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| EVIDENCE FOR EFFICACY (HUMAN DATA) |
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Clinical Trials
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Cochrane evidence-based review of azapirones for generalized anxiety disorder was inconclusive as to whether azapirones were superior to antidepressants, psychotherapy or kava kava.
Chessick 2006
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The pooled sample (n=64) from adult outpatients with DSM-IV generalized anxiety disorder including participants: kava, n=28; placebo, n=30; and venlafaxine, n=6 revealed that these three controlled trials do not support the use of kava in DSM-IV generalized anxiety disorder.
Connor 2006
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Study on 31 healthy volunteers (13 Piper methysticum 30C, 11 placebo and 7 Plumbum metallicum 30C), conludes that open diaries, supervision and double-blind placebo are useful methods in homeopathic pathogenetic trials.
Signorini 2005
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A double-blind randomized placebo-controlled trial involving healthy volunteers found Kava is a potent anxiolytic agent, which, additionally, can facilitate cognitive functioning and increase positive affectivity related to exhilaration.
Thompson 2004
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Randomized open study investigating, in peri-menopausal women, modifications induced by calcium supplementation, calcium plus Kava-Kava at the dose of 100 mg/day, or calcium plus Kava-Kava at a dose 200 mg/day revealed improvement of mood, particularly of anxiety.
Cagnacci 2003
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Update of 2001 & 2002 Cochrane evidence-based reviews found that compared with placebo, kava extract is an effective symptomatic treatment for anxiety although, at present, the size of the effect seems small. Available data suggests that it is relatively safe for short-term treatment (1-24 wks).
Pittler 2003
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Analyses of a study of adults with DSM-IV generalized anxiety disorder revealed significant differences. Kava was superior on the Self Assessment of Resilience and Anxiety (SARA) in low anxiety and placebo was superior on the Hospital Anxiety and Depression Scale and SARA in high anxiety .
Connor 2002
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Participants performed a standardized mental stress task. Blood pressure, heart rate and subjective ratings of pressure were assessed at rest and during the mental stress task. Results suggest that kava and valerian may reduce physiological reactivity during stressful situations.
Cropley 2002
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The combined use of hormone replacement therapy and kava extract seems to be effective against menopausal anxiety. Kava extract accelerates resolution of psychological symptoms while hormone therapy safeguards against osteoporosis and cardiovascular disease.
De Leo 2001
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A 5-week randomized, placebo-controlled, double-blind investigation confirmed the anxiolytic efficacy and good tolerance of kava-kava special extract WS1490 and showed that further symptom reduction is possible after a change-over from benzodiazepine treatment.
Malsch 2001
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Preliminary findings suggest that kava might exert a favourable effect on reflex vagal control of heart rate in generalized anxiety disorder patients.
Watkins 2001
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Total stress severity was significantly relieved by kava and valerian (p < 0.01) with no significant differences between them; as was also insomnia (p < 0.01). The proportion of patients with no side-effects was 58% with each herb respectively.
Wheatley 2001
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Evidence of efficacy for St. John's wort, kava, ginkgo, and valerian in treating psychiatric conditions is growing, but translating the results into effective treatments is hampered by the chemical complexity and non-standardization of the products, and the paucity of well-controlled studies.
Beaubrun 2000
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The results of this study show that the association of Hormone Replacement Therapy and Kava-Kava extract may represent an excellent therapeutic tool for the treatment of women in stabilized menopause, in particular those suffering from anxiety and depression.
De Leo 2000
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The degree of anxiety was acute in that the patients were waiting for the results of a histopathological diagnosis, carried out on account of suspect mammary findings. The preparation under investigation, Kavosporal forte, was found to be well suited for the amelioration of anxiety.
Neuhaus 2000
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The meta-analysis of three trials suggests a significant difference in the reduction of the total score on the Hamilton Rating Scale for anxiety in favor of kava extract. These data imply that kava extract is superior to placebo as a symptomatic treatment for anxiety.
Pittler 2000
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A review of the results of randomized, controlled trials supports the use of kava for anxiety and valerian for insomnia
Fugh-Berman 1999
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Review of therapeutic efficacy, mechanisms of actions, dosages and regimens, preparations, and adverse effects for melatonin, St John's wort, valerian, and kava-kava
Heiligenstein 1998
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WS 1490 kava extract reduced anxiety in a 25-week placebo-controlled double-blind trial with 101 outpatients with anxiety of non-psychotic origin
Volz 1997
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Study methodology for unconventional therapies such as Kava-Kava for patients in the state of anxiety, tension and restlessness
Gaus 1995
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Drug therapy of panic disorders. Kava-specific extract WS 1490 compared to benzodiazepines [Article in German]
anon 1994
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Drug therapy of panic disorders. Kava-specific extract WS 1490 compared to benzodiazepines [Article in German]
anon 1994
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Comparison of oxazepam with WS1490 (kava extract) on reaction time and event-related potentials in a double-blind study of young, healthy males
Heinze 1994
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People with moderate 0.05% blood alcohol had better concentration when using kava extract WS 1490 (3 x 100 mg/d for 8 days) but no better performance in a placebo-controlled randomised double-blind study of 20 adults [Article in German]
Herberg 1993
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Kava slightly improved a word recognition task while oxazepam reduced the scores in a double blind crossover study of 12 healthy people
Munte 1993
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EEG-brain-mapping in healthy adults taking single doses of kawain showed dose-dependent increase in delta, theta and alpha 1 power, and decrease in alpha 2 and beta power. Primary peak in 1st hour and a 2nd peak in the 8th hour [Article in German]
Frey 1991
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Anxiety patients benefited from WS 1490 (3 x 100 mg/day for 4 weeks) in a randomized, double-blind study with 58 people [Article in German]
Kinzler 1991
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Female climacteric symptoms benefited from kava WS 1490 extract 3 X 100 mg/day for 8 weeks in a double-blind placebo-controlled study with 40 patients [Article in German]
Warnecke 1991
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Kavain gave benefit equal to oxazepam in a placebo-controlled double blind trial with 38 out-patients with anxiety [Article in German]
Lindenberg 1990
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400 mg/day of cavain alleviated anxiety in a 4 week double-blind placebo controlled trial with 52 patients
Lehmann 1989
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Continuous increase in memory, vigilance, fluency of mental functions, reaction time, and circulation during 3 weeks of taking 400 mg/d kavain in a double blind study of 84 patients [Article in German]
Scholing 1977
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Effect of kavain on alcoholic patients in the withdrawal phase (author's transl) [Article in German]
Kryspin-Exner 1974
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Studies of the vegetative action mechanism of kavain and magnesium orotate [Article in German]
Prokop 1971
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Studies of the vegetative action mechanism of kavain and magnesium orotate [Article in German]
Prokop 1970
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Treatment of senile hearing disorders and disorders of the inner ear with the geriatric therapeutic agent Kavaform [Article in German]
Kluger 1969
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Treatment of cerebro-organic changes due to age with kavaform [Article in German]
Kurz 1968
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Clinical studies on the geriatric agent Kavaform. Double blind tests [Article in German]
Hun 1967
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Observational Studies/Case Reports
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Among eight different herbals studied Piper methysticum and Bacopa monniera were found to associated with anxiolytic activity in humans.
Ernst 2006
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Review discussing the proposed uses, dosing parameters, adverse effects, toxicology, interactions and mechanism of action of kava (Piper methysticum) detailed.
Ulbricht 2005
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A systematic search using computerized databases shows that Kava is effective in the treatment of tension and anxiety. There may be risk-factors for severe motor and psychiatric responses to kava use.
Cairney 2002
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This validation study found that self-reported kava use may be a poor estimate of current use when obtained from interviews away from a confidential clinic setting. Consensus classification by knowledgeable Aboriginal health workers provided comprehensive coverag with greater reliability.
Clough 2002
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Piper methysticum (kava) under discussion: observations on quality, effectiveness and safety with reference to possible hepatic side effects ratio. [Article in German]
Schmidt 2002a
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This paper systematically reviews the clinical evidence relating to the safety of extracts of the herbal anxiolytic kava (Piper methysticum). Serious adverse events have been reported and further research is required to determine the nature and frequency of such events.
Stevinson 2002
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Echinacea, ephedra, garlic, ginkgo, ginseng, kava, St John's wort, and valerian are commonly used herbal medications that may pose a concern during the perioperative period. Pharmacodynamic herb-drug interactions include potentiation of the sedative effect of anesthetics by kava and valerian.
Ang-Lee 2001
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A 37-year-old female outpatient with generalized anxiety disorder, a simple phobia and a specific social phobia was treated with phytotherapy (Kava kava). Within 4 weeks, symptoms had improved by 75% and by 6 months an almost total remission of symptoms was observed.
Boerner 2001
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Safety parameters including withdrawal symptoms, effect on heart rate, blood pressure, laboratory assessments, and sexual function between kava and placebo revealed usage in treating anxiety at 280 mg of kava lactones/day for 4 weeks to be safe.
Connor 2001
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An analysis of a Germany database providing anonymous access to a panel of physicians and patients indicated that prescriptions of kava overstepped the recommended daily dose in 78% of the cases, explaining why kava prescriptions are associated with high incidence of adverse drug reactions.
Schroder-Bernhardi 2001
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Kava alone has little effect on performance skills on a number of cognitive and visuomotor tests but appears to potentiate both perceived and measured impairment when combined with alcohol.
Foo 1997
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Kava-kava may be indicated in special cases, e.g. low degree of anxiety, abuse or tolerance problems with the drugs of first choice, benzodiazepines and antidepressants [Article in German]
Laux 1997
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The effect of kavaine and magnesium orotate combination in the psycho - organic disorders of the elderly.
Sukyasyan 1980
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The therapeutic effect of kavain and magnesium orotate on traumatic and vascular brain lesions [Article in German]
Wenzel 1971
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Traditional and Folk Use
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Plants including Piper methysticum possessing central activities such as analgesic, anxiolytic, psychoanaleptic, psycholeptic & psychodysleptic effects have been reviewed & crude or semipurified extracts instead of active substances seemingly responsible for therapeutic effect is discussed.
Carlini 2003
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Kava and kavalactones are shown to be effective in the treatment of anxiety at subclinical and clinical levels, anxiety associated with menopause and anxiety due to various medical conditions. Their possible mechanism of action and adverse effects are detailed.
Singh 2002
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The data shows that the more kava consumed by a population the lower the cancer incidence for that population, suggesting a close, inverse relationship between cancer incidence and kava consumption.
Steiner 2000
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Kava, now widely available as a relaxant, was a ceremonial Hawaiian psychoactive causing tranquil intoxication in which thoughts and memory remain clear
Norton 1998
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Review: from Cook's reports (1772-1775) to modern pharmacology and toxicology [Article in Polish]
Nowakowska 1998
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Smoking cessation program in Fiji was successful with combination of group pledge, village rapid inhalation ceremony, social contracting through notices and media, and a tabu formalized through a kava ceremony
Groth-Marnat 1996
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Ceremonially used by many traditional societies of the Southern Pacific, the beverage induces relaxation, enhances a sense of sociability and promotes sleep [Article in German]
Suss 1996
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Kava, a nonfermented psychoactive beverage, has been used ceremonially for thousands of years by Pacific Islanders. The skin eruptions were first reported by members of Captain James Cook's Pacific expeditions
Norton 1994
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Kava lactones were detected in a number of Pacific Island archaeological artefacts using selected-ion monitoring techniques with GC/EI-MS
Hocart 1993
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58 herbs were commonly used by Hawaiians for asthma; noteworthy are Sophora chrysophylla, Piper methysticum, solanum americanum, and Aleurites molucana
Hope 1993
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Multidisciplinary review of kava: from ceremonial usage to modern pharmacology
Singh 1992
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Indiginous psychoactive use of betel, kava and pituri
Cawte 1985
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In Tonga kava use is mainly by men. In urban areas usage is somewhat replaced by alcohol
Finau 1982
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Koni, kona, kava. orange-beer culture of the Cook islands: drinking customs have cultlike forms, provide for social integration, and control drunken aggression
Lemert 1976
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Piper methysticium (kava). The function of kava in modern Samoan culture.
Holmes 1967
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Adverse Effects & Toxicity
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The no observed adverse effect levels of kava (Piper methysticum) were decided as 0.25g/kg in both genders, based on neurotoxic effects, increase in GGT, cholesterol, liver weight, and HP and decrease in body weight.in groups of 10 male and 10 female rats.
Clayton 2007
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Kavalactones (+/-)-kavain, methysticin,yangonin and demethyoxy yangonin, (all 4 of Piper methysticum) failure to inhibit alcohol dehydrogenase in vitro at 1,10 or 100 microM concentrations explains mechanism of hepatotoxicity of kava a folkloric beverage.
Anke 2006
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No satisfactory answer was obtained to ascertain major liver failure cases in which kava kava ( Piper methysticum, Forst. f., Piperaceae) has been implicated in spite of summarizing the major theories and hypotheses as to the mechanism of kava hepatotoxicity.
Anke 2004b
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Kava toxicity appears to be "idiosyncratic" and risk-to-benefit ratio of kava extracts, nevertheless, remains good in comparison with that of other drugs used to treat anxiety.
Clouatre 2004
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After case reports of liver toxicity allegedly associated with its nontraditional use of 'awa (Piper methysticum) the remedy was banned in several European countries.
O'Sullivsan 2004
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3 kava lactones and ethanolic extract of dried kava root produce cell toxicity without being influenced by CYP 1A1, 1A2, 2A6, 2E1, and 3A4 or epoxide hydroxylase suggesting non activation into toxic metabolites.
Zou 2004a
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Hepatotoxic risks under the treatment with kavapyrones might be minimized by limiting to a dose of 120, maximally 210 mg kavapyrones per day for 1 month, or 2 months, monitoring by lab. tests like ALT and gamma-GT estimation and by avoiding co-medication & alcohol consumption.[Article in German]
Teschke 2003
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[Acute liver failure after administration of herbal tranquilizer kava-kava (Piper methysticum).]
Brauer 2003
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Individuals intoxicated from drinking kava (n=11) when compared with a control group (n=17) using saccade and cognitive tests showed ataxia, tremors, sedation, blepharospasm and elevated liver enzymes (GGT and ALP).
Cairney 2003
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No impairment was found in cognitive or saccade function in individuals who were currently heavy kava users but current and ex-kava users showed a higher rate of kava dermopathy, lower body mass index, lowered blood lymphocytes and, showed elevated liver enzymes.
Cairney 2003
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Neurological syndromes associated with the ingestion of plants including Kava and fungi with a toxic component (II).detailed. [Article in Spanish]
Carod Artel 2003
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A case of acute liver failure and death associated with the use of a preparation containing the "natural" anxiolytic kava (Piper methysticum) and passion flower (Passiflora incarnata).
Gow 2003
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A case of acute hepatitis( previously healthy 14-year-old female) associated with the use of kava kava, derived from the root of the pepper plant, Piper methysticum detailed cautioning the clinicians to remain aware of the toxic potential of herbal products.
Humberston 2003
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Due to various reports of liver toxicity, including liver failure, associated with extracts from the Pacific islands plant kava (Piper methysticum), it has been banned from sale as a herbal anxiolytic in many Western countries, to the detriment of Pacific island economies.
Moulds 2003
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Analysis of 29 novel cases of hepatitis along with Kava ingestion revealed hepatic necrosis or cholestatic hepatitis were noticed with both alcoholic and acetonic Kava extracts.
Stickel 2003
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No studies explain liver toxicity of kavalactones and it is unknown which compound might provoke liver disease. It is possible that unknown or unexpected constituents are responsible or contributed to reported liver toxicity.
Bilia 2002
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Kava-induced acute icteric hepatitis. [no abstract[ [article in spanish]
Bujanda 2002
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Kava-induced fulminant hepatic failure. [no abstract]
Campo 2002
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A total of 11 patients who used kava products had liver failure and underwent subsequent liver transplantation in Germany, Switzerland, and the United States due to occurrence of severe hepatic toxicity possibly associated with the consumption of products containing kava.
Centre for diseases control and prevention 2002
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This paper argues that many of the adverse events cited by the German Federal Institute for Drugs and Medical Products should not be attributed to kava, rather that the properties of concentrated standardized kava extracts as opposed to traditional extracts, contribute to adverse events.
Denham 2002
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The Food and Drug Administration (FDA) is advising consumers of the potential risk of severe liver injury associated with the use of Kava (Piper methysticum) - containing dietary supplements.
FDA/CFSAN
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A 45-year-old female, who had a family history of essential tremor, developed severe and persistent parkinsonism after days of treatment with kava extract for anxiety. The symptoms improved with anticholinergics.
Meseguer 2002
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The kavapyrone (+/-) kavain is neurotoxic only at high concentrations when exposed alone to the developing hippocampus,and it appears to adversely affect neuronal recovery following excitotoxic insults.
Mulholland 2002
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Another FDA warning: Kava supplements. [no abstract]
Parkman 2002
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In this analysis, only 4 of 22 case reports established certain probablility of kava hepatotoxicity. In only one case was kava was taken according dosage recommendations of the German commission E monograph. The risk of adverse liver effects from kava seems very low.
Schmidt 2002
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The responses include data on contemporary extracts of kava lactones using either acetone or 95% ethanol versus tradtional methods using 25% ethanol.
eBMJ rapid response to Escher 2001
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A 50 year old man with jaundice had consumed kava extracts capsules (210-280 mg lactones)daily for two months. The patient received a liver transplant two days later and recovered uneventfully. Histology showed extensive and severe hepatocellular necrosis. See eBMJ rapid response to Escher 2001.
Escher 2001
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A 60 year-old woman was admitted to hospital because of jaundice, fatigue, weight loss over several months and icteric skin. The exclusion of other causes and the histological diagnosis made Kava-Kava as the cause of acute liver failure most likely.
Kraft 2001
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This paper reports on adverse drug reactions, its definitions, diagnosis, management and in particularly the timing, pattern of illness, results of investigations, and rechallenge can help attribute causality to a suspected adverse drug reaction. See Denham 2002.
Edwards 2000
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Adverse effects of herbal medicines are an important albeit neglected subject in dermatology, which deserves further systematic investigation, including St John's Wort, kava, aloe vera, eucalyptus, camphor, henna and yohimbine.
Ernst 2000
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An extensively studied genetic polymorphism involves cytochrome P450 2D6. CYP2D6 metabolizes a number of antidepressants, antipsychotics, beta-adrenoceptor blockers, and antiarrhythmic drugs. About 7% of Caucasians and 1% of Asians are poor metabolizers of CYP2D6 substrates. See Denham 2000.
Poolsup 2000
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Sebotropic drug reaction resulting from kava-kava extract therapy: a new entity?
Jappe 1998
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Two unrelated women (aged 39 and 42) had been admitted (at different times) to hospital because of acute hepatitis. Both patients had a history of acute hepatitis. The liver function tests normalized when herbal medication was stopped [Article in German]. See Denham 2002.
Strahl 1998
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Herbal xenobiotics can lead to the brreakdown of hepatocytes, leading to centribular necrosis. See Denham 2002.
Kaplowitz 1997
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Coma associated with a mixture of alprazolam and kava
Almeida 1996
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The ichthyosiform kava dermopathy is a well-known side effect of excessive use of kava; a case of such systemic contact-type dermatitis after oral administration of kava extract is reported here [Article in German]
Suss 1996
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Heavy kava drinkers acquire a peculiar reversible scaly ichthyosiform eruption, kava dermopathy. The cause is unknown but may relate to interference with cholesterol metabolism
Norton 1994
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Ten metabolites seen by GC/MS in human urine indicate hydroxylation of the phenyl ring, reduction of the 7,8-double bond, hydroxylation of the lactone ring with subsequent dehydration and opening of the lactone ring. Most are excreted as conjugates
Koppel 1991
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Heavy chronic consumption of kava is associated with a pellagroid dermopathy. Of 200 Tonga drinkers, 29 with skin changes put in niacin trial 100 mg or placebo for 3 weeks revealed no benefit
Ruze 1990
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The effects of heavy usage of kava on physical health.
anon 1988
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5-Hydroxydihydrokawain found in roots from Vanuatu but not Fiji. N-cinnamoyl pyrrolidine alkaloids & stigmasterol found in kava resin from Fiji and Vanuatu. Efficiency of water extraction (traditional) is only 5-10% of organic solvent
Cheng 1988
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Kava use associated with poor health, "puffy" face, scaly rash, increased patellar reflexes, haematuria, red-cell volume, gamma-glutamyl transferase and HDL cholesterol and decreased weight, albumin, plasma protein, lymphocytes, lung volume, bilirubin
Mathews 1988
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Kava bowl adoption by Australian Aboriginal communities to challenge alcohol usage brought about a new "blissful indolence" condition of detachment and pellagrinous skin reaction
Cawte 1986
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A case report of visual disturbance with reduced near point of accommodation and convergence, increased pupil diameter and disturbance to the oculomotor balance
Garner 1985
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Half of dihydrokawain was eliminated in rat urine in 48 h: 2/3 hydroxylated (esp. para) plus some pryrone ring breakage yielding 9-13% hippuric acid. Less urinary methysticin and yangonin, which are largely demethylated
Rasmussen 1979
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Interactions
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Review on the existing data on interactions of kava and St. John's wort with pharmaceutical agents revealing urgent need for detailed investigations to identify clinically significant interactions that have the potential to cause adverse effects.
Singh 2005
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Kavalactones, active principles of kava extracts, are potent inhibitors of several enzymes of the CYP 450 system which indicates that kava has a high potential for causing pharmacokinetic drug interactions with other herbal products or drugs.
Anke 2004a
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6 Herbs including kava significantly modulate the activity of drug-metabolizing enzymes (notably cytochrome p450 isozymes) and/or the drug transporter P-glycoprotein participate in potential pharmacokinetic interactions with anticancer drugs.
Sparreboom 2004
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A review emphasizes the additive and supra-additive effects of a plant's multiple constituents. Using examples, synergistic action in St. John's wort, kava kava, and valerian has been explained.
Spinella 2002
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This review identified a series of potential interactions between herbal therapies (St. John's wort, ginkgo biloba, kava, valerian, and ginseng) most likely to be used for the treatment of dementia and conventional drug therapy that place older people at risk for an adverse drug event.
Gold 2001
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Kava (Piper methysticum) increases 'off' periods in Parkinson patients taking levodopa and can cause a semicomatose state when given concomitantly with alprazolam.
Izzo 2001
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Ethanol and the lipid soluble extract (kava resin) increase each other's hypnotic action in mice
Jamieson 1990
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Animal Studies
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No suspicion of potential liver toxicity was observed when Wistar rats of both sexes were fed 7.3 or 73 mg/kg body weight of ethanolic kava (Piper methysticum extract for 3 and 6 months.
Sorrentino 2006
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Using chick, social separation-stress procedure as an anxiolytic bioassay, P. methysticum samples containing total kavalactones & fractions containing 1-6 kavalactones of varying concentrations were screened and found that dihydrokavain mediates anxiolytic properties.
Feltenstein 2003
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When various doses of ethanolic extract of kava root administered intraperitoneally to BALB/cByJ inbred mice, production of significant murine anxiolytic-like behavioral changes & sedation that are not mediated through benzodiazepine binding site on GABA(A) receptor complex were observed.
Garrett 2003
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Elevation of none of the markers of liver toxicity (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase, nor malondialdehyde) observed in rats administered with active kavalactones.
Singh 2003
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Acute effects of diazepam and a Kava-Kava preparation, were examined in Wistar rats using the elevated plus maze and at LI 150 (120-240 mg/kg p.o.) kava affected the behaviour measured in the X-maze test, inducing an anxiolytic like behaviour similar to diazepam.
Rex 2002
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This experiment sought to characterize the putative anxiolytic properties of Piper methysticum extract and its six principle kavalactones in the chick social separation-stress paradigm. Findings suggest that the anxiolytic effects may be mediated by dihydrokavain.
Smith 2001
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Kava-kava, a shrub, contains kavapyrones as active substances; these have been pharmacologically investigated in detail and are comparable with the benzodiazepine tranquilizers with regard to their mode and strength of action. [Article in German]
Muller 1999
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[Inhibition of haloperidol-induced catalepsy in rats by root extracts from Piper methysticum F.]
Noldner 1999
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Neither a single oral dose of 100 mg (+)-dihydromethysticin/kg nor chronic feeding for 78 days altered the dopaminergic or serotonergic tissue levels in rat brain significantly
Boonen 1998
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(+/-)-kavain (100 mg/kg, p.o.) reduced veratridine-induced glutamate release from 301% to 219%
Ferger 1998
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Kava extract, methysticin and dihydromethysticin reduced ischemia induced brain infarct as well as memantine (anticonvulsant) while kawain, dihydrokawain, and yangonin failed
Backhauss 1992
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Kavain reduced muscle tone. Effects on EEG indicates limbic structures and, especially, the amygdalar complex as the target, which may explain the promotion of sleep, even in the absence of sedation [Article in German]
Holm 1991
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Aqueous or lipid (resin) extracts had analgesic effects in mice. Of 8 pyrones, kawain, dihydrokawain, methysticin and dihydromethysticin were effective and not reversed by nalaxone
Jamieson 1990
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Both aqueous and lipid kava extracts reduced amphetamine-induced hypermotility in mice. 125 mg/kg of resin i.p. was necessary to decrease avoidance responses by 18%. Increasing to 150 mg/kg caused ataxia and sedation
Duffield 1989
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Kava resin produces a greater range of pharmacological actions (reduced activity and motor control and reflex, analgesia, local anesthetic) than the aqueous extract in mice
Jamieson 1989
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With injected compounds dihydrokawain and kawain reach peak levels of 64.7 and 29.3 ng/mg wet brain tissue while desmethoxyyangonin and yangonin slower broader peaks of 10.4 and 1.2 ng/mg. With crude resin i.p. kawain and yangonin increase
Keledjian 1988
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Comparative studies on the anticonvulsant activity of the pyrone compounds of Piper methysticum Forst [Article in German]
Kretzschmar 1969
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Pharmacodynamics
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Kava roots, leaves, and stem peelings were extracted with methanol, and when partitioned with a different polarity of solvents for evaluation of their cytotoxicity on HepG2 revealed stronger cytotoxicity than water fractions.
Jhoo 2006
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The extract of P. methysticum rhizome (Kava) showed potent stimulatory effect on melanogenesis when compared with Piper longum, P. kadsura, P. methysticum, P. betle, and P. cubeba.
Matsuda 2006
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Desmethoxyyagonin, kavain, 7,8-dihydrokavain, yagonin, methysticin, and dihydromethysticin kava lactones of kava roots (Piper methysticum) showed great herbicidal and antifungal activities.
Xuan 2006
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Development of a high throughput system (HTS) to screen psychoactive compounds including Piper methysticum (Kava Kava) against the receptorome (that portion of the genome encoding ligand reception) enabled the identification of the molecular target of each compound.
O'Connor 2005
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Study undertaken to test the ability of purified kavalactones revealed that only desmethoxyyangonin and dihydromethysticin markedly induced the expression of CYP3A23 leading to transcription activation, through a PXR-independent or PXR-involved indirect mechanism.
Ma 2004
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3 Kava lactones when tested for ability to inhibit catalytic activity of a panel of P450 isoforms present as c-DNA expressed-enzymes and in previously cryopreserved human hepatocytes were found to be potent inhibitors of CYPs 1A2, 2C9, 2C19, 2E1, and 3A4.
Zou 2004
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A risk-benefit profile of commonly used herbs is needed. This article provides a clinically oriented overview of the efficacy and safety of ginkgo, St. John's wort, ginseng, echinacea, saw palmetto, and kava. Kava is an efficacious short-term treatment for anxiety.
Ernst 2002
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Failure of kavain to attenuate PE-mediated contraction of thoracic aortae isolated from Sprague-Dawley rat in calcium (Ca(++))-free buffer, reveals that kavain impairs vascular smooth muscle contraction, likely through inhibition of Ca(++) channels.
Martin 2002
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Kava constituents dihydrokawain and yangonin showed COX-I and COX-II inhibitory activities at 100 microg/ml, respectively. Additionally, yangonin and methysticin showed moderate antioxidant activities in the free radical scavenging assay at 2.5 mg/ml.
Wu 2002
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Constituents, Gingko, kava (desmethoxyyangonin, dihydromethysticin, and methysticin), garlic, evening primrose oil, and St. John's wort significantly inhibited one or more of the cDNA human P450 isoforms at concentrations of less than 10 uM.
Zou 2002
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The assessment of transport properties of drug and natural product molecules was made using a filter-immobilized artificial membrane. The highly mobile kava lactones permeated in the order dihydromethisticin > yangonin > kavain > methisticin desmethoxyyangonin.
Avdeef 2001
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Methanolic leaf and root extracts of different kava (Piper methysticum) cultivars were tested on binding affinities to CNS receptors. Since the cultivars contained similar amounts of kavalactones, while their pharmacological activities differed markedly, other constituents may play a role.
Dinh 2001
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Kava pyrones exhibit a profile of cellular actions that shows a large overlap with several mood stabilizers, especially lamotrigine.
Grunze 2001
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Herbal medicines typically contain a number of active components. As a result, some provide multiple benefits and some a mixture of benefits and adverse effects. Hawthorn, kava, and saw palmetto fall into the first category and licorice into the second.
Petry 2001
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The study examined the effect of kavain, (from Piper methysticum) on murine airway smooth muscle. Nitric oxide mediated relaxation was not observed to play a role in kavain's smooth muscle relaxing properties. Similarly, prostaglandin pathways are not likely involved in these effects .
Martin 2000
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Influence of a synthetic kava pyrone, (+/-)-kavain, on voltage-dependent ion channel currents when studied indicates that (+/-)-kavain reduces currents through voltage-activated Na+ and Ca2+ channels.
Schirrmacher 1999
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The di-enolide yangonin and the enolide enantiomers (+)-kavain, (+)-dihydrokavain, (+)-methysticin, and (+)-dihydromethysticin (at microM) increased bicuculline binding to GABAA receptor. The aromatic methoxy group and angular lactone ring are important
Boonen 1998
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Kava pyrones decreased the number of binding sites for batrachotoxinin with little change in the equilibrium constants (KD) indicating non-competitive inhibition of binding to receptor site 2 of voltage-gated Na+ channels
Friese 1998
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Kavain reduced the amplitudes of extracellular field potential changes evoked by electrical stimulation without change in long-term potentiation. These effects were concentration dependent and reversible
Langosch 1998
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Kava-kava extract was found to be a reversible inhibitor of MAO-B in intact platelets (IC50 24 microM) and disrupted platelet homogenates (IC50 1.2 microM).
Uebelhack 1998
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Kavain dose-dependently diminished arachidonic acid induced aggregation of human platelets, ATP-release, and the synthesis of TXA2 and PGE2 (IC50 78, 115, 71, and 86 mumol/l, respectively). This implies cyclooxygenase (COX) as the primary target
Gleitz 1997
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1-400 microM of (+)-methysticin and (+/-)-kavain exerted a rapid and reversible inhibition of the peak amplitude of Na(+)-currents in whole-cell patch-clamped CA1 hippocampal neurons
Magura 1997
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(+/-)-Kavain (1-1000 microM) dose-dependently reduced contractions of ileum evoked by carbachol, BAY K 8644, substance P, extracellular K+ or barium chloride but no effect on caffeine or Ca(2+) induced contractions
Seitz 1997
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Noradrenaline uptake in rat brain synaptosomes was inhibited by: (+/-)-kavain = (+)-kavain > (+)-methysticine, whereas serotonin uptake little affected
Seitz 1997
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Kawain and dihydromethysticin reduced reversibly the frequency of field potential in hippocampus at 10-40 microM and they enhance the effects of the anxiolytic serotonin-1A agonist ipsapirone by about 20% | | |
