Discipline of Pharmacology, The University of Sydney Medical Schoo, Australia.
Herbresearch Germany, Mattsies, Tussenhausen, Germany.
J Ethnopharmacol. 2021 Mar 25;268:113582. doi: 10.1016/j.jep.2020.113582. Epub 2020 Nov 12.
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.
在美拉尼西亚、波利尼西亚和密克罗尼西亚地区，卡瓦（Piper methysticum G. Forst. f.）是迄今为止最重要的植物，因其放松效果而被广泛使用。卡瓦饮料是南太平洋社会的支柱，也是其经济的基础。2002 年和 2019 年，德国禁止将卡瓦提取物作为草药药物制剂使用，这对南太平洋经济产生了巨大影响。2002 年，禁止卡瓦的主要监管论点是安全问题。2019 年，欧洲药品管理局草药药物委员会（HMPC）的评估报告以所谓的乙醇提取物对卡瓦提取物制剂从未获得批准的适应症缺乏疗效为由，证明了负面的效益-风险比是合理的。在这份 HMPC 报告中，获批适应症“神经性焦虑、紧张和不安”的疗效归因于品牌为“WS 1490”的提取物，据推测该提取物是用丙酮作为提取溶剂制备的。除了改变适应症和将疗效归因于丙酮卡瓦提取物外，德国卫生当局和 HMPC 仍然拒绝讨论质量问题，因为这可能是影响药物安全性的一个因素。在及时引入“两天卡瓦”而不是用于乙醇卡瓦提取物的“高贵卡瓦”后，首次观察到与丙酮提取物相关的肝毒性病例报告。
检查临床疗效与提取物制备类型之间的相关性。
为了确定临床试验中使用的卡瓦材料和提取物类型，将相应的出版物与监管数据库和德国监管咨询委员会的方案进行了比较。
比较结果显示监管决策存在不一致之处。在所有涉及 WS 1490 的研究中，证据都指向使用乙醇提取物。卡瓦提取物对获批适应症的疗效已得到明确证明。因此，HMPC 报告和最近德国对卡瓦的再次监管禁令需要进行重大修订，其中应包括使用“两天卡瓦”对药物安全性的影响。这样的修订可以有助于恢复“高贵卡瓦”在国际市场上的声誉。
