MAJOR CHEMICAL CONSTITUENTS

The main constituents of kava kava rhizome include kavalactones (kavapyrones) kawain, dihydrokawain, methysticin, and dihyrdromethysticin; the alkaloids and amides 1-cinnamoylpyrrolidine, 1-(m-methoxycinnamoyl)-pyrrolidine, and cepharadione A; chalcones, flavonoids, steroids (sitosterol, stigmasterol, and stigmastanol); esters (e.g., bornyl cinnamate); aliphatic alcohols; and long chain fatty acids. Dried material should contain at least 3.5% kavalactones and good-quality rhizomes up to 8.3% kavalactones.

PRINCIPAL GYNECOLOGIC AND OBSTETRIC USES

ADDITIONAL USES

TRADITIONAL AND HISTORICAL USES

Kava kava use is deeply rooted in the ceremonial and daily recreational traditions of South Pacific Islanders, particularly Polynesia, Melanesia, and Micronesia, together known as Oceania, with heavy use found in Fiji, Samoa, and Tonga. Use spread to Australia via missionaries from the South Pacific, and it was traditionally also very popular in Hawaii, although a death penalty instituted for its use there eventually led to decreased consumption among Hawaiians. Legends abound regarding “the kava,” which is believed to be the child of their god of good seasons and rain, and patron deity of farmers. Kava kava use is accompanied by specific rituals, including the use of a special kava bowl (tanoa), strainer (tau’anga), and cup (ipu), also believed to be gifts from the gods accompanying the herb. Kava kava was traditionally taken as a beverage prepared as a cold infusion. The root is chewed, grated, powdered, or macerated and placed inside the kava bowl to which cold water is then added. This mash is steeped and strained repeatedly, then poured into cups for drinking. Kava kava is used in formal ceremonies such as political events, marriages, and births; at important and official meetings such as contract signings; and also more casually and informally

Kava Kava (Piper methysticum).

Photo by Martin Wall.

on social occasions; and even recreationally, for example, at the start of the day by old men, or at the end of a long work day. Reports say that is has also been used to cure illness, help soothe arguments, and even as part of ceremonies at which disputes are resolved or differences between enemies are reconciled. One might say it is considered the beverage of hospitality in the South Pacific.

Traditional medicinal indications for kava kava use include use as an intoxicant, a nervine, and neuromuscular restorative (e.g., calming the nerves, inducing relaxation and sleep, relieving headache, counteracting fatigue or weakness, and restoring muscle strength in asthma and rheumatism). It was used as a diaphoretic in the treatment of chills and head colds, and for asthma. Another important medicinal use was as a diuretic, particularly for difficulty urinating and the treatment of chronic cystitis, syphilis, and gonorrhea.

It was first described and named Piper methysticum, meaning “intoxicating pepper” in 1786, and was not highly used as a medicinal plant in Western botanical medicine. It was recognized by the Eclectics in the late nineteenth century as a local anesthetic, CNS depressant, and cardiac stimulant, and as a treatment for gonorrhea. In the early twentieth century the Eclectics cited its use for neuralgic conditions of the eyes, ears, and teeth, for edema, and for gastric atony and postsurgical anorexia. The herb was listed in the 20th to 24th editions of The United States Dispensatory of the United States of America (1918–1947) and the fluid extract had official status in the 4th and 5th editions of the National Formulary (1888–1926).

CLINICAL INDICATIONS

Herbal practitioners regard kava kava as a highly reliable anxiolytic, antispasmodic, analgesic, and neuroprotective herb, with mild topical anesthetic action. Treatment of anxiety and anxiety disorders is the most common clinical indication for kava kava; however it is also widely used for the treatment of neuromuscular tension, neuralgia, neurovegetative complaints associated with perimenopause and menopause, dysuria, urogenital pain, and hyperactive bladder.

IN VITRO, ANIMAL, AND CLINICAL DATA

The anxiolytic effects of kava kava have been the focus of most clinical trials, and results have generally supported the benefits of kava kava and kavalactones in the treatment of anxiety and anxiety disorders.

A Cochrane systematic review of kava kava monopreparations for the treatment of anxiety identified 12 double-blind placebo-controlled RCTs (n = 700) that met all inclusion criteria, all but one of which used a product standardized to 70% kavalactones, and produced by the same manufacturer. Data from seven trials (n = 380) assessed a common outcome measure—the total score on the HAM-A—and 74% of these patients (n = 282) were diagnosed according to the criteria of the American Psychiatric Association DSM-III-R and DSM-IV. All trials used the HAM-A total score at baseline as an inclusion criterion, and four trials included patients if the total score was 19 or above. One trial included only women with anxiety resulting from climacteric syndrome. The results of the meta-analysis suggest a significant reduction of the HAM-A total score in patients receiving kava kava extract compared with placebo. The results of the five studies that were not submitted to meta-analysis largely support these findings. Five other systematic reviews support these findings. Numerous pharmacologic studies have been conducted with kava kava extracts and isolated kavalactones. The most important findings suggest that kava kava and its preparations possess anxiolytic, anticonvulsive, neuroprotective, sedative, and local anesthetic effects. Kava kava has been demonstrated in animal and human clinical trials to improve sleep parameters. In a human clinical trial (n = 12) kava kava extract was shown to reduce sleep latency, improve deep sleep, and subjects reported a subjective sense of increased quality of sleep, with improved cognitive function compared with oxazepam, which led to impaired function. Additional human clinical trials have demonstrated improvements in cognitive function and performance with kava kava intake. Kava kava and isolated constituents have demonstrated topical analgesic effects in several animal studies. In one study, a 0.5% solution of kavain had an anesthetic effect equivalent to that of cocaine. The effect of a 3% solution of either compound had a comparable effect on the endurance of total anesthesia, extending it from 5.3 minutes for kavain and from 6.5 minutes for cocaine to approximately 31 minutes for both substances. Animal studies have demonstrated dose dependent muscle relaxant capabilities as well as anticonvulsant effects.

MECHANISMS OF ACTION

Animal studies demonstrate CNS penetration of kavalactones shortly after oral administration of extracts of the herb, with a half-life of 1 hour. Although the exact mechanisms of kava kava are not entirely elucidated, a number of sites of action have been proposed, including specific inhibition of voltage-dependent Na⁺ and Ca²⁺ channels, indirect effects on GABA and benzodiazepine receptors, specific binding to cortical neurons, stimulation of the limbic system, and an ability to antagonize clonic strychnine convulsions. Effects on dopamine and serotonin receptors have been inconsistent, but some activity has been noted, including an increase in parkinson-like symptoms in patients taking high-dose kava kava. The muscle relaxing effects of kavalactones is attributed to a centrally induced attenuation of the a- and g-spinal motor systems directed by supraspinal sites. Peritoneal administration of aqueous extracts of kava kava has led to tolerance in animal models.

RATINGS

PREPARATIONS USED CLINICALLY

DOSAGE

Standardized product should be used to control the amount of kavalactones consumed, both for efficacy and safety purposes. Duration of use should not exceed 3 months.

SAFETY INFORMATION: HERB DRUG INTERACTIONS, TOXICITY, AND CONTRAINDICATIONS

A 1997 peer-reviewed appraisal of kava kava safety based on a comprehensive review of the scientific and historical ethnobotanical literature determined that

Since that time, 79 adverse event reports of hepatotoxicity reportedly associated with oral use of kava kava preparations have been reported worldwide, with most in Europe, but also in Canada and the United States, and have led to rigorous investigation of the safety of this herb. Although in most cases prescription pharmaceutical medications were being taken in conjunction with kava kava, there was regular alcohol intake, or prior hepatic disease existed. Several cases of severe hepatic damage, including fulminant hepatic failure, apparently occurred de novo. These cases subsequently led to the withdrawal or restriction of sales of kava kava products from many national commercial markets, particularly in Europe. In the Cochrane systematic review discussed previously, six of twelve trials reported adverse events experienced by patients receiving kava kava extract. Stomach complaints, restlessness, drowsiness, tremor, headache, and tiredness were reported most frequently. Four trials comprising 30% of patients in the reviewed trials report the absence of adverse events while taking kava kava extract. None of the trials reported any hepatotoxic events. Seven of the reviewed trials measured liver enzyme levels as safety parameters and report no clinically significant changes.

Warnings about kava kava and performance safety are common. It has been proposed that Piper methysticum may cause cytotoxic cell death by interfering with hepatocellular mitochondrial function. Performance safety and basic performance under the influence of kava kava were tested in a randomized double-blind crossover study (n = 18) in which healthy subjects were simultaneously given 400 mg kava kava extract (containing 240 mg kavalactones daily) and 4.5 mg bromazepam twice daily over a period of 14 days. This was compared with the effects of the substances administered individually. Stress tolerance, vigilance, and motor coordination were not changed from baseline when only kava kava was taken, whereas the performance of subjects taking bromazepam and the kava-bromazepan combination deteriorated equally. Nonetheless, several cases of individuals being cited for “driving under the influence” after having used kava kava have been reported, and it is generally recommended that individuals not drive or operate machinery or equipment while using this herb.

Kava kava is reported as being generally well tolerated in clinical trials with few reported herb–drug interactions. Potential interaction with benzodiazepines, serotinergic- and dopaminergic-acting medications, and medications that act on sodium ion channels have been proposed. Kava kava should not be used with selective serotonin reuptake inhibitors, tricyclic antidepressants, barbiturates, benzodiazepines, or antipsychotic medications. Kava kava may potentiate the effects of alcohol; thus they should not be taken simultaneously beyond the normal amount present in kava kava extracts.

Kava dermopathy, and ichthyosiform condition, is a well-known side effect of frequent, high-dose kava kava consumption. In fact, in Oceania, this yellowish, scaly skin condition is common among kava kava users, and is reversible upon discontinuation of kava kava intake. Allergic skin reactions also have been associated with kava kava use. Extrapyrimidal symptoms, including torticollis; involuntary neck, head, and trunk movements; oral and lingual dyskinesia; and impairments in movement and visual coordination have been reported occasionally by kava kava users in the absence of cognitive impairment.

Common side effects associated with kava kava use, including stomach complaints, restlessness, drowsiness, tremor, headache, and tiredness were reported most frequently. In the Cochrane review, four trials comprising 30% of patients in the reviewed trials reported the absence of adverse events with kava kava extract.

Kava kava use has been associated with rare but severe liver damage. Kava kava consumption should be discontinued immediately and a qualified health professional should be sought if any of the following signs of hepatotoxicity occur: unusual fatigue, weakness, loss of appetite, unintentional weight loss, yellow discoloration of the skin or ocular conjunctiva, dark urine, or discolored stools. Individuals with a history of liver disease and those taking medications that can cause liver damage should not take kava kava.

USE IN PREGNANCY AND LACTATION

Information on the safety of kava during pregnancy and lactation is limited. Although there is no evidence of mutagenic, teratogenic, or genotoxic potential using standard assays of kava kava, or the synthetic product kavain with identical actions in animal models, use of this herb is entirely contraindicated during pregnancy because of potential hepatotoxic and CNS effects on the maternal–embryonic/fetal dyad. Similarly it is contraindicated for use during lactation and for children under 18 years old.

Kava kava should be avoided entirely during pregnancy and lactation because of uncertainty about hepatic safety and also because of the possible hazards of potential CNS effects of this herb on the unborn baby.