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The Herbal Anxiolytics Kava and Valerian for Anxiety and Insomnia
Abstract
The reviewed studies suggest that although valerian may not be ideal for the active treatment of insomnia, its value may be in the promotion of natural sleep after several weeks of use with no risk of dependence or residual daytime sleepiness.3 More placebo-controlled, double-blind trials and trials comparing valerian with more conventional anxiolytic-hypnotics are needed to better clarify its safety and efficacy (Table).
... It has been suggested to be of potential benefit in Chronic Fatigue Syndrome (CFS) by increasing blood flow [30]. St. John's Wort (Hypericum perforatum) contains hyperforins, valid for treatment of mild depression [31,32]. Valerian root, Valeriana officinalis, has been used as a drug for more than 1,000 years. ...
... Valerian root, Valeriana officinalis, has been used as a drug for more than 1,000 years. It is popular around the world as a sedative and mild hypnotic [32]. It contains iridoid glycosides, terpenoids, valerianic and isovaleric acid, and is used as an anxiolytic, for sleep improvement [30]. ...
... Kava kava, Piper methysticum, contains kavalactones and is used as an anxiolytic [30]. Some studies [32] suggest that kava may be effective for mild anxiety states. ...
Medicinal and aromatic plants play an important role in the pharmaceutical sector, both in the phytotherapy aspect, as in the strictly medicinal significance. Aromatherapy is the use of essential oils for therapeutic purposes. The absorption can be topical, oral or by inhalation. The second group includes all preventive and therapeutic use of MAP or their active ingredients. Active principles from medicinal plants are called phytopharmaceuticals, phytomedicines, herbal medicines or botanicals. Current pharmacopoeia reached more than 7,000 compounds derived from these plants. The uses of these substances include: 1) health care using natural products; 2) The newer drugs against the challenges of the twenty-first century (cancer, cholesterol, diabetes, dementia, depression, malaria, stress, etc.); 3) Essential oils used in aromatherapy; and 4) compounds useful in the veterinary area. The main species used in each of the previous four sections are introduced in this chapter.
... Valerian (Valeriana officinalis) is a popular herbal sedative and mild hypnotic that has been used worldwide for over 1,000 years (78). Its soporific effect is likely due to its active ingredients, including valepotriates and sesquiterpenes, which may function similarly to benzodiazepines or barbiturates (78), with GABA-ergic activity (78). ...
... Valerian (Valeriana officinalis) is a popular herbal sedative and mild hypnotic that has been used worldwide for over 1,000 years (78). Its soporific effect is likely due to its active ingredients, including valepotriates and sesquiterpenes, which may function similarly to benzodiazepines or barbiturates (78), with GABA-ergic activity (78). ...
... Valerian (Valeriana officinalis) is a popular herbal sedative and mild hypnotic that has been used worldwide for over 1,000 years (78). Its soporific effect is likely due to its active ingredients, including valepotriates and sesquiterpenes, which may function similarly to benzodiazepines or barbiturates (78), with GABA-ergic activity (78). ...
Natural and herbal remedies, also known as "alternative" or "complementary" medicines, have grown tremendously in popularity over the past two decades, becoming a major component of health care and general wellness in the United States and worldwide. The ready availability of these remedies over the counter and their generally good tolerability and safety contribute to this popularity, and many people have benefited from them, often in cases when conventional treatments have failed or caused intolerable side effects. Despite many Food and Drug Administration (FDA)-approved psychotropic medications on the market, efficacy has been inconsistent for some, and many treatment responders will eventually relapse. Continued research on the efficacy and safety of these alternative therapies is, therefore, important. This article reviews six of the most commonly used natural remedies for psychiatric conditions, including the antidepressants St. John's wort, omega-3 fatty acids, and S-adenosyl methionine (SAMe); the sedative-hypnotics valerian and melatonin; and the nootropic ginkgo biloba. We outline the general indications for use, suggested doses, possible mechanisms, and adverse effects to give clinicians a good summary of the benefits and liabilities of each. Although there is growing evidence of efficacy and safety to support the use of these remedies, clinicians must be aware of the limitations of the evidence base and take that into account with all the other factors that contribute to clinical decision making.
... Valerian exhibits multiple pharmacological properties, including anxiolytic, sedative, antidepressant, antispasmodic, muscle relaxant, anticonvulsant, and hypotensive effects [3,18]. According to Mischoulon D. (2002), more than 40 clinical trials have been conducted to evaluate the effects of valerian across various populations, including children, the elderly, and menopausal women, yet clinical data remain limited regarding its use in pregnant and lactating women [19]. The conclusions regarding the therapeutic ef icacy of valerian preparations are con licting: On the one hand, valerian has been reported to exhibit comparable effectiveness to benzodiazepines, with the advantage of fewer adverse effects. ...
... The conclusions regarding the therapeutic ef icacy of valerian preparations are con licting: On the one hand, valerian has been reported to exhibit comparable effectiveness to benzodiazepines, with the advantage of fewer adverse effects. On the other hand, metaanalyses and systematic reviews have yielded limited support for its clinical effectiveness [19]. ...
Many medicinal plants used by patients with mental illnesses during pregnancy contain various active compounds. It is essential to guide and inform patients about the potential risks associated with the use of medicinal herbs, teas, plant parts, and plant-based products, as well as the critical time periods during which their use may be particularly harmful. The aim of this article is to highlight the most commonly used medicinal plants with psychotropic effects and to emphasize the risks associated with their use in pregnant patients with mental disorders. Pregnant women worldwide frequently consume herbal medicines (including herbal teas, medicinal herbs, and plant extracts), under the mistaken belief that these substances are inherently safe for the fetus and entirely beneficial because of their natural origin, as opposed to synthetic alternatives. However, natural sedatives, hypnotics, and antidepressants—such as valerian, lemon balm, lavender, passionflower, St. John's wort, mint, and chamomile-can be used without supervision and often in combination with other sedative agents, further increasing the likelihood of unpredictable risks. Methods: This study is a narrative review that involves the analysis and synthesis of scientific literature on the use of medicinal plants in mental health during pregnancy and lactation. The literature search was conducted using keywords, and data were collected from medical databases, including PubMed, Medscape, UpToDate, Elsevier, and Google Scholar. Results and discussions: A significant concern is that patients may self-administer these substances without informing their healthcare provider. Medicinal plants can induce clinical, biochemical, and genomic alterations, modulate maternal immune responses, and interfere with enzymatic and cytochrome pathways, thereby affecting the concentration and pharmacokinetics of prescribed medications in maternal blood plasma. Moreover, the active compounds in herbal medicines can cross the placental barrier, posing potential risks to fetal development, including teratogenicity, toxicity, and delayed adverse effects.
... Physiological effects include central muscle relaxation, seizure attenuation, and cocaine-like local anesthesia. Kava kava has been used to treat depression and anxiety and to induce sleep, but rigorous, well-designed effi cacy and safety studies are lacking (Mischoulon, 2002). Clinical trials of kava kava to treat anxiety found the herb to be JOURNAL OF PSYCHOSOCIAL NURSING, VOL. ...
Introduction: According to the United States Census Bureau (2005), 41.3 million Hispanics reside in the United States and constitute the largest ethnic minority group in the country. Our knowledge base, as it pertains to the nature of the psychopharmacolo-gical responsiveness manifested by Hispanics, continues to lag. While the number of psychopharmacological studies including Hispanic patients has increased, they continue to be plagued by the same methodological problems that have been noted in previous reviews (Mendoza & Smith, 2000) and the data is, therefore, difficult to interpret with confidence. To date, the only substantive pharmacogenetic data that has been generated has been in Mexican Americans (a.k.a. Hispanic-Whites), and Hispanics with a Black racial affiliation remain largely ignored. In the following, we review the extant clinical research investigations that have been conducted utilizing Hispanic subjects that have received antidepressant and antipsychotic medications. Pharmacogenetic findings in the Mexican American subgroup are briefly summar-ized, as is the data regarding drug-diet and drug-herbal interactions. Concluding remarks include a discussion of the limitations and methodological problems associated with this body of research. Antidepressants: Tricyclics: Early landmark studies utilizing Hispanic subjects in the 1980s (Escobar & Tuason, 1980; Marcos & Cancro, 1982) compared the efficacy and response of several tricyclic antidepressants to placebo. They were the first to hint at a possible heightened placebo response in Hispanics and they suggested that certain Hispanic subjects may experience greater side effects at standardized dosages. © C. H. Ng, K.-M. Lin, B. S. Singh and E. Y. K. Chiu 2008 and Cambridge University Press, 2009.
As more and more people are using unregulated herbaceuticals worldwide, counselors need to be alert to the types of herbs clients may be taking; the effects, side effects, and drug interactions associated with different herbaceuticals; and the ethical implications of treating a client who is taking herbaceuticals. This article provides an overview of the psychological, physiological, cultural, and legal issues associated with herbaceuticals and introduces some of the emerging ethical issues.
To assess the cognitive and psychomotor effects of single oral doses of valerian in healthy volunteers in comparison with a placebo and the hypnotic agent triazolam.
In a double-blind, placebo-controlled, four-way crossover study nine healthy subjects (5 males, 4 females) received in random order valerian 500 mg, valerian 1000 mg, triazolam 0.25 mg and placebo. Doses were separated by a wash-out period of at least 1 week. Subjects were tested before each dose and at 2, 4 and 8 h after the dose of each compound using the critical flicker fusion (CFF), choice reaction time (CRT), digit symbol substitution test (DSST), symbol search test (SST), digit span test (DST) and visual analogue scales of mood.
Repeated measures ANOVA was used to examine the changes in performance on tests over time and significant effects were further analysed using simple main effects analysis with least significant difference corrections. Statistically significant differences were only noted for the cognitive tests: SST (F(3, 8)=3.182, p<0.05) and DSST (F(3, 8)=9.688, p<0.005). In both cases the differences between groups were due to the effects of triazolam.
These data confirm that at recommended therapeutic doses, triazolam has detrimental effects on cognitive processes in healthy volunteers as found in previous studies. Valerian was without effect on either cognitive or psychomotor performance in healthy volunteers at the doses used in this study. Should the hypnotic activity of valerian be confirmed in randomized double-blind trials it may be a less troublesome alternative to benzodiazepines in the treatment of insomnia.
Anxiety and pain can be understood with a multidimensional framework that accounts for somatic, emotional, cognitive, and behavioral aspects of these conditions. Patients who have cancer or treatment-related pain are more likely to be anxious than cancer patients without pain. Patients with cancer pain and anxiety cause difficult diagnostic dilemmas because some degree of anxiety is a normal response to having a severe medical illness. Furthermore, the somatic symptoms of anxiety often overlap with symptoms related to underlying disease processes or treatment effects. The degree of disruption in a patient's life often is the critical factor in distinguishing normal from maladaptive anxiety. Making an accurate diagnosis will help guide anxiety treatment and screening instruments can facilitate the recognition of those patients in need of further assessment. The relationship between pain and anxiety is complex and bidirectional, with interactions occurring on physiologic and psychologic levels. There are a variety of psychopharmacologic, psychotherapeutic, and complementary/alternative treatments available. A comprehensive approach to care includes these approaches in an individualized way. Terminal sedation is examined as a compassionate option for relieving intractable distress at the end of life.
A growing number of researchers have examined the use of over-the-counter (OTC) medications and herbal or dietary supplements among college students. There is concern about the efficacy and safety of these products, particularly because students appear to use them at a higher rate than does the general public.
The authors administered surveys to college students (N = 201) to assess the frequency of use in the past week.
A substantial percentage reported using OTC medications (74.1%), herbal or dietary supplements (70.6%), or both concurrently (61.2%). Dose frequency of OTC medications was the best predictor of self-reported emotional distress in the past week. Higher doses of products containing pseudoephedrine or valerian were associated with self-reported anxiety.
These data further reflect an increasing trend toward self-medication among college students. Investigators must conduct reliability and validity studies to evaluate the clinical utility of the measurement tool developed in this study.
Regional differences in the modulation of [3H] muscimol binding to GABAA receptor complexes by kavapyrones, compounds of the rhizome of the plant Piper methysticum which possess sedative activity, were demonstrated using membrane fractions obtained from target brain centers of kavapyrone action: hippocampus (HIP), amygdala (AMY) and medulla oblongata (MED), and from brain centers outside the main kavapyrone effects as frontal cortex (FC) and cerebellum (CER). The kava extract enhanced the binding of [3H] muscimol in a concentration-dependent manner with maximal potentiation of 358% over control in HIP followed by AMY and MED (main target brain centers). Minimal stimulation was observed in CER followed by FC. In contrast, apart from CER, the potency of kavapyrones was similar in the brain areas investigated with EC50 values ranging between 200 and 300 microM kavapyrones. Scatchard analysis revealed that the observed effects of kavapyrones were due to an increase in the number of binding sites (Bmax), rather than to a change in affinity. At a kavapyrone concentration of 500 microM the order of enhancement in Bmax was HIP = AMY > MED > FC > CER. When kavapyrones are included together with pentobarbital or HPO the two classes of compounds produced a more than additive, i.e., synergetic effect on [3H] muscimol binding. Our findings suggest that one way kavapyrones might mediate sedative effects in vivo is through effects on GABAA receptor binding.
The effects of 60 and 120 mg valerian (1 and 2 capsules Harmonicum Much) have been investigated by computer analysis of sleep stages (sleep profiles) and psychometric methods (questionnaires). EOG, EMG of cervical muscles, ECG and EEG (two-sided: centro-occipital and fronto-central) have been recorded from 6 male and 5 (3) female healthy volunteers. Amplified signals have been analysed on-line (power spectral analysis) and the sleep profiles have been calculated accordingly. After one night for adaptation, each subject took orally placebo, 60 and 120 mg valerian (1 and 2 capsules Harmonicum Much) according to a randomized double-blind repeated measures-design. The sleep investigations were carried out at a distance of a week for each condition (dosage per subject). In the morning following this night, the subjects completed a mood scale. Both dosages showed a decrease of sleep stage 4 and a slight reduction of REM-sleep. A slight increase of sleep stage awake, 1 and 2 could be observed. A further increase of sleep stage 3 could be identified. After application of 120 mg valerian, the frequency of REM-phases (in %) declined during the first half of the night, whereas during the second part of the night, a surplus appeared. Changes of the beta-intensity of the EEG during REM-sleep show a stronger hypnotic effect for the 120 mg dosage than for 60 mg. Maximum effect was observed between 2 and 3 hours post medication. Results of the mood scale are not different between the experimental conditions, which indicate no negative (side-) effects either from the drug or from the testing methods.
Previous studies on the efficacy of valerian extracts have given occasional hints of possible side effects involving impaired vigilance. Because of the currently insufficient knowledge about potential impairment of vigilance by plant-based sedatives, we have conducted a controlled study to assess the effects of two plant-based sleep remedies in comparison with flunitrazepam and placebo after single oral administration. Aim of the study was to derive recommendations concerning potential hazards in driving or operating machinery. Residual sedative effects (hangover) were examined in four groups of 20 healthy volunteers, receiving either tablets containing valerian and hops or syrup containing valerian only or flunitrazepam or placebo; furthermore, immediate sedative effects of the two plant preparations have been examined in comparison with placebo (three groups of twelve healthy volunteers). The tests included objective measurements of cognitive psychomotor performance as well as subjective questionnaires on well-being. Tolerability was assessed from spontaneous reports of side effects and a verbal inquiry at the end of the tests. We found that objectively measurable impairment of performance on the morning after medication occurred only in the flunitrazepam group, a finding which was even more pronounced in the subjective questionnaires. In addition, 50% of the volunteers in the flunitrazepam group reported mild side effects in the inquiry at the end of the tests, compared with only 10% from the other groups. The subjective perception of sleep quality was improved in all three medication groups, when compared to placebo. Examination of acute effects of the plant remedies 1 to 2 hours after administration revealed no changes in the more important lead variables; however, a very slight impairment of vigilance after taking the syrup was statistically significant as well as a retardation in the processing of complex information for the tablets. The subjective perception of effects was more pronounced (shaky legs, feeling less active). In conclusion, the residual sedative effects (hangover) observed in some earlier studies cannot be confirmed for the recommended doses of the two plant-based sleep remedies which we have examined with respect to vigilance and cognitive performance. On the contrary: our findings show improved subjective self-assessment (more alert, more active, feeling better). Hangover effects on the following morning need not be a cause for concern, which is of particular interest to car drivers; however, a slight impairment of performance during the first few hours after ingestion should be anticipated. Impairment of vigilance on the morning after ingestion of benzodiazepines, frequently reported and confirmed by our results, constitutes a potential hazard. In this situation, plant remedies such as those examined in this study should be considered as viable alternatives.
Herbal medicinals are being used by an increasing number of patients who typically do not advise their clinicians of concomitant use. Known or potential drug-herb interactions exist and should be screened for. If used beyond 8 weeks, Echinacea could cause hepatotoxicity and therefore should not be used with other known hepatoxic drugs, such as anabolic steroids, amiodarone, methotrexate, and ketoconazole. However, Echinacea lacks the 1,2 saturated necrine ring associated with hepatoxicity of pyrrolizidine alkaloids. Nonsteroidal anti-inflammatory drugs may negate the usefulness of feverfew in the treatment of migraine headaches. Feverfew, garlic, Ginkgo, ginger, and ginseng may alter bleeding time and should not be used concomitantly with warfarin sodium. Additionally, ginseng may cause headache, tremulousness, and manic episodes in patients treated with phenelzine sulfate. Ginseng should also not be used with estrogens or corticosteroids because of possible additive effects. Since the mechanism of action of St John wort is uncertain, concomitant use with monoamine oxidase inhibitors and selective serotonin reuptake inhibitors is ill advised. Valerian should not be used concomitantly with barbiturates because excessive sedation may occur. Kyushin, licorice, plantain, uzara root, hawthorn, and ginseng may interfere with either digoxin pharmacodynamically or with digoxin monitoring. Evening primrose oil and borage should not be used with anticonvulsants because they may lower the seizure threshold. Shankapulshpi, an Ayurvedic preparation, may decrease phenytoin levels as well as diminish drug efficacy. Kava when used with alprazolam has resulted in coma. Immunostimulants (eg, Echinacea and zinc) should not be given with immunosuppressants (eg, corticosteroids and cyclosporine). Tannic acids present in some herbs (eg, St John wort and saw palmetto) may inhibit the absorption of iron. Kelp as a source of iodine may interfere with thyroid replacement therapies. Licorice can offset the pharmacological effect of spironolactone. Numerous herbs (eg, karela and ginseng) may affect blood glucose levels and should not be used in patients with diabetes mellitus.
The enzym system 2-oxoglutarataminotransferase/semisuccinaldehydoxireductase (E. C. 2.6.1.19/E.C. 1.2.1.16, Gabase) catalyzing the catabolism of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) is inhibited by mmol/l concentrations of valerenolic acid (20%) and acetylvalerenolic acid (38%). 1 mmol/l L-glutamic acid inhibited 59%, 0.1 mmol/l chlorogenic acid 69%.
Anamnese und klinischer Befund: Wegen eines »neuerlichen Schubes einer ätiologisch ungeklärten akuten Hepatitis« wurden zwei Patientinnen im Alter von 39 und 42 Jahren aufgenommen. In der Vorgeschichte beider Patientinnen war vor Monaten erstmals eine akute Hepatitis mit maximalen GPT-Konzentrationen von 796 bzw. 755 U/I aufgetreten. Die Medikamentenanamnese ergab eine jedem Hepatitisschub vorausgehende Einnahme eines pflanzlichen Heilmittels (Kavapyrone bzw. Schöllkraut). Die klinische Untersuchung war bei beiden Patientinnen unauffällig.
Untersuchungen: Die Maximalwerte der GPT lagen bei 422 bzw. 350 U/I. Virale, autoimmune oder metabolisch bedingte Ursachen der Hepatitis konnten ausgeschlossen werden, histologisch fand sich jeweils das Bild einer akuten nekrotisierenden Hepatitis.
Diagnose, Therapie und Verlauf: Unter dem dringenden Verdacht einer medikamentös-toxischen Hepatitis kam es nach Absetzen der Phytopharmaka zu einer spontanen Normalisierung der Leberwerte.
Folgerung: In beiden Fällen muß, auch angesichts der Folgen der Re-Exposition, von einem kausalen Zusammenhang zwischen der Einnahme der pflanzlichen Präparate und dem Auftreten der akuten Hepatitis ausgegangen werden.
The increasing promotion of herbal drugs may lead to allergic problems. A case of systemic contact-type dermatitis after oral administration of kava extract illustrates this special problem. The kava plant is a member of the black pepper family; an intoxicant beverage prepared from the roots of this plant is used ceremonially by many traditional societies of the Southern Pacific. The beverage induces relaxation, enhances a sense of sociability and promotes sleep. These effects are utilized in herbal drugs containing kava, which are sold for insomnia, nervousness and depression. The ichthyosiform kava dermopathy is a well-known side effect of excessive use of kava; in this case report we describe an acute allergic side-effect of kava extract.
Kava, an intoxicating beverage prepared from the pepper plant Piper methysticum, is widely consumed by the indigenous peoples in the islands of the South Pacific. As the first of a series of studies on the neuropharmacological interactions of kava with CNS receptors we tested purified pyrones and kava resin for activity on GABA and benzodiazepine binding sites in rat and mouse brain membranes. Only weak activity was observed on GABAA binding sites in washed synaptosomal membranes prepared from rat brain and this was abolished by extraction of the membranes with Triton X-100, suggesting that lipid soluble components were involved. No effects were observed on GABAB binding sites in rat brain membranes in vitro. Kava resin and pyrones exerted some weak effects on benzodiazepine binding in vitro but this did not correlate with pharmacological activity. In addition, in ex vivo studies, no effects were observed on [3H]diazepam binding to brain membranes prepared from mice in which selected kava constituents were injected intraperitoneally, whereas similarly administered diazepam (5 mg/kg) inhibited [3H]diazepam binding by greater than 95%. Similar lack of activity was observed in in vivo binding studies; injection of kava resin failed to influence the CNS binding of the benzodiazepine-receptor ligand [3H]Ro15-1788 injected into mice prior to sacrifice. The pharmacological activities of kava resin and pyrones do not appear to be explained by any significant interaction with GABA or benzodiazepine binding sites.
The purpose of the present study was to test whether kava extract and its constituents kawain, dihydrokawain, methysticin, dihydromethysticin and yangonin provide protection against ischemic brain damage. To this end, we used a model of focal cerebral ischemia in mice and rats. Ischemia was induced by microbipolar coagulation of the left middle cerebral artery (MCA). To quantify the size of the lesion in mice, the area of the infarct on the brain surface was assessed planimetrically 48 h after MCA occlusion by transcardial perfusion of carbon black. In the rat model infarct volume was determined 48 h after MCA occlusion by planimetric analysis and subsequent integration of the infarct areas on serial coronal slices. Compounds were administered i.p., except the kava extract, which was administered orally. The effects of the kava extract and its constituents were compared with those produced by the typical anticonvulsant, memantine. The kava extract, methysticin and dihydromethysticin produced effects similar to those of the reference substance memantine. The kava extract (150 mg/kg, 1 h before ischemia) diminished the infarct area (P less than 0.05) in mouse brains and the infarct volume (P less than 0.05) in rat brains. Methysticin, dihydromethysticin (both 10 and 30 mg/kg, 15 min before ischemia) and memantine (20 mg/kg, 30 min before ischemia) significantly reduced the infarct area in mouse brains. All other compounds failed to produce a beneficial effect on the infarct area in mouse brains. In conclusion, the kava extract exhibited neuroprotective activity, which was probably mediated by its constituents methysticin and dihydromethysticin.
Since the first significant contact with Europeans in the 18th century, the Oceanic plant, Piper methysticum Forst. (Piperaceae) and the beverage prepared from it, both of which are called kava, have become familiar to much of the outside world through both the written and visual media. The ceremonial preparation and consumption of the beverage are probably its most conspicuous and spectacular features. Kava continues to occupy a central place in everyday life in the islands concerned, although its role has been somewhat diminished by time and outside influences. Despite the large body of literature on kava--about 800 entries are listed in a recent bibliography by Singh (1986)--there has been no comprehensive review on the subject. Earlier contributions by Keller and Klohs (1963) and Shulgin (1973) were selective in treatment and dealt primarily with chemical and pharmacological aspects. The monograph by Steinmetz (1960) remains a standard reference but understandably some of the information in it has become dated. The attention of the reader is also drawn to two excellent additions to the recent kava literature, by Lebot and Cabalion (1988) and Brunton (1989), which are, although somewhat restricted in focus, are very significant contributions to the subject. The present review paper provides an updated and a multidisciplinary overview of the subject. It was prepared on the basis of the author's personal experience--he is a native of Fiji and lived in that country for about 30 years--as well as the relevant literature listed in the Singh (1986) bibliography and some more recent publications.
To investigate neurophysiological effects of D,L-kavain, two studies were conducted on unrestrained cats with chronically implanted electrodes. In group A animals (n = 26) we recorded the blood pressure, the EEG of cortical and subcortical areas, the electromyogram, EEG arousal reactions, and subcortical evoked potentials elicited by central stimulation. This was done before and after injection of D,L-kavain (10-50 mg/kg i.p.) or--for comparison--of a kava extract in Ol. arachidis (50-100 mg pyrones/kg i.p.). Group B cats (n = 9) served for polygraphic, 10-h analyses of the sleep-wakefulness rhythm; they received--in a random sequence--0.9% NaCl (3 ml i.p.), D,L-kavain (28 mg/kg p.o.), pentobarbital (1 mg/kg i.m.), or the combination D,L-kavain plus pentobarbital. With both D,L-kavain and the extract, muscle tone was seen to be diminished in about 50% of the experiments. It was only the extract which exerted marked effects on the EEG; it induced high amplitude delta waves, spindle-like formations, and a continuous alpha- or beta-synchronization in the amygdalar recordings (p less than 0.001). Neither D,L-kavain nor the kava extract changed the threshold of the EEG arousal reaction. As to the evoked potentials, the hippocampal response following stimulation of the amygdalar nucleus showed an increase in amplitude in the animals given D,L-kavain (50 mg/kg; p less than 0.05) and in those given the extract (100 mg pyrones/kg; p less than 0.01). In addition, after injection of the extract, further projections arising from the amygdala as well as the connection from the caudate nucleus to the amygdala proved to be activated. The percentage duration of active wakefulness was significantly shortened by both D,L-kavain and pentobarbital, as compared to placebo. There was a likewise significant prolongation of synchronized sleep with D,L-kavain, pentobarbital, and the combination of both these agents. However, a potentiation of drug effects failed to occur. It is concluded from the findings that limbic structures and, in particular, the amygdalar complex represent the preferential site of action for both D,L-kavain and the kava extract. The participation of these structures in modulating emotional processes may explain the promotion of sleep, even in the absence of sedation. There is no congruity of D,L-kavain with either the tricyclic thymoleptics or the benzodiazepines regarding the profile of neurophysiological effects.
1. The development of tolerance to the aqueous extract of kava, and to the lipid soluble extract (kava resin) was tested in mice.
2. Tolerance to the unknown pharmacologically active ingredient(s) developed very rapidly, given parenterally, in the aqueous extract. A minimally effective daily dose (50 mg/kg) of the aqueous extract for 3 days was sufficient to produce tolerance to a test dose of 150 mg/kg, which is close to the ED50. As tolerance was evident at the first test period it can be assumed to be physiological tolerance.
3. Kava resin decreased spontaneous motility and caused a loss of muscle control. A minimally effective daily dose of kava resin (100 mg/kg) did not produce tolerance to the above effects of a weekly test dose of kava resin (166 mg/kg) within 7 weeks. In a further experiment the dose was raised to 150 mg/kg twice daily and this schedule caused partial tolerance to occur within 3 weeks, but very little further tolerance developed over the ensuing 2-week period.
4. To try to induce learned (behaviourally acquired) tolerance a dose of 166 mg/kg kava resin was injected daily and animals were tested each day while under the influence of the drug. However, even under these conditions, there was no tolerance evident within 3 weeks, when the experiment was terminated.
5. It appears difficult to induce the development of physiological or learned tolerance to kava resin in mice.
Clinical Efficacy of a Kava Extract in Patients with Anxiety Syndrome/Double-blind placebo controlled study over 4 weeks. In a randomized, placebo-controlled double-blind study two groups each containing 29 patients with anxiety syndrome not caused by psychotic disorders were treated for a period of 4 weeks with kava extract WS 1490 (Laitan) 3 x 100 mg/day or a placebo preparation. Therapeutic efficacy was assessed by the Hamilton-Anxiety-Scale (main target variable), the Adjectives-List and the Clinical-Global-Impression-Scale (secondary target variables) after 1, 2 and 4 weeks of treatment. The HAMA overall score of anxiety symptomatology revealed a significant reduction in the drug receiving group already after one week of treatment. This difference between the two groups of patients increased in the course of the study. The results of the secondary target variables were in agreement with the HAMA-score and demonstrate the efficacy of WS 1490 in patients with anxiety disorders. No adverse experiences caused by the medication were noted during the 4 week administration of WS 1490.
1. The lipid soluble extract of the psychoactive beverage kava has hypnosedative properties which can be measured by the length of time that the righting reflex is lost.
2. Ethanol and the lipid soluble extract (kava resin) have been shown greatly to increase each others hypnotic action in mice. Ethanol also increases the toxicity of kava markedly.
3. This interaction of kava and alcohol has important clinical and social consequences since, in contrast to traditional usage, kava is now often taken in conjunction with alcoholic drinks.
1. The antinociceptive properties of the aqueous extract of the intoxicating beverage kava, and of the lipid soluble extract (kava resin) were tested in mice, by the tail immersion and abdominal constriction methods. Both extracts showed analgesic effects in both tests.
2. Eight purified pyrones from the lipid soluble extract were also tested for activity in the tail immersion test, and kawain, dihydrokawain, methysticin and dihydromethysticin were found to be very effective in producing analgesia. Using the tail immersion test the time course of action of the extracts of the four effective pyrones of kava were studied.
3. Naloxone, in doses which inhibited morphine-induced analgesia in both tests, was completely ineffective in reversing the antinociceptive activities of the kava extracts, showing that analgesia produced by kava occurs via non-opiate pathways.
Valerian root contains two substances of special pharmacological interest--valepotriates and sesquiterpenes. The former, which has been used for standardization of the drug, is cytotoxic. The latter has no such effect. Both have sedative effects. A double blind test has been carried out on a preparation (VALERINA NATT) containing primarily sesquiterpenes. When compared with placebo it showed a good and significant effect on poor sleep (p less than 0.001). Forty-four percent reported perfect sleep and 89% reported improved sleep from the preparation. No side effects were observed.
A comprehensive review of the constituents of the Valerianaceae is presented with particular reference to the sedative activity of extracts from various constituent species. The sedative activity can be ascribed to the valepotriates present and to a lesser extent to the sesquiterpene constituents of the volatile oils. Recent research into the toxicology of the valepotriates is also considered.
Health status was assessed in 39 kava users and 34 non-users in a coastal Aboriginal community in Arnhem Land. Twenty (27%) respondents were very heavy (mean consumption, 440 g/week) users of kava; 15 (21%) respondents were heavy (310 g/week) users of kava and four (5%) respondents were occasional (100 g/week) users of kava. Kava users were more likely to complain of poor health and a "puffy" face, and were more likely to have a typical scaly rash, and slightly-increased patellar reflexes. Very heavy users of kava were 20% underweight and their levels of gamma-glutamyl transferase were increased greatly. Albumin, plasma protein, urea and bilirubin levels were decreased in kava users, and high-density lipoprotein cholesterol levels were increased. Kava users were more likely to show haematuria, and to have urine which was poorly acidified and of low specific gravity. The use of kava was also associated with an increased red-cell volume, with a decreased platelet volume and with a decreased lymphocyte count. Shortness of breath in kava users was associated with tall P waves on a resting electrocardiogram, which provided suggestive evidence of pulmonary hypertension. In common with other Aboriginal communities, there was evidence of decreased lung volumes, a high carriage rate of hepatitis B surface antigen, and of other morbidity that was unrelated to the use of kava. On the basis of these findings, there is a strong rationale for urgent social action to improve health in Aboriginal communities and, in particular, to reduce the consumption of kava and to improve the nutritional status of kava users.
The effect of an aqueous extract of valerian root on sleep was studied in two groups of healthy, young subjects. One group (N = 10) slept at home, the other (N = 8) in the sleep laboratory. Sleep was evaluated on the basis of questionnaires, self-rating scales and night-time motor activity. In addition, polygraphic sleep recordings and spectral analysis of the sleep EEG was performed in the laboratory group. Under home conditions, both doses of valerian extract (450 and 900 mg) reduced perceived sleep latency and wake time after sleep onset. Night-time motor activity was enhanced in the middle third of the night and reduced in the last third. The data suggest a dose-dependent effect. In the sleep laboratory, where only the higher dose of valerian was tested, no significant differences from placebo were obtained. However, the direction of the changes in the subjective and objective measures of sleep latency and wake time after sleep onset, as well as in night-time motor activity, corresponded to that observed under home conditions. There was no evidence for a change in sleep stages and EEG spectra. The results indicate that the aqueous valerian extract exerts a mild hypnotic action.
The effects of kava, a native drink from Oceania, on neuromuscular transmission and muscle contractility have been examined in mouse phrenic nerve-hemidiaphragm and frog sartorius muscle preparations using twitch tension and intracellular recording techniques. The extent of muscle paralysis induced by kava was similar in both directly and indirectly stimulated mouse hemidiaphragms. The neuromuscular blockade produced was poorly reversed by calcium and by neostigmine. Intracellular recordings from frog sartorius muscles showed that kava depressed the amplitude of both miniature end-plate potentials (mepps) and end-plate potentials (epps) but had no effect on the frequency of mepps. Kava greatly prolonged the duration of mepps and epps and also slowed and depressed directly elicited muscle action potentials. It is concluded that kava causes paralysis by mechanisms similar to local anaesthetics.
The effect of an aqueous extract of valerian (Valeriana officinalis L.) root on subjectively rated sleep measures was studied on 128 people. Each person received 9 samples to test (3 containing placebo, 3 containing 400 mg valerian extract and 3 containing a proprietary over-the-counter valerian preparation). The samples, identified only by a code number, and presented in random order, were taken on non-consecutive nights. Valerian produced a significant decrease in subjectively evaluated sleep latency scores and a significant improvement in sleep quality: the latter was most notable among people who considered themselves poor or irregular sleepers, smokers, and people who thought they normally had long sleep latencies. Night awakenings, dream recall and somnolence the next morning were relatively unaffected by valerian. With the proprietary valerian-containing preparation, the only change was a significant increase in reports of feeling more sleepy than normal the next morning. Thus the questionnaire, simple to use and non-invasive, provides a sensitive means for detecting the effects of mild sedatives on different aspects of sleep in man. It also allows identification within the test population of the subgroups most affected.
The clinical features and risk of hepatotoxicity of 'Sleep-Qik' (valerian dry extract 75 mg, hyoscine hydrobromide 0.25 mg, cyproheptadine hydrochloride 2 mg) were determined in 23 patients treated in our hospital between 1988 and 1991. The main clinical problems were central nervous system depression and anticholinergic poisoning. There was no clinical evidence of acute hepatitis in the 23 patients after taking an average of 2.5 g of valerian (range 0.5 to 12 g). There was no evidence of subclinical liver damage in 12 patients who had routine liver function tests performed approximately 6-12 hours after ingestion. Delayed onset of severe liver damage was excluded in 10 patients in whom a telephone follow-up was possible. However, subclinical liver dysfunction in the acute stage (onset after 12-24 hours) and in the intervening period after discharge from hospital could not be excluded. To establish the risk of hepatotoxicity in long-term users and in those taking an overdosage of valerian, a much larger study of longer duration with serial liver function tests is clearly needed.
Kava is a psychoactive beverage used ceremonially for thousands of years by Pacific Islanders. Kava is made from the root of the pepper plant, Piper methysticum, found in Polynesia, Melanesia, and Micronesia. The beverage is a nonfermented depressant with complex neuropharmacologic properties that causes a tranquil state of intoxication. Kava also affects the skin, causing a peculiar scaly eruption. The cutaneous effects were first reported by members of Captain James Cook's Pacific expeditions, but they have never been described in dermatologic literature. Heavy kava drinkers acquire a reversible ichthyosiform eruption, kava dermopathy. The cause is unknown but may relate to interference with cholesterol metabolism. Today kava is used across the Pacific in both traditional ceremonies and informal social events. In Western nations, kava is sold as a relaxant by health food stores. This article explores the history of kava dermopathy from Cook's early reports to its presence today.
The evaluation of a commercially available valerian root extract (Valdispert) revealed pronounced sedative properties in the mouse with respect to a reduction in motility and an increase in the thiopental sleeping-time. A direct comparison with diazepam and chlorpromazine revealed a moderate sedative activity for the tested extract. The extract showed only weak anticonvulsive properties.
We present the first reported case of valerian (Valeriana officianalis) overdose. This herb is popular as a sedative but little is known about its toxic effects. The patient presented with mild symptoms, all of which resolved within 24 h. Valerian overdose, at approximately 20 times the recommended therapeutic dose, appears to be benign.
The increasing promotion of herbal drugs may lead to allergic problems. A case of systemic contact-type dermatitis after oral administration of kava extract illustrates this special problem. The kava plant is a member of the black pepper family; an intoxicant beverage prepared from the roots of this plant is used ceremonially by many traditional societies of the Southern Pacific. The beverage induces relaxation, enhances a sense of sociability and promotes sleep. These effects are utilized in herbal drugs containing kava, which are sold for insomnia, nervousness and depression. The ichthyosiform kava dermopathy is a well-known side effect of excessive use of kava; in this case report we describe an acute allergic side-effect of kava extract.
Kava pyrones are constituents of the intoxicating pepper (Piper methysticum Forst), which has been shown to be anticonvulsive. The question of how the excitability of neurons is affected was investigated by determining the interaction of (+/-)-kavain with epitopes (site 1, site 2) of voltage-dependent Na+ channels and the action of (+/-)-kavain on 4-aminopyridine-stimulated synaptosomes as model of repetitive firing neurons. [3H]Saxitoxin and [3H]batrachotoxin were used for radioligand-binding assays performed with synaptosomal membranes. Gultamate released from 4-aminopyridine-stimulated cerebrocortical synaptosomes and the cytosolic concentrations of Na+ and Ca2+ ([Na+]i, [Ca+]i) were detected fluorometrically by using an enzyme-linked assay, sodium-binding benzofuranisophthalate (SBFI) and Fura-2, respectively. (+/-)-Kavain failed to compete with [3H]saxitoxin up to 400 mumol/l but dose-dependently suppressed binding of [3H]batrachotoxin with an IC50 value of 88 mumol/l (Ki = 72 mumol/l) although displacement of [3H]batrachotoxin was restricted to 33% of control at 400 mumol/l (+/-)-kavain. In stimulated synaptosomes, 5 mmol/l 4-aminopyridine provoked an increase in [Na+]i and [Ca2+]i by 9 mmol/l Na+ and 235 nmol/l Ca2+. Comparable to the reduction in [3H]batrachotoxin binding, 400 mumol/l (+/-)-kavain suppressed the increase in [Na+]i and [Ca2+]i to 38 and 29% of control, respectively. Consistent with the increase in [Na+]i and [Ca2+]i, 5 mmol/l 4-aminopyridine provoked glutamate release (rate: 38 pmol/s*mg protein) which was dose-dependently diminished to 60% of control by 400 mumol/l (+/-)-kavain. KCl depolarization (40 mmol/l) provoked an increase in [Ca2+]i and glutamate release almost identical to the responses elicited by 4-aminopyridine but 400 mumol/l (+/-)-kavain suppressed only the rate of glutamate release by 9% of control. The data suggest an interaction of (+/-)-kavain with voltage-dependent Na+ and Ca2+ channels, thereby suppressing the 4-aminopyridine-induced increase in [Na+]i, [Ca2+]i and the release of endogenous glutamate.
101 outpatients suffering from anxiety of non-psychotic origin (DSM-III-R criteria: agoraphobia, specific phobia, generalized anxiety disorder, and adjustment disorder with anxiety) were included in a 25-week multicenter randomized placebo-controlled double-blind trial with WS 1490, a special extract of kava-kava. In the main outcome criterion, the Hamilton Anxiety Scale (HAMA), there was a significant superiority of the test drug starting from week 8 on. WS 1490 was also found to be superior with respect to the secondary outcome variables. HAMA subscores somatic and psychic anxiety, Clinical Global Impression, Self-Report Symptom Inventory-90 Items revised, and Adjective Mood Scale. Adverse events were rare and distributed evenly in both groups. These results support WS 1490 as a treatment alternative to tricyclic antidepressants and benzodiazepines in anxiety disorders, with proven long-term efficacy and none of the tolerance problems associated with tricyclics and benzodiazepines.
1. The kava-pyrones kawain and dihydromethysticin are constituents of Piper methysticum which exert anticonvulsant, analgesic and anxiolytic properties. 2. In the present study the effect of these kava-pyrones were tested on field potential changes (fp) induced by omission of the extracellular Mg2+, recorded from the area CA1 and CA3 of the hippocampal slice preparation of guinea pigs. These fp are generated by an activation of NMDA receptors and voltage dependent calcium channels. 3. Kawain and dihydromethysticin reduced reversibly the frequency of occurrence of fp in a concentration range from 5 to 40 mumol/l and 10 to 40 mumol/l, respectively. 4. Reduction of the fp frequency after addition of subthreshold concentrations of 5 mumol/l kawain and 10 mumol/l dihydromethysticin indicated additive actions of both drugs. 5. Since the serotonin-1A agonist ipsapirone also exerts anxiolytic effects, subthreshold concentrations of kawain or dihydromethysticin were combined with a subthreshold concentration of ipsapirone in another set of experiments. Combining kawain and ipsapirone or dihydromethysticin and ipsapirone caused a reduction of the rate of fp to 0.76 and 0.81 of the baseline value, respectively. 6. The findings suggest that (i) single constituents of Piper methysticum may have additive actions, (ii) that the two components kawain and dihydromethysticin may enhance the effects of the anxiolytic serotonin-1A agonist ipsapirone and (iii) that activation of NMDA receptors and/or voltage dependent calcium channels may be involved in the elementary mechanism of action of some kava-pyrones.
Kava pyrones are the pharmacologically active compounds of Piper methysticum Forst. In the present study, the effect of the synthetic kava pyrone (+/-)-kavain was investigated on evoked contractile activity of isolated guinea-pig ileum. (+/-)-Kavain (1 microM-1 mM) dose-dependently reduced contractions of ileum evoked by carbachol (10 microM), by BAY K 8644 (0.3 microM), or by substance P (0.05 microM). (+/-)-Kavain also inhibited the contractile responses induced by raising the extracellular K+ concentration from 4 to 20 mM and by blocking the K+ channel by barium chloride (1 mM) or 4-aminopyridine (0.3 mM). After pre-incubation with 1 microM nifedipine, carbachol (1 microM) evoked 18.2 +/- 14.3% of contraction at control (i.e. prior pre-incubation with nifedipine). This remaining response was completely abolished by high concentrations of (+/-)-kavain (400 microM). After treatment of the longitudinal ileum strips with pertussis toxin (PTX), carbachol (1 microM) evoked 27.0 +/- 6.2% of the control response in untreated ileum. These contractions were also blocked by (+/-)-kavain (400 microM). However, (+/-)-kavain had no effect on the caffeine-induced (20 mM) contractions of ileum strips, which were permeabilized with digitonin or beta-escin. Moreover, it failed to affect Ca(2+)-evoked contractions of skinned muscles. These results suggest that the kava pyrone (+/-)-kavain may act in a non-specific musculotropic way on the smooth muscle membrane.
Three kava pyrones, the natural compounds (+)-methysticine and (+)-kavain, and the synthetic racemate (+/-)-kavain, were tested concerning their action on in vitro uptake of monoamines in synaptosomes prepared from the cerebral cortex and hippocampus of rats. (+/-)-Kavain and (+)-kavain were found to potently inhibit the uptake of [3H]-noradrenaline. Uptake of [3H]-noradrenaline was inhibited in the following order of potency: (+/-)-kavain = (+)-kavain > (+)-methysticine, whereas none of the kava pyrones efficiently blocked the uptake of [3H]-serotonin. The results indicate a pyrone-specific non-stereo-selective inhibition of the [3H]-noradrenaline uptake which might be responsible for or, at least, contribute to the psychotropic properties of kava pyrones.
Herbal medicinals are being used by an increasing number of patients who typically do not advise their clinicians of concomitant use. Known or potential drug-herb interactions exist and should be screened for. If used beyond 8 weeks, Echinacea could cause hepatotoxicity and therefore should not be used with other known hepatoxic drugs, such as anabolic steroids, amiodarone, methotrexate, and ketoconazole. However, Echinacea lacks the 1,2 saturated necrine ring associated with hepatoxicity of pyrrolizidine alkaloids. Nonsteroidal anti-inflammatory drugs may negate the usefulness of feverfew in the treatment of migraine headaches. Feverfew, garlic, Ginkgo, ginger, and ginseng may alter bleeding time and should not be used concomitantly with warfarin sodium. Additionally, ginseng may cause headache, tremulousness, and manic episodes in patients treated with phenelzine sulfate. Ginseng should also not be used with estrogens or corticosteroids because of possible additive effects. Since the mechanism of action of St John wort is uncertain, concomitant use with monoamine oxidase inhibitors and selective serotonin reuptake inhibitors is ill advised. Valerian should not be used concomitantly with barbiturates because excessive sedation may occur. Kyushin, licorice, plantain, uzara root, hawthorn, and ginseng may interfere with either digoxin pharmacodynamically or with digoxin monitoring. Evening primrose oil and borage should not be used with anticonvulsants because they may lower the seizure threshold. Shankapulshpi, an Ayurvedic preparation, may decrease phenytoin levels as well as diminish drug efficacy. Kava when used with alprazolam has resulted in coma. Immunostimulants (eg, Echinacea and zinc) should not be given with immunosuppressants (eg, corticosteroids and cyclosporine). Tannic acids present in some herbs (eg, St John wort and saw palmetto) may inhibit the absorption of iron. Kelp as a source of iodine may interfere with thyroid replacement therapies. Licorice can offset the pharmacological effect of spironolactone. Numerous herbs (eg, karela and ginseng) may affect blood glucose levels and should not be used in patients with diabetes mellitus.
Kava-kava, a psychoactive beverage, induces relaxation, improves social interaction, promotes sleep and plays an important role in the sociocultural life in the islands of the South Pacific. On the other hand, standardized extracts of kava-kava roots are used for the therapy of anxiety, tension and restlessness. Kava pyrones, the major constituents of kava kava, are generally considered to be responsible for the pharmacological activity in humans and animals. To obtain more information on the mechanisms by which kava-kava exerts psychotropic properties we investigated the in vitro effects of kava-kava extract and pure synthetic kava pyrones on human platelet MAO-B, in comparison to amitriptyline, imipramine and brofaromine. Kava-kava extract was found to be a reversible inhibitor of MAO-B in intact platelets (IC50 24 microM) and disrupted platelet homogenates (IC50 1.2 microM). Structural differences of kava pyrones resulted in a different potency of MAO-B inhibition. The order of potency was desmethoxyyangonin > (+/-)-methysticin > yangonin > (+/-)-dihydromethysticin > (+/-)- dihydrokavain > (+/-)-kavain. The two most potent kava pyrones, desmethoxyyangonin and (+/-)-methysticin displayed a competetive inhibition pattern with mean Ki 0.28 microM and 1.14 microM respectively. The inhibition of MAO-B by kava pyrone-enriched extracts might be an important mechanism for their psychotropic activity.
Two unrelated women, aged 39 and 42 years, had been admitted (at different times) to hospital because of "recurrence of an aetiologically uncertain acute hepatitis". Both patients had a history of acute hepatitis with GPT concentration of 796 and 755 U/l, respectively. Each of them had experienced recurrences of hepatitis, each of them preceded by taking herbal remedies as alternative medication, containing kava or common (or lesser) celandine, respectively. In each patient physical examination had been unremarkable.
Maximal values of GPT in the two patients were 422 and 350 U/l, respectively. Viral, autoimmune and metabolic causes of the hepatitis were excluded. In each of them liver biopsy revealed the picture of acute necrotizing hepatitis.
As it was suspected that the hepatitis was medication-induced, the intake of the mentioned herbal preparations was stopped. The liver function tests quickly became normal.
In view of the rapid response to their withdrawal, a causal connection between intake of the herbal preparations and the recurrences of acute hepatitis is the most likely explanation in both cases.
Natural, or “alternative,” remedies—derived from natural products but not approved by the US Food and Drug Administration (FDA) for their putative indications—have been used for millenia,1 but they have generally received little attention in Western industrialized societies. Over the last few years, however, their popularity has been increasing dramatically both in the United States and worldwide.2-5 Current news programs and popular magazines often feature stories about natural remedies, and bookstores routinely have entire sections devoted to alternative treatments. Recently the National Institutes of Health recognized that up to 25% of people in the United States seek and obtain non-traditional treatments.6
A group of 8 volunteers suffering from mild insomnia received a placebo, 450 mg or 900 mg of an aqueous extract of valerian root in a double-blind, repeated measures, random-order design. Subjective sleep ratings were assessed by questionnaire and movements were recorded throughout the night with wrist-worn activity meters. Using the first period of 5 consecutive minutes without movement as a criterion of sleep onset, there was a significant decrease in sleep latency with 450 mg valerian compared to placebo (15.8 +/- 2.2 min vs 9.0 +/- 1.5 min; paired "t" = 3.37;p < 0.01). The higher dose of valerian produced no further improvement in sleep latency.
Valerenic acid, isolated from VALERIANA OFFICINALIS L. s.l. affected the rotarod and traction performance of mice in a similar manner to that of pentobarbital which was used together with chlorpromazine and diazcpam as reference substance in both tests. A decrease of locomotility of mice was also noticed after administration of valerenic acid, in particular when this compound was administered to the same group of mice a week later than the vehicle. In addition valerenic acid was found to prolong the pentobarbital induced sleeping time. It can be concluded, that valerenic acid has aspecific central nervous depressent properties. This factor should be taken into account when considering the sedative action of Valerian preparations.
Rational Phytotherapy: A Physician's Guide to Herbal Medicine
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Valepotriate mit Epoxidstruktur-beachtliche Alkylantien
- M Braun R Dittmar W Machut
Therapie von Insomnien: Wirksamkeit and Vertraglichkeit eines Baldrian-Preparates
- Vorbach
- J Gortelmayer R Brunning
The effect of harmonicum on human sleep: a polyff-aphic EEG investigation. EEGEMG: Zeitschrift fur Elektroenzephalographie Elektromyographie und Verwandte Gebiete
- Gessner
- M Klassner
Bacterial mutagenicity of the tranquilizing constituents of valerianaceae roots. Naunyn-Schmiedebag's Archives of Pharmacology Supplement
- W Braun R Dittmar W Von Der Hude
Die Darstellung setherender /tranquilisierender Wirkungen von Phytopharmaka im quantifizierten EEG
- Schultz
- M Jobert