For Patients & Caregivers
How It Works
Kava may be effective in reducing anxiety, but liver toxicity is a major concern.
The active compounds in kava are called kavalactones. In studies in animals and humans, these compounds provide pain relief and act as muscle relaxants and anticonvulsants. Kavalactones might act the same way as the antidepressant drugs, monoamine oxidase inhibitors (MAOIs). Scientists are not sure whether they change the levels of the hormones dopamine and serotonin in the brain.
Kava is known to cause liver damage.
- Kava may cause liver damage. The British, French, German, and Swiss governments have requested that kava be removed from the market. The Canadian government has warned consumers not to use kava-containing products.
- Overdose or long-term use can cause low blood platelets and white blood cells, dry flaking skin known as kava dermopathy, respiratory problems, and hearing impairment. Inform your doctor immediately if you have any of these symptoms.
- Kava may impair your ability to drive or operate heavy machinery.
Do Not Take If
- You have liver or kidney problems: Kava may worsen them.
- You are taking benzodiazepines such as Ativan®, Xanax®, Serax®, Valium®, or Tranxene®: Kava may increase sedation.
- You drink alcoholic beverages: Kava may increase sedation. Avoid using kava and alcohol at the same time.
- You are taking barbiturates: In theory, kava may increase sedation and muscle-relaxant effects.
- You take sedatives: In theory, kava may increase sedation.
- If you take CYP450 substrate drugs, especially CYP1A2 or CYP2E1 substrate drugs: Kava may increase both their effects and side effects.
- You take acetaminophen: Kava increased the liver toxicity caused by acetaminophen in laboratory studies.
- Impaired reflexes or judgment
- Visual disturbances
- Hangover effect
- Liver damage (rare): Immediately inform your doctor if you have yellowish discoloration of the skin, eyes, fingernails or toenails, nausea, or vomiting.
- Low blood platelets and white blood cells with overdose or long-term use. Can also can cause dry flaking skin, respiratory problems, and hearing impairment. Inform your doctor immediately if you have any of these symptoms.
- Skin eruptions with itching and burning: A few cases were associated with using kava tea or supplements.
- Impaired driving behavior and signs of intoxication: Associated with kava use.
For Healthcare Professionals
Derived from the rhizome of the plant, kava is from the Pacific Rim and Hawaiian Islands. It is used as a social beverage in those areas and to relieve anxiety, stress, and insomnia. Kavalactones in kava are thought to be the active constituent that produces skeletal muscle relaxation, non-narcotic anesthesia, and local anesthetic effects.
Clinical data suggest moderate benefits with kava as short-term use for generalized anxiety disorder (39), and no differences in withdrawal or addiction versus placebo (40). Several other studies also support the use of kava for relieving anxiety (1) (25) (26). It has further been suggested as an alternative to benzodiazepines, which are used to treat anxiety. However, an internet-based study suggests that kava is not superior to placebo in reducing anxiety (3), and a randomized clinical trial reported similar findings (36).
Although a systematic review showed that kava does not have negative effects on cognition (37), there have been case reports of impairment consistent with CNS depressant effects, including slow, slurred speech and flaccid muscle tone (45). In addition, due to concerns of hepatotoxicity, the Canadian, French, and British governments withdrew availability of kava and kava-containing products (4) (11) (23).
The Food and Drug Administration (FDA) has advised consumers about the potential risks of liver injury associated with kava consumption. However, following a World Health Organization (WHO) recommendation to study aqueous extracts of kava, initial research results support the benefits of kava (27) (28). Case analyses of 14 patients with hepatic injury resulting from kava use revealed low-quality products, overdose, prolonged use and co-medication as causative factors (29). Additional studies are needed to confirm these findings.
Kava consumption has been associated with low cancer incidence (30), but one of its constituents was shown to stimulate growth of melanoma cells (31).
Mechanism of Action
Kavapyrones are centrally-acting skeletal muscle relaxants, anticonvulsants, and peripherally-acting local anesthetics. There are conflicting data on the effects of kavapyrones on CNS levels of dopamine and serotonin (14). Possible hepatotoxicity mechanisms are thought to be cytochrome P450 inhibition, reduction in liver glutathione content, or inhibition of cyclooxygenase (COX) activity (4) (15).
In vitro and in vivo studies suggest that kavapyrone- and pipermethystine-containing extracts induce mitochondrial dysfunction, oxidative stress, and apoptosis of Hep2G cells (16) (17). The major constituent kavain was found to potentiate GABAA receptors (38).
Kava enhances acetaminophen-induced cytotoxicity by increasing glutathione (GSH) depletion, resulting in oxidative stress and mitochondrial dysfunction, ultimately resulting in cell death (35).
- Kava may cause hepatotoxicity, and elevated gamma-glutamyl transpeptidase (GGT) levels were detected in regular kava drinkers (20).
- The British, French, and Swiss governments have requested that kava be removed from the market (11).
- The Canadian government has warned consumers not to use kava-containing products (21).
- Discontinue kava use before surgery as it may interact with anesthetics. Kava may also impair ability to drive or operate heavy machinery (6) (45) (53).
- Sebotropic eruptions: Related either to kava supplements or kava tea ingestion (41) (42).
- Hepatotoxicity: Increased risk with prolonged kava usage or co-medication with other botanicals, supplements, or prescription drugs (43).
- Hepatotoxicity that led to acute liver failure and liver transplant: In a patient who used kava for almost 2 months without evidence of excess dosage (44).
- Impaired driving behavior and signs of intoxication: In 4 cases of self-reported kava use in Iowa which were confirmed with urinalysis to reveal the presence of kavalactones and lack of other drug presence (45).
- Benzodiazepines: Kava may enhance sedation when administered concurrently. Kava indirectly increases the affinity of GABA receptor binding sites in vitro (24).
- Barbiturates: Theoretically, kava may have an additive effect on sedation and muscle-relaxant activity, as this has been demonstrated in animals (46).
- Sedatives: Theoretically, kava may have an additive effect with any centrally-acting medication that can potentially cause sedation (5).
- Acetaminophen: Kava enhances hepatic cell cytotoxicity induced by acetaminophen in vitro (35).
- P-gp: Although inhibition has been shown in vitro (51), kava does not appear to modulate P-gp activity In healthy subjects (52).
- Cytochrome P450 substrates (particularly CYP1A2 or CYP2E1): Several reviews have covered the topic of kava HDIs. Generally, the interaction risk is believed to be low (43), with the greatest caution attributed to taking kava with CYP1A2 or CYP2E1 substrate drugs as it may enhance both therapeutic and adverse effects (48). It is also noted that study discrepancies are likely due to variations in formulations or the extraction process (43). Nevertheless, the following have been observed:
1A1: In animal models at very high doses, kava enhanced hepatic CYP1A1 expression (47). However, the researchers point out that some may be more sensitive to induction or ingest more kavalactones than acceptable for daily intakes, and that increased CYP1A1 expression may partly contribute to kava-induced hepatotoxicity.