Kava (Piper methysticum G. Forst. f.) is by far the most important plant used in the islands of Melanesia, Polynesia and Micronesia for its relaxing effects. Kava drinking is a pillar of South ...Pacific societies and is also the foundation of their economies. Preparations of kava extract as herbal medicinal drugs were banned in Germany in 2002 and again in 2019, with dramatic consequences for the South Pacific economies. In 2002, the major regulatory argument for the ban of kava was safety issues. In 2019, the assessment report of the European Medicines Agency's Herbal Medicinal Product Committee (HMPC) justified a negative benefit-to-risk ratio by a supposed lack of efficacy of ethanolic extracts for an indication of which kava extract preparations never had an approval. In this HMPC report the efficacy in the approved indications ‘nervous anxiety, tension and restlessness’ was attributed to the extract branded as ‘WS 1490’, which was assumed to have been prepared with acetone as an extraction solvent. In addition to this change of indication and the attribution of efficacy to acetone kava extract alone, the German health authorities and the HMPC still refuse to discuss quality issues as a likely factor impacting drug safety. The first case reports of liver toxicity were observed with an acetone extract in a timely relationship with the introduction of ‘two-day kava’ instead of ‘noble kava’ as used in ethanolic kava extracts.
The correlation between clinical benefits and the type of extract preparation was examined.
In order to identify the types of kava material and extracts used in clinical trials, the respective publications were compared with regulatory databases and protocols of a German regulatory advisory board.
The comparison reveals inconsistencies in the regulatory decisions. In all studies with WS 1490, the evidence points to the use of an ethanolic extract. The efficacy of kava extract for the approved indication was clearly demonstrated. The HMPC report and the recent renewed German regulatory ban of kava therefore require major revision, which should include the impact of the use of “two-day kava” on drug safety. Such a revision could contribute to restoring the reputation of “noble kava” on the international markets.
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•Kava extract preparations are efficacious in nervous anxiety, tension and restlessness.•The HMPC’s assumption of generalized anxiety as the indication of kava is unfounded.•The attribution of the clinical evidence to acetone extracts must be questioned.•There is evidence that the branded extract “WS 1490” was prepared with ethanol.•There are inconsistencies in the procedures, which led to the prohibition of kava.•The substitution of noble with two-day kava has never been examined.
Self-medication and the belief that herbal products are free of health risks are common in Brazil. The kava (Piper methysticum), known for its anxiolytic action, has a widespread popular use. ...Hepatotoxicity of kava is reported, including cases of liver transplantation and death. The kava had its use prohibited or restricted in countries like Germany, France, among others. Toxicity may be related to overdosage; however, factors such as botanical characteristics of the plant, the harvesting, storage, and production process may be associated with the development of hepatotoxic substances, such as triggering idiosyncratic reactions.
In this case, there is a suspicion that the toxicide is intrinsic to the drug; however, the possibility of adulterants and contaminants must be ruled out.
This study reports the case of a patient who, after using the herbal kava for 52 days, evolved into acute liver failure and liver transplantation.
The data were collected directly with the patient and compared with their clinical records. Causality was determined through the RUCAM algorithm. In addition, a phytochemical analysis of the drug used was performed.
According to the patient's report, there is no evidence of overdosage. Results from RUCAM algorithm infer causality between liver damage and the use of kava. The analysis chemical constituents did not find any possible contaminants and major changes in the active compounds. Seven months after transplantation, the patient is well and continues to be followed up by a medical team.
Our investigation indicates that there was kava-induced hepatotoxicity at standard dosages. In Brazil, self-medication by herbal medicines is frequent and many patients and health professionals do not know the risks associated with their use. Diagnosing and notifying cases in which plants and herbal medicine induce liver damage is of paramount importance to increase the knowledge about DILI and to prevent or treat similar cases quickly.
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Kava (Piper methysticum) is a major cash crop in the Pacific. The aim of this study was to assess genetic variation among 103 accessions of kava using SSRs and DArTs. Genetic structure was determined ...using clustering analyses (WPGMA) and principal coordinate analyses (PCA). Thirteen SSR primers and 75 DArT markers were found polymorphic, and the two types of markers generated similar clustering patterns. Genetic distances ranged from 0 to 0.65 with an average of 0.24 using SSRs and from 0 to 0.64 with an average of 0.24 using DArT. Eleven genotypes were identified with SSR while 28 genotypes were identified with DArT markers. By combining the two sets of markers, a total of only 30 distinct genotypes were observed. In the Vanuatu archipelago, noble cultivars originating from different islands clustered together within a very narrow genetic base despite their diversity of morphotypes. SSR and DArT fingerprints allowed the identification of kava cultivars unsuitable for consumption, so called two-days, and clearly differentiated the wild types classified as P.methysticum var. wichmannii from the cultivars as var. methysticum. Molecular data reveals that all noble cultivars evolved by the predominance of clonal selection. Although they are represented by clearly distinct morphotypes, these cultivars are genetically vulnerable and their potential to adapt to forthcoming changes is limited. These newly developed markers provide high resolution and will be useful for kava diversity analyses and quality assessment.
Sleep is considered as one of the most important aspects for maintaining a healthy life. For a person to function normally, at least 6-8 hours of sleep daily is necessary. Sleep not only affects our ...mood, but also regulates the efficiency of work done. Many complications arise due to inadequacy of sleep. The unhealthy food and lifestyle choices have made us more prone to sleep disorders. The medications used for the treatment of sleep disorders are mainly habit forming and have tendencies of withdrawal symptoms. This inadequacy in medication has lead to search for newer, better options. The field of nutraceuticals fits apt for treating such disorders. The quality of being non-toxic, non-habit forming, and being practically more efficient has had made it an excellent option. Nutraceuticals make use of food or part of food for the treatment or to prevent any disease. Remarkable positive effects of nutraceuticals like Caffeine, Chamomile, Kava kava, Cherries and Cherry juice, L tryptophan, Valerian, Vitamin D, Marijuana, melatonin, Lemon balm had been mentioned in the treatment of sleep disorders. The present review gives a general overview of nutraceuticals and discusses their use in sleep disorders.
Reflects on his projects over the years to document the use of kava through photographs, particularly in Tonga and in Auckland. Considers the evolution of its use in traditional and non-traditional ...settings. Discusses the most recent scientific studies of the drink, especially around kava drinking and driving safety. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.
This article examines deep and contemporary history through analysis of the Tongan kava origin story, a kava chant, the rise of the kalapu 'kava club' in the twentieth century and the growing ...expansion of contemporary kava. It is argued that a key function of past and present kava practices is a ritual liminality of noa 'neutralisation of protective restrictions' that results from mediating mana 'potency, honour' and tapu 'protective restrictions, set apart'. This is supported through ethnohistorical literature, song lyrics and ethnographic data. While the expressions, purpose, material and uses of kava evolve and change throughout time and space, from the titular ceremonies to the social rituals, they are connected through contextually specific mediations that establish noa. The kava origin story indicates a performance of mediations between ancient power relations, while the kava chant describes material culture alongside the establishment of the ritualised chiefly kava ceremony. Kalapu and the expanding contemporary kava practices today maintain connections to past practices while adapting to current circumstances such as global Tongan mobility and cultural diversity.
Piper methysticum G. Forst. (Piperaceae), commonly known as kava, has been used as a traditional beverage for centuries for its relaxing properties. Kavalactones are considered to be the major ...constituents responsible for kava's beneficial effects. Despite the extensive use of kava, clinical pharmacokinetic data is not available in the literature; therefore, the findings of this study will be critical for the dosage calculations for future clinical evaluation of kava.
The aim of the current study is to examine the clinical pharmacokinetics of six major kavalactones following oral dosing of flavokavain A/B-free standardized kava extract capsules in healthy volunteers using two dosage regimens.
A sensitive, reliable, and specific ultra-high pressure liquid chromatography-mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous quantification of six major kavalactones (kavain, dihydrokavain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin) and two flavokavains (A and B) in human plasma. Pharmacokinetic profiles were assessed in ten healthy volunteers after oral doses of standardized kava product, and plasma samples were analyzed for six kavalactones and two flavokavains using the validated UPLC-MS/MS method. Concentration-time data was subjected to pharmacokinetic analysis.
The systemic exposure of the kavalactones was found to be in the following order: dihydrokavain > dihydromethysticin > kavain > methysticin > yangonin. Desmethoxyyangonin was quantifiable only at a couple of time points, while flavokavain A and flavokavain B were not present in any of the plasma samples. Fast absorption of five kavalactones was observed with time to reach the maximum plasma concentration of 1–3 h. A dose proportionality in pharmacokinetics was established from 75 to 225 mg of kavalactone doses. In the multiple-dose study, a significant reduction in the extent of absorption of kavalactones with food was observed.
Single and multiple-dose clinical pharmacokinetic studies for kava were performed in healthy volunteers, and higher exposure to the kavalactones was observed after single-dosing (225 mg), while a longer duration of exposure was observed after three times a day (3 x 75 mg) dosing.
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•A bioanalytical method has been developed for the simultaneous analysis of six major kavalactones and two flavokavains.•A clinical pharmacokinetic study of kavalactones was performed in healthy volunteers for the first time.•Food intake altered the absorption of kavalactones and lowered their systemic exposure.
Kava-induced liver injury has been demonstrated in a few patients worldwide and appears to be caused by inappropriate quality of the kava raw material. When cases of liver disease in connection with ...the use of kava emerged, this was an unexpected and challenging event considering the long tradition of safe kava use. In order to prevent kava hepatotoxicity in future, a set of quality specifications as standard is essential for the preparation not only of kava drugs and kava dietary supplements in the Western world but also for traditional kava drinks in the South Pacific Islands.
For all these purposes a uniform approach is required, using water based extracts from the peeled rhizomes and roots of a noble cultivar such as Borogu with at least 5 years of age at the time of harvest. Cultivated in Vanuatu for centuries, noble varieties (as defined in the Vanuatu Kava Act of December 2002) are well tolerated traditional cultivars with a good safety record. At present, Vanuatu kava legislation is inadequately enforced to meet quality issues for kava, and further efforts are required in Vanuatu, in addition to similar legislation in other kava producing South Pacific Islands. Future regulatory and commercial strategies should focus not only on the standardization of kava drugs, kava dietary supplements, and traditional kava extracts, but also on thorough surveillance during the manufacturing process to improve kava quality for safe human use. The efficacy of kava extracts to treat patients with anxiety disorders is well supported, but further clinical trials with aqueous kava extracts are necessary.
We thereby propose a six-point kava solution plan: (1) use of a noble kava cultivar such as Borogu, at least 5 years old at time of harvest, (2) use of peeled and dried rhizomes and roots, (3) aqueous extraction, (4) dosage recommendation of ≤250mg kavalactones per day (for medicinal use), (5) systematic rigorous future research, and (6) a Pan Pacific quality control system enforced by strict policing.
In conclusion, at different levels of responsibility, new mandatory approaches are now required to implement quality specification for international acceptance of kava as a safe and effective anxiolytic herb.
Kava (Piper methysticum) is an ethnomedicinal shrub native to the Polynesian islands with well-established anxiolytic and analgesic properties. Its main psychoactive principles, kavalactones, form a ...unique class of polyketides that interact with the human central nervous system through mechanisms distinct from those of conventional psychiatric drugs. However, an unknown biosynthetic machinery and difficulty in chemical synthesis hinder the therapeutic use of kavalactones. In addition, kava also produces flavokavains, which are chalconoids with anticancer properties structurally related to kavalactones. Here, we report de novo elucidation of the key enzymes of the kavalactone and flavokavain biosynthetic network. We present the structural basis for the evolutionary development of a pair of paralogous styrylpyrone synthases that establish the kavalactone scaffold and the catalytic mechanism of a regio- and stereo-specific kavalactone reductase that produces a subset of chiral kavalactones. We further demonstrate the feasibility of engineering styrylpyrone production in heterologous hosts, thus opening a way to develop kavalactone-based non-addictive psychiatric therapeutics through synthetic biology.
Cases of Kava Impairment in Iowa Drivers Berry, Jonna; Gilbert, Ashley; Grodnitzky, Justin
Journal of forensic sciences,
November 2019, 2019-Nov, 2019-11-00, 20191101, Letnik:
64, Številka:
6
Journal Article
Recenzirano
Kava is an Oceanic plant in which the root is consumed as a beverage and is becoming increasingly popular. The effects of kava consumption may include sedation, euphoria, and impairment of motor ...coordination. This article demonstrates kava impairment through four cases of self‐reported kava use supported with Drug Recognition Expert (DRE) evaluations of each subject. Subject's urines screened negative for common drugs of abuse by immunoassay analysis. Urine from cases 3 and 4 were analyzed by liquid chromatography–tandem mass spectrometry, and gas chromatography–mass spectrometry, which yielded the presence of kavalactones. Subjects exhibited poor driving behavior and signs of intoxication. Indicators of impairment from multiple drug categories, central nervous system (CNS) depressants, CNS stimulants, and cannabis were observed, which may be consistent with the presence of multiple kavalactones and their diverse array of mechanisms of action. The consumption of kava can hinder one's ability to operate a vehicle safely.
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