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Introduction: Kava, a substance derived from the Piper methysticum plant, is enjoying a surge in popularity in the United States due to its purported anxiolytic and analgesic effects. Though ichthyosiform dermopathy is a known adverse effect associated with chronic kava exposure in adults, dermopathy in a newborn due to maternal kava use has not yet been described. Case Report: This is a case of a 41-year-old woman who was taking a combination kava/kratom product throughout her pregnancy. She developed an ichthyosiform dermopathy that resolved after she stopped using the product postpartum. Her male infant had a neonatal course complicated by both neonatal opioid withdrawal syndrome, attributed to maternal kratom and buprenorphine use, as well as a diffuse ichthyosiform rash similar to descriptions of kava ichthyosiform dermopathy in adults. His neonatal course was complicated by Group B streptococcus and Serratia marscecens bacteremia (treated with antibiotics) and seizures (treated with lorazepam and phenobarbital). His rash resolved completely by day of life 22. At 9-month outpatient follow-up, he had no dermatologic abnormalities or rash recurrence. Discussion: Maternal kava use during pregnancy may cause fetal dermopathy presenting as an acquired ichthyosis. More public education is needed about the potential consequences of kava use, particularly during pregnancy. [ABSTRACT FROM AUTHOR]

Background Military special operators, elite athletes, and others requiring uninterrupted optimal performance currently lack options for sleep and mood support without performance-inhibiting effects. Kavalactones, derived from the root of the kava plant (Piper methysticum Forst), have been shown to elevate mood and wellbeing by producing a feeling of relaxation without addiction or cognitive impairment.Methods In this placebo-controlled, crossover study (NCT05381025), we investigated the effects of 2 weeks of kavalactones use on cortisol (diurnal salivary), sleep (RSQ-W; Restorative Sleep Questionnaire, Weekly), mood (DASS-21; Depression Anxiety Stress Scale-21), and motivation state to expend (Move) or conserve (Rest) energy (CRAVE; Cravings for Rest and Volitional Energy Expenditure, Right Now) in a cohort of 15 healthy, physically fit young males engaged in a rigorous, two-a-day preparation class for special operations forces qualification.Results Cortisol, sleep, and mood were within normal, healthy parameters in this cohort at baseline. This remained unchanged with kavalactones use with no significant findings of clinical interest. However, a statistically similar, positive slope for within-group Move scores was seen in both groups during kavalactones loading (first group Move slope 2.25, second group Move slope 3.29, p = 0.299). This trend was seen regardless of order and with no apparent effects on the Rest metric (all p ≥ 0.05). Moreover, a significant between-group difference appeared after 1 week of kavalactones use in the first phase (p = 0.044) and persisted through the end of the first loading period (p = 0.022). Following the 10-day washout, this between-groups divergence remained significant (p = 0.038) but was reversed by 1 week after the crossover (p = 0.072), with Move scores once again statistically similar between groups and compared to baseline at study end. Furthermore, the group taking kavalactones first never experienced a significant decrease in Move motivation state (lowest mean score 21.0, highest 28.6, all p ≥ 0.05), while the group receiving kavalactones in the last 2 weeks of the study had Move scores that were statistically lower than baseline (lowest mean score 8.6, highest 25.9, all p ≤ 0.05) at all time points but the last (p = 0.063) after 2 weeks of kavalactones exposure.Conclusions We report a novel finding that kavalactones may support performance by maintaining or rescuing the desire to expend energy in the context of significant physical and mental strain in well-conditioned individuals, even in a context of already normal cortisol, sleep, and mood.

Epidemiological evidence suggests that kava (Piper methysticum Forst) drinks may reduce the risk of cancer in South Pacific Island smokers. However, little is known about the anti-carcinogenic effects of kava on tobacco smoking-related bladder cancer and its underlying mechanisms. Here we show that dietary feeding of kawain (a major active component in kava root extracts) to mice either before or after hydroxy butyl(butyl) nitrosamine (OH-BBN) carcinogen exposure slows down urinary bladder carcinogenesis and prolongs the survival of the OH-BBN-exposed mice. OH-BBN-induced bladder tumors exhibit significantly increased expression of lysine-specific demethylase 1 (LSD1), accompanied by decreased levels of H3K4 mono-methylation compared to normal bladder epithelium, whereas dietary kawain reverses the effects of OH-BBN on H3K4 mono-methylation. Human bladder cancer tumor tissues at different pathological grades also show significantly increased expression of LSD1 and decreased levels of H3K4 mono-methylation compared to normal urothelium. In addition, kava root extracts and the kavalactones kawain and methysticin all increase the levels of H3K4 mono- and di-methylation, leading to inhibitory effects on cell migration. Taken together, our results suggest that modification of histone lysine methylation may represent a new approach to bladder cancer prevention and treatment and that kavalactones may be promising agents for bladder cancer interception in both current and former smokers.

Kava consumption is a traditional practice in Polynesian and Micronesian cultures. It has recently gained popularity in the United States for therapeutic and recreational use. We report the following case. A man presented to the emergency department after a fall while intoxicated on kava. He was medically admitted for altered mental status, facial and clavicle fractures, and hyponatremia. Psychiatry was consulted for management of delirium. On interview, he reported consuming escalating amounts of kava for weeks despite attempts to stop. He was diagnosed with acute kava withdrawal with hyperactive delirium, treatedwith phenobarbital load (860 mg) and taper (390mg). Continuous dexmedetomidine drip to hospital day 3 treated sympathetic activation and breakthrough agitation. By day 4, his delirium resolved and remained in remission until discharge. We performed a systematic review for reports of kava withdrawal, returning 9 studies. Eight assessed withdrawal symptoms after cessation of a low controlled dose of kava extract with no symptoms noted. One reported a case series of heavy kava users with seizure-like events. No publications discussed treatment of kava withdrawal. To our knowledge, this is the first publication to describe kava withdrawal syndrome and its effective treatment with phenobarbital. [ABSTRACT FROM AUTHOR]

Kava is a South Pacific plant‐based medicine with anxiolytic properties, but little is known about the impact kava has on gene expression or whether gene expression can serve as a marker of kava response. This study aimed to determine whether kava treatment alters the expression of genes with physiological relevance to anxiety pathophysiology and whether the baseline expression of these physiologically relevant genes modifies the efficacy of kava treatment. In this post hoc analysis, we examined the expression of 48 genes relevant to the pathophysiology of anxiety collected from a double‐blind randomized controlled trial that assessed the efficacy of kava treatment in generalized anxiety disorder. Peripheral blood gene expression was measured in 71 (34 kava, 37 placebo) adults at baseline and in 40 (19 kava, 21 placebo) after 8 weeks of treatment by reverse transcription polymerase chain reaction (PCR). Results revealed that kava decreased the expression of a subunit of the GABAA‐rho receptor gene (GABRR2) and catechol‐O‐methyltransferase (COMT), a gene related to catecholamine metabolism. Kava efficacy was not found to be modified by baseline (pretreatment) expression of relevant genes. Although these results did not withstand statistical correction for multiple comparisons and require external validation, they support the notion that kava's mechanism of action includes interaction with GABAergic and catecholaminergic systems. [ABSTRACT FROM AUTHOR]

Generalised Anxiety Disorder (GAD) is a prevalent, chronic mental health disorder. The measurement of regional brain gamma-aminobutyric acid (GABA) offers insight into its role in anxiety and is a potential biomarker for treatment response. Research literature suggests Piper methysticum (Kava) is efficacious as an anxiety treatment, but no study has assessed its effects on central GABA levels. This study investigated dorsal anterior cingulate (dACC) GABA levels in 37 adult participants with GAD. GABA was measured using proton magnetic resonance spectroscopy (1H-MRS) at baseline and following an eight-week administration of Kava (standardised to 120 mg kavalactones twice daily) (n = 20) or placebo (n = 17). This study was part of the Kava for the Treatment of GAD (KGAD; ClinicalTrials.gov: NCT02219880), a 16-week intervention study. Compared with the placebo group, the Kava group had a significant reduction in dACC GABA (p = 0.049) at eight weeks. Baseline anxiety scores on the HAM-A were positively correlated with GABA levels but were not significantly related to treatment. Central GABA reductions following Kava treatment may signal an inhibitory effect, which, if considered efficacious, suggests that GABA levels are modulated by Kava, independent of reported anxiety symptoms. dACC GABA patterns suggest a functional role of higher levels in clinical anxiety but warrants further research for symptom benefit. Findings suggest that dACC GABA levels previously un-examined in GAD could serve as a biomarker for diagnosis and treatment response. [ABSTRACT FROM AUTHOR]

AimHere, we aim to evaluate the chemopreventive efficacy of kava root extracts (KRE) in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice and investigate potential molecular targets of kavalactones, the main components of kava.MethodsTRAMP mice were administrated with KRE formulated food for different periods of time, and then the incidences of high-grade prostatic intraepithelial neoplasia (HG-PIN) and adenocarcinomas and tumor burdens were compared between vehicle control and KRE food fed groups. In addition, the inhibitory effect of the KRE and kavalactones on monoamine oxidase A (MAO-A) and lysine-specific demethylase 1 (LSD1) enzyme activities were examined by commercially available inhibitor screening kits. Histone H3 lysine 9 dimethylation was also evaluated in prostate cancer cells and tumor tissues using Western blotting analysis.ResultsDietary feeding of 0.3% and 0.6% KRE to TRAMP mice from ages of 6 weeks to 12 weeks inhibited HG-PIN by 43.5% and 59.7%, respectively, and prostate adenocarcinoma by 53.5% and 66.4%, respectively. In addition, 0.6% KRE fed TRAMP mice from ages of 6 weeks to 24 weeks exhibited a significant reduction of genitourinary weight (a surrogate of tumor burden) by 54.5% and reduced body weight gain. Furthermore, the KRE and kavalactones showed a significant inhibition of LSD1 and MAO-A enzyme activities.ConclusionOur results suggest that consumption of kava products through diet can delay prostate cancer development and progression and that kavalactones may be a new structure model for developing a potent dual inhibitor of LSD1 and MAO-A.

Abstract Background Tobacco use is the leading cause of many preventable diseases, resulting in premature death or disease. Given that the majority of adult who smoke want to stop, this health burden could be significantly reduced if the success rate of tobacco cessation can be improved. In addition, most adults planning to quit were interested in trying complementary approaches to facilitating tobacco cessation, which is currently lacking. Therefore, there is an unmet and urgent need for novel interventions to improve the success of tobacco cessation. If such an intervention can reduce tobacco-associated lung carcinogenesis, that will be more desirable. The goal of this project is to develop a safe and effective kava-based intervention to enable tobacco cessation and reduce lung cancer risk, which will improve the health of smokers. Methods A randomized controlled trial will enroll 80 adults who currently smoke at least 10 cigarettes daily and randomize 1:1 into the placebo and AB-free kava arms, being exposed for 4 weeks, with a total of six visits (weeks 0, 1, 2, 4, 8, and 12) to evaluate the compliance and potential issues of AB-free kava use among the participants, explore the potential effect of the AB-free kava intervention on tobacco dependence, tobacco use, and lung carcinogenesis biomarkers. Participants will be enrolled during their primary care clinic visit. Discussion Primary care settings play a critical role in tobacco-related disease screening, counseling, and early intervention, as the majority of adults who smoke visit their physicians annually. Building upon our promising pilot human trial results in conjunction with ample compelling lab animal results, and consistent with evidence of kava’s benefits from epidemiological data, this trial will evaluate the compliance of AB-free kava among adults who currently smoke with no intention to quit. The other exploratory aims include (1) whether AB-free kava intervention can reduce tobacco use and tobacco dependence; (2) whether AB-free kava use suppresses tobacco-induced carcinogenesis; and (3) the potential of the mechanism-based noninvasive biomarkers in precision AB-free kava intervention. The positive results from this study are expected to provide a great opportunity to effectively reduce smoking rates and tobacco-related diseases. Trial registration ClinicalTrials.gov with the identifier: NCT05081882. Registered on October 18, 2021.

Lung cancer is the leading cause of cancer-related deaths due to its high incidence, late diagnosis, and limited success in clinical treatment. Prevention therefore is critical to help improve lung cancer management. Although tobacco control and tobacco cessation are effective strategies for lung cancer prevention, the numbers of current and former smokers in the USA and globally are not expected to decrease significantly in the near future. Chemoprevention and interception are needed to help high-risk individuals reduce their lung cancer risk or delay lung cancer development. This article will review the epidemiological data, pre-clinical animal data, and limited clinical data that support the potential of kava in reducing human lung cancer risk via its holistic polypharmacological effects. To facilitate its future clinical translation, advanced knowledge is needed with respect to its mechanisms of action and the development of mechanism-based non-invasive biomarkers in addition to safety and efficacy in more clinically relevant animal models. [ABSTRACT FROM AUTHOR]

Background: Tobacco use is the leading cause of many preventable diseases, resulting in premature death or disease. Given that the majority of adult who smoke want to stop, this health burden could be significantly reduced if the success rate of tobacco cessation can be improved. In addition, most adults planning to quit were interested in trying complementary approaches to facilitating tobacco cessation, which is currently lacking. Therefore, there is an unmet and urgent need for novel interventions to improve the success of tobacco cessation. If such an intervention can reduce tobacco-associated lung carcinogenesis, that will be more desirable. The goal of this project is to develop a safe and effective kava-based intervention to enable tobacco cessation and reduce lung cancer risk, which will improve the health of smokers. Methods: A randomized controlled trial will enroll 80 adults who currently smoke at least 10 cigarettes daily and randomize 1:1 into the placebo and AB-free kava arms, being exposed for 4 weeks, with a total of six visits (weeks 0, 1, 2, 4, 8, and 12) to evaluate the compliance and potential issues of AB-free kava use among the participants, explore the potential effect of the AB-free kava intervention on tobacco dependence, tobacco use, and lung carcinogenesis biomarkers. Participants will be enrolled during their primary care clinic visit. Discussion: Primary care settings play a critical role in tobacco-related disease screening, counseling, and early intervention, as the majority of adults who smoke visit their physicians annually. Building upon our promising pilot human trial results in conjunction with ample compelling lab animal results, and consistent with evidence of kava's benefits from epidemiological data, this trial will evaluate the compliance of AB-free kava among adults who currently smoke with no intention to quit. The other exploratory aims include (1) whether AB-free kava intervention can reduce tobacco use and tobacco dependence; (2) whether AB-free kava use suppresses tobacco-induced carcinogenesis; and (3) the potential of the mechanism-based noninvasive biomarkers in precision AB-free kava intervention. The positive results from this study are expected to provide a great opportunity to effectively reduce smoking rates and tobacco-related diseases. Trial registration: ClinicalTrials.gov with the identifier: NCT05081882. Registered on October 18, 2021. [ABSTRACT FROM AUTHOR]

Background: Piper methysticum, commonly called kava, has long been consumed in beverage form in the Pacific Islands. Kava use in the US has slowly increased since the 1990s, but is not assessed in major epidemiological surveys. Objectives: To analyze social-media posts about kava from current, past, and prospective users, for motivations, patterns of co-use, and effects. Methods: Text from Reddit posts, and accompanying metadata, were collected and thematically coded by two independent raters. Results: 423 posts were collected, spanning January 2006 through December 2021. Of the 1,211 thematic codes applied, 1,098 (90. 7%) were concordant. Motivations for use bifurcated into self-treatment (for psychiatric or physical health conditions) and recreation; these were not mutually exclusive. Kava was rarely considered strongly euphoriant, but was valued as an anxiolytic. Kava was frequently used with other substances, most commonly kratom. Kava was used at lower doses for self-treatment than for other purposes (pseudo-R2 = 0.11). Undesirable effects (gastrointestinal upset, fatigue) were mentioned, though less often than benefits. Hepatotoxicity, reported elsewhere as a rare, non-dose-related risk, was disputed on the basis of its not having been experienced by those posting. Conclusion: Kava appears to be conceptualized among Reddit posters as an anxiolytic with few risks or adverse effects. As it grows in popularity, especially among people who use other drugs that are more liable to misuse or addiction, it should be assessed in probability samples (i.e. in the major national drug surveys) and clinical practice for its risks, potential benefits, and possible drug-drug interactions. [ABSTRACT FROM AUTHOR]

The study focuses on the consumption of beverages in Czechoslovakia in the 1950s when it evaluated the consumption of alcoholic and non-alcoholic beverages in a broader perspective. At the same time, it analyzes the consumption of milk and hot drinks, especially coffee and tea. The text is based on professional scientific articles published on the pages of Výživa lidu (People's Nutrition) and Průmysl potravin (Food Industry) in the period 1951 - 1960. While milk consumption declined, beer consumption continued to grow. Alcohol consumption was clearly dominated by traditional beer which showed increase despite expert complaints. Wine was generally consumed very little. Other alcoholic beverages, with the exception of spirits, also grew, but not as much as the beer mentioned, promoted musts, juices and mineral water did not become a suitable alternative. Consumption of coffee and tea increased slightly, while in the period under review did not exceed pre-war consumption. In general, we can say that there were still differences between the Czech and Slovak parts of the Socialist Republic, where beer consumption predominated in the west and wine and spirits in the east. [ABSTRACT FROM AUTHOR]

The emergence of the COVID-19 virus has significantly shifted the lives of Pacific families and communities from face-to-face communal settings to digital spaces. While there has been a multitude of opportunities for Pacific people to express themselves in digital spaces, little is known about the impacts of this on social life, including on quality time within families, exposure to misinformation, and the adoption of online addictive behaviours. This article sets out to critically review and explore the impacts and influences of digital experiences and behaviours on Pacific peoples in Aotearoa/New Zealand, shifting from ordinary practices such as church, kava-drinking and educational learning, to online platforms. Vā (space) and tauhi vā (nurturing relationships) are also discussed as theoretical concepts in navigating the shift from ordinary practices to extraordinary spaces. Findings include the exposure to COVID-19-related misinformation and online addictive behaviours, which will better inform community leaders, services providers, and policy makers in addressing the digital impacts and influences that Pacific people may be facing in Aotearoa/NZ. [ABSTRACT FROM AUTHOR]

This article poses the question of what analytical insight can be gained by comparing ritual and cliché, both of which involve evaluations of the significance of repetition. The case study is kava-drinking sessions in indigenous Fiji. Whether purposeful or casual, kava-drinking sessions always follow rules which give them significant form and regularity of the kind some anthropologists consider definitive of ritual practice. Yet many indigenous Fijians criticise present-day kava-drinking sessions for several reasons. One prominent line of criticism is that kava drinking is now a matter of too much repetition – too many people drinking too much too often – and losing the meaningful link to chiefly tradition as a result. Analysing criticism of ritual in terms of cliché clarifies situations in which the iconic force of repetition is treated as an index of excess. [ABSTRACT FROM AUTHOR]

Purpose of Review: The goal of this paper is to summarize the evidence for the use of botanical medicines for the treatment of anxiety disorders. We sought to make this review practical for psychiatrists and psychiatric prescribers. Recent Findings: In 2018, the Natural Medicines database produced a Clinical Management of Anxiety guide that summarized the conventional and natural treatments of anxiety disorders. Based on this guide, four herbal supplements (also referred to as botanicals) were selected for deeper study including kava, lavender, lemon balm and passionflower. All four were considered possibly safe and possibly effective according to the Natural Medicines database. Summary: There is scientific evidence supporting the use of kava, lavender, lemon balm and passionflower in anxiety disorders. Lavender appears to have the best available evidence including comparable efficacy to conventional first line treatments and is available in a patented form that was used in the cited studies (Silexan). [ABSTRACT FROM AUTHOR]

Background: Military special operators, elite athletes, and others requiring uninterrupted optimal performance currently lack options for sleep and mood support without performance-inhibiting effects. Kavalactones, derived from the root of the kava plant ( Piper methysticum Forst), have been shown to elevate mood and wellbeing by producing a feeling of relaxation without addiction or cognitive impairment., Methods: In this placebo-controlled, crossover study (NCT05381025), we investigated the effects of 2 weeks of kavalactones use on cortisol (diurnal salivary), sleep (RSQ-W; Restorative Sleep Questionnaire, Weekly), mood (DASS-21; Depression Anxiety Stress Scale-21), and motivation state to expend (Move) or conserve (Rest) energy (CRAVE; Cravings for Rest and Volitional Energy Expenditure, Right Now) in a cohort of 15 healthy, physically fit young males engaged in a rigorous, two-a-day preparation class for special operations forces qualification., Results: Cortisol, sleep, and mood were within normal, healthy parameters in this cohort at baseline. This remained unchanged with kavalactones use with no significant findings of clinical interest. However, a statistically similar, positive slope for within-group Move scores was seen in both groups during kavalactones loading (first group Move slope 2.25, second group Move slope 3.29, p  = 0.299). This trend was seen regardless of order and with no apparent effects on the Rest metric (all p  ≥ 0.05). Moreover, a significant between-group difference appeared after 1 week of kavalactones use in the first phase ( p =  0.044) and persisted through the end of the first loading period ( p  = 0.022). Following the 10-day washout, this between-groups divergence remained significant ( p  = 0.038) but was reversed by 1 week after the crossover ( p =  0.072), with Move scores once again statistically similar between groups and compared to baseline at study end. Furthermore, the group taking kavalactones first never experienced a significant decrease in Move motivation state (lowest mean score 21.0, highest 28.6, all p  ≥ 0.05), while the group receiving kavalactones in the last 2 weeks of the study had Move scores that were statistically lower than baseline (lowest mean score 8.6, highest 25.9, all p  ≤ 0.05) at all time points but the last ( p  = 0.063) after 2 weeks of kavalactones exposure., Conclusions: We report a novel finding that kavalactones may support performance by maintaining or rescuing the desire to expend energy in the context of significant physical and mental strain in well-conditioned individuals, even in a context of already normal cortisol, sleep, and mood.

Macro- and microscopic techniques have long been used to describe plant materials and establish plant structural profiles. These techniques are commonly used in botanical authentication to identify the genuine and closely allied species used in botanical research. Advanced microscopic techniques were used in this study to differentiate three different Piper species used as kava or kava-kava. The genuine species is Piper methysticum and the other two species commonly called false-kava or kava-kava, are Piper auritum and Piper excelsum. Macroscopic characteristics, including a black-spotted stem and fibrous root, are characteristic of P. methysticum, whereas the stem of P. auritum is greenish with no spots, and the P. excelsum stem is purple-pink. Microscopic attributes include the characteristic collenchyma of stems and the pattern of arrangement of peripheral and medullary vascular bundles. The starch grains are smaller in P. excelsum than in the other two species. Energy-dispersive X-ray spectroscopy analysis of the crystals indicates the expected calcium, magnesium, and silica, along with lesser amounts of sodium, and potassium. The crystals present in the Piper species vary in shape, size, and elemental composition. Combining macro- and microscopical techniques and resulting characteristics are instrumental in differentiating the three Piper species., Competing Interests: Conflict of Interest: The authors declare that they have no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Microscopy Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Obesity prevalence has increased in low- and middle-income countries (LMICs) over the past several decades, with generally greater occurrence among adult females compared with males. Gendered variation in health behaviors, such as substance use, may play a role in how differences in obesity, body size, and composition manifest in association with sex. This study examines sex-moderated relationships of tobacco smoking and kava consumption with body composition and obesity among 301 Ni-Vanuatu (local self-identification meaning "of Vanuatu") adults. Data collected included self-reported frequency of substance use as well as anthropometric measurements to assess body mass, composition, and obesity. Tobacco and kava use were associated with reduced measurements of body mass and adiposity in males, and kava use was associated with some elevated measurements of body mass and hip circumference in females. Kava use was also negatively associated with obesity based on waist-to-height ratio among males. These results have implications for evaluation and future research on substance control programs in this population. [ABSTRACT FROM AUTHOR]

Piper methysticum G. Forst, popularly known as kava, is a traditional medicinal plant widely used for the treatment of anxiety and insomnia. The aim of this study was to investigate new therapeutic applications of this plant. Nociceptive response induced by heat (hot-plate) was used as pain model. Susceptibility of different strains to kava ethanolic dried extracts was evaluated by broth microdilution method. Acute oral toxicity was performed according to Organisation for Economic Cooperation and Development (OECD) guideline. Administration of kava dried extracts and kavain inhibited the nociceptive response in the hot-plate model and did not affect the time mice spent in the rota-rod apparatus. The samples showed no significant antibacterial activity, however slight antifungal activity was verified. The extracts may be considered of low oral acute toxicity. Kava extracts exhibited promising antinociceptive activity in model of nociceptive pain, which should be deeper explored as a new therapeutic application of kava. [ABSTRACT FROM AUTHOR]

Kava (Piper methysticum) has been widely consumed for many years in the South Pacific Islands and displays psychoactive properties, especially soothing and calming effects. This plant has been used in Western countries as a natural anxiolytic in recent decades. Kava has also been used to treat symptoms associated with depression, menopause, insomnia, and convulsions, among others. Along with its putative beneficial health effects, kava has been associated with liver injury and other toxic effects, including skin toxicity in heavy consumers, possibly related to its metabolic profile or interference in the metabolism of other xenobiotics. Kava extracts and kavalactones generally displayed negative results in genetic toxicology assays although there is sufficient evidence for carcinogenicity in experimental animals, most likely through a non-genotoxic mode of action. Nevertheless, the chemotherapeutic/chemopreventive potential of kava against cancer has also been suggested. Both in vitro and in vivo studies have evaluated the effects of flavokavains, kavalactones and/or kava extracts in different cancer models, showing the induction of apoptosis, cell cycle arrest and other antiproliferative effects in several types of cancer, including breast, prostate, bladder, and lung. Overall, in this scoping review, several aspects of kava efficacy and safety are discussed and some pertinent issues related to kava consumption are identified. [ABSTRACT FROM AUTHOR]

In Pohnpei Island, sakau (kava) is a symbol of the traditional culture. Although the use of sakau was once limited to people of high rank and used only during ceremonial occasions, it is now consumed in bars and sold in bottles around the island. Recently, negative medical and environmental effects correlated with the increase sale of sakau have attracted scholarly attention. However, the current use of sakau is not fully understood. This study aims to describe the current use of sakau and consider by whom, on what occasions, and for what purpose sakau is consumed, and whether it continues to play a traditional role. Fieldwork was conducted from July to September 2019 in Kolonia (where people of Pohnpeian ethnicity live) and Mand (where non-Pohnpeians live). The latter was included to investigate whether sakau was consumed by people of ethnic groups that have never used it traditionally. Data were collected via interviews using a questionnaire, direct observation, and casual conversations. A total of 89 people (41 in Kolonia; 48 in Mand) participated in the study. Most (71% of those in Kolonia and 58% of those in Mand) reported they drank sakau at some point in their lives. Although the frequency of sakau consumption was significantly lower in Mand (P=.027), it was consumed regardless of their original culture. Commonly reported reasons for drinking sakau included treating anxiety and socializing. The use of sakau in Pohnpeian society continues in traditional contexts, such as feasts, marriage proposals, and forgiveness. Additionally, increased consumption has been profitable for people engaged in businesses related to sakau. [ABSTRACT FROM AUTHOR]

The author has been documenting the use of kava in different parts of the Pacific for several years, particularly in Tonga and in Auckland where its use is popular among members of communities that consume kava as part of their cultural tradition, and more recently a growing non-traditional user group. In this article, he reflects on his project to document the use of kava through photographs, the evolution of its use in traditional and non-traditional settings and discusses the most recent scientific studies of the drink. [ABSTRACT FROM AUTHOR]

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Yaqona (kava) is a culturally significant, non-alcoholic drink consumed nightly by many Fijians. Although yaqona is not consumed by primary or secondary school students, cultural protocols related to yaqona preparation and presentation are often taught in their schools, with students then presenting this indigenous drink to acknowledge visitors to the school, open events and support fundraisers. In the early 2000s, some within the Fiji Ministry of Education began questioning whether yaqona use by teachers was negatively impacting their teaching ability, suggesting it should be banned from the school campus. In this study, Fijian teachers were cognitively tested and interviewed following an evening of yaqona consumption with the results suggesting this indigenous substance can disrupt cognition and in turn negatively impact teaching quality the morning after consumption. Although development theory prescribes prohibition and situational bans in cases where indigenous substances negatively impact productivity, the author argues that prohibiting yaqona in Fijian schools would be short-sighted as the findings show that this traditional substance is critical to the facilitation of school function, identity formation and academic achievement, all elements necessary to development.

Photoessay: The author has been documenting the use of kava in different parts of the Pacific for several years, particularly in Tonga and in Auckland where its use is popular among members of communities that consume kava as part of their cultural tradition, and more recently a growing non-traditional user group. In this article, he reflects on his project to document the use of kava through photographs, the evolution of its use in traditional and non-traditional settings and discusses the most recent scientific studies of the drink.

Dis/articulation offers critical insight into exclusionary practices embedded in global commodity chains. In Fiji, powerful actors engage in dis/articulation strategies to limit access to kava consumption domestically while ensuring its availability to Western audiences. Repurposing colonial rhetoric associated with Fijian kava consumption, state officials and lead firms portray kava as over-consumed, unhealthy and harmful in relation to Indigenous Fijians who are its primary producers, harvesters and domestic consumer base. These same actors (e.g. state officials and lead firms) promote kava to Western markets, publicizing it as healthful and beneficial to primarily white consumers. Their marketing and promotional efforts perpetuate colonial tropes and racialized discourses in an effort to simultaneously decrease value domestically (via downgrading) and increase value abroad (via upgrading). This study advances our understanding of the lesser-known historical and relational dimensions of race in global commodity chains. [ABSTRACT FROM AUTHOR]

Epidemiological evidence suggests that kava (Piper methysticum Forst) drinks may reduce the risk of cancer in South Pacific Island smokers. However, little is known about the anti-carcinogenic effects of kava on tobacco smoking-related bladder cancer and its underlying mechanisms. Here we show that dietary feeding of kawain (a major active component in kava root extracts) to mice either before or after hydroxy butyl(butyl) nitrosamine (OH-BBN) carcinogen exposure slows down urinary bladder carcinogenesis and prolongs the survival of the OH-BBN-exposed mice. OH-BBN-induced bladder tumors exhibit significantly increased expression of lysine-specific demethylase 1 (LSD1), accompanied by decreased levels of H3K4 mono-methylation compared to normal bladder epithelium, whereas dietary kawain reverses the effects of OH-BBN on H3K4 mono-methylation. Human bladder cancer tumor tissues at different pathological grades also show significantly increased expression of LSD1 and decreased levels of H3K4 mono-methylation compared to normal urothelium. In addition, kava root extracts and the kavalactones kawain and methysticin all increase the levels of H3K4 mono- and di-methylation, leading to inhibitory effects on cell migration. Taken together, our results suggest that modification of histone lysine methylation may represent a new approach to bladder cancer prevention and treatment and that kavalactones may be promising agents for bladder cancer interception in both current and former smokers.

S phase kinase-associated protein 2 (Skp2) has been shown to be required for spontaneous tumor development that occurs in the retinoblastoma protein (pRb) deficient mice. Here we have demonstrated that flavokawain A (FKA), a novel chalcone from the kava plant, selectively inhibited the growth of pRb deficient cell lines and resulted in a proteasome-dependent and ubiquitination-mediated Skp2 degradation. Degradation of Skp2 by FKA was found to be involved in a functional Cullin1, but independent of Cdh1 expression. Further studies have demonstrated that FKA docked into the ATP binding pocket of the precursor cell-expressed developmentally down-regulated 8 (NEDD8)-activating enzyme (NAE) complex, inhibited NEDD8 conjugations to both Cullin1 and Ubc12 in PC3 cells and Ubc12 NEDDylation in an in vitro assay. Finally, dietary feeding of the autochthonous transgenic adenocarcinoma of the mouse prostate (TRAMP) mice with FKA inhibited the formation of high-grade prostatic intra-epithelial neoplasia lesions (HG-PIN) and prostate adenocarcinomas, reduced the tumor burden and completely abolished distant organ metastasis. Immunohistochemistry studies revealed that dietary FKA feeding resulted in marked anti-proliferative and apoptotic effects via down-regulation of Skp2 and NEDD8 and up-regulation of p27/Kip1 in the prostate of TRAMP mice. Our findings therefore provide evidence that FKA is a promising NEDDylation inhibitor for targeting Skp2 degradation in prostate cancer prevention and treatment.

Introduction: Dried extracts of Piper methysticum G. Forst, also known as kava, has been widely used due to its anxiolytic and sedative properties. In order to assure the quality of these extracts, it is essential to accurately quantify kavalactones, known as the active principle. Objectives: To develop and validate an analytical method for the simultaneous quantification of six major kavalactones (kavain, dihydrokavain, methysticin, dihydromethysticin, yangonin and demethoxyyangonin) in kava extracts, comparing multi‐standards and single standard validation approaches. Material and methods: Separation was performed using a C18 column, water/methanol/acetonitrile/2‐propanol (66:07:09:18 v/v/v/v) and detection at 245 and 350 nm. A full method validation was performed, employing analytical standards for each compound. Commercial kava dried extracts were assayed and the results obtained using the method validated for six kavalactone standards were compared with those obtained when only kavain was used as standard. Results: Baseline resolution for all kavalactones was obtained in short run time (15 min). Although the total kavalactone content varied between samples, a similar distribution profile was observed. When the method validated with all six analytical standards was compared to the calibration using only kavain standard, kavalactone contents were considerably different (from 7.57 to 36.53%). Conclusion: The obtained results demonstrate the importance of a validated method using individual kavalactone standards for the effective quality control of kava extracts. In a next step, the method needs to be adapted to also include flavokavin B (FKB), as an important authentication marker to distinguish between the accepted variety "noble Kava" and the toxic "two‐day Kava". A fast and effective analytical method has been developed and validated for the simultaneous quantification of six kavalactones in kava dry extracts. When comparing the method developed using the six kavalactone standards with the kavaína‐only validated method, significant difference between the content values was observed. Although the total kavalactone content varied between samples, a similar distribution profile was observed. The results demonstrated the importance of a validated method using individual kavalactone standards for the effective quality control of kava extracts. [ABSTRACT FROM AUTHOR]

The article deals with the distribution of coffee production by continents and by analysing selected economic indicators presents the extent of its trade in the world and in the countries of the European Union. The main characteristics of the Slovenian coffee market are revealed in the second part of the article, where the authors synthesize experiences and opinions of the selected coffee stakeholders in Slovenia, with a special focus on the social consequences of coffee production and trade. [ABSTRACT FROM AUTHOR]

Cultural interventions that reflect the history and traditions of Native Hawaiians in therapeutic settings are not a mainstay of standard addiction treatment. In an attempt to address the disproportionately high rates of substance use with comparably low rates of voluntary treatment participation among the Native Hawaiian population, the first Native Hawaiian culturally informed treatment program emerged in the early 1980s to utilize various types of indigenous methods intended to improve treatment response and expected clinical outcomes. This article explores the historical basis and cultural precedence for the contemporary use of Native Hawaiian cultural practices in drug treatment facilities. The history of indigenous healing traditions and the Kingdom of Hawai'i's government policy interventions between 1810, when Kamehameha unified the Hawaiian islands under his rule, and 1893, when the U.S. government backed the illegal overthrow of Queen Lili'uokalani's constitutional monarchy, are considered in addressing substance misuse. [ABSTRACT FROM AUTHOR]

Flavokawain A (FKA), a major chalcone in the Kava plant, has recently demonstrated promising anti-cancer activities. A systematic evaluation of FKA's safety profile has not been reported before. In this study, male FVB/N mice were fed with an AIN-76A diet or AIN-76A diet supplemented with 0.6% (6 g/kg food) FKA or 0.6% commercial kava root extract (KRE) for three weeks. Dietary feeding of FKA did not affect food consumption and body weight. Histopathological examination of liver, kidney, colon, lung, heart, spleen, and thymus revealed no signs of FKA-induced toxicity. Biochemical serum analysis and histological examination confirmed normal organ function in FKA-treated mice. The cytotoxicity profile showed FKA had minimal side effects on bone marrow and small intestinal epithelial cells compared with Adriamycin. In addition, oral feeding of FKA increased activities of both glutathione S-transferase and quinone reductase in the liver, lung, prostate and bladder tissues of mice. In comparison, dietary feeding of 0.6% KRE increased liver/body weight ratio and decreased spleen, thymus, and testis/body weight ratios, as well as induced nodular proliferation in liver tissues. Therefore, dietary feeding FKA showed no adverse effects on major organ function and homeostasis in mice, suggesting the potential of FKA for chemoprevention study of human cancers.

This documentary film is a result of multi-sited ethnographic research between 2015-2019, which explores cultural identity, gender, music, and spirituality through contemporary and common kava practices. Drawing from over 17 years of participation in kava communities, this film is grounded in Tongan experiences, while also including a mobile and expanding Moana/Wansolwara/Oceanic perspective with contributions from Fijians, Sāmoans, Māori, and more. The knowledge holders in this film span across four territories, including Te Ika a Māui in Aotearoa, Utah (US) on Turtle Island, The Kingdom of Tonga, and Kamberra, Australia. They share a complex web of experiences, purpose, and tensions within the contemporary practices of common kava gatherings known in Tongan as faikava. Contemporary kava gatherings are spaces to release the pressures of modern life, nurture ancestral and social relationships, reveal truths, build community, produce and transmit knowledge, negotiate identity, heal, and foster positive well-being through comradery and openness. This film cannot cover all of the complexity of kava culture, yet attempts to be a meaningful introduction to the dynamic practices that are alive and expanding throughout the world.

This article builds on an existing body of scholarship on historical and intergenerational cultural trauma to elucidate deliberate attempts to eliminate Native Hawaiian cultural practices related to psychoactive drug use and replace them with the foreign (Western) tradition of alcohol use. This action, to instill alcohol as a component of colonial domination, was one example of the resulting assault on cultural identity that has often been overlooked, particularly in relation to transgenerational trauma in the history of Hawai'i and the Hawaiian context. In this article, we argue for the use of the term historical trauma, introduced by Brave Heart, which allows for a more inclusive consideration of the many aspects of trauma. Drawing on literature related both to alcohol use in indigenous Hawaiian society and to the wider historical context of Hawai'i since the late eighteenth century, we endeavor to demonstrate the correlation between the historical trauma experienced by the population and the incidence of alcohol consumption and alcohol use disorder. The article is intended to augment the existing paradigm on cultural trauma as it specifically relates to Hawaiians, and potentially to widen the explanatory power of this paradigm with regard to present-day psychoactive drug use among Hawaiians as well as the implications for treatments. [ABSTRACT FROM AUTHOR]

Flavokawain A (FKA) is the predominant chalcone identified from the kava plant. We have previously shown that FKA preferentially inhibits the growth of p53 defective bladder cancer cell lines. Here, we examined whether FKA could inhibit bladder cancer development and progression in vivo in the UPII-SV40T transgenic model that resembles human urothelial cell carcinoma (UCC) with defects in the p53 and the retinoblastoma (Rb) protein pathways. Genotyped UPII-SV40T mice were fed orally with vehicle control (AIN-93M) or FKA (6 g/kg food; 0.6%) for 318 days starting at 28 days of age. More than 64% of the male mice fed with FKA-containing food survived beyond 318 days of age, whereas only about 38% of the male mice fed with vehicle control food survived to that age (P = 0.0383). The mean bladder weights of surviving male transgenic mice with the control diet versus the FKA diet were 234.6 ± 72.5 versus 96.1 ± 69.4 mg (P = 0.0002). FKA was excreted primarily through the urinary tract and concentrated in the urine up to 8.4 μmol/L, averaging about 38 times (males) and 15 times (females) more concentrated than in the plasma (P = 0.0001). FKA treatment inhibited the occurrence of high-grade papillary UCC, a precursor to invasive urothelial cancer, by 42.1%. A decreased expression of Ki67, survivin, and X-linked inhibitor of apoptotic proteins (XIAP) and increased expression of p27 and DR5, and the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive apoptotic cells were observed in the urothelial tissue of FKA-fed mice. These results suggest a potential of FKA in preventing the recurrence and progression of non-muscle-invasive UCC.

COVID-19 has had a major impact on collectivist cultures and their means of social interaction and maintaining contact with those in their wider community. This has particularly been the case for Pacific peoples living in diaspora, with COVID-19 preventing travel home and social distancing and forced lockdowns restricting the ability to gather. This has also impacted vā, the Pacific concept of 'relational space' critical to connectivity and maintaining relationships. This paper explains the creation of virtual faikava; online meeting environments in which Pacific kava users meet, maintain vā, connect with those at home and in the wider diasporic community and learn, while consuming their traditional beverage kava. [ABSTRACT FROM AUTHOR]

The Queensland fruit fly, Bactrocera tryoni (Froggatt) (Diptera: Tephritidae), is a crop pest of global economic importance because of its wide range of hosts and its invasiveness capacities. To develop a novel integrated and sustainable crop protection, we have investigated the insecticidal properties of different varieties of kava (Piper methysticum [Frost]) extracted by two methods and the attractive effects of six plant volatiles identified from B. tryoni host plants to female, mated or not. We did not identify any significant insecticidal effect of the traditional Pacific kava plant at the tested concentrations. Among mated females, ethyl acetate compared to the no odor control elicited the highest attraction (87%, of which 60% for this odor), while ethyl butyrate was preferred compared with ethyl acetate in dual choice assays. Flies' preferences for specific odors depended on their mating status and the odor landscape they were confronted with. Combination with the commercial ingestion insecticide (Success 4: spinosad, 480 g/l, Dow AgroSciences, Valbonne, France) with the plant volatiles were tested to detect an increase in mortality related to the addition of an attractant. The 2-heptanone slightly showed a tend to increase the attractiveness of mated females within 4-6 h to the food bait, but the results were not statistically significant after 8 h. Further tests should be performed with other concentrations or mixtures of the identified host plant volatiles to develop a strong lure and kill strategy., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Coffee is one of the most popular and most frequently consumed beverages in the world due to its stimulating effects on the central nervous system, but also due to its taste and aroma. Roasted coffee is a complex mixture of more than 1,000 bioactive compounds. Caffeine and chlorogenic acid are among the basic and most well-known components in coffee. Caffeine in one cup of coffee exerts its effect through antagonism of adenosine receptors, which binds to specific sites in brain cells instead of adenosine, thereby delaying the onset of sleep. New epidemiological studies and experimental research suggest that coffee consumption may help prevent several chronic diseases, including cardiovascular, diabetes mellitus type 2. degenerative cognitive disorders and colon cancer. The results of most prospective cohort studies on the effects of coffee have not confirmed the fact that coffee consumption is associated with a significantly increased risk of cardiovascular disease. There is also evidence that decaffeinated coffee may have similar benefits in some respects as regular coffee, suggesting that other coffee ingredients also help protect our health. In adults who consume moderate amounts of coffee (3–4 cups/day providing 300–400 mg/day of caffeine), there is little evidence of the health risks of coffee. [ABSTRACT FROM AUTHOR]

Purpose: Oral mucositis is a debilitating inflammatory disorder observed in patients undergoing active cancer treatment, particularly cancer of the head and neck region. A key pathway believed to be involved in the pathogenesis of oral mucositis is the formation of reactive oxygen species (ROS). The identification of compounds that can inhibit this pathway may therefore be of benefit in treating this disorder. The kava plant (Piper methysticum) contains various constituents, including flavokawain A (FKA), flavokawain B (FKB), yangonin, methysticin and kavain. These constituents are known to be biologically active and possess anti-oxidative properties. This study therefore focused on examining these constituents for their effect on ROS formation in an in vitro oral mucositis model. Methods: Cell proliferation was assessed in normal oral keratinocytes (OKF6) treated with and without kava constituents, namely FKA, FKB, yangonin, methysticin and kavain using an MTS in vitro assay. Oxidative stress was assessed by co-treating and pre-treating OKF6 cells with H2O2. The effects were quantified by analysis of ROS production, using a CM-H2DCFDA assay. Results: Pre-treatment of cells for 24 h with 2.5 μg/ml kavain and 5 μg/ml FKA demonstrated a significant protective anti-oxidative effect. Similarly, FKB at a concentration of 2.5 μg/ml, demonstrated a trend of ROS reduction but was observed to be cytotoxic at concentrations greater than 5 μg/ml. Reduction in ROS production by methysticin and yangonin was compromised by their cell cytotoxicity. Conclusion: This was the first study to identify the anti-oxidative effects and safety of FKA and kavain with regard to oral keratinocytes, highlighting their potential use in the development of a preventative treatment for oral mucositis. [ABSTRACT FROM AUTHOR]

Objective: Previous randomised, double-blind, placebo-controlled studies have shown that Kava (a South Pacific medicinal plant) reduced anxiety during short-term administration. The objective of this randomised, double-blind, placebo-controlled study was to perform a larger, longer-term trial assessing the efficacy and safety of Kava in the treatment of generalised anxiety disorder and to determine whether gamma-aminobutyric acid transporter (SLC6A1) single-nucleotide polymorphisms were moderators of response. Methods: The trial was a phase III, multi-site, two-arm, 16-week, randomised, double-blind, placebo-controlled study investigating an aqueous extract of dried Kava root administered twice per day in tablet form (standardised to 120 mg of kavalactones twice/day) in 171 currently non-medicated anxious participants with diagnosed generalised anxiety disorder. The trial took place in Australia. Results: An analysis of 171 participants revealed a non-significant difference in anxiety reduction between the Kava and placebo groups (a relative reduction favouring placebo of 1.37 points; p = 0.25). At the conclusion of the controlled phase, 17.4% of the Kava group were classified as remitted (Hamilton Anxiety Rating Scale score < 7) compared to 23.8% of the placebo group (p = 0.46). No SLC6A1 polymorphisms were associated with treatment response, while carriers of the rs2601126 T allele preferentially respond to placebo (p = 0.006). Kava was well tolerated aside from poorer memory (Kava = 36 vs placebo = 23; p = 0.044) and tremor/shakiness (Kava = 36 vs placebo = 23; p = 0.024) occurring more frequently in the Kava group. Liver function test abnormalities were significantly more frequent in the Kava group, although no participant met criteria for herb-induced hepatic injury. Conclusion: While research has generally supported Kava in non-clinical populations (potentially for more 'situational' anxiety as a short-term anxiolytic), this particular extract was not effective for diagnosed generalised anxiety disorder. [ABSTRACT FROM AUTHOR]

Background: Kava drinking is a tradition among Pacific Island people, although growing in popularity with other ethnicities. However, drinking substantial quantities of kava has raised concerns regarding physical manifestations of slow response and lack of precision in bodily control. These impairments can have significant consequences when after consuming large volumes of kava an individual makes a choice to drive. Aims: The objective of this study was to measure selected cognitive functions following high traditionally consumed kava volumes (greater than 2,000 mg of kavalactones) aimed at identifying potential risks for kava drink‐drivers. Methods: The reaction and divided attention of 20 control participants was assessed against 20 active kava‐drinking participants during and following a 6‐hr kava session in a "naturalised" setting. Assessment measures were drawn from Vienna Test System—Traffic's test battery. Results/Outcomes Results showed no statistical significant difference between control and active participants at any measurement point over a 6‐hr testing period regardless that the movements and speech of the active participants were observed to slow as the test session and kava consumption progressed. Conclusion: Inconsistencies between test results and observations during testing and by road policing officers demonstrate an urgent need for more research in this field. [ABSTRACT FROM AUTHOR]

The Selekā art and kava collective is found in the heart of the Kingdom of Tonga's urban centre and capital. Selekā is a transformed nickname which is a play on the word kasele, meaning toilet or outhouse, an external othering and internal acceptance of divergence within Tongan society. Selekā is a site where urban Tongans paint and drink kava together while listening to rebellious music, incorporating some of the aesthetics and politics of these musical genres into their group. They have a broader musical playlist than most kava clubs in Tonga, which includes punk, rock and metal. This article explores the character of Selekā as a radical critique to Western introduced social constructs such as puritan respectability, which have become part of Tonga's modern cultural norms. Selekā performs and generates mana (potency/prestige) through noa (profanity/neutralization) by desecrating the 'sacred' and recreating a new alternative. This act of rebellion is presented as a contemporary manifestation of an ancient Tongan practice where the 'profane' was used to identify and bring balance to the most tapu ('sacred'/protected). [ABSTRACT FROM AUTHOR]

The function of kavis and the concept of kch'va have been variously treated in Iranian studies, given their diverging paths in Indo-Iranian traditions. The Indo-Iranian myth of kari seems to be inherited from a Proto-Indo-European "insightful" smith in conjunction with dragon slaying. The special knowledge and thus the wondrous power of fashioning the mace for dragon slaying, termed ktlvya, was expanded to include the power of healing shared with the dragon slayer. From the original myth, the Indian tradition highlights the special knowledge, which obtained a verbal attribute; while the smith f'unction and his product, i.e. the metallic weapon are singled out in the Iranian tradition. This latter association presumably led to the adoption of the title of kauui by local chieftains in the Iranian world as early as the Old Avestan period, consequently leading to a dynasty of kaltuis, known as Kay~ni~n or Kayanids. It is argued that this dynasty, postdating the Ga()ic kauuis and having the primordial mythical kattifi as its eponym, can be historical and the authority behind the first iranian kingdom in East Iran. [ABSTRACT FROM AUTHOR]