK and DHM.( 20) Kava resin, kava lactones and a lactone-free aqueous extract of kava all demonstrated analgesic properties in animal models when given by injection.( 21) Naloxone, a morphine antagonist, had no effect on the analgesic activity, showing that analgesia produced by kava occurs via non-opiate pathways.( 21)

D. Antifungal Activity

Kava has been traditionally used as an antibacterial agent, especially for urinary tract infections, but in vitro studies failed to establish significant antibacterial activity.( 22, 23) However, some of the lactones exhibited remarkable fungistatic properties against a wide variety of pathogenic fungi, but not species of Candida.( 23) It is possible that the reputed effectiveness of kava in bacterial urinary tract infections is for different reasons. Or perhaps the lactones undergo chemical changes before being excreted in the urine which may affect antibacterial activity.( 24, 25)

E. Other Effects

The kava lactones also relax smooth muscle. They have shown a papaverine-like spasmolytic action in vitro.( 1) Kava extract, methysticin and DHM, but not other kava lactones, protected brain tissue in mice and rats against ischaemic damage.( 26) The results were similar to those produced by the anticonvulsant compound memantine.

Kava shows some activity in the antitetrabenazine test which is used as a preliminary screening for antidepressant activity.( 9) This is consistent with the mild euphoria which typically follows kava consumption.

High doses of ethanol potentiate the sedative and hypnotic activity of kava resin in mice.( 27) They also markedly increase the toxicity of kava.( 27)

Kava resin did not produce tolerance in mice when given at a minimally effective daily dose for seven weeks.( 28) A considerably higher dose caused partial physiological tolerance. Learned tolerance was also not evident after three weeks of daily dosing.( 28)


The metabolism of several kava lactones was studied in the rat after oral doses.( 25) Approximately half the dose of DHK was found in the urine in 48 hours, of which two-thirds was hydroxylated metabolites. Lower amounts of urinary metabolites were recorded for the other major lactones, possibly reflecting reduced absorption.

Kava lactones are more rapidly absorbed when given orally as an extract of the root than when given as single compounds.( 29) In fact, the bioavailability of lactones, as measured by peak plasma concentrations, is up to three to five times higher for the extract than when given as single substances.

Kava lactones showed a range of uptake rates into brain tissue when administered as single compounds by intraperitoneal (ip) injection to mice.( 30) However when crude kava resin was administered the same way, the concentrations of two lactones were markedly increased (2 to 20 times), while the others remained at the level of incorporation established by their individual injection,( 30)

Much of the above data, and that from the pharmacological studies, support the concept that the kava lactones are more bioactive and bioavailable when administered as the complex found in the living plant, rather than as isolated compounds.


The LD(50) of kava lactones given by ip injection to various test animals ranged from 300 to 400 mg/kg.( 7) After oral doses, the LD(50) in the mouse was 920 mg/kg for DHK and 1050 mg/kg for DHM.( 7) Doses of 50 mg/kg of DHM three times a week for three months to rats produced no evidence of chronic toxicity.( 31)

Human Pharmacology

In a single-blind study with placebo of six healthy volunteers, a standardized extract of kava improved cognitive performance and stabilized emotional disposition without causing sedation,( 32) EEG changes after taking kava were typical of those produced by known antianxiety agents.( 32) However the EEG profile did not support a sedating or hypnotic effect for kava at the tested dosage.( 32) There were no side effects from taking the kava extract,( 32)

Forty healthy subjects given standardized extract of kava under double-blind conditions were subjected to a battery of tests to assess the effect on performance capability relevant to operating machines and driving.( 33) No significant changes were found, which confirmed the safety of the kava extract at the tested dosage.( 33)

Twelve healthy volunteers were tested in a double-blind crossover study to compare the effects of oxazepam (a benzodiazepine drug) and a standardized kava extract.( 34) While there was a significant decrease in the quality and speed of responses with oxazepam in several psychometric tests, no changes were observed with kava treatment. In a memory test using word recognition, there was a tendency for kava to improve reaction time and correct answers which was not statistically significant, whereas oxazepam significantly slowed reaction time and reduced the number of correct answers.( 34) The changes in event-related potentials induced by kava during the word recognition task were quite different from changes caused by oxazepam.( 34)

A standardized kava extract was tested in a placebo-controlled double-blind study to assess any adverse effects on the safety of alcohol use.( 35) A battery of tests revealed no negative effect of kava on safety-related performance after alcohol consumption (0.05% blood alcohol concentration). In fact the kava extract tended to counter the adverse effect of alcohol on concentration.

When 500 mL of kava beverage prepared in the traditional Fijian manner was given to a volunteer, marked changes in visual function occurred.( 36) A reduced near-point of accommodation and convergence, an increase in pupil diameter and disturbance of the ocular muscle balance were noted. Maximum changes occurred thirty to forty minutes after taking the kava drink.

Clinical Trials

Earlier trials used purified kavain at a dose of 400 mg per day. In one placebo-controlled double-blind study of 84 patients with anxiety symptoms, kavain improved vigilance, memory and reaction time.( 37) Kavain was compared with oxazepam in a placebo-controlled double-blind trial of 38 patients with anxiety associated with neurotic disturbances.( 36) The substances proved to be equivalent in the nature and the potency of their anxiolytic action. Both treatments caused progressive improvement in two different anxiety scores over a four week period.

In a randomized placebo-controlled double-blind study of 58 patients with anxiety not caused by psychotic disorders, a standardized kava extract significantly improved measures of anxiety and depression.( 39) For patients receiving the kava extract, there was a significant reduction of anxiety after the first week of treatment, and the difference between kava and placebo increased throughout the four weeks of the study. There were no adverse effects reported for the kava extract.

The effect of a standardized kava extract was assessed in a randomized placebo-controlled double-blind trial on 40 patients with neurovegetative symptoms associated with menopause.( 40) Compared to placebo, the kava extract effected a significant reduction in anxiety, depression, severity of symptoms and menopausal symptoms. The subjective well-being of patients improved with kava and the treatment was well tolerated.

Therapeutic Indications

- Kava is a safe stabilizing treatment for anxiety, which at normal therapeutic doses does not dampen alertness or interact with mild alcohol consumption. Unlike the benzodiazepine drugs there is no risk of tolerance or addiction with kava. Its slight antidepressant activity makes it particularly suitable for the treatment of anxiety associated with minor forms of depression.

- Kava is one of the few safe skeletal muscle relaxants known in the plant kingdom. This property makes it useful for the treatment of nervous tension and conditions associated with skeletal muscle spasm and tension, such as headaches due to neck tension.

- Although pharmacological tests indicate that kava is not a sedative in the same sense as the antipsychotic and benzodiazepine drugs, it is an excellent hypnotic for the treatment of mild insomnia. High doses of kava do cause marked sedation, but such doses are not relevant to normal clinical use.

- The mild anticonvulsant action of kava may be useful in the treatment of epilepsy, but kava is not sufficiently active to control this condition on its own.

- The local anaesthetic action on mucous membranes makes kava useful for pain control in oral conditions. Kava douches have been successfully used for vaginal pruritus.

- The analgesic activity of kava has not been tested clinically but may prove helpful in the control of pain.

- Kava is active as a topical antifungal agent.

Additional Traditional Uses

Traditionally kava has been mainly used for chronic irritation of the urogenital tract, especially gonorrhoea. Very early research found that kavain was active against the gonococcus, although later research found kava to be devoid of antibacterial activity (activity against the gonococcus was not tested).( 23)

Adverse Effects

Long term consumption of large quantities of kava causes a characteristic skin lesion. The skin becomes pigmented, dry and covered with scales. It has been suggested that this rash may be due to a deficiency of one of the B vitamins, but a clinical trial of 100 mg of nicotinamide per day failed to have a significant effect.( 41) The rash quickly regresses if kava intake is ceased. A clinical pharmacological evaluation of DHM found that doses of 300 to 800 mg per day produced a scaly skin rash in a high percentage of subjects.( 4)

The adverse effects of heavy kava usage in an Australian aboriginal community have been reported.( 42) Kava users were more likely to have adverse biochemical and haematological changes and the typical scaly rash. However the kava consumption was extremely high, more than 310 g/week for 35 of the 39 kava users. Also it has been questioned whether all the adverse effects reported were only due to kava consumption,( 43) since ethanol in large doses can potentiate the toxicity of kava.( 27)

The use of a standardized extract of kava equivalent to a daily dose of 210 mg of kava lactones did not result in adverse effects during up to eight weeks of continuous use.( 39, 40) A potentiation of central acting agents such as alcohol, barbiturates, antidepressants and sedatives is possible however.


For anxiolytic activity the following doses are recommended:

Standardized preparations -100 to 200 mg of kava lactones per day

Dried rhizome -1.5 to 3 g per day

Alcoholic 1:2 extract - 3 to 6 ml per day (20 to 40 ml/per week)

The daily dose should be divided throughout the day. Clinical trials on the standardized extract employed doses at the higher end of this range. For hypnotic activity the same daily quantity should be taken as a single dose one hour before bed.

For the other effects of kava, similar or higher doses may be required. Long term use of a dose equivalent to 400 mg or more of kava lactones per day is likely to cause a scaly skin rash in some patients.

To put therapeutic doses of kava in perspective, a standard bowl of kava beverage contains about 250 mg of kava lactones,( 44) and several bowls may be consumed at one sitting.

(1.) Singh YN, Kava: an overview. Journal of Ethnopharmacology 1992; 37:13-45.

(2.) Shulgin AT, The Narcotic Pepper- the Chemistry and Pharmacology of Piper methysticum and Related Species. Bulletin on Narcotics 1973; 25:59-74.

(3.) Hänsel R, Lazar J, Kava pyrone. Deutsche Apotheker Zeitung 1985; 125:2056.

(4.) Keller F, Klohs MW, A Review of the Chemistry and Pharmacology of the Constituents of Piper methysticum. Lloydia 1963; 26:1-15.

(5.) Hänsel R, Beiersdorff HV, Zur Kenntnis der sedativen Prinzipien des Kawa-Rhizoms. Arzneim-Forsch 1959; 9:581.

(6.) Klohs MW, Keller WF, Williams RE, Toekes MI, Cronheim GE, A Chemical and Pharmacological Investigation of Piper methysticum Forst. J. Med. Pharm Chem 1959; 1:95-103.

(7.) Meyer HJ, Pharmakologie der Wirksamen Prinzipien des Kawa-Rhizoms (Piper methysticum Forst). Arch Int Pharmacodyn 1962; 138:505-535.

(8.) Kretzschmar R, Teschendorf H J, Pharmakologische Untersuchungen zur sedativ-tranquilisierenden Wirkung des Rauschpfeffers Piper methysticum Forst. Chemiker Zeitung 1974; 98:24.

(9.) Jamieson DD, Duffield PH, Cheng D, Duffield AM, Comparison of the Central Nervous System Activity of the Aqueous and Lipid Extract of Kava (Piper methysticum). Arch Int Pharmacodyn. 1989; 301:66-80.

(10.) Furgiuele AR, Kinnard WJ, Aceto MD, Buckley JP, Central Activity of Aqueous Extracts of Piper methysticum (Kava). Journal of Pharmaceutical Sciences 1965; 54:247-252.

(11.) Duffield PH, Jamieson D, Duffield AM, Effect of Aqueous and Lipid-Soluble Extracts of Kava on the Conditioned Avoidance Response in Rats. Arch Int Pharmacodyn 1989; 301:81-90.

(12.) Holm E, Staedt U, Heep J, Kortsik C, Behne F, Kaske A, Mennicke I, Untersuchungen zum Wirkungsprofil von D,L-Kavain. Arzneim-Forsch 1991; 41:673-683.

(13.) Davies LP, Drew CA, Duffield P, Johnston GA, Jamieson DD, Kava Pyrones and Resin: Studies on GABA(A), GABA(B) and Benzodiazepine Binding Sites in Rodent Brain. Pharmacol Toxicol 1992;71: 120-126.

(14.) Meyer HJ, Kretzschmar R, Kawa-Pyroneeine neuartige Substanzgruppe zentraler Muskelrelaxantien vom Typ des Mephenesins. Klin Wschr 1966; 44:902-903.

(15.) Singh YN, Effects of Kava on Neuromuscular Transmission and Muscle Contractility. Journal of Ethnopharmacology 1983;7:267-276.

(16.) Kretzschmar R, Meyer HJ, Teschendorf HJ, Strychnine Antagonistic Potency of Pyrone Compounds of the Kava Root (Piper methysticum Forst). Experientia 1970; 26:283-284.

(17.) Kretzschmar R, Meyer HJ, Vergleichende Untersuchungen Uber Die Antikonvulsive Wirksamkeit Der Pyronverbindungen Aus Piper methysticum Forst. Arch Int Pharmacodyn 1969; 177:261-277.

(18.) Meyer HJ, Kretzschmar R, Untersuchungen Uber Beziehungen zwischen Molekularstruktur and pharmakologischer Wirkung C6-arylsubstituierter 4-Methoxy-alpha-pyrone vom Typ der Kawa-Pyrone. Arzneim-Forsch (1969); 19:617-623.

(19.) Meyer HJ, May HU, Lokalanaesthetische Eigenschaften naturlicher Kawa-Pyrone. Klin Wschr 1964; 42:407.

(20.) Bruggenmann F, Meyer HJ, Die analgetische Wirkung der Kawa-Inhaltsstoffe Dihydrokawain und Dihydromethysticin. Arzneim-Forsch 1963; 13:407-409.

(21.) Jamieson DD, Duffield PH, The Antinociceptive Actions of Kava Components in Mice. Clinical and Experimental Pharmacology and Physiology 1990; 17:495-508.

(22.) Hansel R, Characterization and Physiological Activity of some Kava Constituents. Pacific Sconce 1966; 22:293-313.

(23.) Hansel R, Weiss D, Schmidt B, Fungistatische Wirkung der Kawa droge und Ihrer Inhaltsstoffe. Planta Med 1966; 14:1-9.

(24.) Duffield AM, Jamieson DD, Lingard RO, Duffield PH, Bourne DJ, Identification of Some Human Urinary Metabolites of the Intoxicating Beverage Kava. J Chromatogr 1989; 475:273-281.

(25.) Rasmussen AK, Scheme RR, Solheim E, Hansel R, Metabolism of some Kava Pyrones in the Rat. Xenobiotica 1979; 9:1-16.

(26.) Backhauss C, Krieglstein J, Extract of Kava (Piper methysticum) and its Methysticin Constituents Protect Brain Tissue Against Ischaemic Damage in Rodents. European Journal of Pharmacology 1992; 215:265-269.

(27.) Jamieson DD, Duffield PH, Positive Interaction of Ethanol and Kava Resin in Mice. Clinical and Experimental Pharmacology and Physiology 1990; 17:509-514.

(28.) Duffield PH, Jamieson D, Development of Tolerance to Kava in Mice. Clinical and Experimental Pharmacology and Physiology 1991; 18:571-578.

(29.) Biber A, Vergleichende Bioverfugbarkeit von Kava-Laktonen aus Extrakten bzw. Mischung der Einzelsubstanzen am Hund. Internal Publications of Dr Willmar Schwabe, Karlsruhe 1989.

(30.) Keledjian J, Duffield PH, Jamieson DD, Lingard RO, Duffield AM, Uptake into Mouse Brain of Four Compounds Present in the Psychoactive Beverage Kava. J Pharm Sci 1988; 77;1003-1006.

(31.) Meyer HJ, Pharmakologie der Kawa-Droge (Piper methysticum Forst). Habilitationsschrift, Freiburg 1966.

(32.) Johnson D, Frauendorf A, Stecker K, Stein U, Neurophysiologisches Wirkprofil und Vertraglichkeit von Kava-Extrakt WS 1490. Eine Pilotstudie mit randomisierter Auswertung. T W Neurologie Psychiatrie 1991; 5:349.

(33.) Herberg KW, Fahrtuchtigkeit nach Einnahme von Kava-Spezial-Extrakt WS 1490. Doppelblinde placebokontrollierte Probandenstudie. Zeitschr Allgemein Med 1991; 67:842.

(34.) 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 Recognition Task. Neuropsychobiology 1993; 27:46-53.

(35.) Herberg KW, Effect of Kava-Special Extract WS 1490 Combined with Ethyl Alcohol on Safety-relevant Performance Parameters. Blutalkohol 1993; 30:96-105.

(36.) Garner LF, Klinger JD, Some Visual Effects Caused by the Beverage Kava. Journal of Ethnopharmacology 1985; 13:307-311.

(37.) Scholing WE, Clausen H D, On the Effect of D,L-Kavain: Experience With Neuronika. Med Klin 1977; 72:1301-1306.

(38.) Lindenberg D, Pitule-Schodel H, D,L-Kavain in Comparison with Oxazepam in Anxiety Disorders. A double-blind Study of Clinical Effectiveness. Fortschr Med 1990; 108:49-50.

(39.) 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. Arzneim-Forsch 1991; 41:584-588.

(40.) Warnecke G, Psychosomatic Dysfunctions in the Female Climacteric. Fortschr Med 1991; 109:119-122.

(41.) Ruze P, Kava-induced Dermopathy: A Niacin Deficiency? The Lancet 1990; 335:1442-1445.

(42.) Mathews JD, Riley MD, Fejo L, Munoz E, Milns NR, Gardner ID, Powers JR, Ganygulpa E, Gununuwawuy BJ, Effects of the Heavy Usage of Kava on Physical Health: Summary of a Pilot Survey in an Aboriginal Community. The Medical Journal of Australia 1988; 148:548-555.

(43.) Douglas W, The Effects of Heavy Usage of Kava on Physical Health. The Medical Journal of Australia 1988; 149:341-342.

(44.) Duve RN, Prasad J, Efficacy of Extraction of Constituents in the Preparation of Yaqona Beverage. Part 2: Mijor Active Constituents. Fiji Agric J 1984; 46:11-16.

Townsend Letter for Doctors & Patients.


By Kerry Bone

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