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Kava-kava extract in anxiety disorders: An outpatient observational study

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Abstract

Fifty-two outpatients suffering from anxiety of nonpsychotic origin were included in an observational study of a kava-kava preparation. Drug efficacy was evident on measures of a global improvement scale, with 42 patients (80.8%) rating treatment as "very good" or "good". Adverse events were rare. These results support kava-kava extract as an effective and safe alternative to antidepressants and tranquilizers in anxiety disorder without the tolerance problems associated with benzodiazepines.
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... Adverse liver effects were unknown, despite the extensive use of kava preparations, which points to a potential change in quality of certain kava products [18,19]. The safety and the anxiolytic effects of the specific study preparation has been examined in an observational study [24], and in a clinical double-blind trial [25]. Preclinical safety of the extract was demonstrated in a toxicological study in rats orally treated with an equivalent exposure to 73 mg kavalactones per kg of body weight for six months [26]. ...
Article
Aim Prior to the kava ban of 2002, the indication for kava (Piper methysticum) extracts defined by the German Commission E was “nervous anxiety, tension and restlessness”. In 2000, an observational trial was started in Germany with the aim of defining symptoms of these indications best treated with kava extract. The trial was interrupted and archived “unevaluated” in 2001 due to the upcoming safety debate on kava. The data from this study has now been analyzed in order to identify symptoms best treated with kava. Methods Documentation was available from 156 patients. Twelve typical symptoms of nervous anxiety, tension and restlessness were assessed on a five-item rating scale, together with the therapeutic context, the perceived time of onset of effects and the safety of application. Results The median duration of treatment was 28 days. All individual symptoms showed significant and clinically relevant improvements. The most effective results were seen for nervous tension and restlessness, with better effects in patients with acute versus chronic complaints. The safety of the treatment was found to be excellent, which included the assessment of laboratory data. Conclusions Overall, the study confirms the effective and safe short-term use of kava in the Commission E-defined indication of “nervous anxiety, tension and restlessness”, especially in other than chronic cases. The clinical use of kava might be translated into context-related phobias according to ICD-10 F40, or to nervous tension (ICD10 R45.0) or restlessness and excitation (ICD-10 R45.1).
... This however has been denied by long-term heavy kava users who report that periods of kava abstinence, as part of cultural observance, are common, with users reporting or showing no addictive symptoms during these times. Such commentary aligns with a gathering body of research and ethnographic comment, showing that kava use, even at high volumes and regular use, is not generally addictive (Bilia et al., 2001;Connor et al., 2001;Geier and Konstantinowicz, 2004;Keltner and Folkes, 2005;MediHerb, 2004;Scherer, 1998;Thompson et al., 2004). Drawing on earlier research, Aporosa (2014) summarizes by suggesting that 'if the label ''addiction'' is to be applied to yaqona [kava], I would hesitantly use ''socially addictive'' in the sense that it has been habituated to most aspects of Fijian socialization' (147). ...
Article
What seemed impossible 50 years ago is today becoming a reality as ‘soft drugs’ such as cannabis are being decriminalized and accepted for their calming effects as well as their legitimate medicinal properties. Several countries have now made the possession of cannabis legal, with others considering this, while the coffee shops in the Netherlands have been supplying cannabis in different forms for many years. It is now the turn of kava to be re-evaluated, to see whether there are properties in this plant that might be readily substituted for more conventional and harmful drugs, for instance tobacco and alcohol. However, as highlighted by Norton and Ruze (1994), kava like cannabis, has an enduring reputation that still makes it difficult for many to accept. Kava has been mythologized as an illicit alcohol, highly addictive, and causing physical harm. When examining the history of kava use in traditional contexts and considering the evidence now available, it is possible to demythologize this characterization. Looking at the potential benefits, it is time to re-brand kava, not only on the grounds as a relaxant, but in possessing life enhancing medicinal properties and as an alternative to alcohol, understanding that will be beneficial to policy makers, doctors and pharmacists.
... The specific ethanolic kava extract preparation used in the present study has already been used in previous clinical trials, namely in a study on acute effects in pre-medication for surgery, and in an open, observational trial [15,16]. The present study was mainly inspired by the current debate on the benefits and risks of kava [17]. ...
Article
Aim Kava, an aqueous drink from the roots and peeled rootstock of the plant Piper methysticum G.Forst., is renowned in Melanesia, Polynesia and Micronesia for its relaxant effect. Modern extract preparations with defined contents of kavalactones – the major active constituents – are well established as herbal medicinal products on the European market. The aim of this trial was to present data on the clinical efficacy of an ethanolic kava extract. Methods In the present double‐blind clinical trial, the differences in clinical outcome between a low dose of ethanolic kava extract (equivalent to 20 mg kavalactones daily) and a respective high dose (equivalent to 200 mg kavalactones daily) were investigated. Patients with anxiety disorders were randomized into the two groups, resulting in 33 patients in the high‐dose group and 36 patients in the low‐dose group. The study duration was 4 weeks; the primary parameter was the Hamilton anxiety (HAMA) score. Global efficacy was rated by the physician at the end of the study. Safety of application was based on the documentation of adverse events. Results The high‐dose group was statistically significantly superior to the low‐dose group on HAMA total score and its subscores for psychological and physical manifestations of anxiety (P < 0.001), with a total improvement of −41.5% versus −13.6% relative to baseline HAMA total score on day 28. No adverse events occurred. Conclusion Kava preparations have a dose‐dependent anxiolytic effect.
... Estudos farmacológicos demonstraram que os princípios ativos da kava-kava promovem efeito relaxante nos músculos, particularmente útil em estados de tensão, possuem efeito analgésico, controlam a ansiedade, previnem convulsões e podem proteger o cérebro contra as injúrias provocadas por pancadas. Porém, o complexo natural de cavapirona é farmacologicamente superior aos componentes individuais isolados devido ao sinergismo existente entre todas as cavapironas ativas (Scherer, 1998). ...
Article
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The objective of this study was to evaluate the effect of dietary kava-kava (Piper methysticum) during the laying period on performance (feed intake, feed conversion, weight of eggs and production), egg quality, tonic immobility time (TIT), intensity of injuries and blood heterophil/lymphocyte ratio (H:L). A total of 90 female Japanese quails of 21 weeks of age were distributed in a completely randomized experimental design and submitted to three treatments (0, 300 and 600mg of dried extract of kava-kava/kg of feed), with fi ve replicates and six birds, in each batch. Kava-kava fed to laying quails has no effect on performance, egg quality, intensity of injury or H:L ratio. However, there is a reduction in time spent in tonic immobility with the inclusion of kava-kava that predisposes the quail to a reduction of stress.
... Kava is best known for its powerful anti-anxiety profile [3]. Studies suggest that kava extracts decrease anxiety and might work as well as prescription anti-anxiety drugs, benzodiazepines [4,[10][11][12][13][14][15][16][17]. ...
Chapter
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Kava has been widely used as a herbal medicine for alternative treatment of anxiety and insomnia. In Europe, kava has been used for the treatment of anxiety and nervous disorders such as stress and restlessness, and in the United States kava is used as a natural alternative to anti-anxiety drugs and sleeping remedies. The most important medical application of kava is associated with its anti-psychotic effects. This chapter discusses the detailed mechanisms of kava-mediated hepatotoxicity, including (i) inhibition of cytochrome P450 enzyme activities that are important for drug metabolism; (ii) decreasing liver glutathione content that is linked to drug detoxification; (iii) inhibition of cyclooxygenase enzyme activity; (iv) induction of inflammatory responses; (v) inhibition of hepatic transporter function, which results in accumulation of drugs, toxins, and bile acids; and (vi) direct mitochondrial damage that plays a central role in drug-induced liver injury.
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Cordate leaves of young kava seedling
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Background: Complementary and alternative medicine (CAM) therapies have considerable patient appeal. Perceived as better, safer and more economical than conventional treatments, such as pharmacotherapy and psychotherapy, they are often used by patients to self-treat symptoms of depression and anxiety, usually in combination with existing medications and without medical supervision. CAM therapies include physical therapies (e.g. exercise), herbal remedies (e.g. St. John’s wort) and nutraceuticals/dietary supplements (e.g. omega-3 fatty acids). This chapter will review the published evidence for the use of herbal and dietary supplements as augmenting or adjunctive agents in depressive and anxiety disorders.
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Context.-Complementary and alternative medicine (herbal medicines) can affect laboratory test results by several mechanisms. Objective.-In this review, published reports on effects of herbal remedies on abnormal laboratory test results are summarized and commented on. Data Sources.-All published reports between 1980 and 2005 with the key words herbal remedies or alternative medicine and clinical laboratory test, clinical chemistry test, or drug-herb interaction were searched through Medline. The authors' own publications were also included. Important results were then synthesized. Data Synthesis.-Falsely elevated or falsely lowered digoxin levels may be encountered in a patient taking digoxin and the Chinese medicine Chan Su or Dan Shen, owing to direct interference of a component of Chinese medicine with the antibody used in an immunoassay. St John's wort, a popular herbal antidepressant, increases clearance of many drugs, and abnormally low cyclosporine, digoxin, theophylline, or protease inhibitor concentrations may be observed in a patient taking any of these drugs in combination with St John's wort. Abnormal laboratory results may also be encountered owing to altered pathophysiology. Kava-kava, chaparral, and germander cause liver toxicity, and elevated alanine aminotransferase, aspartate aminotransferase, and bilirubin concentrations may be observed in a healthy individual taking such herbal products. An herbal product may be contaminated with a Western drug, and an unexpected drug level (such as phenytoin in a patient who never took phenytoin but took a Chinese herb) may confuse the laboratory staff and the clinician. Conclusions.-Use of alternative medicines may significantly alter laboratory results, and communication among pathologists, clinical laboratory scientists, and physicians providing care to the patient is important in interpreting these results.
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Zusammenfassung Natürliche Kawa-Pyrone, vor allem Kawain, zeigen bemerkenswerte Hemmeffekte sowohl beim Formalin-, Serotonin-, Carrageenin- und Dextranödem der Rattenpfote als auch bei der UV-Licht-Entzündung der Rattenhaut. Hierbei wurden Phenylbutazon und Aminopyrin in ihrer Wirksamkeit im allgemeinen übertroffen. Die Wirkung auf das Hefefieber der Ratte entsprach derjenigen von Phenylbutazon; das Pyrifer- und Pyrexalfieber des Kaninchens war durch Pyron-Gabe weniger gut zu beeinflussen. In Kombination mit Phenylbutazon wirkte Kawain bei unteradditivem Verhalten der akuten Toxicität rein additiv.
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The kava lactone compositions of the leaves, stems and roots of Piper methysticum from Fiji were markedly different but no differences were found between two cultivars. The leaves also contain the alkaloid pipermethystine as a major component.
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The kava lactones from different plant parts of piper methysticum have been examined using normal and reversed-phase high-performance liquid chromatography. An unexpected photoisomerisation of yangonin in the mobile phase occurred during sample preparation which complicated the analysis.
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1. The development of tolerance to the aqueous extract of kava, and to the lipid soluble extract (kava resin) was tested in mice. 2. Tolerance to the unknown pharmacologically active ingredient(s) developed very rapidly, given parenterally, in the aqueous extract. A minimally effective daily dose (50 mg/kg) of the aqueous extract for 3 days was sufficient to produce tolerance to a test dose of 150 mg/kg, which is close to the ED50. As tolerance was evident at the first test period it can be assumed to be physiological tolerance. 3. Kava resin decreased spontaneous motility and caused a loss of muscle control. A minimally effective daily dose of kava resin (100 mg/kg) did not produce tolerance to the above effects of a weekly test dose of kava resin (166 mg/kg) within 7 weeks. In a further experiment the dose was raised to 150 mg/kg twice daily and this schedule caused partial tolerance to occur within 3 weeks, but very little further tolerance developed over the ensuing 2-week period. 4. To try to induce learned (behaviourally acquired) tolerance a dose of 166 mg/kg kava resin was injected daily and animals were tested each day while under the influence of the drug. However, even under these conditions, there was no tolerance evident within 3 weeks, when the experiment was terminated. 5. It appears difficult to induce the development of physiological or learned tolerance to kava resin in mice.
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1. The antinociceptive properties of the aqueous extract of the intoxicating beverage kava, and of the lipid soluble extract (kava resin) were tested in mice, by the tail immersion and abdominal constriction methods. Both extracts showed analgesic effects in both tests. 2. Eight purified pyrones from the lipid soluble extract were also tested for activity in the tail immersion test, and kawain, dihydrokawain, methysticin and dihydromethysticin were found to be very effective in producing analgesia. Using the tail immersion test the time course of action of the extracts of the four effective pyrones of kava were studied. 3. Naloxone, in doses which inhibited morphine-induced analgesia in both tests, was completely ineffective in reversing the antinociceptive activities of the kava extracts, showing that analgesia produced by kava occurs via non-opiate pathways.
Article
The central nervous activity of the aqueous extract of kava was examined in mice, and compared to the effect of the lipid-soluble extract. The aqueous extract caused a loss of spontaneous activity without loss of muscle tone. No hypnotic effect was seen, but some analgesia was produced. The anticonvulsant effect against strychnine was very slight and there was no evidence of local anesthetic action. There was a slight anti-apomorphine effect and tetrabenazine-induced ptosis was decreased. The lipid-soluble extract (kava resin) also decreased spontaneous motility, together with a marked reduction of motor control. Hypnosis, determined by loss of righting reflex, was produced, analgesia was marked, and a local anesthetic action evident. Kava resin also decreased apomorphine-induced hyperreactivity and partially reversed tetrabenazine-induced ptosis. Kava resin produces a greater range of pharmacological actions than the aqueous extract, and the latter is orally inactive in mice and rats. The pharmacological effects of kava ingestion appear to be due to the activity of the compounds present in the lipid-soluble fraction.
Article
A technique using gas chromatography-mass spectrometry and deuterated internal standards is described for the quantitation in brain tissue of four constituents of the intoxicating beverage kava. Dihydrokawain, kawain, desmethoxyyangonin, and yangonin were administered ip to mice at a dosage of 100 mg/kg. At specific time intervals (5, 15, 30, and 45 min), the mice were sacrificed and the brain concentrations of these four compounds determined. After 5 min, dihydrokawain and kawain attained maximum concentrations of 64.7 +/- 13.1 and 29.3 +/- 0.8 ng/mg wet brain tissue, respectively, and were rapidly eliminated. In contrast, desmethoxyyangonin and yangonin had poorly defined maxima corresponding to concentrations of 10.4 +/- 1.5 and 1.2 +/- 0.3 ng/mg wet brain tissue, respectively, and these compounds were more slowly eliminated from brain tissue. When crude kava resin was administered ip at a dosage of 120 mg/kg, the concentration in brain of kawain and yangonin markedly increased (2 and 20 times, respectively) relative to the values measured from their individual injection. In contrast, dihydrokawain and desmethoxyyangonin, after the administration of crude resin, remained at the percentage incorporation into brain tissue established for their individual ip injection.