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Kavalactone

Kavalactones, also known as kavapyrones, are a group of lipophilic, structurally related compounds classified as substituted 4-methoxy-5,6-dihydro-α-pyrones that serve as the primary bioactive constituents in the roots and rhizomes of the kava plant (Piper methysticum), a shrub native to the Pacific Islands.^[1] These compounds, which constitute 3–20% of the dried rootstock, are responsible for kava's traditional and medicinal uses, including anxiolytic, sedative, and muscle-relaxant effects through modulation of γ-aminobutyric acid type A (GABA_A) receptors and other pharmacological mechanisms.^[2] The six major kavalactones—kavain, dihydrokavain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin—account for approximately 95–96% of the total kavalactone content in kava extracts.^[3] Chemically, kavalactones feature a core α-pyrone ring with varying methoxy and methylenedioxy substitutions on the aromatic ring, contributing to their low water solubility and lipophilic nature, which influences their bioavailability and extraction methods.^[1] Kavain, the most abundant kavalactone, exemplifies this structure and has been extensively studied for its direct positive allosteric modulation of GABA_A receptors, particularly enhancing activity at extrasynaptic subtypes like α4β2δ, which underlies its anxiolytic properties without significant sedation at therapeutic doses.^[2] These compounds are traditionally consumed in aqueous extracts as a ceremonial beverage in Pacific cultures but are also available in standardized supplements for anxiety and insomnia management in Western markets.^[3] Pharmacologically, kavalactones exhibit a range of effects beyond anxiolysis, including neuroprotection via inhibition of pro-inflammatory pathways like nuclear factor kappa B and potential analgesic activity through non-opiate mechanisms.^[3] However, their use has raised safety concerns, particularly hepatotoxicity, with reports of severe liver injury, including hepatitis and failure, linked to kavalactone metabolites that inhibit cytochrome P450 enzymes and form reactive quinones.^[1] Regulatory bodies, such as the FDA, issued warnings in 2002 about kava products due to over 30 documented cases of hepatotoxicity in Europe alone, emphasizing risks from high-dose extracts, stem peelings containing additional alkaloids like pipermethystine, and interactions with alcohol or hepatotoxic drugs. While the FDA advisory remains, several European countries have lifted bans since 2014, and as of 2025, efforts are underway to reintroduce kava in the EU with safety guidelines.^[3]^[4] Despite these issues, ongoing research explores safer formulations and lower-risk cultivars to harness their therapeutic potential; as of 2025, recent studies investigate kavalactones' applications in PTSD symptom relief, lung cancer risk reduction, and enhancing motivation during physical training.^[1]^[5]^[6]

Chemistry

Major Compounds

Kavalactones are a class of α-pyrone derivatives characterized by a 4-methoxy-2H-pyran-2-one core structure substituted at the 6-position with styryl or dihydrostyryl side chains, primarily isolated from the roots and rhizomes of Piper methysticum (kava). These compounds contribute to the plant's lipid-soluble resin, accounting for 3–20% of the dry weight depending on the cultivar and growth conditions. More than 18 kavalactones have been identified, with six major ones—kavain, dihydrokavain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin—comprising over 96% of the total kavalactone content in noble kava varieties.^[7]^[8] The major kavalactones include:

Kavain (C₁₄H₁₄O₃, MW 230.09 g/mol): Features a trans-styryl side chain attached to the α-pyrone ring.
Dihydrokavain (C₁₄H₁₆O₃, MW 232.11 g/mol): The saturated analog of kavain with a phenethyl side chain.
Methysticin (C₁₅H₁₄O₅, MW 274.08 g/mol): Contains a methylenedioxy-substituted styryl group.
Dihydromethysticin (C₁₅H₁₆O₅, MW 276.10 g/mol): The dihydro form of methysticin, with a saturated methylenedioxyphenethyl chain.
Yangonin (C₁₅H₁₄O₄, MW 258.09 g/mol): Possesses a dimethoxy-substituted styryl side chain.
Desmethoxyyangonin (C₁₄H₁₂O₃, MW 228.08 g/mol): Lacks the methoxy group on the side chain phenyl ring compared to yangonin.

At least 18 additional minor kavalactones have been characterized, including 5,6-dehydrokavain (C₁₄H₁₂O₃, MW 228.08 g/mol), 7,8-dihydro-5,6-dehydrokavain (C₁₄H₁₄O₃, MW 230.09 g/mol), 5,6-dehydromethysticin (C₁₅H₁₂O₅, MW 272.07 g/mol), 5,6-dihydromethysticin (C₁₅H₁₆O₅, MW 276.10 g/mol), 5,6,7,8-tetrahydrokavain (C₁₄H₁₈O₃, MW 234.13 g/mol), 5,6,7,8-tetrahydrodihydrokavain (C₁₄H₁₈O₃, MW 234.13 g/mol), 11-methoxyyangonin (C₁₆H₁₆O₅, MW 288.10 g/mol), 12-methoxyyangonin (C₁₆H₁₆O₅, MW 288.10 g/mol), 4'-methoxyyangonin (C₁₆H₁₆O₅, MW 288.10 g/mol), 10-methoxyyangonin (C₁₆H₁₆O₅, MW 288.10 g/mol), 11,12-dimethoxyyangonin (C₁₇H₁₈O₆, MW 318.11 g/mol), and 4',11-dimethoxyyangonin (C₁₇H₁₈O₆, MW 318.11 g/mol). These minor variants often feature additional methoxy substitutions or varying degrees of saturation on the side chains.^[8] Kavalactones exhibit low solubility in water but are readily soluble in organic solvents such as ethanol, chloroform, and DMSO. For instance, kavain has a reported melting point of 82–85 °C and demonstrates solubility in ethanol up to 20 mg/mL. The average elimination half-life of kavalactones in humans is approximately 9 hours, reflecting their lipophilic nature and slow clearance.^[7]^[9]^[10] Variations in kavalactone profiles occur across kava chemotypes, defined by the relative abundance of the six major compounds (e.g., chemotype 4-2-6-3-5-1 denotes kavain > dihydrokavain > desmethoxyyangonin > yangonin > dihydromethysticin > methysticin). Noble kava varieties, traditionally cultivated in regions like Vanuatu and Fiji, feature higher levels of kavain (up to 20% of total) and lower dihydromethysticin, resulting in profiles dominated by anxiolytic compounds. In contrast, tudei (or "two-day") kava from wild or non-traditional sources shows elevated dihydromethysticin and methysticin, often exceeding 30% combined, alongside higher flavokavain content (though flavokavains are chalcone derivatives). These differences arise from genetic, environmental, and cultivation factors, with root peels containing up to twice the concentration of peeled roots. Kavalactones are also present in other sources, such as Alpinia zerumbet (shell ginger), where dihydro-5,6-dehydrokavain and 5,6-dehydrokavain predominate in the pericarps, and certain fungi including Gymnopilus aeruginosus (producing bis-styrylpyrone derivatives like phaeolschidin F) and Phellinus spp. (yielding hispidin-related styrylpyrones).^[7]^[11]^[12] The identification of kavalactones began in the 1860s, with the isolation of methysticin by Gobley in 1860 and Cuzent in 1861 from kava resin. Subsequent efforts in the late 19th and early 20th centuries identified additional compounds like yangonin (1914) and kavain (1928), though early isolations relied on crude fractionation. Modern quantification emerged in the 1970s with chromatographic techniques, evolving to high-performance liquid chromatography (HPLC) by the 1990s for precise profiling of all major kavalactones in extracts.^[13]^[14]^[7]

Biosynthesis

Kavalactones in Piper methysticum are primarily biosynthesized in the plant's roots via a specialized polyketide pathway that initiates with the condensation of malonyl-CoA and cinnamoyl-CoA.^[15] The core scaffold is established by a pair of paralogous type III polyketide synthase enzymes, including styrylpyrone synthase 1 (SPS1), which catalyzes the iterative assembly and Claisen-Dieckmann-like cyclization to yield α-pyrones.^[15] Subsequent tailoring steps involve hydroxylation at specific positions and O-methylation, mediated by enzymes such as the O-methyltransferase KOMT1, to produce the characteristic 5,6-dehydro-α-pyrones and their dihydro derivatives.^[15] This pathway, comprising seven dedicated enzymes, was fully elucidated in 2019 through genomic mining, transcriptomics, and heterologous expression in Nicotiana benthamiana.^[15] Advances in synthetic biology have enabled de novo production of kavalactones outside the native plant host. In 2022, an engineered pathway in Saccharomyces cerevisiae successfully generated 7,8-saturated styrylpyrones, including desmethoxyyangonin (DDK) and dihydroyangonin, at titers up to 4.40 μM.^[16] This modular system integrated yeast-endogenous enzymes for hydroxycinnamoyl-CoA precursor synthesis (e.g., via 4-coumarate-CoA ligase At4CL3 and double-bond reductases like TSC13) with kava-derived PmSPS1 for scaffold formation and PmKOMT1 for methylation, demonstrating scalability through CRISPR-mediated integration.^[16] Chemoenzymatic approaches have further refined kavalactone synthesis by leveraging biosynthetic enzymes for stereoselective modifications. In 2024, the O-methyltransferase JerF was heterologously produced in Escherichia coli as an MBP fusion, purified via affinity chromatography, and biochemically characterized with kinetic parameters k_cat = 0.383 min⁻¹ and K_M = 4.01 μM for its substrate projerangolid. JerF enables regioselective 4-O-methylation to form 4-methoxy-5,6-dihydro-2H-pyran-2-one cores, facilitating dynamic kinetic resolution of racemic precursors and yielding compounds like (+)-kavain and (+)-11,12-dimethoxykavain with 37–57% yields and 70–86% enantiomeric excess on a 100 μmol scale. Kavalactones also occur in select fungal species, such as Gymnopilus spp., where their production likely involves convergent polyketide mechanisms distinct from the plant pathway, potentially relying on fungal-specific synthases.^[17] These inter-kingdom variations underscore opportunities for sustainable bioproduction, as microbial engineering in yeast or fungi could bypass agricultural limitations of P. methysticum cultivation while enabling scalable, eco-friendly synthesis of these compounds.^[16]

Pharmacology

Mechanisms of Action

Kavalactones, the primary bioactive compounds in kava (Piper methysticum), exert their central nervous system (CNS) effects primarily through positive allosteric modulation of GABA_A receptors, with the exception of desmethoxyyangonin, which does not significantly alter receptor binding or function.^[18] Major kavalactones such as kavain, dihydrokavain, methysticin, dihydromethysticin, and yangonin enhance GABA binding and facilitate chloride ion influx, leading to neuronal hyperpolarization and CNS depression.^[7] This modulation occurs at a distinct allosteric site, independent of the benzodiazepine binding pocket, as evidenced by insensitivity to flumazenil antagonism.^[19] For instance, kavain potentiates GABA-elicited currents across various GABA_A subtypes (e.g., α1β2γ2L and α4β2δ) in a concentration-dependent manner (10–300 μM), with greater enhancement at extrasynaptic receptors containing δ subunits, supporting anxiolytic and sedative outcomes through increased inhibitory neurotransmission.^[19] In addition to GABA_A modulation, kavalactones inhibit the reuptake of monoamines, particularly norepinephrine and dopamine, contributing to their mood-regulating properties. Kavain inhibits norepinephrine uptake in rat synaptosomes (70-80% at 400 μM), while methysticin exhibits moderate activity; kavalactones also inhibit dopamine reuptake at micromolar concentrations.^[20]^[21] Kavalactones also interact with the endocannabinoid system, notably through yangonin's binding to CB1 receptors as a novel ligand (Ki = 0.72 μM), displaying selectivity over CB2 receptors (Ki > 10 μM) and minimal effects on fatty acid amide hydrolase or monoacylglycerol lipase.^[22] This affinity suggests a role in modulating endocannabinoid signaling, potentially enhancing kava's anxiolytic profile. Furthermore, several kavalactones block voltage-gated ion channels: kavain and methysticin inhibit sodium channels in hippocampal neurons by stabilizing resting and inactivated states (IC50 ≈ 80–180 μM), reducing neuronal excitability, while broader kava extracts demonstrate calcium channel blockade, limiting excitatory neurotransmitter release.^[23]^[24] Enzyme modulation by kavalactones includes potent, reversible inhibition of monoamine oxidase B (MAO-B), with yangonin showing the highest affinity (IC50 = 0.085 μM), followed by desmethoxyyangonin (Ki = 0.28 μM) and kavain (IC50 = 5.34 μM), compared to weaker MAO-A inhibition.^[25]^[7] Kavalactones also affect cytochrome P450 (CYP450) enzymes; methysticin potently inhibits CYP1A2 (≈56% at 100 μM extract equivalent) and CYP2C9 (IC50 = 13.35 μM), while yangonin and related compounds suppress CYP3A4 activity (≈40–78% inhibition at 10–100 μM), potentially altering drug metabolism through competitive mechanisms.^[26] These interactions vary in potency, with methysticin and dihydromethysticin generally more effective against CYP1A2 and CYP3A4 than kavain, underscoring dose-dependent CNS influences from combined receptor and enzymatic modulation.^[26]

Bioactivity

Kavalactones, the primary bioactive constituents of the kava plant (Piper methysticum), exhibit a range of psychoactive effects in vivo, including anxiolytic, sedative, analgesic, euphoric, and muscle-relaxant properties. These effects arise from dose-dependent central nervous system (CNS) depression, with onset within 20-40 minutes and peak effects around 1-2 hours post-ingestion, leading to relaxation and reduced anxiety without significant impairment of cognitive function. At low doses, kavalactones can induce mild euphoria and increased talkativeness, contributing to an overall sense of well-being and sociability.^[27]^[28] Preclinical studies indicate kavalactones interact with various herbal and pharmaceutical agents through inhibition of cytochrome P450 enzymes, particularly CYP1A2 and CYP2E1, which may alter the metabolism of co-administered substances, though clinical effects vary. For instance, inhibition of CYP1A2 may prolong the effects of caffeine by slowing its clearance, while CYP2E1 inhibition can extend the half-life of acetaminophen, potentially enhancing its pharmacological actions (with one study showing 40% reduction in CYP2E1 activity). These pharmacokinetic interactions highlight the need for caution when combining kavalactones with medications reliant on these enzymes for metabolism.^[29]^[30] The compounds also demonstrate anti-inflammatory potential by modulating pro-inflammatory cytokines, such as reducing TNF-α and IL-17A levels in stressed tissues, which supports their role in dampening inflammatory responses. Neuroprotective effects have been observed in animal models, where kavalactones like methysticin activate pathways such as Nrf2 to mitigate oxidative stress and improve cognitive function under stress conditions. These properties extend to broader modulation of stress responses, enhancing resilience to physiological stressors. Briefly, these bioactivities involve interactions with GABA_A receptors and voltage-gated ion channels, as detailed in the mechanisms of action.^[27]^[28] Recent studies (as of 2024) suggest kavalactones may enhance motivation and performance during intensive training, potentially via interactions with reward pathways.^[31] In species-specific contexts, kavalactones produce observable effects in animal models, including reduced locomotion indicative of sedative action in rodents administered doses of 75–100 mg/kg. Elevated mood markers, such as increased dopamine levels in brain regions like the nucleus accumbens, have been noted in rats, correlating with anxiolytic behaviors and reduced stress-induced hyperactivity. These findings underscore the compounds' influence on locomotor and affective responses across species.^[27]^[32]

Clinical Research

Anxiolytic and Sedative Effects

Kavalactones, the primary active compounds in kava (Piper methysticum), have been traditionally used in Pacific Island cultures for their calming effects during social ceremonies, where the beverage promotes relaxation and facilitates communal bonding without impairing cognitive function.^[33] In these rituals, particularly in Fiji and Vanuatu, kava consumption fosters a sense of tranquility and social ease, historically aiding in dispute resolution and alliance-building among participants.^[5] Clinical research has substantiated these anxiolytic properties through randomized controlled trials (RCTs), demonstrating kavalactones' efficacy in reducing symptoms of generalized anxiety disorder (GAD) at doses of 100–300 mg per day. A 2011 systematic review of six RCTs found that kava extracts produced significant anxiety reduction comparable to benzodiazepines like oxazepam, with equivalent improvements in Hamilton Anxiety Rating Scale (HAM-A) scores over 4–8 weeks, though with fewer cognitive side effects.^[34] For instance, one double-blind trial involving patients pretreated with benzodiazepines showed that switching to 300 mg/day of kavalactones maintained anxiolytic benefits while allowing benzodiazepine tapering, supporting its role as an alternative for short-term GAD management.^[35] Meta-analyses further confirm short-term efficacy for anxiety, stress, and insomnia. A 2022 network meta-analysis of 53 RCTs on herbal treatments for anxiety showed kava with moderate effect sizes for reducing HAM-A scores versus placebo overall, though possibly ineffective specifically for GAD.^[36] Earlier meta-analyses, including one from 2000 analyzing seven trials, reported significant HAM-A reductions (weighted mean difference of -3.89 points) favoring kava over placebo, with benefits evident within 1–8 weeks at 60–240 mg kavalactones daily.^[37] These effects are attributed briefly to kavalactones' potentiation of GABA_A receptors, enhancing inhibitory neurotransmission without the dependency risks of conventional sedatives.^[38] However, evidence remains mixed for long-term use, with calls for larger RCTs to confirm efficacy and safety. Modern supplement use aligns with clinical findings. For long-term application in anxiety management, noble kava varieties—cultivated for higher kavain content and lower flavokavains—are recommended over tudei types, which may cause prolonged sedation and skin irritation with repeated use. Dosage guidelines suggest limiting intake to under 250 mg kavalactones daily to minimize tolerance development, with noble extracts showing favorable safety profiles in trials up to 24 weeks.^[8]

Emerging Therapeutic Applications

Recent research from 2023 to 2025 has explored kavalactones' potential in reducing lung cancer risk among smokers, particularly through AB-free kava varieties that mitigate tobacco-induced genetic damage and lower tumor markers. A 2024 preclinical study from the University of Florida demonstrated that AB-free kava enhances resilience against adverse health effects of tobacco smoke in mice, reducing inflammation and oxidative stress in lung tissues.^[39] A separate 2020 pilot clinical trial suggested genetic predictors, such as polymorphisms in UGT2B10, may identify individuals benefiting from kava's enhancement of carcinogen detoxification.^[6] This preclinical and pilot data suggests kavalactones could serve as a supportive intervention for high-risk populations, though clinical translation remains ongoing. In tobacco cessation efforts, a 2024 protocol for a randomized clinical trial is investigating AB-free kava's promise for managing associated stress and insomnia, potentially facilitating quitting without exacerbating dependence.^[40] Complementing this, a 2025 proposal describes kava-talanoa—a culturally integrated approach combining kavalactone-rich kava with traditional dialogic storytelling—as a potential therapy for PTSD symptom reduction in Pacific cultures, with pilot insights suggesting benefits for hyperarousal and avoidance; full clinical trials are planned.^[5] Anticancer and anti-inflammatory applications of kavalactones are gaining attention, particularly through modulation of cytochrome P450 (CYP) enzymes to support chemotherapy efficacy. A 2025 review highlighted how major kavalactones inhibit specific CYP isoforms, potentially enhancing drug metabolism and reducing toxicity in cancer treatments while exhibiting anti-inflammatory effects via COX-2 pathway suppression.^[41] Additionally, a 2024 randomized study found that 225 mg/day of kavalactones supported motivation to move and resilience in military trainees undergoing intensive training.^[42] Neuroprotective effects of kavalactones, including those explored in bioengineered or fungi-associated derivations, underscore their role in combating neurodegeneration. Recent computational analyses from 2025 indicate potential benefits of Piper-derived compounds, including kavalactones, in conditions like Parkinson's disease, by addressing anxiety, sleep, and related symptoms.^[43] These findings align with growing U.S. adoption patterns, where a 2025 national survey reported that 33.7% of kava users purchase from kava bars, reflecting increased interest in novel therapeutic contexts beyond traditional use.^[44]

Safety and Toxicity

Hepatotoxicity

In the 1990s and early 2000s, multiple case reports emerged linking kava extracts containing kavalactones to acute liver failure, including instances requiring liver transplantation and fatalities.^[45] These reports, primarily from Europe and the United States, prompted regulatory actions such as the European Union's ban on kava products in 2002 due to concerns over severe hepatotoxicity.^[46] The estimated incidence of such events was extremely low, approximately 1 in 1 million users or daily doses, based on sales data and reported cases during that period.^[47] Proposed mechanisms for kava-induced hepatotoxicity include inhibition of cytochrome P450 enzymes, which may lead to idiosyncratic reactions by altering drug metabolism and promoting toxic metabolite formation.^[3] Additionally, the alkaloid pipermethystine, present in non-noble or "tudei" kava varieties, has been identified as a potential hepatotoxin contributing to liver damage in susceptible individuals.^[8] In heavy users, altered metabolic profiles—such as reduced liver glutathione levels—have been associated with both hepatotoxicity and secondary effects like kava dermopathy, a reversible skin condition marked by dryness and scaling.^[3] In 2024, Hawaii's Department of Health issued a GRAS determination for traditional noble kava preparations, affirming low toxicity risk when used appropriately, though federal FDA warnings persist for certain extracts.^[48] As of August 2025, global regulatory overviews, including updates from FSANZ and European assessments, continue to affirm that hepatotoxicity remains rare in traditional noble kava use contexts.^[4] However, acetone-based extracts continue to carry warnings due to their association with higher hepatotoxicity potential compared to traditional aqueous preparations.^[49] Key risk factors for hepatotoxicity include high daily doses exceeding 300 mg of kavalactones, consumption of poor-quality or contaminated extracts (e.g., those including stems or leaves), and underlying comorbidities such as preexisting liver conditions.^[50] A 2025 global systematic review noted elevated total and LDL cholesterol levels among regular kava users, potentially linked to heavy consumption patterns, yet overall hepatotoxicity remained rare in traditional contexts.^[51]

Drug Interactions

Kavalactones, the primary active compounds in kava (Piper methysticum), can significantly interact with other medications primarily through inhibition of cytochrome P450 (CYP) enzymes, altering drug metabolism and leading to pharmacokinetic changes. In vivo studies have demonstrated that kavalactones inhibit CYP1A2 activity by up to 56%, with methysticin identified as a key contributor to this effect, potentially prolonging the half-life of substrates like theophylline, a xanthine oxidase inhibitor metabolized by CYP1A2.^[1]^[26] Similarly, kavalactones reduce CYP2E1 activity by approximately 40% in human volunteers, as measured by chlorzoxazone probe assays, which may impact the clearance of drugs reliant on this enzyme.^[52] A 2025 review of major kavalactones, including kavain, methysticin, and dihydromethysticin, further highlights their modulation of CYP3A4 and CYP2D6, with inhibition levels reaching 73% for CYP2D6 in clinical probe studies, raising concerns for interactions with a broad range of pharmaceuticals.^[41]^[1] Specific pharmacodynamic interactions amplify the risks associated with certain drug classes. Kavalactones enhance sedation when combined with alcohol or benzodiazepines due to synergistic effects on GABAA receptors, potentially leading to excessive drowsiness or semicomatose states, as reported in case studies involving concurrent use.^[53]^[3] They also potentiate acetaminophen-induced hepatotoxicity in animal models, where kava extracts significantly increased liver enzyme elevations and histological damage in mice pretreated with acetaminophen, likely through CYP-mediated alterations in acetaminophen metabolism.^[54] Additionally, warnings exist for co-administration with antipsychotics, as kavalactones inhibit dopamine reuptake, which may counteract the therapeutic effects of these agents and exacerbate extrapyramidal symptoms.^[21] The pharmacokinetic profile of kavalactones contributes to their interaction potential, with an elimination half-life of approximately 9 hours in humans following oral administration, promoting accumulation upon repeated dosing and prolonged enzyme inhibition.^[56] Animal studies corroborate altered drug clearance; for instance, kava administration in rats led to a roughly 50% reduction in caffeine metabolism, attributable to CYP1A2 inhibition, as evidenced by prolonged caffeine plasma levels and delayed paraxanthine formation.^[1]^[57] Clinical recommendations emphasize caution with kavalactones to mitigate these risks. Concurrent use with hepatotoxic drugs, such as acetaminophen or certain statins, should be avoided due to enhanced liver injury potential.^[58] For individuals on selective serotonin reuptake inhibitors (SSRIs) or monoamine oxidase inhibitors (MAOIs), close monitoring is advised, as kavalactones' inhibition of MAO-B and potential serotonergic modulation have been linked to prolonged serotonin syndrome symptoms in case reports.^[59]^[60]

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Jul 15, 2024 · We report a novel finding that kavalactones may support performance by maintaining or rescuing the desire to expend energy in the context of significant ...Missing: animal | Show results with:animal
[34]
Flavokavains A- and B-Free Kava Enhances Resilience against the ...
Oct 2, 2024 · AB-free kava has the potential to reduce tobacco-smoking-induced lung cancer risk, mitigate tobacco dependence, and reduce tobacco use.
[35]
Genetics may predict benefits of kava in reducing lung cancer risk
Sep 18, 2024 · UF Health Cancer Center researchers have bolstered their findings that kava may reduce lung cancer risk caused by tobacco smoke.
[36]
The potential of AB-free kava in enabling tobacco cessation via ...
Dec 21, 2024 · Another study aim is to investigate if AB-free kava can help patients quit smoking, reduce stress, and enhance sleep quality. Tobacco dependence ...
[37]
The potential of major kavalactones in modulating cytochrome P450 ...
Oct 21, 2025 · Several key CYP isoforms exhibited more than 50% inhibition, including CYP1A2 (56%), CYP3A4 (78%), and CYP4A9/11 (65%) by the kava extract, ...
[38]
Computational analysis of therapeutic potential for simplified Piper ...
In PD patients, Kava may be a potential therapeutic for anxiety and sleep quality issues, and there is some interest in potential neuroprotective effects of ...
[39]
Prevalence and use patterns of kava (Piper methysticum) in a US ...
Sep 15, 2025 · In recent years, its use in the US has grown as we understand more about its active constituents, kavalactones, which have demonstrated ...
[40]
Hepatic Toxicity Possibly Associated with Kava-Containing Products
A total of 11 patients who used kava products had liver failure and underwent subsequent liver transplantation (1--7). On March 25, 2002, in response to five ...
[41]
Kava kava: examining new reports of toxicity - ScienceDirect.com
Nevertheless, by January 2003 kava extracts had been banned in the entire European Union ... Kava safety questioned due to case reports of liver toxicity ...
[42]
https://pmc.ncbi.nlm.nih.gov/articles/PMC11254123/
[43]
Ask the Doctors - What are the risks and benefits of kava?
Dec 5, 2023 · Kava can help reduce anxiety. One interesting aspect is that kava binds to a different GABA receptor than benzodiazepines, such as Xanax, Valium, or Ativan.Missing: reuptake | Show results with:reuptake
[44]
[PDF] GRAS Determination for 'Awa January 23, 2024
Jan 23, 2024 · The substituted 4-methoxy-5, 6-dihydro-alpha-pyrones or kava pyrones, commonly called kavalactones, possesses the highest purported ...
[45]
Kava: herbal panacea or liver poison?
May 5, 2003 · A major deficiency of the Pacific experience is that liver toxicity, possibly caused by kava, has never been systematically looked for. Apart ...Missing: incidence | Show results with:incidence
[46]
Kava hepatotoxicity in traditional and modern use - NIH
Kava, a Pacific herb consumed worldwide for medicinal, recreational and cultural purposes, has been associated with rare hepatotoxicity.
[47]
Global Perspectives on Kava: A Narrative Systematic Review of the ...
Jun 25, 2025 · We conducted a systematic search of eight databases for records published between January 1980 and December 2022. Records on kava prevalence, ...<|separator|>
[48]
In Vivo Effects of Goldenseal, Kava Kava, Black Cohosh, and ...
May 16, 2005 · Kava produced significant reductions (approximately 40%) in CYP2E1 only (difference, −0.192; 95% CI, −0.325 to −0.060). Black cohosh also ...
[49]
Common Herbal Dietary Supplement–Drug Interactions - AAFP
Jul 15, 2017 · Caution should be exercised in patients using central nervous system depressants, such as benzodiazepines or alcohol, because of the increased ...
[50]
Flavokawains A and B in Kava, Not Dihydromethysticin, Potentiate ...
Sep 3, 2014 · Our results showed that kava was safe when given alone but significantly enhanced acetaminophen (APAP)-induced hepatotoxicity in C57BL/6 mice.
[51]
When It Comes to Kava, 'Natural' Doesn't Mean Safe
Feb 8, 2023 · But kava inhibits dopamine reuptake, which can prevent your meds from working properly. Advertisement. Kava may interact with other substances, ...
[52]
Kava - an overview | ScienceDirect Topics
Kavalactones facilitate the functioning of GABA A receptors, in a manner that is similar to benzodiazepines, but kavalactones do not appear to bind to ...<|separator|>
[53]
Kinetics of kavain and its metabolites after oral application
The peak plasma concentration is reached in ∼1.8 h. Kavain concentration in blood decreases with a half-life of ∼9 h, and the distribution phase lasts 3–5 h [2] ...
[54]
interaction with kava extract and kavalactones in vivo and in vitro
The human hepatic microsomal P450s most strongly inhibited by kava extract (CYP2C9, CYP2C19, CYP2D6, CYP3A4) were inhibited to the same degree by a "composite" ...Missing: JM | Show results with:JM<|separator|>
[55]
Does Kava interact with any drugs?
Apr 30, 2025 · Important drug interactions include alcohol, medicines that may cause liver toxicity, and other herbs or medicines that may cause drowsiness or dizziness.Missing: acetaminophen antipsychotics
[56]
Kava as a Clinical Nutrient: Promises and Challenges - PMC
In this study, 21 smokers took kava capsules three times daily (standardized to 225 mg kavalactones per 3 capsules). Kava was shown to increase urinary ...
[57]
Prolonged Serotonergic Symptoms in a Pediatric Patient - NIH
May 12, 2025 · We present a pediatric patient who developed prolonged serotonin syndrome after daily use of kava while transitioning from duloxetine to venlafaxine.Missing: SSRIs | Show results with:SSRIs