Ava Pepper, Ava Root, Awa, Gea, Gi, Intoxicating Long Pepper, Intoxicating Pepper, Kao, Kavain, Kavapipar, Kawa, Kawa Kawa, Kawa Pepper, Kawapfeffer, Kew, Lawena, Long Pepper, Malohu, Maluk, Maori Kava, Meruk, Milik, Piper methysticum, Poivre des Cannibales, Poivre des Papous, Rauschpfeffer, Rhizome Di Kava-Kava, Sakau, Tonga, Waka, Wurzelstock, Yagona, Yangona, Yaqona, Yaquon, Yongona.
Kava is a beverage or extract that is made from Piper methysticum, a plant native to the western Pacific islands. The name "kava" comes from the Polynesian word "awa," which means bitter. In the South Pacific, kava is a popular social drink, similar to alcohol in Western societies.
There have been some safety concerns about kava. Cases of liver damage and even some deaths have been traced to kava use. Because of these reports, kava was withdrawn from the market in Europe and Canada in the early 2000s. However, in 2012 and 2015, the market withdrawals in Canada and Germany were lifted. These countries decided that there was not enough research to show that kava was the direct cause of liver toxicity in many of these cases. Kava has never been taken off the market in the U.S.
Some people take kava by mouth to calm anxiety, stress, and restlessness, and to treat sleeping problems (insomnia). It is also used for attention deficit-hyperactivity disorder (ADHD), withdrawal from benzodiazepine drugs, epilepsy, psychosis, depression, migraines and other headaches, chronic fatigue syndrome (CFS), common cold and other respiratory tract infections, tuberculosis, muscle pain, and cancer prevention.
Kava is also consumed as a beverage in ceremonies to promote relaxation.
How does it work?
Kava affects the brain and other parts of the central nervous system. The kava-lactones in kava are believed to be responsible for its effects.
Possibly Effective for...
- Anxiety. Most research shows that taking kava extracts that contain 70% kavalactones can lower anxiety and might work as well as some prescription anti-anxiety medications. Most studies have used a specific kava extract (WS 1490, Dr. Willmar Schwabe Pharmaceuticals). But some inconsistent evidence exists. One reason for the conflicting results may be the duration of treatment. It's possible that treatment for at least 5 weeks is necessary for symptoms to improve. Also, kava might be more effective in people with severe anxiety, in female patients, or in younger patients.
Insufficient Evidence to Rate Effectiveness for...
- Benzodiazepine withdrawal symptoms. Early research suggests that slowly increasing the dose of a specific kava extract ((WS1490, Dr. Willmar Schwabe Pharmaceuticals) over the course of one week while decreasing the dose of benzodiazepines over the course of two weeks can prevent withdrawal symptoms and reduce anxiety in people who have been taking benzodiazepines for a long period of time.
- Cancer prevention. There is some early evidence that taking kava might help to prevent cancer.
- Insomnia. Research on the effectiveness of kava in people with sleeping problems is inconsistent. Some research shows that taking a specific kava extract (WS1490, Dr. Willmar Schwabe Pharmaceuticals) daily for 4 weeks reduces sleeping problems in people with anxiety disorders. But other research suggests that taking kava three times daily for 4 weeks does not reduce insomnia in people with anxiety.
- Menopausal symptoms. Early research shows that taking a specific kava extract (WS1490, Dr. Willmar Schwabe Pharmaceuticals) daily for 8 weeks reduces anxiety and hot flashes in menopausal women. Other research shows that taking kava daily for 3 months might reduce depression, anxiety, and hot flashes.
- Stress. Early research suggests that taking a single dose of kava by mouth might reduce symptoms associated with mentally stressful tasks.
- Attention deficit-hyperactivity disorder (ADHD).
- Chronic fatigue syndrome (CFS).
- Common cold.
- Respiratory tract infections.
- Muscle pain.
- Urinary tract infections (UTIs).
- Swelling of the uterus.
- Sexually transmitted diseases.
- Menstrual problems.
- Sexual arousal.
- Skin diseases.
- Wound healing.
- Other conditions.
Natural Medicines Comprehensive Database rates effectiveness based on scientific evidence according to the following scale: Effective, Likely Effective, Possibly Effective, Possibly Ineffective, Likely Ineffective, and Insufficient Evidence to Rate (detailed description of each of the ratings).
Kava is POSSIBLY SAFE when taken by mouth, short-term. Kava extracts have been used safely under medical supervision for up to 6 months.
People may have heard that use of kava may cause liver damage. The use of kava for as little as 1-3 months has resulted in the need for liver transplants, and even death in some people. Early symptoms of liver damage include yellowed eyes and skin (jaundice), fatigue, and dark urine. However, these cases appear to be relatively rare. Most patients who have used kava have not experienced liver toxicity. Also, some experts believe that the liver toxicity seen in these cases cannot be directly linked to kava. Other factors may have contributed to the toxic effects. To be on the safe side, people who choose to use kava should get liver function tests.
Using kava can make you unable to drive or operate machinery safely. Do not take kava before you plan on driving. "Driving-under-the-influence" citations have been issued to people driving erratically after drinking large amounts of kava tea.
Depression: Kava use might make depression worse.
Liver problems: Kava can cause liver problems even in healthy people. Taking kava if you already have liver disease is taking a risk. People with a history of liver problems should avoid kava.
Parkinson's disease: Kava might make Parkinson's disease worse. Do not take kava if you have this condition.
Surgery: Kava affects the central nervous system. It might increase the effects of anesthesia and other medications used during and after surgery. Stop using kava at least 2 weeks before a scheduled surgery.
Sedative medications (CNS depressants)Interaction Rating: Major Do not take this combination.
Kava might cause sleepiness and drowsiness. Medications that cause sleepiness are called sedatives. Taking kava along with sedative medications might cause too much sleepiness.
Alprazolam (Xanax)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.
Kava can cause drowsiness. Alprazolam (Xanax) can also cause drowsiness. Taking kava along with alprazolam (Xanax) may cause too much drowsiness. Avoid taking kava and alprazolam (Xanax) together.
Haloperidol (Haldol)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.
Haloperidol (Haldol) is broken down by the liver. Kava might decrease how quickly the liver breaks down this medication, which might increase side effects. There is a report of heart complications following haloperidol injections in a patient who was also taking kava by mouth.
LevodopaInteraction Rating: Moderate Be cautious with this combination.Talk with your health provider.
Levodopa affects the brain by increasing a brain chemical called dopamine. Kava might decrease dopamine in the brain. Taking kava along with levodopa might decrease the effectiveness of levodopa.
Medications changed by the liver (Cytochrome P450 1A2 (CYP1A2) substrates)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.
Some medications are changed and broken down by the liver. Kava might decrease how quickly the liver breaks down some medications. Taking kava along with some medications that are changed by the liver might increase the effects and side effects of some medications. Before taking kava, talk to your healthcare provider if you take any medications that are changed by the liver.
Some of these medications that are changed by the liver include clozapine (Clozaril), cyclobenzaprine (Flexeril), fluvoxamine (Luvox), haloperidol (Haldol), imipramine (Tofranil), mexiletine (Mexitil), olanzapine (Zyprexa), pentazocine (Talwin), propranolol (Inderal), tacrine (Cognex), theophylline, zileuton (Zyflo), zolmitriptan (Zomig), and others.
Medications changed by the liver (Cytochrome P450 2C19 (CYP2C19) substrates)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.
Some medications are changed and broken down by the liver. Kava might decrease how quickly the liver breaks down some medications. Taking kava along with some medications that are broken down by the liver can increase the effects and side effects of your medication. Before taking kava, talk to your healthcare provider if you take any medications that are changed by the liver.
Some of these medications changed by the liver include amitriptyline (Elavil), clomipramine (Anafranil), cyclophosphamide (Cytoxan), diazepam (Valium), lansoprazole (Prevacid), omeprazole (Prilosec), lansoprazole (Protonix), phenytoin (Dilantin), phenobarbital (Luminal), progesterone, and others.
Medications changed by the liver (Cytochrome P450 2C9 (CYP2C9) substrates)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.
Some medications are changed and broken down by the liver. Kava might decrease how quickly the liver breaks down some medications. Taking kava along with some medications that are broken down by the liver can increase the effects and side effects of some medications. Before taking kava, talk to your healthcare provider if you take any medications that are changed by the liver.
Some medications that are changed by the liver include amitriptyline (Elavil), diazepam (Valium), zileuton (Zyflo), celecoxib (Celebrex), diclofenac (Voltaren), fluvastatin (Lescol), glipizide (Glucotrol), ibuprofen (Advil, Motrin), irbesartan (Avapro), losartan (Cozaar), phenytoin (Dilantin), piroxicam (Feldene), tamoxifen (Nolvadex), tolbutamide (Tolinase), torsemide (Demadex), warfarin (Coumadin), and others.
Medications changed by the liver (Cytochrome P450 2E1 (CYP2E1) substrates)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.
Some medications are changed and broken down by the liver. Kava might decrease how quickly the liver breaks down some medications. Taking kava along with some medications that are changed by the liver can increase the effects and side effects of your medication. Before taking kava, talk to your healthcare provider if you take any medications that are changed by the liver.
Some medications that are changed by the liver include acetaminophen, chlorzoxazone (Parafon Forte), ethanol, theophylline, and drugs used for anesthesia during surgery such as enflurane (Ethrane), halothane (Fluothane), isoflurane (Forane), and methoxyflurane (Penthrane).
Medications changed by the liver (Cytochrome P450 3A4 (CYP3A4) substrates)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.
Some medications are changed and broken down by the liver. Kava might decrease how quickly the liver breaks down some medications. Taking kava along with some medications that are broken down by the liver can increase the effects and side effects of some medications. Before taking kava, talk to your healthcare provider if you are taking any medications that are changed by the liver.
Medications moved by pumps in cells (P-Glycoprotein Substrates)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.
Some medications are moved by pumps in cells. Kava might make these pumps less active and increase how much of some medications get absorbed by the body. This might increase the amount of some medications in the body, which could lead to more side effects. But there is not enough information to know if this is a big concern.
Some medications that are moved by these pumps include etoposide, paclitaxel, vinblastine, vincristine, vindesine, ketoconazole, itraconazole, amprenavir, indinavir, nelfinavir, saquinavir, cimetidine, ranitidine, diltiazem, verapamil, corticosteroids, erythromycin, cisapride (Propulsid), fexofenadine (Allegra), cyclosporine, loperamide (Imodium), quinidine, and others.
Medications that can harm the liver (Hepatotoxic drugs)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.
Kava might harm the liver. Taking kava along with medication that might also harm the liver can increase the risk of liver damage. Do not take kava if you are taking a medication that can harm the liver.
Some medications that can harm the liver include acetaminophen (Tylenol and others), amiodarone (Cordarone), carbamazepine (Tegretol), isoniazid (INH), methotrexate (Rheumatrex), methyldopa (Aldomet), fluconazole (Diflucan), itraconazole (Sporanox), erythromycin (Erythrocin, Ilosone, others), phenytoin (Dilantin), lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), and many others.
Ropinirole (Requip)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.
Ropinirole (Requip) is broken down by the liver. Kava might decrease how quickly the liver breaks down this medication, which might increase side effects. There is a report of hallucinations and delusions in a patient who used kava together with Ropinirole (Requip).
Medications changed by the liver (Cytochrome P450 2D6 (CYP2D6) substrates)Interaction Rating: Minor Be cautious with this combination.Talk with your health provider.
Some medications are changed and broken down by the liver. Kava might decrease how quickly the liver breaks down some medications. Taking kava along with some medications that are changed by the liver can increase the effects and side effects of your medication. Before taking kava, talk to your healthcare provider if you take any medications that are changed by the liver.
Some medications that are changed by the liver include amitriptyline (Elavil), clozapine (Clozaril), codeine, desipramine (Norpramin), donepezil (Aricept), fentanyl (Duragesic), flecainide (Tambocor), fluoxetine (Prozac), meperidine (Demerol), methadone (Dolophine), metoprolol (Lopressor, Toprol XL), olanzapine (Zyprexa), ondansetron (Zofran), tramadol (Ultram), trazodone (Desyrel), and others.
The following doses have been studied in scientific research:
- For Anxiety: 50-100 mg of a specific kava extract (WS 1490, Dr. Willmar Schwabe Pharmaceuticals), taken three times daily for up to 25 weeks, has been used. Also, 400 mg of another specific kava extract (LI 150, Lichtwer Pharma) taken daily for 8 weeks has been used. Five kava tablets each containing 50 mg of kavalactones have been taken in three divided doses daily for one week. One to two kava extract tablets has been taken twice daily for 6 weeks. Calcium supplements plus 100-200 mg of kava taken daily for 3 months has also been used.
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Assessment of the Risk of Hepatotoxicity with Kava Products. 2000;
Bhate H, Gerster G, and Gracza E. Orale Prämedikation mit Zubereitungen aus Piper methysticum bei operativen Eingriffen in Epiduralanästhesie. Erfahrungsheilkunde 1989;6:339-345.
Boerner, R. J. and Klement, S. Attenuation of neuroleptic-induced extrapyramidal side effects by Kava special extract WS 1490. Wien.Med Wochenschr. 2004;154(21-22):508-510. View abstract.
Boerner, R. J. Kava kava in the treatment of generalized anxiety disorder, simple phobia and specific social phobia. Phytother Res 2001;15(7):646-647. View abstract.
Boon, H. S. and Wong, A. H. Kava: a test case for Canada's new approach to natural health products. CMAJ. 11-25-2003;169(11):1163-1164. View abstract.
Boonen, G., Ferger, B., Kuschinsky, K., and Haberlein, H. In vivo effects of the kavapyrones (+)-dihydromethysticin and (+/-)- kavain on dopamine, 3,4-dihydroxyphenylacetic acid, serotonin and 5- hydroxyindoleacetic acid levels in striatal and cortical brain regions. Planta Med 1998;64(6):507-510. View abstract.
Buckley, J. P., Furgiuele, A. R., and O'Hara, M. J. Pharmacology of kava. Ethnopharm Search Psych Drugs 1967;1:141-151.
Bujanda, L., Palacios, A., Silvarino, R., Sanchez, A., and Munoz, C. [Kava-induced acute icteric hepatitis]. Gastroenterol.Hepatol. 2002;25(6):434-435. View abstract.
Cairney, S., Clough, A. R., Maruff, P., Collie, A., Currie, B. J., and Currie, J. Saccade and cognitive function in chronic kava users. Neuropsychopharmacology 2003;28(2):389-396. View abstract.
Cairney, S., Maruff, P., and Clough, A. R. The neurobehavioural effects of kava. Aust.N.Z.J Psychiatry 2002;36(5):657-662. View abstract.
Cawte, J. Parameters of kava used as a challenge to alcohol. Aust.N.Z.J Psychiatry 1986;20(1):70-76. View abstract.
Center for Food Safety and Applied Nutrition (US Food and Drug Administration). Kava-containing dietary supplements may be associated with severe liver injury (document issued March 25, 2002).
Center for Food Safety and Applied Nutrition (US Food and Drug Administration). Letter to health care professionals: FDA issues consumer advisory that kava products may be associated with severe liver injury (document issued March 25, 2002), contact information for FDA Medwatch program: 1-800-332-1088.
Chanwai, L. G. Kava toxicity. Emergency Medicine 2002;12:142-145.
Christl, S. U., Seifert, A., and Seeler, D. Toxic hepatitis after consumption of traditional kava preparation. J.Travel.Med. 2009;16(1):55-56. View abstract.
Currie, B. J. and Clough, A. R. Kava hepatotoxicity with Western herbal products: does it occur with traditional kava use? Med J Aust. 5-5-2003;178(9):421-422. View abstract.
De Leo, V, La Marca, A., Lanzetta, D., Palazzi, S., Torricelli, M., Facchini, C., and Morgante, G. [Assessment of the association of Kava-Kava extract and hormone replacement therapy in the treatment of postmenopause anxiety]. Minerva Ginecol. 2000;52(6):263-267. View abstract.
Duffield, A. M., Jamieson, D. D., Lidgard, R. O., Duffield, P. H., and Bourne, D. J. Identification of some human urinary metabolites of the intoxicating beverage kava. J Chromatogr. 7-28-1989;475:273-281. View abstract.
Emser W and Bartylla K. Improvement of sleep quality. Effect of kava extract WS 1490 on the sleep pattern in healthy subjects. Neurologie/Psychiatrie 1991;5(11):636-642.
Ernst, E. [Recall of the herbal anxiolytic kava. Underestimation of its value or overestimation of its risks?]. MMW.Fortschr.Med 10-10-2002;144(41):40. View abstract.
Ernst, E. Herbal remedies for anxiety - a systematic review of controlled clinical trials. Phytomedicine 2006;13(3):205-208. View abstract.
Faustino, T. T., Almeida, R. B., and Andreatini, R. [Medicinal plants for the treatment of generalized anxiety disorder: a review of controlled clinical studies]. Rev Bras.Psiquiatr. 2010;32(4):429-436. View abstract.
Feltenstein, M. W., Lambdin, L. C., Ganzera, M., Ranjith, H., Dharmaratne, W., Nanayakkara, N. P., Khan, I. A., and Sufka, K. J. Anxiolytic properties of Piper methysticum extract samples and fractions in the chick social-separation-stress procedure. Phytother Res 2003;17(3):210-216. View abstract.
Folmer, F., Blasius, R., Morceau, F., Tabudravu, J., Dicato, M., Jaspars, M., and Diederich, M. Inhibition of TNFalpha-induced activation of nuclear factor kappaB by kava (Piper methysticum) derivatives. Biochem Pharmacol 4-14-2006;71(8):1206-1218. View abstract.
Foo, H. and Lemon, J. Acute effects of kava, alone or in combination with alcohol, on subjective measures of impairment and intoxication and on cognitive performance. Drug Alcohol Rev. 1997;16(2):147-155. View abstract.
Food and Drug Administration. Consumer advisory: kava-containing dietary supplements may be associated with severe liver injury. FDA Center for Food Safety and Nutrition. 2002;1.
Furgiuele AR, Kinnard WJ, Aceto MD, and et al. Central activity of aqueous extracts of Piper methysticum (kava). J Pharm Sci 1965;54:247-252.
Garrett, K. M., Basmadjian, G., Khan, I. A., Schaneberg, B. T., and Seale, T. W. Extracts of kava (Piper methysticum) induce acute anxiolytic-like behavioral changes in mice. Psychopharmacology (Berl) 2003;170(1):33-41. View abstract.
Geller, S. E. and Studee, L. Botanical and dietary supplements for mood and anxiety in menopausal women. Menopause. 2007;14(3 Pt 1):541-549. View abstract.
Gessner B and Cnota P. Extract of the kava-kava rhizome in comparison with diazepam and placebo. Z Phytother 1994;15(1):30-37.
Gleitz J, Gottner N, Ameri A, and et al. Kavain inhibits non-stereospecifically veratridine-activated Na
Gleitz, J., Beile, A., and Peters, T. (+/-)-kavain inhibits the veratridine- and KCl-induced increase in intracellular Ca2+ and glutamate-release of rat cerebrocortical synaptosomes. Neuropharmacology 1996;35(2):179-186. View abstract.
Gleitz, J., Friese, J., Beile, A., Ameri, A., and Peters, T. Anticonvulsive action of (+/-)-kavain estimated from its properties on stimulated synaptosomes and Na+ channel receptor sites. Eur.J Pharmacol 11-7-1996;315(1):89-97. View abstract.
HAMILTON, M. The assessment of anxiety states by rating. Br.J.Med.Psychol. 1959;32(1):50-55. View abstract.
Holm, E., Staedt, U., Heep, J., Kortsik, C., Behne, F., Kaske, A., and Mennicke, I. [The action profile of D,L-kavain. Cerebral sites and sleep-wakefulness- rhythm in animals]. Arzneimittelforschung. 1991;41(7):673-683. View abstract.
Humberston, C. L., Akhtar, J., and Krenzelok, E. P. Acute hepatitis induced by kava kava. J Toxicol.Clin Toxicol. 2003;41(2):109-113. View abstract.
Izzo AA and Ernst E. Interactions between herbal medicines and prescribed drugs: a systematic review. Drugs 2001;61(15):2163-2175.
Johnson D, Frauendorf A, Stecker K, and et al. Neurophysiological active profile and tolerance of kava extract WS 1490, A pilot study with randomized evaluation. TW Neurolgie Psychiatrie 1991;5(6):349-354.
Kava: first suspended, now prohibited. Prescrire.Int 2003;12(66):142. View abstract.
Kelley, K. W. and Carroll, D. G. Evaluating the evidence for over-the-counter alternatives for relief of hot flashes in menopausal women. J.Am.Pharm.Assoc.(2003.) 2010;50(5):e106-e115. View abstract.
Kinzler, E., Kromer, J., and 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]. Arzneimittelforschung. 1991;41(6):584-588. View abstract.
Kraft, M., Spahn, T. W., Menzel, J., Senninger, N., Dietl, K. H., Herbst, H., Domschke, W., and Lerch, M. M. [Fulminant liver failure after administration of the herbal antidepressant Kava-Kava]. Dtsch Med Wochenschr 9-7-2001;126(36):970-972. View abstract.
Lakhan, S. E. and Vieira, K. F. Nutritional and herbal supplements for anxiety and anxiety-related disorders: systematic review. Nutr J 2010;9:42. View abstract.
Langosch, J. M., Normann, C., Schirrmacher, K., Berger, M., and Walden, J. The influence of (+/-)-kavain on population spikes and long-term potentiation in guinea pig hippocampal slices. Comp Biochem.Physiol A Mol.Integr.Physiol 1998;120(3):545-549. View abstract.
Laporte, E., Sarris, J., Stough, C., and Scholey, A. Neurocognitive effects of kava (Piper methysticum): a systematic review. Hum.Psychopharmacol. 2011;26(2):102-111. View abstract.
Lehmann E, Kinzler E, and Friedemann J. Efficacy of a special Kava extract (Piper methysticum) in patients with states of anxiety, tension and excitedness of non-mental origin - a double-blind placebo-controlled study of four weeks treatment. Phytomedicine 1996;3(2):113-119.
Lehmann, E., Klieser, E., Klimke, A., Krach, H., and Spatz, R. The efficacy of Cavain in patients suffering from anxiety. Pharmacopsychiatry 1989;22(6):258-262. View abstract.
Leung, N. Acute urinary retention secondary to kava ingestion. Emerg Med Australas 2004;16(1):94.
Lindenberg, D. and Pitule-Schodel, H. [D,L-kavain in comparison with oxazepam in anxiety disorders. A double- blind study of clinical effectiveness]. Fortschr.Med. 1-20-1990;108(2):49-53. View abstract.
Ma, Y., Sachdeva, K., Liu, J., Ford, M., Yang, D., Khan, I. A., Chichester, C. O., and Yan, B. Desmethoxyyangonin and dihydromethysticin are two major pharmacological kavalactones with marked activity on the induction of CYP3A23. Drug Metab Dispos 2004;32(11):1317-1324.
Magura, E. I., Kopanitsa, M. V., Gleitz, J., Peters, T., and Krishtal, O. A. Kava extract ingredients, (+)-methysticin and (+/-)-kavain inhibit voltage-operated Na(+)-channels in rat CA1 hippocampal neurons. Neuroscience 1997;81(2):345-351. View abstract.
Malsch U and Kieser M. Efficacy of kava-kava in the treatment of non-psychotic anxiety, following pretreatment with benzodiazepines. Psychopharm 2001;157(3):277-283.
Matthias, A., Blanchfield, J. T., Penman, K. G., Bone, K. M., Toth, I., and Lehmann, R. P. Permeability studies of Kavalactones using a Caco-2 cell monolayer model. J Clin Pharm Ther 2007;32(3):233-239. View abstract.
Meolie, A. L., Rosen, C., Kristo, D., Kohrman, M., Gooneratne, N., Aguillard, R. N., Fayle, R., Troell, R., Townsend, D., Claman, D., Hoban, T., and Mahowald, M. Oral nonprescription treatment for insomnia: an evaluation of products with limited evidence. J Clin.Sleep Med 4-15-2005;1(2):173-187. View abstract.
Meyer HG. Pharmakologie der wirksamen prinzipien de kawarhizoms (Piper methysticum Forst.). Arch Int Pharmacodyn Ther 1962;138:505-536.
Mills, E., Singh, R., Ross, C., Ernst, E., and Ray, J. G. Sale of kava extract in some health food stores. CMAJ. 11-25-2003;169(11):1158-1159. View abstract.
Mittmann, U., Schmidt, M., and Vrastyakova, J. Akut-anxiolytische wirksamkeit von Kava-Spissum-Spezialextrakt studie. Journal Pharmakoogie und Therapie 2000;9(4):99-108.
Musch, E., Chrissafidou, A., and Malek, M. [Acute hepatitis due to kava-kava and St John's Wort: an immune-mediated mechanism?]. Dtsch Med Wochenschr. 5-26-2006;131(21):1214-1217. View abstract.
Neuhaus, W., Ghaemi, Y., Schmidt, T., and Lehmann, E. [Treatment of perioperative anxiety in suspected breast carcinoma with a phytogenic tranquilizer]. Zentralbl.Gynakol. 2000;122(11):561-565. View abstract.
Parkman, C. A. Another FDA warning: Kava supplements. Case.Manager. 2002;13(4):26-28. View abstract.
Pfeiffer, C. C., Murphree, H. B., and Goldstein, L. Effect of kava in normal subjects and patients. Psychopharmacol Bull 1967;4(3):12. View abstract.
Pittler, M. H. and Ernst, E. Kava extract for treating anxiety. Cochrane Database.Syst Rev 2002;(2):CD003383. View abstract.
Prescott, J., Jamieson, D., Emdur, N., and Duffield, P. Acute effects of kava on measures of cognitive performance, physiological function and mood. Drug Alcohol Rev. 1993;12(1):49-57. View abstract.
Rasmussen, A. K., Scheline, R. R., Solheim, E., and Hansel, R. Metabolism of some kava pyrones in the rat. Xenobiotica 1979;9(1):1-16. View abstract.
Russell P, Bakker D, and Singh N. The effects of kava on alerting and speed of access of information from long-term memory. Bull Psychonom Soc 1987;25:236-237.
Saletu B, Grünberger J, Linzmayer L, and et al. EEG-brain mapping, psychometric and psychophysiological studies on central effects of kavain-a kava plant derivative. Hum Psychopharm 1989;4:169-190.
Sarris, J. and Kavanagh, D. J. Kava and St. John's Wort: current evidence for use in mood and anxiety disorders. J.Altern.Complement Med. 2009;15(8):827-836. View abstract.
Sarris, J., Kavanagh, D. J., Adams, J., Bone, K., and Byrne, G. Kava Anxiety Depression Spectrum Study (KADSS): a mixed methods RCT using an aqueous extract of Piper methysticum. Complement Ther.Med. 2009;17(3):176-178. View abstract.
Sarris, J., Kavanagh, D. J., Deed, G., and Bone, K. M. St. John's wort and Kava in treating major depressive disorder with comorbid anxiety: a randomised double-blind placebo-controlled pilot trial. Hum.Psychopharmacol. 2009;24(1):41-48. View abstract.
Sarris, J., Laporte, E., and Schweitzer, I. Kava: a comprehensive review of efficacy, safety, and psychopharmacology. Aust.N.Z.J.Psychiatry 2011;45(1):27-35. View abstract.
Sarris, J., Panossian, A., Schweitzer, I., Stough, C., and Scholey, A. Herbal medicine for depression, anxiety and insomnia: a review of psychopharmacology and clinical evidence. Eur.Neuropsychopharmacol. 2011;21(12):841-860. View abstract.
Scherer, J. Kava-kava extract in anxiety disorders: an outpatient observational study. Adv.Ther. 1998;15(4):261-269. View abstract.
Schmidt, M. Are kavalactones the hepatotoxic principle of kava extracts? The pitfalls of the glutathione theory. J Altern Complement Med 2003;9(2):183-187. View abstract.
Singh Y and Blumenthal M. Kava: an overview. Distribution, mythology, botany, culture, chemistry and pharmacology of the South Pacific's most revered herb. HerbalGram 1997;39(Suppl 1):34-56.
Stafford N. Germany may ban kava kava herbal supplement, Reuter's News Service Germany (November 19, 2001).
Stickel, F., Baumuller, H. M., Seitz, K., Vasilakis, D., Seitz, G., Seitz, H. K., and Schuppan, D. Hepatitis induced by Kava (Piper methysticum rhizoma). J Hepatol. 2003;39(1):62-67. View abstract.
Stoller, R. Reports of hepatotoxicity with kava. Proceedings of the 24th Annual Meeting of Representatives of National Centres Participating in the WHO Drug Monitoring Programme, Dunedin, New Zealand 2008;
Teschke, R., Genthner, A., and Wolff, A. Kava hepatotoxicity: comparison of aqueous, ethanolic, acetonic kava extracts and kava-herbs mixtures. J.Ethnopharmacol. 6-25-2009;123(3):378-384. View abstract.
Thompson, R., Ruch, W., and Hasenohrl, R. U. Enhanced cognitive performance and cheerful mood by standardized extracts of Piper methysticum (Kava-kava). Hum.Psychopharmacol. 2004;19(4):243-250. View abstract.
van der Watt, G., Laugharne, J., and Janca, A. Complementary and alternative medicine in the treatment of anxiety and depression. Curr.Opin.Psychiatry 2008;21(1):37-42. View abstract.
Walden J, von Wegerer J, Winter U, and et al. Actions of kavain and dihydromethysticin on ipsapirone-induced field potential changes in the hippocampus. Human Psychopharm 1997;12:265-270.
Watkins, L. L., Connor, K. M., and Davidson, J. R. Effect of kava extract on vagal cardiac control in generalized anxiety disorder: preliminary findings. J Psychopharmacol. 2001;15(4):283-286. View abstract.
Wheatley D. Kava and valerian in the treatment of stress-induced insomnia. Phytother Res 2001;15:549-551. View abstract.
Whitton, P. A., Lau, A., Salisbury, A., Whitehouse, J., and Evans, C. S. Kava lactones and the kava-kava controversy. Phytochemistry 2003;64(3):673-679. View abstract.
Woelk H, Kapoula O, Lehrl S, and et al. [Treatment of patients suffering from anxiety- double-blind study: kava special extract versus benzodiazepines]. Z Allg Med 1993;69:271-277.
Zhou, S. F., Xue, C. C., Yu, X. Q., and Wang, G. Metabolic activation of herbal and dietary constituents and its clinical and toxicological implications: an update. Curr Drug Metab 2007;8(6):526-553. View abstract.
Almeida JC, Grimsley EW. Coma from the health food store: interaction between kava and alprazolam. Ann Intern Med 1996;125:940-1. View abstract.
Anon. Hepatic toxicity possibly associated with kava-containing products-United States, Germany, Switzerland, 1999-2002. MMWR 2002;1:1065-1067.. View abstract.
Baum SS, Hill R, Rommelspacher H. Effect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of rats. Prog Neuropsychopharmacol Biol Psychiatry 1998;22:1105-20. View abstract.
Bilia AR, Gallori S, Vincieri FF. Kava-kava and anxiety: growing knowledge about the efficacy and safety. Life Sci 2002;70:2581-97. View abstract.
Bodkin R, Schneider S, Rekkerth D, et al. Rhabdomyolysis associated with kava ingestion. Am J Emerg Med 2012;30:635.el-3. View abstract.
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. View abstract.
Boonen G, Pramanik A, Rigler R, Haberlein H. Evidence for specific interactions between kavain and human cortical neurons monitored by fluorescence correlation spectroscopy. Planta Med 2000;66:7-10. View abstract.
Cagnacci A, Arangino S, Renzi A, et al. Kava-Kava administration reduces anxiety in perimenopausal women. Maturitas 2003;44:103-9. View abstract.
Cairney S, Maruff P, Clough AR, et al. Saccade and cognitive impairment associated with kava intoxication. Hum Psychopharmacol 2003;18:525-33. View abstract.
Connor KM, Davidson JR. A placebo-controlled study of Kava kava in generalized anxiety disorder. Int Clin.Psychopharmacol 2002;17:185-8. View abstract.
Connor KM, Payne V, Davidson JR. Kava in generalized anxiety disorder: three placebo-controlled trials. Int Clin Psychopharmacol 2006;21:249-53. View abstract.
Consultation letter MLX 286: Proposals to prohibit the herbal ingredient Kava-Kava (Piper methysticum) in unlicensed medicines. Medicines Control Agency, United Kingdom, July 19, 2002.
Cropley M, Cave Z, Ellis J, Middleton RW. Effect of kava and valerian on human physiological and psychological responses to mental stress assessed under laboratory conditions. Phytother Res 2002;16:23-7.. View abstract.
Davies LP, Drew CA, Duffield P, et al. Kava Pyrones and Resin: Studies on GABA-A, GABA-B, and Benzodiazepine Binding Sites in Rodent Brain. Pharmacol Toxicol 1992;71:120-6. View abstract.
Denham A, McIntyre M, Whitehouse J. Kava--the unfolding story: report on a work-in-progress. J Altern Complement Med 2002;8:237-263.. View abstract.
Donadio V, Bonsi P, Zele I, et al. Myoglobinuria after ingestion of extracts of guarana, Ginkgo biloba and kava. Ginkgo biloba and kava. Neurol Sci 2000;21:124. View abstract.
Escher M, Desmeules J, Giostra E, Mentha G. Hepatitis associated with Kava, a herbal remedy for anxiety. BMJ 2001;322:139. View abstract.
Fetrow CW, Avila JR. Professional's Handbook of Complementary & Alternative Medicines. 1st ed. Springhouse, PA: Springhouse Corp., 1999.
Garner LF, Klinger JD. Some visual effects caused by the beverage kava. J Ethnopharmacol 1985;13:307-311.. View abstract.
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;10:631-9. View abstract.
Geier FP, Konstantinowicz T. Kava treatment in patients with anxiety. Phytother Res 2004;18:297-300. View abstract.
Gleitz J, Beile A, Wilkens P, et al. Antithrombotic action of the kava pyrone (+)-kavain prepared from Piper methysticum on human platelets. Planta Med 1997;63:27-30. View abstract.
Gow PJ, Connelly NJ, Hill RL, et al. Fatal fulminant hepatic failure induced by a natural therapy containing kava. Med J Aust 2003;178:442-3. View abstract.
Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005;77:415-26. View abstract.
Gurley BJ, Swain A, Barone GW, et al. Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans. Drug Metab Dispos 2007;35:240-5. View abstract.
Gurley BJ, Swain A, Hubbard MA, et al. Clinical assessement of CYP2D6-mediated herb-drug interactions in humans: Effects of milk-thistle, black cohosh, goldenseal, kava kava, St. John's wort, and Echinacea. Mol Nutr Food Res 2008;52:755-63. View abstract.
Hannam S, Murray M, Romani L, Tuicakau M, J Whitfeld M. Kava dermopathy in Fiji: an acquired ichthyosis? Int J Dermatol 2014;53(12):1490-4. View abstract.
Heinze HJ, Munthe TF, Steitz J, Matzke M. Pharmacopsychological effects of oxazepam and kava-extract in a visual search paradigm assessed with event-related potentials. Pharmacopsychiatry 1994;27:224-30. View abstract.
Jacobs BP, Bent S, Tice JA, et al. An internet-based randomized, placebo-controlled trial of kava and valerian for anxiety and insomnia. Medicine (Baltimore) 2005;84:197-207. View abstract.
Jorm, A. F., Christensen, H., Griffiths, K. M., Parslow, R. A., Rodgers, B., and Blewitt, K. A. Effectiveness of complementary and self-help treatments for anxiety disorders. Med J Aust 2004;181(7 Suppl):S29-S46. View abstract.
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 1994;116:469-74. View abstract.
Ketola RA, Viinamäki J, Rasanen I, Pelander A, Goebeler S. Fatal kavalactone intoxication by suicidal intravenous injection. Forensic Sci Int 2015;249:e7-e11. View abstract.
Kuchta K, Schmidt M, Nahrstedt A. German Kava Ban Lifted by Court: The Alleged Hepatotoxicity of Kava (Piper methysticum) as a Case of Ill-Defined Herbal Drug Identity, Lacking Quality Control, and Misguided Regulatory Politics. Planta Med. 2015;81(18):1647-53. View abstract.
Lehmann E, Kinzler E, Friedemann J. Efficacy of a special Kava extract (Piper methysticum) in patients with states of anxiety, tension and excitedness of non-mental origin - a double-blind placebo-controlled study of four weeks treatment. Phytomedicine 1996;3:113-9. View abstract.
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;78:101-10. View abstract.
Li XZ, Ramzan I. Role of ethanol in kava hepatotoxicity. Phytother Res 2010;24:475-80. View abstract.
Liver Toxicity With Kava. Pharmacist's Letter/Prescriber's Letter. January 2001.
Logan JL, Ahmed J. Critical hypokalemic renal tubular acidosis due to Sjogren's syndrome: association with the purported immune stimulant echinacea. Clin Rheumatol 2003;22:158-9. View abstract.
Malsch U, Kieser M. Efficacy of kava-kava in the treatment of non-psychotic anxiety, following pretreatment with benzodiazepines. Psychopharmacology (Berl) 2001;157:277-83. View abstract.
Mathews JD, Riley MD, Fejo L, et al. Effects of heavy usage of kava on physical health: Summary of a pilot survey in an aboriginal community. Med J Aust 1988;148:548-55. View abstract.
Mathews JM, Etheridge AS, Black SR. Inhibition of human cytochrome P450 activities by kava extract and kavalactones. Drug Metab Dispos 2002;30:1153-7. View abstract.
Meseguer E, Taboada R, Sanchez V, et al. Life-threatening parkinsonism induced by kava-kava. Mov Disord 2002;17:195-6. View abstract.
Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Int Med 1998;158:2200-11.. View abstract.
Moulds RF, Malani J. Kava: herbal panacea or liver poison? Med J Aust 2003;178:451-3. View abstract.
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. View abstract.
Norton SA, Ruze P. Kava dermopathy. J Am Acad Dermatol 1994;31:89-97. View abstract.
Ostermayer D. News: Kava, Popular as Alcohol Alternative, May Cause Toxicity. Emerg Med News. 2016;38(1B).
Pierce A. The American Pharmaceutical Association Practical Guide to Natural Medicines. New York: The Stonesong Press, 1999:19.
Pittler MH, Ernst E. Efficacy of kava extract for treating anxiety: systematic review and meta-analysis. J Clin Psychopharmacol 2000;20:84-9. View abstract.
Pittler MH, Ernst E. Kava extract for treating anxiety. Cochrane Database Syst Rev 2003;(1):CD003383. View abstract.
Pizzorno JE, Murray MT, eds. Textbook of Natural Medicine. 2nd ed. Edinburgh:Churchill Livingstone, 1999.
Russmann S, Lauterburg BH, Helbling A. Kava hepatotoxicity [letter]. Ann Intern Med 2001;135:68-9. View abstract.
Ruze P. Kava-induced dermopathy: a niacin deficiency? Lancet 1990;335:1442-5. View abstract.
Sarris J, Kavanagh DJ, Byrne G, et al. The Kava Anxiety Depression Spectrum Study (KADSS): a randomized, placebo-controlled crossover trial using an aqueous extract of Piper methysticum. Psychopharmacology 2009;205:399-407. View abstract.
Sarris J, Scholey A, Schweitzer I, et al. The acute effects of kava and oxazepam on anxiety, mood, neurocognition; and genetic correlates: a randomized, placebo-controlled, double-blind study. Hum Psychopharmacol 2012;27:262-9. View abstract.
Sarris J, Stough C, Bousman CA, Wahid ZT, Murray G, Teschke R, Savage KM, Dowell A, Ng C, Schweitzer I. Kava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled study. J Clin Psychopharmacol 2013;33(5):643-8. View abstract.
Sarris J, Stough C, Teschke R, Wahid ZT, Bousman CA, Murray G, Savage KM, Mouatt P, Ng C, Schweitzer I. Kava for the treatment of generalized anxiety disorder RCT: analysis of adverse reactions, liver function, addiction, and sexual effects. Phytother Res 2013;27(11):1723-8. View abstract.
Schelosky L, Raffaup C, Jendroska K, Poewe W. Kava and dopamine antagonism. J Neurol Neurosurg Psychiatry 1995;58:639-40. View abstract.
Schmidt M. German Court Ruling Reverses Kava Ban; German Regulatory Authority Appeals Decision. HerbalEGram. 2014;11(7).
Schmidt P, Boehncke WH. Delayed-type hypersensitivity reaction to kava-kava extract. Contact Dermatitis 2000;42:363-4. View abstract.
Schulze J, Raasch W, Siegers CP. Toxicity of kava pyrones, drug safety and precautions--a case study. Phytomedicine 2003;10:68-73.. View abstract.
Seitz U, Schule A, Gleitz J. [3H]-monoamine uptake inhibititon properties of kava pyrones. Planta Med 1997;63:548-549.. View abstract.
Singh YN, Blumenthal M. Kava an overview. HerbalGram 1997;39:33-44, 46-55.
Singh YN. Effects of kava on neuromuscular transmission and muscle contractility. J Ethnopharmacol 1983;7:267-76.. View abstract.
Singh YN. Kava: an overview. J Ethnopharmacol 1992;37:13-45. View abstract.
Spillane PK, et al. Neurological manifestations of kava intoxication. Med J Aust 1997;167:172-3. View abstract.
Steiner GG. The correlation between cancer incidence and kava consumption. Hawaii Med J 2000;59:420-2. View abstract.
Strahl S, Ehret V, Dahm HH, Maier KP. [Necrotizing hepatitis after taking herbal medication]. Dtsch Med Wochenschr 1998;123:1410-4. View abstract.
Swensen JN. Man convicted of driving under the influence of kava. Salt Lake City, UT: Deseret News, 1996.
Teschke R, Gaus W, Loew D. Kava extracts: safety and risks including rare hepatotoxicity. Phytomedicine 2003;10:440-6. View abstract.
Teschke R, Lebot V. Proposal for a Kava Quality Standardization Code. Food Chem Toxicol 2011;49(10):2503-16. View abstract.
Teschke R, Sarris J, Schweitzer I. Kava hepatotoxicity in traditional and modern use: the presumed Pacific kava paradox hypothesis revisited. Br J Clin Pharmacol 2012;73(2):170-4. View abstract.
Teschke R. Kava hepatotoxicity: pathogenetic aspects and prospective considerations. Liver Int 2010;30(9):1270-9. View abstract.
Toohey TP, Lu BY, Wada C. Toxic effects of psychotropics related to possible p450 enzyme inhibition by kava:report of 2 cases. Prim Care Companion CNS Disord 2013;15(5). View abstract.
Uebelhack R, Franke L, Schewe HJ. Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava). Pharmacopsychiatry 1998;31:187-92. View abstract.
Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;18:2273-81. View abstract.
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. View abstract.
Warnecke G. [Psychosomatic dysfunctions in the female climacteric. Clinical effectiveness and tolerance of Kava extract WS 1490]. Fortschr Med 1991;109:119-22. View abstract.
Weiss J, Sauer A, Frank A, Unger M. Extracts and kavalactones of Piper methysticum G. Forst (kava-kava) inhibit P-glycoprotein in vitro. Drug Metab Dispos 2005;33:1580-3. View abstract.
Welihinda J, et al. Effect of Momordica charantia on the glucose tolerance in maturity onset diabetes. J Ethnopharmacol 1986;17:277-82. View abstract.
Wheatley D. Stress-induced insomnia treated with kava and valerian: singly and in combination. Hum Psychopharmacol 2001;16:353-6. View abstract.
Witte S, Loew D, Gaus W. Meta-analysis of the efficacy of the acetonic kava-kava extract WS1490 in patients with non-psychotic anxiety disorders. Phytother Res 2005;19:183-8. View abstract.
Woelk H, Kapoula O, Lehrl S, et al. [Comparison of kava special extract WS 1490 and benzodiazepines in patients with anxiety]. Z Allg Med 1993;69:271-7.
Wooltorton E. Herbal kava: reports of liver toxicity. CMAJ 2002;166:777. View abstract.
Wu D, Yu L, Nair MG, et al. Cyclooxygenase enzyme inhibitory compounds with antioxidant activities from Piper methysticum (kava kava) roots. Phytomedicine 2002;9:41-7. View abstract.