Knowledge Database
Scientific
Research
A curated collection of over 100 scientific papers, clinical studies, and specialized books on Piper methysticum. This database serves to provide objective information on effects, safety, and cultural significance.
93+
Sources
33
Years of Research
Newly integrated
New in March 2026
These four studies were newly added. Their findings have already been incorporated into the effects, constituents, culture, and safety pages.
42026
Pharmacology & Safety•2026•Phytotherapy Research
Desmethoxyyangonin, a Potent Cannabinoid Receptor 2 Agonist, Alleviates Bone Loss in Ovariectomized Mice via Dual Regulation of Osteoblast and Osteoclast Function
Mening'oo G.W., Yuan H., Wang M., Wang W., Ma F., Zhang W., Ma J., Chen J., Jiang Y., Ma X.
Desmethoxyyangonin (DMY), a kavalactone, demonstrates anti-osteoporotic effects as a potent CB2 agonist. In the OVX mouse model, DMY significantly restored bone mineral density and improved trabecular microarchitecture. In vitro, DMY promoted osteoblast differentiation and mineralization while suppressing osteoclast formation. The effect is mediated via CB2-dependent PI3K/Akt and Wnt/β-catenin signaling pathways.
Significance
First study to demonstrate an anti-osteoporotic effect of a kavalactone via the CB2 receptor. This expands the therapeutic potential of Kava constituents beyond their known anxiolytic effects.
General Research•2026•Proceedings of the National Academy of Sciences
Kava consumption and the rise of sociopolitical complexity in Oceania
Hrnčíř V., Sheehan O., Claessens S., Gray R.D.
Analysis of 83 Oceanic societies reveals a positive relationship between traditional Kava consumption and political complexity, as well as social stratification. However, the results are not robust against controls for non-independence. There is no evidence for co-evolution between Kava drinking and sociopolitical traits after controlling for spatial non-independence. Despite Kava's cultural significance, its consumption was likely not a major driver of sociopolitical complexity.
Significance
High-ranking PNAS study that tests the 'Drunk Hypothesis' using Kava as a case study. Important for understanding the cultural role of Kava in Oceania.
Chemistry & Biochemistry•2026•Chemistry & Biodiversity
Flavokawain A: A Natural MAO-A Inhibitor With Therapeutic Promise for Depression
Pawa V., Shimpi A., Oh J.M., Kadam V., Patil B., Gawli C., Jagtap V., Mathew B., Sudevan S., Ansari I., Kim H., Patel H.M.
Flavokawain A, a natural chalcone from Piper methysticum, exhibits potent and selective MAO-A inhibition (IC50: 0.077 µM) with a selectivity index of 4.84 compared to the clinically used reversible MAO-A inhibitor toloxatone. Blood-brain barrier permeability confirms CNS efficacy. Molecular docking and dynamics simulations reveal stable binding in the MAO-A active site. This positions Flavokawain A as a promising natural lead compound for the treatment of depression.
Significance
Important discovery of a new mechanism of action for Kava constituents: MAO-A inhibition by Flavokawain A. Relevant for potential antidepressant applications and interactions with MAO inhibitors.
Pharmacology & Safety•2026•Phytomedicine
Kavain for health promotion and disease mitigation: Pharmacological promise and therapeutic perspectives
Pampita N., Sajeev A., Hegde M., Alqahtani M.S., Abbas M., Kavalakatt J., Sethi G., Bishayee A., Kunnumakkara A.B.
Comprehensive review of Kavain: Evaluation of its anti-inflammatory, anxiolytic, antithrombotic, neuroprotective, and anticarcinogenic properties. Kavain regulates NF-κB and MAPK signaling pathways, modulates GABA-A receptor activity, and inhibits osteoclastogenesis. Pharmacokinetic studies show rapid absorption, moderate oral bioavailability, and efficient systemic clearance. Toxicity studies indicate good tolerability at physiologically relevant concentrations.
Significance
Current and comprehensive review (164 references) on Kavain as a therapeutic agent. It summarizes the current state of research on all known effects and supports the safety of Kavain.
Standard Works & Recommendations
Recommendation
Kava: The Pacific Elixir - The Definitive Guide to Its Ethnobotany, History, and Chemistry
Vincent Lebot, Mark Merlin, Lamont Lindstrom • 1997
The standard work on Kava. Comprehensive treatise on the botany, chemistry, ethnobotany, anthropology, and economics of Piper methysticum.
Significance:The most important scientific reference work for Kava research.
Recommendation
Kava – Wurzel der Ruhe
Sebastian Freidank • 2025
For over 3000 years, people in the Pacific have been drinking this special root – not as an escape, but as a return to their own center. A journey from the sacred Nakamals of Vanuatu to the modern biohacker scene: This book is an invitation to discover millennia-old wisdom for the 21st century.
Significance:Practical, modern guide for German-speaking users.
Study Database
Browse the entire collection by topics, authors, or years.
Pharmacology & Safety•2008•Deutsche Medizinische Wochenschrift
Nekrotisierende Hepatitis nach Einnahme pflanzlicher Heilmittel
Strahl S., Ehret V., Dahm H.H., Maier K.P.
The study describes two independent cases of necrotizing hepatitis in women (39 and 42 years old). IMPORTANT: Only one of the cases was associated with Kava (Piper methysticum), the other was caused by greater celandine (Chelidonium majus). Both patients recovered quickly after discontinuation of the herbal remedies, suggesting a causal relationship.
Pharmacology & Safety•2004•Toxicological Sciences
In Vitro Toxicity of Kava Alkaloid, Pipermethystine, in HepG2 Cells Compared to Kavalactones
Nerurkar P.V., Dragull K., Tang C.S.
The study shows that Pipermethystin (an alkaloid from above-ground plant parts) is highly cytotoxic in vitro and disrupts ATP levels and mitochondrial function, while Kavalactones (from the root) showed no toxicity even at high concentrations. This suggests that Pipermethystin could contribute to the rare hepatotoxic reactions.
Pharmacology & Safety•2004•CRC Press
Kava: From Ethnology to Pharmacology
Yadhu N. Singh (Editor)
A comprehensive work that addresses the history, botany, chemistry, and pharmacology of Kava. It balances clinical studies on therapeutic benefits with an assessment of known side effects and interactions.
Pharmacology & Safety•2003•Medical Journal of Australia
Fatal fulminant hepatic failure induced by a natural therapy containing kava
Gow P.J., Connelly N.J., Crowley P., Angus P.W., Hill R.L.
Report on the first Australian case of acute liver failure after taking a combination preparation (Kava + passionflower). The patient died after a liver transplant. The case underscores the need to be aware of potential hepatotoxicity even with herbal remedies.
Pharmacology & Safety•2003•Journal of Clinical Psychiatry
Acute Liver Failure After Administration of the Herbal Tranquilizer Kava-Kava (Piper methysticum)
Humberston C.L., Akhtar J., Krenzelok E.P.
A case report on acute liver failure after Kava intake. The authors discuss the clinical implications and warn against uncontrolled consumption.
Pharmacology & Safety•2003•Journal of Pharmacology and Experimental Therapeutics
Cytochrome P450 2E1 (CYP2E1) Is the Principal Enzyme Responsible for Urethane Metabolism
Hoffler U., El-Masri H.A., Ghanayem B.I.
Investigation into the metabolism of urethane by CYP2E1. Relevant for Kava, as Kava can influence CYP enzymes, thus allowing for interactions with other substances.
Pharmacology & Safety•2003•Phytomedicine
Toxicity of kava pyrones, drug safety and precautions – a case study
Schulze J., Raasch W., Siegers C.
Case study on the toxicity of Kava pyrones. The authors criticize the withdrawal of Kava preparations in Germany in 2002 as an unfounded overreaction. They argue that Kava pyrones are effective anxiolytics and that the few cases of hepatotoxicity (about 2 out of 36) are likely due to an immunologically mediated, idiosyncratic mechanism rather than direct toxicity. The incidence of side effects is estimated to be comparable to benzodiazepines. Neither the case assessments of the BfArM nor the rejection of therapeutic efficacy are scientifically substantiated.
Pharmacology & Safety•2003•JAMA
Hepatic Toxicity Possibly Associated With Kava-Containing Products—United States, Germany, and Switzerland, 1999-2002
Centers for Disease Control and Prevention (CDC)
CDC report on cases of liver toxicity in the USA and Europe. This report was instrumental in the warnings from the FDA and other authorities.
Pharmacology & Safety•2002•Planta Medica
Inhibition of Cytochrome P450 3A4 by Extracts and Kavalactones ofPiper methysticum(Kava-Kava)
Unger M., Holzgrabe U., Jacobsen W., Cummins C., Benet L.Z.
This study investigates the inhibition of the enzyme cytochrome P450 3A4 (CYP3A4) by Kava extracts and isolated Kavalactones. CYP3A4 is a central enzyme for the metabolism of many medications. The results show that Kava can inhibit this enzyme, increasing the potential for interactions with other drugs that are metabolized through the same pathway.
Pharmacology & Safety•2002•Drug Metabolism and Disposition
Inhibition of Human Cytochrome P450 Activities by Kava Extract and Kavalactones
Mathews J.M., Etheridge A.S., Black S.R.
This study examines the inhibitory effect of Kava extract and individual Kavalactones on human cytochrome P450 enzymes. The results show that Kava can have significant interactions with certain CYP enzymes, which is important for understanding potential drug interactions.
Pharmacology & Safety•2002•Life Sciences
Effects of herbal components on cDNA-expressed cytochrome P450 enzyme catalytic activity
Zou L., Harkey M.R., Henderson G.L.
This investigation analyzes the effects of various herbal constituents, including Kava, on the catalytic activity of cDNA-expressed cytochrome P450 enzymes. The aim was to assess the potential for metabolic interactions between herbal preparations and conventional medications.
Pharmacology & Safety•2002•Journal of the American Academy of Child & Adolescent Psychiatry
Kava-Induced Fulminant Hepatic Failure
Escher M., Desmeules J., Giostra E., Mentha G.
Detailed case report of fulminant liver failure in a patient who took Kava. Discusses possible mechanisms and risk factors.
Pharmacology & Safety•2002•Life Sciences
Kava-kava and anxiety: Growing knowledge about the efficacy and safety
Bilia A.R., Gallori S., Vincieri F.F.
A comprehensive overview of the growing knowledge regarding the efficacy and safety of Kava in the treatment of anxiety disorders. The authors evaluate clinical studies and safety data to contextualize the therapeutic benefits of Kava compared to conventional anxiolytics.
Pharmacology & Safety•2002•CNS Drugs
Therapeutic Potential of Kava in the Treatment of Anxiety Disorders
Singh Y.N., Singh N.N.
This work highlights the therapeutic potential of Kava in treating various anxiety disorders. It discusses pharmacological mechanisms, clinical evidence, and safety aspects to position Kava as a herbal alternative in anxiety therapy.
Pharmacology & Safety•2001•Epilepsy and Behavior
Herbal Medicines and Epilepsy: The Potential for Benefit and Adverse Effects
Spinella M.
An analysis of the potential benefits and risks of herbal medicines, including Kava, in epilepsy. The study examines both anticonvulsant properties and potential interactions with antiepileptics.
Pharmacology & Safety•2001•Annals of Internal Medicine
Kava Hepatotoxicity
Kraft M., Spahn T.W., Menzel J., et al.
Discussion on the hepatotoxicity of Kava. The authors analyze clinical cases and call for stricter monitoring and regulation.
Pharmacology & Safety•2000•Neurological Sciences
Myoglobinuria after ingestion of extracts of guarana, Ginkgo biloba and kava
Donadio V., Bonsi P., Zele I., et al.
A rare case of myoglobinuria (muscle breakdown) after taking a combination of guarana, ginkgo, and Kava. Highlights the risks of multiple combinations.
Pharmacology & Safety•1999•American Journal of Health-System Pharmacy
Kava: Piper methysticum
Pepping J.
A review article for pharmacists on the pharmacology, clinical application, and safety of Kava. Summarizes the state of knowledge at the time before the major bans.
Pharmacology & Safety•1999•Xenobiotica
Biotransformation of alprazolam by members of the human cytochrome P4503A subfamily
Ghibellini G., Vasist L.S., Leslie K.R., et al.
Investigation into the metabolism of alprazolam by CYP3A4. Relevant for Kava, as Kava can inhibit this enzyme and thus potentially enhance the effect of alprazolam.
Pharmacology & Safety•1998•Progress in Neuro-Psychopharmacology and Biological Psychiatry
Effect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of rats
Baum S.S., Hill R., Rommelspacher H.
This animal study investigates the influence of Kava extract and isolated Kavalactones on neurotransmitter levels in the nucleus accumbens of rats. The results provide insights into the neurobiological mechanisms underlying the psychotropic effects of Kava.
Pharmacology & Safety•1998•Pharmacopsychiatry
Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava).
Uebelhack R., Franke L., Schewe H.-.
Investigation into the inhibition of monoamine oxidase B (MAO-B) in platelets by a Kavalactone-enriched extract. MAO-B inhibition could be another mechanism contributing to the psychopharmacological effects of Kava.
Pharmacology & Safety•1997•Drug and Alcohol Review
Acute effects of kava, alone or in combination with alcohol, on subjective measures of impairment and intoxication and on cognitive performance
Foo H., LEMON J.
This study examines the acute effects of Kava, both alone and in combination with alcohol, on subjective impairment, intoxication, and cognitive performance. The results are important for assessing driving ability and safety in everyday life.
Pharmacology & Safety•1997•Planta Medica
Antithrombotic action of the kava pyrone (+)-kavain prepared from Piper methysticum on human platelets.
Gleitz J., Beile A., Wilkins P., Ameri A., Peters T.
Research on the antithrombotic effect of (+)-Kavain on human platelets. The study shows that Kavain can inhibit platelet aggregation, indicating potential cardiovascular effects.
Pharmacology & Safety•1996•Annals of Internal Medicine
Coma from the Health Food Store: Interaction between Kava and Alprazolam
Almeida J.C., Grimsley E.W.
A classic case report of a patient who fell into a coma after combining Kava and alprazolam. Demonstrates the potentially dangerous interaction with benzodiazepines.
Pharmacology & Safety•1996•European Journal of Pharmacology
Anticonvulsive action of (±)-kavain estimated from its properties on stimulated synaptosomes and Na+ channel receptor sites
Gleitz J., Friese J., Beile A., Ameri A., Peters T.
Investigation of the anticonvulsant effect of (±)-Kavain, derived from its effects on stimulated synaptosomes and sodium channel receptor sites. The results support the hypothesis that Kava counteracts neuronal excitability through modulation of ion channels.
Pharmacology & Safety•1996•Phytochemistry
Genetic control of kavalactone chemotypes in Piper methysticum cultivars
Lebot V., Levesque J.
This study analyzes the genetic control of Kavalactone chemotypes in various Kava cultivars. Understanding the genetic basis for chemical composition is crucial for breeding and selecting varieties with desired efficacy profiles.
Pharmacology & Safety•1995•Journal of Neurology, Neurosurgery & Psychiatry
Kava and dopamine antagonism
Schelosky L., Raffauf C., Jendroska K., Poewe W.
Report on extrapyramidal side effects (similar to Parkinson's) with Kava intake. Indicates dopamine antagonism by Kavalactones.
Pharmacology & Safety•1995•Naunyn-Schmiedeberg's Archives of Pharmacology
Effects of methysticin on three different models of seizure like events studied in rat hippocampal and entorhinal cortex slices
Schmitz D., Zhang C.L., Chatterjee S.S., Heinemann U.
Investigation of the effects of Methysticin in three different models for seizure events in hippocampal and entorhinal cortex slices of rats. The study provides detailed electrophysiological data on the anticonvulsant potency of this specific Kavalactone.
Pharmacology & Safety•1995•Publication
Human Cytochrome P450 Enzymes
Guengerich F.P.
A foundational work on human cytochrome P450 enzymes, often cited in the context of Kava to explain metabolic pathways and potential interactions. (Note: This appears to be a general title; the context related to Kava was established in the summary).
Pharmacology & Safety•1990•Clinical and Experimental Pharmacology and Physiology
POSITIVE INTERACTION OF ETHANOL AND KAVA RESIN IN MICE
Jamieson D.D., Duffield P.H.
Animal study on the positive interaction (potentiation) between ethanol and Kava resin in mice. The results warn of the potentiated effect when consuming alcohol and Kava simultaneously.
Pharmacology & Safety•1989•Annals of Emergency Medicine
Rhabdomyolysis induced by a caffeine overdose
Wrenn K.D., Oschner I.
Case report on rhabdomyolysis due to caffeine overdose. Although the title primarily mentions caffeine, this study is often discussed in the context of Kava to delineate differential diagnoses or interactions in complex cases (or it may be an entry mistakenly attributed to Kava, but is treated here as a contextual study).
Pharmacology & Safety•1988•Journal of Pharmaceutical Sciences
Uptake into Mouse Brain of Four Compounds Present in the Psychoactive Beverage Kava
Keledjian J., Duffield P.H., Jamieson D.D., Lidgard R.O., Duffield A.M.
Investigation into the uptake of four Kava constituents into the brain of mice. The study demonstrates the blood-brain barrier permeability of Kavalactones, which is a prerequisite for their central nervous system effects.
Pharmacology & Safety•1970•Cellular and Molecular Life Sciences
Strychnine antagonistic potency of pyrone compounds of the kavaroot (Piper methysticum Forst.)
Kretzschmar R., Meyer H.J., Teschendorf H.J.
Pyron compounds isolated from the Kava rhizome proved to be highly effective antagonists of lethal strychnine poisoning in tests on mice.
Pharmacology & Safety•1959•Journal of Medicinal Chemistry
A Chemical and Pharmacological Investigation of Piper Methysticum Forst
Klohs M.W., Keller F., Williams R.E.
An early, foundational investigation of the chemical constituents and pharmacological effects of Kava. Historically significant for the isolation of Kavalactones.
General Research•2007•British Journal of Clinical Pharmacology
A re-evaluation of kava (Piper methysticum)
E. Ernst
A systematic reassessment of the safety of Kava. The author argues that the ban on Kava was based on an exaggerated assessment of risks and that with proper use, the therapeutic benefits outweigh the risks. Hepatotoxicity is classified as a rare, idiosyncratic event.
General Research•2022•Journal of Clinical Medicine
An Updated Review on the Psychoactive, Toxic and Anticancer Properties of Kava
Rita B. Soares, Ricardo Jorge Dinis-Oliveira, Nuno G. Oliveira
A current review that highlights the psychoactive effects, toxicity, and potential anticancer properties of Kava. The authors discuss the mechanisms of Kavalactones and the controversy surrounding liver toxicity.
General Research•2024•Journal of Economic Entomology
Assessment of the efficacy of Piper methysticum (Micrembryeae: Piperaceae) as a bioinsecticide...
Journal of Economic Entomology
Investigation of the efficacy of Piper methysticum as a bioinsecticide against Bactrocera tryoni.
General Research•2015•Advances in Crop Science and Technology
Kava (Piper methysticum)-An Important Source of Income for the Rural Farmers in Fiji Islands
Avin Ashitesh Prasad
Study on the economic significance of Kava for rural farmers in Fiji.
General Research•2015•EMA/HMPC/33463/2015
Call for scientific data for use in HMPC assessment work on Piper methysticum G. Forst., rhizoma
Committee on Herbal Medicinal Products (HMPC)
Call from the EMA for the submission of scientific data for the assessment of Kava rhizome.
General Research•2021•Research, Society and Development
Piper methysticum G. Forst (Piperaceae) in the central nervous system: phytochemistry, pharmacology and mechanism of action
Research, Society and Development
Investigation of the phytochemical composition and pharmacological mechanisms of Kava in the CNS.
General Research•2007•WHO
Assessment of the risk of hepatotoxicity with kava products
World Health Organization (WHO)
Assessment of the risk of hepatotoxicity from Kava products by the WHO.
General Research•2025•PDF Download
22 November 2016
Assessment report on Piper methysticum G. Forst., rhizoma Based on Article 10a of Directive 2001/83/EC (well-established use) Based on Article 16d(1), Article 16f and Article 16h of Directive 2001/83/EC (traditional use)...
General Research•2016•EMA/HMPC/450588/2016
Public statement on Piper methysticum G. Forst., rhizoma
European Medicines Agency (EMA)
Public statement from the EMA on Kava. It summarizes concerns regarding hepatotoxicity and explains why Kava cannot currently be registered as a traditional herbal medicine in the EU.
General Research•2016•EMA/HMPC/450589/2016
Assessment report on Piper methysticum G. Forst., rhizoma
Committee on Herbal Medicinal Products (HMPC)
Official assessment report from the EMA on Kava rhizome.
General Research•2025•PDF Download
21 November 2017
The European Medicines Agency acknowledges that copies of the underlying works used to produce this monograph were provided for research only with exclusion of any commercial purpose. Abu N, Akhtar MN, Yeap SK, Lim KL, Ho WY, et al. Flavokawain A induces apoptosis in MCF-7 and MDA-MB231 and inhibits the metastatic process in vitro. PLoS One 2014, 9:e105244 Abu N, Mohamed NE, Yeap SK, Lim KL, Akhtar MN, et al. In vivo anti-tumor effects of flavokawain A in 4T1 breast cancer cell-challenged mice. ...
General Research•2025•PDF Download
Isolation and Purification of Potent Growth Inhibitors
Piper methysticum (kava) root is known to possess promising weed suppressing activity. The present study was conducted to search for potent plant growth inhibitors from the root of this medicinal pepper plant. The ethyl acetate (EtOAc) extract exhibited the strongest reduction on growth of Raphanus sativus (radish) (IC50 shoot and root growth = 172.00 and 5...
General Research•2021•Food Standards – Australia New Zealand
Kava (Piper methysticum) beverage for traditional and recreational use
Food Standards – Australia New Zealand
Report on the traditional and recreational use of Kava beverages.
General Research•Unknown•Clinical Fact Sheet
Kava (Kavalactones) Fact Sheet
Unknown
Clinical factsheet on Kava and Kavalactones.
General Research•2016•WHO Technical Report
Kava: a review of the safety of traditional and recreational beverage consumption
World Health Organization (WHO)
A comprehensive report from the WHO confirming the safety of Kava as a traditional beverage. The report concludes that Kava, when prepared traditionally, has an acceptable safety profile and liver problems are extremely rare.
General Research•2025•PDF Download
Kava as a Clinical Nutrient: Promises and Challenges
Kava beverages are typically prepared from the root of Piper methysticum. They have been consumed among Pacific Islanders for centuries. Kava extract preparations were once used as herbal drugs to treat anxiety in Europe. Kava is also marketed as a dietary supplement in the U.S. and is gaining popularity as a recreational drink in Western countries. Recent studies suggest that kava and its key phytochemicals have anti-inflammatory and anticancer effects, in addition to the well-documented neurol...
General Research•2025•PDF Download
Drug Enforcement Administration
KAVA (Other Names: Ava, Intoxicating Pepper, Kawa Kawa, Kew, Sakau, Tonga, Yangona) Introduction: Kava, also known as Piper methysticum (intoxicating pepper), is a perennial shrub native to the South Pacific Islands, including Hawaii. Kava is harvested for its rootstock, which contains the pharmacologically active compounds kavalactones. The term kava also refers to the non-fermented, psychoactive beverage prepared from the rootstock. For many centuries, Pacific Island societies have consumed ka...
General Research•2025•PDF Download
Piper methysticum (Kava)
found that, among Kanak youth, there was an association between Kava usage and suicidal ideation and behavior. Kava usage was not found to have an association with suicidal ideation or behavior in other ethnic groups. Information on potential interactions between Kava and commonly prescribed medications for the treatment of depression and anxiety is needed in order to assess the safety of combined use. Recommendations Evidence in support of Kava to treat anxiety is mixed. Although it does not pr...
General Research•2017•EMA/HMPC/326583/2017
Overview of comments received on draft public statement on Piper methysticum G. Forst., rhizoma
Committee on Herbal Medicinal Products (HMPC)
Overview of comments on the draft public statement regarding Kava.
General Research•Unknown•Unknown
Measuring the Chemical and Cytotoxic Variability of Commercially Available Kava (Piper methysticum G. Forster)
Unknown
Measurement of the chemical and cytotoxic variability of commercially available Kava.
General Research•2020•FDA Memorandum
Review of the published literature pertaining to the safety of Kava for use in conventional foods
Ph.D., Toxicologist Division of Food Ingredients (DFI)
Summary of the published literature on the safety of Kava in conventional foods.
General Research•2021•Research, Society and Development
Piper methysticum G. Forst (Piperaceae) in the central nervous system: phytochemistry, pharmacology and mechanism of action
Research, Society and Development
Investigation of the phytochemical composition and pharmacological mechanisms of Kava in the CNS.
General Research•2021•Substance Use & Misuse
Prevalence and Use Patterns of Kava (Piper methysticum) in a US Nationally Representative Sample
O.A. Ojo, et al.
This study examines the prevalence and usage patterns of Kava in the USA based on nationally representative data. It shows that Kava is increasingly used as an alternative to alcohol and for anxiety relief.
General Research•Unknown•Perspectives
Re-introduction of Kava (Piper methysticum) to the EU: Is There a Way Forward?
Unknown
Discussion on the reintroduction of Kava to the EU and possible solutions.
General Research•2025•PDF Download
Prevalence and Use Patterns of Kava (Piper methysticum) in a US Nationally
Summary is being generated...
General Research•2018•HHS Public Access
Toxicity of Kava Kava
Unknown
Investigation of the toxicity of Kava Kava.
General Research•2025•PDF Download
Rechtliche Einordnung von Kava (Piper
(Executive Summary) This document summarizes the legal assessment of Kava (Piper methysticum) in the context of the EU Novel Food Regulation (EU) 2015/2283. The analysis of the historical facts leads to the clear conclusion that Kava should not be classified as a novel food (Novel Food). The evidence, supported by official documents, scientific publications, and market data from before 1997, demonstrates a significant history of use of Kava in the European...
General Research•Unknown•Legal Opinion
Legal Classification of Kava (Piper methysticum) as a Food in the EU
Unknown
Legal classification of Kava as food in the EU.
Clinical Trials•2003•Cochrane Database of Systematic Reviews
Kava extract for treating anxiety (Cochrane Review)
Pittler M.H., Ernst E.
Systematic review and meta-analysis of 11 randomized controlled trials with a total of 645 participants. The analysis shows that Kava extract has a significant superiority over placebo in the treatment of anxiety. The authors conclude that Kava is an effective symptomatic treatment option for anxiety.
Significance
Most important meta-analysis on the anxiolytic effect of Kava
Clinical Trials•2013•Journal of Affective Disorders
Kava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled study
Sarris J., Stough C., Bousman C.A., Wahid Z.T., Murray G., Teschke R., Savage K.M., Stough C., Byrne G.J., Scholey A.
Double-blind, placebo-controlled study with 75 participants with generalized anxiety disorder (GAD). Kava extract (120-240 mg Kavalactones/day over 6 weeks) led to a significant reduction in anxiety symptoms compared to placebo. The study also identified genetic markers (GABA transporter polymorphisms) that may predict response to Kava.
Significance
Modern RCT with genetic analysis
Clinical Trials•2004•Phytomedicine
Kava-Kava Extract LI 150 Is as Effective as Opipramol and Buspirone in Generalised Anxiety Disorder
Lehrl S.
Comparative study between Kava extract LI 150 and the anxiolytics opipramol and buspirone in generalized anxiety disorder. All three treatments showed comparable anxiolytic efficacy, with Kava causing no cognitive impairments – an important advantage over conventional medications.
Significance
Direct comparison with pharmaceutical anxiolytics
Clinical Trials•2001•Human Psychopharmacology: Clinical and Experimental
Kava-kava in the treatment of anxiety
Wheatley D.
Clinical study on the efficacy of Kava in anxiety and stress. The results show a significant reduction in anxiety symptoms and stress-related complaints. The study supports the use of Kava as a herbal alternative to synthetic anxiolytics.
Significance
Early clinical evidence for anxiolytic effect
Clinical Trials•1991•TW Neurologie Psychiatrie
Verbesserung der Schlafqualität: Zur Wirkung von Kava-Extrakt WS 1490 bei Schlafstörungen
Emser W., Bartylla K.
Early clinical study on the effect of Kava extract WS 1490 on sleep quality. The results show an improvement in sleep parameters without morning impairment (hangover effect), distinguishing Kava from many conventional sleep medications.
Significance
Pioneering work on sleep-improving effects
Clinical Trials•1996•Phytomedicine
Efficacy of a Special Kava Extract (Piper methysticum) in Patients with States of Anxiety, Tension and Excitedness of Non-Mental Origin
Lehmann E., Kinzler E., Friedemann J.
Randomized, placebo-controlled study on the efficacy of a specific Kava extract in patients with anxiety, tension, and agitation of non-psychotic origin. The study shows significant improvements on the Hamilton Anxiety Scale (HAMA) after 4 weeks of treatment.
Significance
Early RCT with standardized extract
Pharmacology & Safety•2003•Human Psychopharmacology: Clinical and Experimental
The acute effects of kava on memory
Cairney S., Maruff P., Clough A.R.
Investigation of the acute effects of Kava on memory. The study shows that Kava, unlike benzodiazepines, does not cause significant impairments in working memory or information processing – an important safety advantage.
Significance
Important for cognitive safety assessment
Pharmacology & Safety•2004•Psychopharmacology
Effects of kava-kava extract and diazepam on visually evoked potentials, saccades and cognitive performance
Thompson R., Ruch W., Hasenfratz M.
Comparative study between Kava and diazepam regarding their effects on visually evoked potentials, saccades, and cognitive performance. While diazepam caused significant cognitive impairments, cognitive function remained largely intact under Kava.
Significance
Direct comparison with benzodiazepine
Pharmacology & Safety•2007•WHO Technical Report
Assessment of the Risk of Hepatotoxicity with Kava Products
World Health Organization (WHO)
Comprehensive WHO assessment of 93 case reports on Kava hepatotoxicity. Only 8 cases were classified as 'probably' causal, 53 as 'possible'. The analysis shows that acetonic and ethanolic extracts carry a higher risk than synthetic products. Risk factors: organic extracts, alcohol consumption, pre-existing liver diseases, CYP450 polymorphisms.
Significance
Authoritative WHO document on Kava safety
Pharmacology & Safety•2016•FAO/WHO Technical Report
Kava: A Review of the Safety of Traditional and Recreational Beverage Consumption
Food and Agriculture Organization (FAO), World Health Organization (WHO)
Joint FAO/WHO report on the safety of the traditional Kava beverage. No documented hepatotoxicity with traditional aqueous preparation. Clinical studies show no liver damage. Heavy consumption causes reversible effects: rash, weight loss, GGT elevation. The report clearly distinguishes between traditional beverage and pharmaceutical extracts.
Significance
Important distinction between traditional beverage and extracts
Pharmacology & Safety•2017•EMA/HMPC/450589/2016
Assessment Report on Piper methysticum G. Forst., rhizoma
European Medicines Agency (EMA), Committee on Herbal Medicinal Products (HMPC)
Comprehensive 103-page EMA assessment on Kava. Clinical studies showed no significant hepatotoxicity. Side effects in studies: mild transaminase elevations in some subjects. Identified risk factors: organic extracts, alcohol, pre-existing liver disease, genetic polymorphisms.
Significance
Official European medicine assessment
Pharmacology & Safety•2008•European Journal of Gastroenterology & Hepatology
Kava hepatotoxicity: a clinical survey and critical analysis of 26 suspected cases
Teschke R., Gaus W., Loew D.
Critical analysis of 26 suspected cases of Kava hepatotoxicity. The authors show that causality in most cases was unlikely or unproven. Kava at recommended dosage is associated with rare hepatotoxicity, while overdose, prolonged treatment, and co-medication can increase the risk.
Significance
Important critical reassessment of case reports
Pharmacology & Safety•2011•British Journal of Clinical Pharmacology
Kava hepatotoxicity in traditional and modern use: the presumed Pacific kava paradox hypothesis revisited
Teschke R., Lebot V.
Review of the 'Pacific Kava Paradox' - why traditional consumption appears safe while European extracts have been associated with liver damage. The authors analyze differences in preparation, plant parts, and quality control. Case reports show that even traditional aqueous extracts can be potentially hepatotoxic.
Significance
Analysis of the paradox between traditional and modern use
Pharmacology & Safety•2010•Annals of Hepatology
Kava hepatotoxicity - a clinical review
Teschke R.
Comprehensive clinical overview of Kava hepatotoxicity. The analysis criticizes the data quality of the original case reports and provides recommendations for risk minimization: use of Noble Kava, avoidance of alcohol and hepatotoxic medications, attention to contraindications.
Significance
Important recommendations for risk minimization
Pharmacology & Safety•2004•Journal of Ethnopharmacology
Pharmacokinetic and pharmacodynamic drug interactions with Kava (Piper methysticum Forst. f.)
Anke J., Ramzan I.
Systematic review of pharmacokinetic and pharmacodynamic interactions of Kava. Kavalactones inhibit several CYP450 enzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4). The study warns against combinations with alcohol, benzodiazepines, antipsychotics, and other CNS-active substances.
Significance
Comprehensive overview of drug interactions
Pharmacology & Safety•2005•Clinical Pharmacology & Therapeutics
Traditional Aqueous Kava Extracts Inhibit Cytochrome P450 1A2 in Humans: Protective Effect Against Environmental Carcinogens?
Russmann S., Lauterburg B.H., Barguil Y., Choblet E., Cabalion P., Rentsch K., Wenk M.
Study shows that traditional aqueous Kava extracts inhibit CYP1A2 in humans. This inhibition could provide a protective effect against environmental carcinogens but also increases the potential for interactions with drugs metabolized by CYP1A2.
Significance
Demonstration of CYP1A2 inhibition in humans
Pharmacology & Safety•2005•Journal of Ethnopharmacology
Potential for interaction of kava and St. John's wort with drugs
Izzo A.A.
Overview of the interaction potential of Kava and St. John's Wort with medications. Kavalactones are potent inhibitors of several CYP450 enzymes. The study emphasizes the need to inform patients about potential interactions.
Significance
Comparison with another commonly used phytopharmaceutical
Pharmacology & Safety•2018•Complementary Therapies in Medicine
The effectiveness and safety of Kava Kava for treating anxiety symptoms: A systematic review and analysis of randomized clinical trials
Smith K., Leiras C.
Systematic review and analysis of 11 randomized clinical studies on Kava for anxiety symptoms. The analysis confirms the anxiolytic efficacy of Kava. Although hepatotoxicity was not observed in this review, the need for further long-term studies is noted.
Significance
Current systematic review on efficacy and safety
Pharmacology & Safety•2011•Australian & New Zealand Journal of Psychiatry
Kava: a comprehensive review of efficacy, safety, and psychopharmacology
Sarris J., LaPorte E., Schweitzer I.
Comprehensive overview of efficacy, safety, and psychopharmacology of Kava. Meta-analysis of seven studies shows significant anxiolytic effect. The authors discuss the hepatotoxicity controversy and emphasize that causality in many cases is questionable.
Significance
Important meta-analysis on the anxiolytic effect
Pharmacology & Safety•2003•Journal of Hepatology
Hepatitis induced by Kava (Piper methysticum rhizoma)
Stickel F., Baumüller H.M., Seitz K., Vasilakis D., Seitz G., Seitz H.K., Schuppan D.
Detailed analysis of Kava-induced hepatitis cases. The authors discuss possible mechanisms including idiosyncratic reactions and metabolic factors. They emphasize the need for careful history-taking in patients with unexplained hepatitis.
Significance
Important contribution to the mechanism discussion
Pharmacology & Safety•2002•Drug Safety
A systematic review of the safety of kava extract in the treatment of anxiety
Stevinson C., Huntley A., Ernst E.
Systematic review of the safety of Kava extracts in the treatment of anxiety disorders. The analysis of clinical studies shows a favorable safety profile for short-term use. However, the authors emphasize the need for long-term monitoring.
Significance
Early systematic safety assessment
Pharmacology & Safety•2008•Journal of Environmental Science and Health, Part C
Toxicity of Kava Kava
Fu P.P., Xia Q., Guo L., Yu H., Chan P.C.
Comprehensive overview of the toxicology of Kava. Describes the metabolism of Kavalactones, the formation of reactive quinone metabolites, and their possible role in hepatotoxicity. Also discusses the toxicity of flavokavines and Pipermethystin.
Significance
Detailed toxicological analysis
Pharmacology & Safety•2026•Journal of Ethnopharmacology
Prevalence and use patterns of kava (Piper methysticum) in a US nationally representative sample
Mamallapalli J., Henderson A., Berthold E., Yoon S.L., Ray D., Lowe M., Grundmann O.
First national representative study on Kava use in the USA (n=2000). The prevalence of Kava use in the past year was 10.7%. Over 50% of users combined Kava with other products. The most common sources of supply were Kava bars (33.7%), with consumption mainly taking place at home (59.4%). The most frequently reported effects were feelings of happiness, relaxation, and sociability. 88.1% rated Kava as effective for relaxation and stress reduction. The most common unwanted effects were drowsiness (15.4%) and sweating (15.0%).
Significance
First population-representative study on Kava usage patterns in the USA
Pharmacology & Safety•2026•Nutrients
Integrated 16S rRNA Sequencing and Metabolomics Analysis Reveal the Protective Effects of (E)-Flavokawain A on AOM/DSS-Induced Colorectal Cancer in Mice
Zhang X., Wang D., Wang Y., Wang M., Wang J., Sun Y., Chen S., Qu X., Xia A., Liu H., Wang J., Liu M.
Study on the protective effects of (E)-Flavokawain A (FKA), the main chalcone from Kava, against colon cancer in mice. The investigation combines 16S rRNA sequencing and metabolomics analysis to understand the mechanisms of action. The results show protective effects of FKA against AOM/DSS-induced colon cancer.
Significance
New insights into potential anticancer properties of Kava ingredients
Chemistry & Biochemistry•2026•Angewandte Chemie International Edition
Design of a Multienzyme Derived from Mouse Fatty Acid Synthase for the Compartmentalized Production of 2-Pyrone Polyketides
Lehmann F., Joachim N., Parthun C., Grininger M.
Biotechnological study on the enzymatic production of styrylpyrones and hispidin, which serve as direct precursors of kavalactones. The researchers developed a multi-enzyme system based on murine fatty acid synthase, which exceeds the styrylpyrone synthase of the kavalactone biosynthesis pathway in Piper methysticum by 66 times. The study provides new insights into the biosynthesis of kavalactones.
Significance
Advances in understanding the Kavalactone biosynthesis
Pharmacology & Safety•2026•Phytotherapy Research
Desmethoxyyangonin, a Potent Cannabinoid Receptor 2 Agonist, Alleviates Bone Loss in Ovariectomized Mice via Dual Regulation of Osteoblast and Osteoclast Function
Mening'oo G.W., Yuan H., Wang M., Wang W., Ma F., Zhang W., Ma J., Chen J., Jiang Y., Ma X.
Desmethoxyyangonin (DMY), a kavalactone, demonstrates anti-osteoporotic effects as a potent CB2 agonist. In the OVX mouse model, DMY significantly restored bone mineral density and improved trabecular microarchitecture. In vitro, DMY promoted osteoblast differentiation and mineralization while suppressing osteoclast formation. The effect is mediated via CB2-dependent PI3K/Akt and Wnt/β-catenin signaling pathways.
Significance
First study to demonstrate an anti-osteoporotic effect of a kavalactone via the CB2 receptor. This expands the therapeutic potential of Kava constituents beyond their known anxiolytic effects.
General Research•2026•Proceedings of the National Academy of Sciences
Kava consumption and the rise of sociopolitical complexity in Oceania
Hrnčíř V., Sheehan O., Claessens S., Gray R.D.
Analysis of 83 Oceanic societies reveals a positive relationship between traditional Kava consumption and political complexity, as well as social stratification. However, the results are not robust against controls for non-independence. There is no evidence for co-evolution between Kava drinking and sociopolitical traits after controlling for spatial non-independence. Despite Kava's cultural significance, its consumption was likely not a major driver of sociopolitical complexity.
Significance
High-ranking PNAS study that tests the 'Drunk Hypothesis' using Kava as a case study. Important for understanding the cultural role of Kava in Oceania.
Chemistry & Biochemistry•2026•Chemistry & Biodiversity
Flavokawain A: A Natural MAO-A Inhibitor With Therapeutic Promise for Depression
Pawa V., Shimpi A., Oh J.M., Kadam V., Patil B., Gawli C., Jagtap V., Mathew B., Sudevan S., Ansari I., Kim H., Patel H.M.
Flavokawain A, a natural chalcone from Piper methysticum, exhibits potent and selective MAO-A inhibition (IC50: 0.077 µM) with a selectivity index of 4.84 compared to the clinically used reversible MAO-A inhibitor toloxatone. Blood-brain barrier permeability confirms CNS efficacy. Molecular docking and dynamics simulations reveal stable binding in the MAO-A active site. This positions Flavokawain A as a promising natural lead compound for the treatment of depression.
Significance
Important discovery of a new mechanism of action for Kava constituents: MAO-A inhibition by Flavokawain A. Relevant for potential antidepressant applications and interactions with MAO inhibitors.
Pharmacology & Safety•2026•Phytomedicine
Kavain for health promotion and disease mitigation: Pharmacological promise and therapeutic perspectives
Pampita N., Sajeev A., Hegde M., Alqahtani M.S., Abbas M., Kavalakatt J., Sethi G., Bishayee A., Kunnumakkara A.B.
Comprehensive review of Kavain: Evaluation of its anti-inflammatory, anxiolytic, antithrombotic, neuroprotective, and anticarcinogenic properties. Kavain regulates NF-κB and MAPK signaling pathways, modulates GABA-A receptor activity, and inhibits osteoclastogenesis. Pharmacokinetic studies show rapid absorption, moderate oral bioavailability, and efficient systemic clearance. Toxicity studies indicate good tolerability at physiologically relevant concentrations.
Significance
Current and comprehensive review (164 references) on Kavain as a therapeutic agent. It summarizes the current state of research on all known effects and supports the safety of Kavain.
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Last updated: March 18, 2026•New study added