Cases of Kava Impairment in Iowa Drivers Berry, Jonna; Gilbert, Ashley; Grodnitzky, Justin
Journal of forensic sciences,
November 2019, 2019-Nov, 2019-11-00, 20191101, Volume:
64, Issue:
6
Journal Article
Peer reviewed
Kava is an Oceanic plant in which the root is consumed as a beverage and is becoming increasingly popular. The effects of kava consumption may include sedation, euphoria, and impairment of motor ...coordination. This article demonstrates kava impairment through four cases of self‐reported kava use supported with Drug Recognition Expert (DRE) evaluations of each subject. Subject's urines screened negative for common drugs of abuse by immunoassay analysis. Urine from cases 3 and 4 were analyzed by liquid chromatography–tandem mass spectrometry, and gas chromatography–mass spectrometry, which yielded the presence of kavalactones. Subjects exhibited poor driving behavior and signs of intoxication. Indicators of impairment from multiple drug categories, central nervous system (CNS) depressants, CNS stimulants, and cannabis were observed, which may be consistent with the presence of multiple kavalactones and their diverse array of mechanisms of action. The consumption of kava can hinder one's ability to operate a vehicle safely.
Overview: Kava (Piper methysticum) is a South Pacific psychotropic plant medicine that has anxiolytic activity. This effect is achieved from modulation of GABA activity via alteration of lipid ...membrane structure and sodium channel function, monoamine oxidase B inhibition, and noradrenaline and dopamine re-uptake inhibition. Kava is available over the counter in jurisdictions such as the USA, Australia and New Zealand. Due to this, a review of efficacy, safety and clinical recommendations is advised.
Objective: To conduct a comprehensive review of kava, in respect to efficacy, psychopharmacology, and safety, and to provide clinical recommendations for use in psychiatry to treat generalized anxiety disorder (GAD).
Methods: A review was conducted using the electronic databases MEDLINE, CINAHL, PsycINFO and the Cochrane Library during mid 2010 of search terms relating to kava and GAD. A subsequent forward search was conducted of key papers using Web of Science cited reference search.
Results: The current weight of evidence supports the use of kava in treatment of anxiety with a significant result occurring in four out of six studies reviewed (mean Cohen's d = 1.1). Safety issues should however be considered. Use of traditional water soluble extracts of the rhizome (root) of appropriate kava cultivars is advised, in addition to avoidance of use with alcohol and caution with other psychotropic medications. Avoidance of high doses if driving or operating heavy machinery should be mandatory. For regular users routine liver function tests are advised.
Conclusions: While current evidence supports kava for generalized anxiety, more studies are required to assess comparative efficacy and safety (on the liver, cognition, driving, and sexual effects) versus established pharmaceutical comparators.
About one third of the world's population is affected by insomnia. Insomnia may be due to various reasons such as physiological, psychological, genetic etc. It affects the health as well as the ...professional and social life of the affected person. There are many treatment of insomnia, among them pharmacological treatment with benzodiazepine and related tricyclic antihistamines are quite popular. But due to several side effects of these drugs, non-pharmacological and herbal treatments of insomnia are becoming popular day by day. Many types of herbs are reported to have sedative properties in the ethnobotanical evidences around the world. Among them Valerian, Kava Kava, Ginseng, St. John's Wort are most common. Besides these plants there are several other plants which are also used in insomnia treatment. Though there are lot of work to be done on herbal treatment of insomnia due to scarcity of reliable data and lack of proper preclinical (using animal models) and/or clinical evidences.
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.
Kava-kava is a traditional beverage of the South Pacific islanders and has had centuries of use without major side effects. Standardised extracts of kava-kava produced in Europe have led to many ...serious health problems and even to death. The extraction process (aqueous vs. acetone in the two types of preparations) is responsible for the difference in toxicity as extraction of glutathione in addition to the kava lactones is important to provide protection against hepatotoxicity. The Michael reaction between glutathione and kava lactones, resulting in opening of the lactone ring, reduces the side effects of the kava kava extracts. This protective activity was demonstrated using
Acanthamoebae castellanii in which 100% cell death occurred with 100 mg ml
−1 kava lactones alone, and 40% cell death with a mixture of 100 mg ml
−1glutathione and 100 mg ml
−1 kava lactones. A comparison of kava lactone toxicity with other pharmaceutical products is discussed and recommendations made for safe usage of kava-kava products
Extraction of glutathione with kava lactones from roots of
Piper methysticum prevents hepatotoxic side effects of the kava lactones.
Kava hepatotoxicity is a well described disease entity, yet there is uncertainty as to the culprit(s). In particular, there is so far no clear evidence for a causative role of kavalactones and ...non‐kavalactone constituents, such as pipermethystine and flavokavain B, identified from kava. Therefore, novel enzymatic, analytical, toxicological, ethnobotanical and clinical studies are now required. Studies should focus on the identification of further potential hepatotoxic constituents, considering in particular possible adulterants and impurities with special reference to ochratoxin A and aflatoxins (AFs) producing Aspergillus varieties, which should be urgently assessed and published. At present, Aspergillus and other fungus species producing hepatotoxic mycotoxins have not yet been examined thoroughly as possible contaminants of some kava raw materials. Its occurence may be facilitated by high humidity, poor methods for drying procedures and insufficient storage facilities during the time after harvest. Various experimental studies are recommended using aqueous, acetonic and ethanolic kava extracts derived from different plant parts, such as peeled rhizomes and peeled roots including their peelings, and considering both noble and non‐noble kava cultivars. In addition, ethnobotanical studies associated with local expertise and surveillance are required to achieve a good quality of kava as the raw material. In clinical trials of patients with anxiety disorders seeking herbal anxiolytic treatment with kava extracts, long‐term safety and efficacy should be tested using traditional aqueous extracts obtained from peeled rhizomes and peeled roots of a noble kava cultivar, such as Borogu, to evaluate the risk: benefit ratio. Concomitantly, more research should be conducted on the bioavailability of kavalactones and non‐kavalactones derived from aqueous kava extracts. To be on the side of caution and to ensure lack of liver injury, kava consuming inhabitants of the kava producing or importing South Pacific islands should undergo assessment of their liver function values and serum aflatoxin levels. The primary aim is to achieve a good quality of kava raw material, without the risk of adulterants and impurities including ochratoxin A and AFs, which represent the sum of aflatoxin B1, B2, G1 and G2. Although it is known that kava may naturally be contaminated with AFs, there is at present no evidence that kava hepatotoxicity might be due to aflatoxicosis. However, appropriate studies have yet to be done and should be extended to other mould hepatotoxins, with the aim of publishing the obtained results. It is hoped that with the proposed qualifying measures, the safety of individuals consuming kava will substantially be improved.
Herbal products as supplements and therapeutic intervention have been used for centuries. However, their toxicities are not completely evaluated and the mechanisms are not clearly understood. Dried ...rhizome of the plant kava (Piper methysticum) is used for its anxiolytic, and sedative effects. The drug is also known for its hepatotoxicity potential. Major constituents of the plant were identified as kavalactones, alkaloids and chalcones in previous studies. Kava hepatotoxicity mechanism and the constituent that causes the toxicity have been debated for decades. In this paper, we illustrated the use of computational tools for the hepatotoxicity of kava constituents. The proposed mechanisms and major constituents that are most probably responsible for the toxicity have been scrutinized. According to the experimental and prediction results, the kava constituents play a substantial role in hepatotoxicity by some means or other via glutathione depletion, CYP inhibition, reactive metabolite formation, mitochondrial toxicity and cyclooxygenase activity. Some of the constituents, which have not been tested yet, were predicted to involve mitochondrial membrane potential, caspase-3 stimulation, and AhR activity. Since Nrf2 activation could be favorable for prevention of hepatotoxicity, we also suggest that these compounds should undergo testing given that they were predicted not to be activating Nrf2. Among the major constituents, alkaloids appear to be the least studied and the least toxic group in general. The outcomes of the study could help to appreciate the mechanisms and to prioritize the kava constituents for further testing.
•The hepatotoxicity potential of kava was illustrated via in silico tools.•The possible mechanisms for kava hepatotoxicity was scrutinized.•The kava constituents were prioritized for testing.•The possible synergistic effect was pointed out.
Extracts of the pepper plant kava (Piper methysticum) are effective in alleviating anxiety in clinical trials. Despite the long-standing therapeutic interest in kava, the molecular target(s) of the ...pharmacologically active constituents, kavalactones have not been established. gamma-Aminobutyric acid type A receptors (GABA.sub.A Rs) are assumed to be the in vivo molecular target of kavalactones based on data from binding assays, but evidence in support of a direct interaction between kavalactones and GABA.sub.A Rs is scarce and equivocal. In this study, we characterised the functional properties of the major anxiolytic kavalactone, kavain at human recombinant alpha1beta2, beta2gamma2L, alphaxbeta2gamma2L (x = 1, 2, 3 and 5), alpha1betaxgamma2L (x = 1, 2 and 3) and alpha4beta2delta GABA.sub.A Rs expressed in Xenopus oocytes using the two-electrode voltage clamp technique. We found that kavain positively modulated all receptors regardless of the subunit composition, but the degree of enhancement was greater at alpha4beta2delta than at alpha1beta2gamma2L GABA.sub.A Rs. The modulatory effect of kavain was unaffected by flumazenil, indicating that kavain did not enhance GABA.sub.A Rs via the classical benzodiazepine binding site. The beta3N265M point mutation which has been previously shown to profoundly decrease anaesthetic sensitivity, also diminished kavain-mediated potentiation. To our knowledge, this study is the first report of the functional characteristics of a single kavalactone at distinct GABA.sub.A R subtypes, and presents the first experimental evidence in support of a direct interaction between a kavalactone and GABA.sub.A Rs.
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.
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.
PDF
