Research - Anxiety
Effects of Aromatherapy on the Anxiety, Vital Signs, and Sleep Quality of Percutaneous Coronary Intervention Patients in Intensive Care Units
Mi-Yeon Cho,1 Eun Sil Min,2 Myung-Haeng Hur,2 and Myeong Soo Lee
The purpose of this study was to investigate the effects of aromatherapy on the anxiety, sleep, and blood pressure (BP) of percutaneous coronary intervention (PCI) patients in an intensive care unit (ICU). Fifty-six patients with PCI in ICU were evenly allocated to either the aromatherapy or conventional nursing care. Aromatherapy essential oils were blended with lavender, roman chamomile, and neroli with a 6 : 2 : 0.5 ratio. Participants received 10 times treatment before PCI, and the same essential oils were inhaled another 10 times after PCI. Outcome measures patients' state anxiety, sleeping quality, and BP. An aromatherapy group showed significantly low anxiety (t=5.99, P < .001) and improving sleep quality (t=-3.65, P=.001) compared with conventional nursing intervention. The systolic BP of both groups did not show a significant difference by time or in a group-by-time interaction; however, a significant difference was observed between groups (F=4.63, P=0.36). The diastolic BP did not show any significant difference by time or by a group-by-time interaction; however, a significant difference was observed between groups (F=6.39, P=.011 ). In conclusion, the aromatherapy effectively reduced the anxiety levels and increased the sleep quality of PCI patients admitted to the ICU. Aromatherapy may be used as an independent nursing intervention for reducing the anxiety levels and improving the sleep quality of PCI patients.
Source : Evidence Based Complementary and Alternative Medicine
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The effects of ginseng on stress-related depression, anxiety, and the hypothalamicpituitary-adrenal axis
Seungyeop Lee, Dong-Kwon Rhee
Ginseng effectively regulates the immune response and the hormonal changes due to stress, 23 thus maintaining homeostasis. In addition to suppressing the occurrence of psychological 24 diseases such as anxiety and depression, ginseng also prevents stress-associated physiological 25 diseases. Recent findings have revealed that ginseng is involved in adjusting the 26 hypothalamic-pituitary-adrenal axis and controlling hormones, thus producing beneficial 27 effects on the heart and brain, and in cases of bone diseases, as well as alleviating erectile 28 dysfunction. Recent studies have highlighted the potential use of ginseng in the prevention 29 and treatment of chronic inflammatory diseases such as diabetes, rheumatoid arthritis, and 30 allergic asthma. However, the mechanism underlying the effects of ginseng on these stress31 related diseases has not been completely established. In this review, we focus on the disease 32 pathways caused by stress in order to determine how ginseng acts to improve health. Central to our discussion is how this effective and stable therapeutic agent alleviates the anxiety and 34 depression caused by stress and ameliorates inflammatory diseases.
Source : Journal of Ginseng Research
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Effects of Group Drumming Interventions on Anxiety, Depression, Social Resilience and Inflammatory Immune Response among Mental Health Service Users
Growing numbers of mental health organizations are developing community music-making interventions for service users; however, to date there has been little research into their efficacy or mechanisms of effect. This study was an exploratory examination of whether 10 weeks of group drumming could improve depression, anxiety and social resilience among service users compared with a non-music control group (with participants allocated to group by geographical location.) Significant improvements were found in the drumming group but not the control group: by week 6 there were decreases in depression (-2.14 SE 0.50 CI -3.16 to -1.11) and increases in social resilience (7.69 SE 2.00 CI 3.60 to 11.78), and by week 10 these had further improved (depression: -3.41 SE 0.62 CI -4.68 to -2.15; social resilience: 10.59 SE 1.78 CI 6.94 to 14.24) alongside significant improvements in anxiety (-2.21 SE 0.50 CI -3.24 to -1.19) and mental wellbeing (6.14 SE 0.92 CI 4.25 to 8.04). All significant changes were maintained at 3 months follow-up. Furthermore, it is now recognised that many mental health conditions are characterised by underlying inflammatory immune responses. Consequently, participants in the drumming group also provided saliva samples to test for cortisol and the cytokines interleukin (IL) 4, IL6, IL17, tumour necrosis factor alpha (TNFα), and monocyte chemoattractant protein (MCP) 1. Across the 10 weeks there was a shift away from a pro-inflammatory towards an anti-inflammatory immune profile. Consequently, this study demonstrates the psychological benefits of group drumming and also suggests underlying biological effects, supporting its therapeutic potential for mental health
Source : PLOS One
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A double-blind, randomized and placebo-controlled trial of Saffron (Crocus sativus L.) in the treatment of anxiety and depression
Mohsen Mazidi1, 9 / Maryam Shemshian2 / Seyed Hadi Mousavi3 / Abdolreza Norouzy2 / Tayebe Kermani4 / Toktam Moghiman2 / Akram Sadeghi5 / Naghme Mokhber6 / Majid Ghayour-Mobarhan2, 7 / Gordon A. A. Ferns8
1Key State Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Chaoyang, Beijing, P.R. China
2Biochemistry of Nutrition Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
3Pharmacological Research Center of Medicinal Plant, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
4Department of Anatomy and Cell biology, Birjand University of Medical Sciences, Birjand, Iran
5Department of Anatomy and Cellular Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
6Psychiatry and Behavioral Sciences Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
7Cardiovascular Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
8Division of Medical Education, Brighton & Sussex Medical School, University of Brighton, Brighten, UK
9Institute of Genetics and Developmental Biology, International College, University of Chinese Academy of Science (IC-UCAS), West Beichen Road, Chaoyang, P.R. China
BACKGROUND:Depression and anxiety are prevalent serious psychiatric disorders. Several drugs are used to treat these conditions but these are often associated with serious side effects. For this reason alternative therapies, including herbal medication such as saffron, have been proposed. We aimed to assess the effects of saffron extract for the treatment of anxiety and depression using a 12-week double-blind, placebo-controlled trial design.
METHODS:Sixty adult patients with anxiety and depression were randomized to receive a 50 mg saffron capsule (Crocus sativus L. stigma) or a placebo capsule twice daily for 12 weeks. Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) questionnaires were used at baseline, 6 and 12 weeks after initiating medication. 54 subjects completed the trial.
RESULTS:Saffron supplements had a significant effect on the BDI and BAI scores of subjects in comparison to placebo at the 12 week time-point (p<0.001).
CONCLUSIONS:Saffron appears to have a significant impact in the treatment of anxiety and depression disorder. Side effects were rare.
Source : Journal Complement Integr Med.
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Effect of Lemongrass Aroma on Experimental Anxiety in Humans
Tiago Costa Goes, MSc,1 Fábio Reis Carvalho Ursulino, MD,1 Thiago Henrique Almeida-Souza, BSc,1Péricles Barreto Alves, PhD,2 and Flavia Teixeira-Silva, PhD1
1Departamento de Fisiologia, Centro de Ciências Biológicas e da Saúde, Universidade Federal de Sergipe, São Cristóvão, Sergipe, Brazil.
2Departamento de Química, Centro de Ciências Exatas e Tecnológia, Universidade Federal de Sergipe, São Cristóvão, Sergipe, Brazil.
Objectives: The objective of this study was to evaluate the potential anxiolytic effect of lemongrass (Cymbopogon citratus) aroma in healthy volunteers submitted to an anxiogenic situation.
Design: Forty male volunteers were allocated to four different groups for the inhalation of lemongrass essential oil (test aroma: three or six drops), tea tree essential oil (control aroma: three drops), or distilled water (nonaromatic control: three drops). Immediately after inhalation, each volunteer was submitted to an experimental model of anxiety, the video-monitored version of the Stroop Color-Word Test (SCWT).
Outcome measures: Psychologic parameters (state anxiety, subjective tension, tranquilization, and sedation) and physiologic parameters (heart rate and gastrocnemius electromyogram activity) were evaluated before the inhalation period and before, during, and after the SCWT.
Results: Individuals exposed to the test aroma (three and six drops), unlike the control groups, presented a reduction in state anxiety and subjective tension, immediately after treatment administration. In addition, although they presented an anxious response to the task, they completely recovered from it in 5 min, unlike the control groups. Physiologic alterations along the test were not prevented by any treatment, in the same way as has previously been observed for diazepam.
Conclusions: Although more investigations are necessary to clarify the clinical relevance of lemongrass essential oil as an anxiety treatment, this work shows that very brief exposure to this aroma has some perceived anxiolytic effects.
Source : Journal Alternative and Complementary Medicine
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Oral Lavender Essential Oil Reduces Restlessness and Anxiety in Patients with Subthreshold Anxiety Disorders
Kasper S, Anghelescu I, Dienel A. Efficacy of orally administered Silexan in patients with anxiety-related restlessness and disturbed sleep – A randomized, placebo-controlled trial. Eur Neuropsychopharmacol. August 7, 2015; [epub ahead of print]. doi: 10.1016/j.euroneuro.2015.07.024.
Restlessness and sleep disturbances are among the symptoms of anxiety disorders. Patients with anxiety need a treatment that is calming but not sedating. Restlessness and disturbed sleep are the main indications for lavender (Lavandula angustifolia, Lamiaceae) flower essential oil. Silexan® (Dr. Willmar Schwabe GmbH & Co. KG; Karlsruhe, Germany) is a patented product containing 80 mg of standardized lavender flower essential oil in each soft gelatin capsule. Clinical studies show that Silexan produces anxiolysis in patients with generalized anxiety disorder (GAD) and subthreshold anxiety disorder. The purpose of this randomized, placebo-controlled, multicenter study was to evaluate the efficacy and tolerability of Silexan in patients with subthreshold anxiety disorder who suffer from restlessness and disturbed sleep.
The study was conducted at 17 general and psychiatric practices in Germany. Patients (n=170, aged 18-65 years) were included if they had restlessness and agitation according to the International Statistical Classification of Diseases and Related Health Problems (ICD-10); ≥ 5 of 10 points on a visual analog scale of restlessness and agitation; substantial disease-related impairment of daily living; ≥ 18 points on the Hamilton Anxiety Rating Scale (HAMA); ≥ 2 points for HAMA items "Tension" and "Insomnia"; and disturbed sleep as confirmed with a score of ≥ 6 points on the Pittsburgh Sleep Quality Index (PSQI). Patients were excluded for the following reasons: HAMA total score decrease of ≥ 25% between study inclusion and baseline measurements; psychiatric or neurological disease diagnosis ≥ 6 months before study entry (except anxiety); depression; somatoform disorders; neurasthenia; personality disorder; primary insomnia; suicidal; substance abuse; taking psychotropic medication or muscle relaxants; and undergoing psychotherapy. During a 3- to 7-day screening/run-in period, all patients took 1 placebo capsule. After baseline assessment, patients received either placebo or Silexan 80 mg/day for 10 weeks. The placebo contained 1/1000 of the amount of lavender oil found in Silexan to match the smell of Silexan. The primary outcome measure of anxiolytic effect was HAMA total score change; the primary outcome measure of sleep improvement was PSQI score change. The secondary outcome measures were the number of treatment responders and remitters, HAMA sub-scores, Zung Self-Rating Anxiety Scale (SAS), Clinical Global Impressions (CGI) observer rating scale, and the State Check (SC) self-check scale. Response to treatment was defined as ≥ 50% change from baseline to study end on the HAMA, and clinical remission (remitter) was defined as having a HAMA total score < 10 points at study end.
Baseline demographic characteristics were similar between groups. After randomization, the full analysis set (FAS) consisted of n=86 in the Silexan group and n=84 in the placebo group; the per-protocol (PP) analysis included n=73 in the Silexan group and n=65 in the placebo group. Exclusions from the PP analysis were comparable between the 2 groups except for non-compliance (n=8 placebo patients and n=0 Silexan patients).
Significant improvements in HAMA total score were observed in the Silexan group after 4 weeks of treatment, compared to placebo. After 10 weeks, the 12-point decrease in HAMA total score in the Silexan group was significantly greater than the 9.3-point decrease in the placebo group (P=0.03). The Silexan treatment effect was more pronounced in the PP analysis. Patients with more severe baseline HAMA total scores had greater Silexan-induced improvements. The number of responders in the Silexan group (48.8%) was significantly greater than the number (33.3%) in the placebo group (P=0.04); there was no significant difference between the 2 groups in the number of remitters. Compared with placebo, the number of patients reporting that they never, seldom, or sometimes felt restless on the SC scale significantly increased in the Silexan group (P=0.01). The CGI assessments also reflected greater improvements in the Silexan group compared to placebo. There was no significant difference between groups in the PSQI total score change, indicating that Silexan does not have a sedative effect. This finding is supported by the lack of adverse events (AEs) related to sedation.
The frequency of AEs was similar between groups, and there were no serious AEs in either group. In double-blinded assessment, 9 patients in the Silexan group and 4 patients in the placebo group had an AE in which a causal relationship to the treatment could not be excluded. All potentially related AEs in the Silexan group were gastrointestinal complaints. Overall, Silexan was well tolerated.
The authors conclude that this study not only confirms the anxiolytic effect of Silexan observed in other clinical trials but also shows it significantly reduces restlessness without causing sedation. Therefore, Silexan may be beneficial irrespective of whether the patient presents to the clinician with restlessness or anxiety. A limitation of the study is that there is no validated psychiatric scale for assessing restlessness, and the authors had to develop their own scale. The study was funded by the manufacturer of Silexan, Dr. Willmar Schwabe GmbH & Co. KG. The lead author (SK) has received funding from and served as a consultant to numerous pharmaceutical companies, including Dr. Willmar Schwabe; another author (AD) is employed by Dr. Willmar Schwabe.
—Heather S. Oliff, PhD
Source : American Botanical Council - Herbclip
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Ameliorating effects of gypenosides on chronic stress-induced anxiety disorders in mice
Ting Ting Zhao1 , Keon Sung Shin1 , Hyun Sook Choi2 and Myung Koo Lee1*
Background: Ethanol extract from Gynostemma pentaphyllum (GP) shows anti-stress and anxiolytic functions in mice, and also protects dopamine neurons in 6-hydroxydopamine-lesioned rat model of Parkinson’s disease. In addition, gypenosides (the gypenoside-enriched components of GP, GPS) have a protective effect on 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson’s disease. In this study, the ameliorating effects of GPS on chronic stress-induced anxiety disorders in mice were investigated.
Methods: Mice were orally treated with GPS (100 and 200 mg/kg) once a day for 10 days, followed by exposure to electric footshock (EF) stress (0.6 mA, 1 s every 5 s, 3 min). After the final administration of either GPS, water extract of GP (GP-WX) or ethanol extract of GP (GP-EX, positive control), the behavioral tests such as elevated plus-maze, marble burying and locomotor activity tests, and the biochemical parameters including dopamine, serotonin and corticosterone levels, and c-Fos expression were examined.
Results: Treatment with GPS (100 and 200 mg/kg) increased the number of open arm entries and the time spent on open arms in elevated plus-maze which were reduced by chronic EF stress. GPS (100 and 200 mg/kg) reduced the number of marbles buried which increased by chronic EF stress. In these states, the brain levels of dopamine and serotonin decreased by chronic EF stress and they were recovered by GPS. The serum levels of corticosterone increased by chronic EF stress were also reduced by GPS (100 and 200 mg/kg). Finally, chronic EF stress-induced c-Fos expression was markedly reduced by GPS (100 and 200 mg/kg) in the brain. GPS (100 and 200 mg/kg) also showed an equivalent efficacy on anxiolytic functions, as compared with GP-EX (50 mg/kg). However, GP-WX (50 mg/kg) showed a less effect on anxiety disorders than GP-EX (50 mg/kg) and GPS (100 and 200 mg/kg).
Conclusion: These results suggest that GPS (100 and 200 mg/kg) has anxiolytic effects on chronic EF stress-induced anxiety disorders by modulating dopamine and serotonin neuronal activities, c-Fos expression and corticosterone levels. GPS may serve as a phytonutrient in chronic stress-induced anxiety disorders.
Source : BMC Complementary and Alternative Medicine
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Systematic Review of Ashwagandha for the Treatment of Anxiety
Pratte MA, Nanavati KB, Young V, Morley CP. An alternative treatment for anxiety: a systematic review of human trial results reported for the Ayurvedic herb ashwagandha (Withania somnifera). J Altern Complement Med. 2014;20(12):901-908.
Ashwagandha (Withania somnifera, Solanaceae; WS) root is used in Ayurvedic medicine as a broad-spectrum remedy or tonic, and has been shown to have anti-inflammatory, antioxidant, and anxiolytic properties. The purpose of this systematic review was to evaluate human studies of WS as a treatment for anxiety.
The PubMed, SCOPUS, CINAHL, Google Scholar, Google, and AYUSH Research Portal databases were searched using the key words ashwagandha or withania in combination with mental health terms such as anxiety, behavior, mood, and stress. The searches were limited to English language reports of randomized, controlled clinical trials evaluating WS as a treatment for anxiety. Studies investigating formulas containing WS, review articles, and duplicate publications were excluded.
Five studies met the inclusion/exclusion criteria. Validity and risk of bias for each study was evaluated using the Cochrane Collaboration risk-of-bias tool. A meta-analysis could not be conducted because the trials had different primary outcome measures and durations (six to 12 weeks), and evaluated different doses (12,000 mg/day raw herb, 125-2,500 mg/day extract), dosage schedules (one to three times daily), and formulations (raw root, ethanol extracts, or water extracts containing 1.5%, 5%, or 12% withanolides).
One study evaluated 39 patients who were treated with 500 mg twice daily (1000 mg/day) of placebo or WS root ethanol extract (manufacturer and composition not reported) for six weeks. The dose was increased every two weeks as necessary, up to a maximum of 2,500 mg/day. There was a significant improvement on the Hamilton Anxiety Scale (HAM-A) in the WS group compared with the placebo group (P = 0.026). The risk of bias was rated as high. Limitations of the study were the relatively small sample size and short study duration, inconsistent dosing (500-2,500 mg/day), and 48.7% drop-out rate.
The second study included 130 patients who were treated with 125 mg/day or 250 mg/day Sensoril® (Natreon Inc; New Brunswick, New Jersey); 500 mg/day Essentra® (NutraGenesis LLC; Brattleboro, Vermont); or placebo for 60 days. The Sensoril and Essentra products contained root and leaf material derived from a withaferin A and withanolide glycoside-predominant genetically uniform WS chemotype and extracted using a water-based protocol. The product composition cited in the review (minimum of 8% withanolide glycosides and 32% oligosaccharides) is not consistent with the data reported in the original article (11.90% withanolide glycosides, 1.05% withaferin A, and 40.25% oligosaccharides). There was a significant WS dose-dependent increase on the modified HAM-A (P < 0.001) compared to placebo. The risk of bias was rated as unclear. Limitations of the study were the 24.6% drop-out rate and potential reporting bias (two authors were employed by the company funding the trial).
The third study included 81 patients who were treated with naturopathic counseling plus 300 mg twice daily (600 mg/day) WS root extract standardized to 1.5% withanolides (manufacturer not reported) or psychotherapy plus placebo for 12 weeks. Beck Anxiety Inventory scores significantly improved in the WS group compared with the placebo group (P < 0.0001). The risk of bias was rated as high. Limitations of the study were the 21% drop-out rate, the lack of a true control group, and potential performance bias because the therapists could not be blinded.
The fourth study included 64 patients who were treated with 300 mg twice daily (600 mg/day) WS root extract containing at least 5% withanolides (KSM-66®; Ixoreal Biomed; Hyderabad, Telangana, India) or placebo for 60 days. KSM-66 is produced using an alcohol-free and synthetic solvent-free "green chemistry" extraction process. There was significant improvement on the Perceived Stress Scale and in cortisol levels in the WS group compared with the placebo group (P < 0.0001 and P = 0.0006, respectively). The risk of bias was rated as unclear. A limitation of the study was the relatively small sample size.
The fifth study included 86 patients who were treated with anupana (milk) plus 4 g raw WS root (source not provided) or placebo three times daily (12,000 mg/day) for 60 days. To prepare the WS treatment, dried root was pulverized, combined with equal quantities of sugar syrup, sieved (40#), and dried to create granules (chemical composition/standardization was not reported). Changes in HAM-A scores were not significant compared with placebo, except for the anxious mood domain (P < 0.001). The risk of bias was rated as unclear.
All five studies concluded that WS was safe. Adverse events in the WS groups were mild and did not differ in frequency or duration compared with the control groups.
In summary, WS significantly improved measures of anxiety compared to the control in most trials. However, most of the studies were methodologically flawed and underpowered, and none attained a low risk-of-bias rating. In addition, the primary outcomes for all of these studies were patient-reported measures. The authors suggest that the addition of objective data obtained from blinded diagnostic interviews and the assessment of biomarkers would strengthen future studies. They also point out several limitations of this review, including the exclusion of studies published in other languages and trials evaluating the traditional use of WS (Ayurvedic formulas containing WS).
The authors conclude that while these "somewhat promising but early, and possibly biased, results" suggest that WS may significantly improve symptoms of stress, "additional research in larger samples and in more clinical contexts is essential to validate its therapeutic capabilities for widespread use." In addition, the optimal WS preparation form, chemical composition, dose, and dosage schedule for the treatment of anxiety remains to be determined.
—Heather S. Oliff, PhD
Source : American Botanical Council
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An Alternative Treatment for Anxiety: A Systematic Review of Human Trial Results Reported for the Ayurvedic Herb Ashwagandha (Withania somnifera)
Morgan A. Pratte, BS,1,2 Kaushal B. Nanavati, MD,1 Virginia Young, MLS,3 and Christopher P. Morley,PhD1,4,5
1Department of Family Medicine, SUNY Upstate Medical University, Syracuse, NY.
2Yale School of Public Health, New Haven, CT.
3Health Sciences Library, SUNY Upstate Medical University, Syracuse, NY.
4Department of Public Health & Preventive Medicine, SUNY Upstate Medical University, Syracuse, NY.
5Department of Psychiatry & Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY.
Objective: To assess existing reported human trials of Withania somnifera (WS; common name, ashwagandha) for the treatment of anxiety.
Design: Systematic review of the literature, with searches conducted in PubMed, SCOPUS, CINAHL, and Google Scholar by a medical librarian. Additionally, the reference lists of studies identified in these databases were searched by a research assistant, and queries were conducted in the AYUSH Research Portal. Search terms included “ashwagandha,” “Withania somnifera,” and terms related to anxiety and stress. Inclusion criteria were human randomized controlled trials with a treatment arm that included WS as a remedy for anxiety or stress. The study team members applied inclusion criteria while screening the records by abstract review.
Intervention: Treatment with any regimen of WS.
Outcome measures: Number and results of studies identified in the review.
Results: Sixty-two abstracts were screened; five human trials met inclusion criteria. Three studies compared several dosage levels of WS extract with placebos using versions of the Hamilton Anxiety Scale, with two demonstrating significant benefit of WS versus placebo, and the third demonstrating beneficial effects that approached but did not achieve significance (p=0.05). A fourth study compared naturopathic care with WS versus psychotherapy by using Beck Anxiety Inventory (BAI) scores as an outcome; BAI scores decreased by 56.5% in the WS group and decreased 30.5% for psychotherapy (p<0.0001). A fifth study measured changes in Perceived Stress Scale (PSS) scores in WS group versus placebo; there was a 44.0% reduction in PSS scores in the WS group and a 5.5% reduction in the placebo group (p<0.0001). All studies exhibited unclear or high risk of bias, and heterogenous design and reporting prevented the possibility of meta-analysis.
Conclusions: All five studies concluded that WS intervention resulted in greater score improvements (significantly in most cases) than placebo in outcomes on anxiety or stress scales. Current evidence should be received with caution because of an assortment of study methods and cases of potential bias.
Source : Alternative and Complementary Medicine
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Herbal triplet in treatment of nervous agitation in children
Inga Trompetter, Bianka Krick, and Gabriele Weiss
Emotional and behavioral problems in children and adolescents are no exception. To what extent a fixed plant extract combination is able to support children suffering from nervous agitation due to agitated depression among others for approximately 2 years has been investigated in a multicenter, prospective observational study (2008) with 115 children between 6 and 12 years. Assessments of the parents showed a distinct improvement in children who had attention problems, showed social withdrawal, and/or were anxious/depressive. Based on the physicians’ assessment, 81.6–93.9 % of the affected children had no or just mild symptoms at the end of observation concerning nine of thirteen evaluated symptoms such as depression, school/examination anxieties, further anxieties, sleeping problems, and different physical problems. Therapeutic success was not influenced by additional medication or therapies. The treatment was well tolerated. The used plant extracts have been gained from St. John’s Wort herb, valerian root, and passionflower herb.
Source : Wien Med Wochenschr.
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Antidepressant- and anxiolytic-like activities of an oil extract of propolis in rats.
Purpose: Propolis biological effects are mainly attributed to its polyphenolic constituents such as flavonoids and phenolic acids that were recently described in the chemical composition of an extract of propolis obtained with edible vegetal oil (OEP) by our group. The aim of this study was to evaluate the effect of OEP on the behavior of rats.
Materials and methods: An in vivo open field (OF), elevated Plus-maze (EPM), and forced swimming (FS) tests were performed to evaluate locomotor activity, anxiolytic- and antidepressant effects of the extract. Besides, oxidative stress levels were measured in rat blood samples after the behavioral assays by evaluation of the Trolox equivalent antioxidant capacity (TEAC) and nitric oxide levels.
Results: OEP increased locomotion in the OF test (50 mg/kg) and central locomotion and open arm entries in the OF and EPM tests (10-50 mg/kg) and decreased the immobility time in the FS test (10-50 mg/kg). Moreover, OEP reduced nitric oxide levels in response to swim stress induced in rats.
Conclusion: OEP exerted stimulant, anxiolytic and antidepressant effects on the Central Nervous System and antioxidant activity in rats, highlighting propolis as a potential therapeutic compound for behavior impairment of anxiety and depression
Source : International Journal of Phytotherapy and Phytopharmacology
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Effect of Morus alba L. (mulberry) leaves on anxiety in mice
A.V. Yadav, L.A. Kawale,1 and V.S. Nade1
Objective:The aim of the present work is to evaluate the anxiolytic effect of a methanolic extract of Morus alba L. leaves in mice.
Materials and Methods:The hole-board test, elevated plus-maze paradigm, open field test, and light/dark paradigm were used to assess the anxiolytic activity of the methanolic extract of M. alba L. Morus alba extract (50, 100, and 200 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.) were administered 30 min before the tests.
Results:The results showed that the methanolic extract of M. alba significantly increased the number and duration of head poking in the hole-board test. In the elevated plus-maze, the extract significantly increased the exploration of the open arm in similar way to that of diazepam. At a dose of 200 mg/kg i.p. the extract significantly increased both the time spent in and the entries into the open arm by mice. Further, in the open field test, the extract significantly increased rearing, assisted rearing, and number of squares traversed, all of which are demonstrations of exploratory behavior. In the light/dark paradigm, the extract produced significant increase in time spent in the lighted box as compared to vehicle. The spontaneous locomotor activity count, measured using an actophotometer, was significantly decreased in animals pretreated with M. alba extract, indicating a remarkable sedative effect of the plant.
Conclusion:The results of the present study suggest that a methanolic extract of M. alba leaves may possess an anxiolytic effect.
Source : Indian Journal of Pharmacology
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Meditation programs for psychological stress and well-being: a systematic review and meta-analysis Review published: 2014.
Bibliographic details: Goyal M, Singh S, Sibinga EM, Gould NF, Rowland-Seymour A, Sharma R, Berger Z, Sleicher D, Maron DD, Shihab HM, Ranasinghe PD, Linn S, Saha S, Bass EB, Haythornthwaite JA.
IMPORTANCE: Many people meditate to reduce psychological stress and stress-related health problems. To counsel people appropriately, clinicians need to know what the evidence says about the health benefits of meditation.
OBJECTIVE: To determine the efficacy of meditation programs in improving stress-related outcomes (anxiety, depression, stress/distress, positive mood, mental health-related quality of life, attention, substance use, eating habits, sleep, pain, and weight) in diverse adult clinical populations.
EVIDENCE REVIEW: We identified randomized clinical trials with active controls for placebo effects through November 2012 from MEDLINE, PsycINFO, EMBASE, PsycArticles, Scopus, CINAHL, AMED, the Cochrane Library, and hand searches. Two independent reviewers screened citations and extracted data. We graded the strength of evidence using 4 domains (risk of bias, precision, directness, and consistency) and determined the magnitude and direction of effect by calculating the relative difference between groups in change from baseline. When possible, we conducted meta-analyses using standardized mean differences to obtain aggregate estimates of effect size with 95% confidence intervals.
FINDINGS: After reviewing 18 753 citations, we included 47 trials with 3515 participants. Mindfulness meditation programs had moderate evidence of improved anxiety (effect size, 0.38 [95% CI, 0.12-0.64] at 8 weeks and 0.22 [0.02-0.43] at 3-6 months), depression (0.30 [0.00-0.59] at 8 weeks and 0.23 [0.05-0.42] at 3-6 months), and pain (0.33 [0.03- 0.62]) and low evidence of improved stress/distress and mental health-related quality of life. We found low evidence of no effect or insufficient evidence of any effect of meditation programs on positive mood, attention, substance use, eating habits, sleep, and weight. We found no evidence that meditation programs were better than any active treatment (ie, drugs, exercise, and other behavioral therapies).
CONCLUSIONS AND RELEVANCE: Clinicians should be aware that meditation programs can result in small to moderate reductions of multiple negative dimensions of psychological stress. Thus, clinicians should be prepared to talk with their patients about the role that a meditation program could have in addressing psychological stress. Stronger study designs are needed to determine the effects of meditation programs in improving the positive dimensions of mental health and stress-related behavior.
Source : Jama Internal Medicine
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American skullcap (Scutellaria lateriflora L): a study of its effects on mood in healthy volunteers
Christine A. Brock
School of Life Sciences
American skullcap (Scutellaria lateriflora) has long been an important herb in North American traditional medicine systems and western materia medica for anxiety and related disorders. A previous clinical study assessing acute effects of S. lateriflora
indicated it has anxiolytic actions with minimal loss of energy or cognition. The aim of the present study was to extend these findings by determining the putative mood enhancing effects and safety of S. lateriflora following its chronic administration to healthy volunteers. Based on a randomised, double - blind, placebo-controlled crossover design, it examined the effects of S. lateriflora
on psychologic symptoms using the Beck Anxiety Inventory (BAI) and the Profile of Mood States (POMS) questionnaires, and its potential physiological effects on stress by measuring free cortisol levels in saliva, at baseline and following administration of
S. lateriflora or placebo. Liver function was assessed at the same time points by measuring levels of serum alanine
aminotransferase (ALT). Pre and post intervention blood pressure and pulse rate were also measured. Freeze -dried S. lateriflora
for use in the present study was authenticated by the use of high performance liquid chromatography. Participants (n = 43) were randomised to either freeze-dried S. lateriflora (350 mg) or Urtica dioica folia (300 mg) placebo three times daily for 14 days. There was a 7 day washout period prior to crossover. Analysis of results was from 31 participants completing the study.
Results from the BAI demonstrated no significant difference between S. lateriflora and placebo (p= 0.191) in anxiety scores. The results from the POMS factors demonstrated there was no significant difference between S. lateriflora and placebo in scores for Tension -Anxiety (p= 0.473), Anger-Hostility(p= 0.070) or for Depression - Dejection (p= 0.067). Overall results from subjective measures of global mood as measured by Total Mood Disturbance (TMD) on the POMS also demonstrated no significant difference between S. lateriflora and placebo (p= 0.137). Additionally, the POMS showed there was no reduction in energy or cognition
following chronic administration of S. lateriflora , evidenced by there being no difference between S. lateriflora and placebo for Vigour-Activity (p= 0.244) and Confusion-Bewilderment (p= 0.838) scores respectively. From inspection of the means for both BAI and the POMS factors, however, there was an enhanced effect of S. lateriflora compared to placebo in those who took the placebo first (n = 15) and an enhanced effect of placebo compared to S. lateriflora for those who took S. lateriflora ii first (n = 16) suggesting a residual effect of S.lateriflora due to insufficient washout. There was no significant difference between S. lateriflora and placebo (p
= 0.524) in salivary cortisol measurements, suggesting no attenuation of the hypothalamic -pituitary adrenal (HPA) axis by
S.lateriflora. The ALT measurements revealed no significant difference between S. lateriflora and placebo (p= 0.801), suggesting there was no acute toxicity fromS. lateriflora. Furthermore, there was no significant difference between S.lateriflora and
placebo in effects on systolic (p=0.410) or diastolic (p=0.834) blood pressures or pulse rate (p=0.144), all of which remained within the normal range for healthy adults . According to the participants’ diary reports, there were no adverse reactions and only mild and infrequent side-effects, which may not have been attributable to S. lateriflora. The results suggested that S. lateriflora may have anxiolytic and mood enhancing effects in some individuals without notable side-effects or reduction in energy or cognition. Contrary to anecdotal evidence, there was no worsening of depression following administration of S. lateriflora. Further research is needed in a larger study population, using a sample with self - reported and/or diagnosed anxiety and mood disturbances, in order to further determine the effects of the herb on these paradygms.
Source : University of Westminster Research
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Worry, Jealousy, Moodiness Linked to Higher Risk of Alzheimer’s in Women
Women who are anxious, jealous, or moody and distressed in middle age may be at a higher risk of developing Alzheimer’s disease later in life, according to a nearly 40-year-long study published in the October 1, 2014, online issue of Neurology®, the medical journal of the American Academy of Neurology.
“Most Alzheimer’s research has been devoted to factors such as education, heart and blood risk factors, head trauma, family history and genetics,” said study author Lena Johannsson, PhD, of the University of Gothenburg in Gothenburg, Sweden. “Personality may influence the individual’s risk for dementia through its effect on behavior, lifestyle or reactions to stress.”
For the study, 800 women with an average age of 46 were followed for 38 years and given personality tests that looked at their level of neuroticism and extraversion or introversion, along with memory tests. Of those, 19 percent developed dementia.
Neuroticism involves being easily distressed and personality traits such as worrying, jealousy or moodiness. People who are neurotic are more likely to express anger, guilt, envy, anxiety or depression. Introversion is described as shyness and reserve and extraversion is associated with being outgoing.
The women were also asked if they had experienced any period of stress that lasted one month or longer in their work, health, or family situation. Stress referred to feelings of irritability, tension, nervousness, fear, anxiety or sleep disturbances. Responses were categorized as zero to five, with zero representing never experiencing any period of stress, to five, experiencing constant stress during the last five years. Women who chose responses from 3 and 5 were considered to have distress.
The study found that women who scored highest on the tests for neuroticism had double the risk of developing dementia compared to those who scored lowest on the tests. However, the link depended on long-standing stress.
Being either withdrawn or outgoing did not appear to raise dementia risk alone, however, women who were both easily distressed and withdrawn had the highest risk of Alzheimer’s disease in the study. A total of 16 of the 63 women, or 25 percent, who were easily distressed and withdrawn developed Alzheimer’s disease, compared to eight out of the 64 people, or 13 percent, of those who were not easily distressed and were outgoing.
Source : Newswise
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Effect of Aromatherapy on Cognitive Test Anxiety Among Nursing Students
Catherine E. Johnson, PhD, RN, MSN, MBA
Objective: To assess the effect of aromatherapy (Citrus limon [lemon] essential oil) on cognitive test anxiety among nursing students, Cognitive Test Anxiety Survey (CTAS) scores were measured pre- and postintervention.
Participants: Thirty-nine (39) sophomore nursing students(35 female and 4 male) from a private, 4-year college participated in this study.
Materials and Methods: A quantitative, randomized, pretest–post test design was used. One nursing examination was used for baseline data and all participants were e-mailed the CTAS. The experimental group completed the second examination in a room with diffused aromatherapy, and the control group remained in a classroom without aromatherapy. The CTAS was e-mailed for comparison data.
Results: There were no significant differences between the control and study groups in relation to preintervention cognitive anxiety scores (mean [M] = 78.17 and M = 73.62), respectively .In the control group, there was a 3-point decrease in cognitive test anxiety scores between pretest and post-test. However, there was a significant decrease in cognitive test anxiety scores in the students who received aromatherapy compared to those who did not (P = 0.10). Age and gender were not moderating variables in this study.
Conclusions: Diffused lemon essential oil is a safe, cost effective intervention that had a positive effect on cognitive test anxiety among nursing students.
Source : Alternative and Complementary Medicine
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The Anxiolytic Effect of Aromatherapy on Patients Awaiting Ambulatory Surgery: A Randomized Controlled Trial
Cheng-Hua Ni,1,2,3,4 Wen-Hsuan Hou,4,5,6 Ching-Chiu Kao,1,2 Ming-Li Chang,2 Lee-Fen Yu,1,2 Chia-Che Wu,7,8 and Chiehfeng Chen6,9,10,11
1School of Nursing, College of Nursing, Taipei Medical University, Taipei 11031, Taiwan
2Department of Nursing, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan
3Head Nurse of Operating Room, Department of Nursing, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan
4Department of Physical Medicine and Rehabilitation, Taipei Medical University Hospital, Taipei Medical University, Taipei 11031, Taiwan
5School of Gerontology Healthcare Management, College of Nursing, Taipei Medical University, Taipei 11031, Taiwan
6Center for Evidence-Based Medicine, Taipei Medical University, Taipei 11031, Taiwan
7Department of Otolaryngology, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan
8Department of Otolaryngology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
9Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
10Division of Plastic Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan
11Evidence-Based Medicine Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan
The aim of this study was to determine if aromatherapy could reduce preoperative anxiety in ambulatory surgery patients. A total of 109 preoperative patients were randomly assigned to experimental (bergamot essential oil) and control (water vapor) conditions and their responses to the State Trait Anxiety Inventory and vital signs were monitored. Patients were stratified by previous surgical experience, but that did not influence the results. All those exposed to bergamot essential oil aromatherapy showed a greater reduction in preoperative anxiety than those in the control groups. Aromatherapy may be a useful part of a holistic approach to reducing preoperative anxiety before ambulatory surgery.
Source : Evidence Based Complementary and Alternative Medicine
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The Role of Mindfulness and Psychological Flexibility in Somatization, Depression, Anxiety, and General Psychological Distress in a Nonclinical College Sample
Akihiko Masuda, PhD1 and Erin C. Tully, PhD1
The current study investigated whether mindfulness and psychological flexibility uniquely and separately accounted for
variability in psychological distress (somatization, depression, anxiety, and general psychologicaldistress).Anethnicallydiverse,
nonclinical sample of college undergraduates (N=494, 76% female) completed a Web-based survey that included the self-
report measures of interest. Consistent with prior research, psychological flexibility and mindfulness were positively associated
with each other, and tested separately, both variables were negatively associated with somatization, depression, anxiety, and
general psychological distress. Results also revealed that psychological flexibility and mindfulness accounted for unique variance
in all 4 measures of distress. These findings suggest that mindfulness and psychological flexibility are interrelated but not redun-
dant constructs and that both constructs are important for understanding the onset and maintenance of somatization, depres-
sion,anxiety,and general distress.
Source : Journal of Evidence Based Complementary and Alternative Medicine
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Neuropharmacological studies of Piper auritum Kunth (Piperaceae): antinociceptive and anxiolytic-like effects
R. Estrada-Reyes*, A. Martínez-Laurrabaquio, D. Ubaldo Suárez and A.G. Araujo-Escalona
Laboratorio de Fitofarmacología, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calzada México-Xochimilco 101, Col. San Lorenzo Huipulco, Delegación Tlalpan, Mexico City, 14370, Mexico.
P. auritum Kunth leaves commonly known as “hierba santa” or “acuyo” or false Kava is used in Mexican Traditional Medicine as a tranquilizing and appetite stimulant agent, as well as a remedy for the relief of headache. The objective of the present work was to evaluate the effects of organic and aqueous extracts of Piper auritum Kunth (Piperaceae) leaves on the Central Nervous System (CNS) in mice. For acute toxicity evaluation, the LD50 of all extracts were determined according to Locke's method. Effects of both the organic and aqueous extracts of P. auritum leaves were tested in sodium pentobarbital-induced sleep, hot plate and open field tests. The anxiolytic-like effects were determined in burying behavior and hole-board models. In this study we demonstrated for the first time that both organic andaqueous extracts of the leaves of P. auritum possess antinociceptive effect while at higher doses the organic extracts exert a depressant effect on the CNS in mice. The aqueous extract showed antinociceptive and anxiolytic-like effects in the model tested, without affecting the locomotor activity of experimental animals. Acute toxicity tests show that the intake of extracts of different polarities of P. auritum involves no health risks. The present study supports, in part, the uses of P. auritum leaves as a tranquilizer, sedative agent, and as a remedy for the relief of pain in Mexican traditional medicine.
Source : Journal of Medicinal Plant Research
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Effects of a Brief Qigong-based Stress Reduction Program (BQSRP) in a distressed Korean population: a randomized trial
Eun-Young Hwang1†, Sun-Yong Chung1†, Jae-Heung Cho2, Mi-Yeon Song2, Sehyun Kim3 and Jong-Woo Kim1*
1 Departments of Korean Neuropsychiatry, College of Korean Medicine and Institute of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea
2 Department of Korean Rehabilitation, College of Korean Medicine and Institute of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea
3 Graduate School of Dankook University Jukjeon Campus, 152 Jukjeon-ro, Suji-gu, Yongin-si, Gyeonggi-do 448-701, Republic of Korea
Background Distressed individuals in Korea may benefit from the practice of mind–body exercises such as Qigong. However, the effectiveness of such techniques needs to be investigated.
Methods Fifty participants who were eligible to this study were randomized into a group receiving a 4-week intervention of a brief Qigong-based stress reduction program (BQSRP) or a wait-list control group. Before and after the intervention period, saliva samples were collected and questionnaires were completed on perceived stress, anxiety, “Hwa-Byung” (anger syndrome), and quality of life. Salivary cortisol has emerged in mind-body therapy research as an easy-to-collect, relatively inexpensive, biologic marker of stress. Salivary corisol were collected to evaluate physiological effect of BQSRP. Between-group comparisons of change from baseline to study completion were analyzed by analysis of covariance for the Perceived Stress Scale and independent two sample t-tests for other measures.
Results Compared with the control group, the BQSRP intervention group displayed significantly larger decreases in Perceived Stress Scale scores (p = 0.0006), State Anxiety scores (p = 0.0028), Trait Anxiety scores (p < 0.0001), personality subscale scores of the Hwa-Byung Scale (p = 0.0321), symptoms scores of the Hwa-Byung Scale (p = 0.0196), and a significantly larger increase in World Health Organization Quality of Life Abbreviated version scores (ps < .05). Salivary cortisol levels were not changed.
Conclusions The BQSRP appears to be effective in reducing stress perception, anxiety, anger, and improving quality of life
Source : BMC Complementary and Alternative Medicine
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Nutritional and herbal supplements for anxiety and anxiety-related disorders: systematic review
Lakhan SE, Vieira KF.
Global Neuroscience Initiative Foundation, Los Angeles, CA, USA. email@example.com
BACKGROUND: Over the past several decades, complementary and alternative medications have increasingly become a part of everyday treatment. With the rising cost of prescription medications and their production of unwanted side effects, patients are exploring herbal and other natural remedies for the management and treatment of psychological conditions. Psychological disorders are one of the most frequent conditions seen by clinicians, and often require a long-term regimen of prescription medications. Approximately 6.8 million Americans suffer from generalized anxiety disorder. Many also suffer from the spectrum of behavioural and physical side effects that often accompany its treatment. It is not surprising that there is universal interest in finding effective natural anxiolytic (anti-anxiety) treatments with a lower risk of adverse effects or withdrawal.
METHODS: An electronic and manual search was performed through MEDLINE/PubMed and EBSCO. Articles were not discriminated by date of publication. Available clinical studies published in English that used human participants and examined the anxiolytic potential of dietary and herbal supplements were included. Data were extracted and compiled into tables that included the study design, sample population, intervention, control, length of treatment, outcomes, direction of evidence, and reported adverse events.
RESULTS: A total of 24 studies that investigated five different CAM monotherapies and eight different combination treatments and involved 2619 participants met the inclusion criteria and were analyzed. There were 21 randomized controlled trials and three open-label, uncontrolled observational studies. Most studies involved patients who had been diagnosed with either an anxiety disorder or depression (n = 1786). However, eight studies used healthy volunteers (n = 877) who had normal levels of anxiety, were undergoing surgery, tested at the upper limit of the normal range of a trait anxiety scale, had adverse premenstrual symptoms or were peri-menopausal, reported anxiety and insomnia, or had one month or more of elevated generalized anxiety. Heterogeneity and the small number of studies for each supplement or combination therapy prevented a formal meta-analysis. Of the randomized controlled trials reviewed, 71% (15 out of 21) showed a positive direction of evidence. Any reported side effects were mild to moderate.
CONCLUSIONS: Based on the available evidence, it appears that nutritional and herbal supplementation is an effective method for treating anxiety and anxiety-related conditions without the risk of serious side effects. There is the possibility that any positive effects seen could be due to a placebo effect, which may have a significant psychological impact on participants with mental disorders. However, based on this systematic review, strong evidence exists for the use of herbal supplements containing extracts of passionflower or kava and combinations of L-lysine and L-arginine as treatments for anxiety symptoms and disorders. Magnesium-containing supplements and other herbal combinations may hold promise, but more research is needed before these products can be recommended to patients. St. John's wort monotherapy has insufficient evidence for use as an effective anxiolytic treatment.
Source :Nutr J. 2010 Oct 7;9:42. doi: 10.1186/1475-2891-9-42
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The Influence of Olfactory Stimulation by Essential Oils on Salivary Alpha-Amylase Activity and State Anxiety Level
Yoshie NAGATA1,2,*, Yoko MIYASHITA2,3, Mitsuru MORI2
1 Department of Nursing, Hokkaido Bunkyo University School of Faculty of Human Science
2 Department of Public Health, Sapporo Medical University School of Medicine
3 Department of Health and Nutrition, Hokkaido Bunkyo University School of Faculty of Human Science
It is considered that olfactory stimulation by fragrance inhalation is one of the methods of relaxation. We examined the possibility by using fragrance inhalation essential oils, such as sweet orange oil and peppermint oil. We measured salivary alpha-amylase activity and stateanxiety levels in undergraduate students before and after inhalation. Salivary alpha-amylase activity levels have been utilized to assess the sympathetic nervous activity. Our results indicate that both salivary alpha-amylase activity and state anxiety levels are significantly reduced after fragrance inhalation of the sweet orange oil. Consequently, our research suggests that sweet orange essential oil has a relaxation effect.
Source : Journal Japanese of Complementary and Alternative Medicine
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Kava for the Treatment of Generalized Anxiety Disorder Shows Efficacy and No Adverse Effects in Liver Function
Evidence suggests that kava (Piper methysticum) is efficacious; however, cases of hepatotoxicity have led to its withdrawal or restricted use in many Western countries. Considering that kava has benzodiazepine-like effects, questions arise as to whether kava is addictive, has adverse sexual side effects, or has withdrawal effects. Hence, the purpose of this randomized, double-blind, placebo-controlled study was to evaluate adverse events (AEs), withdrawal/addiction effects, and liver function effects associated with kava use in patients with generalized anxiety disorder (GAD). Also, genetic polymorphism of the liver enzyme cytochrome P450 2D6 (CYP2D6), which metabolizes kava, was evaluated to determine whether subjects who were poor or extensive metabolizers have different AEs.
Patients (n = 58; aged 18-65 years) with DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) diagnosed GAD were recruited from the Greater Melbourne area in Victoria, Australia via mass media. Excluded patients had major depressive disorder or elevated depressive symptomatology (> 17 on the Montgomery-Asberg Depression Rating Scale); a DSM-IV diagnosis of a psychotic or bipolar disorder illness; significant suicidal ideation in the previous 6 months; current use of antidepressants, mood stabilizers, antipsychotics, opioid analgesics, or St. John's wort (Hypericum perforatum); diagnosed hepatobiliary disease/inflammation; substance abuse or dependency disorder in the previous 6 months; a previous adverse reaction to kava or benzodiazepines; kava or benzodiazepine use in the previous 12 months; or abnormal baseline liver function. The study began with a 1-week placebo run-in phase. Any subject who showed a 50% improvement on the Hamilton Anxiety Scale (HAM-A) score was excluded from the study.
For 6 weeks, patients received placebo or 120 mg of kavalactones/day, which was titrated to 240 mg/day in patients showing no response at 3 weeks. The kava was formulated from pressed, dried, aqueous peeled rootstock of kava (Integria Healthcare; Eight Mile Plains, Queensland, Australia). At weeks 2 and 7, AEs were assessed via questionnaire, and blood was drawn for liver function tests and to determine polymorphisms.
There were no significant AEs reported. There was 1 case of dermatitis and 1 case of minor stomach upset that were attributed to kava intake. Withdrawal was assessed by treating all patients with placebo for 1 week at study end. There was no significant increase in AEs in either treatment group. Addiction was assessed by evaluating the number of patients who said that they wanted an increase in dose. Both treatment groups had the same number of patients who wanted to increase the dosage. There were no significant differences from baseline in liver function tests, and no patient developed clinical signs of hepatic abnormality. However, gamma-glutamyl transpeptidase (GGT) was elevated in kava-treated patients compared with those who took placebo at week 7 (P = 0.08). This finding may be due to an outlier; 1 patient had an isolated increase in GGT. Intermediate or extensive CYP2D6 metabolizer status had no significant impact on the type or frequency of AEs or abnormal liver function tests. Kava did not diminish sexual performance or enjoyment in men and women. However, there was a trend for kava-treated men to have more difficulty reaching orgasm (P = 0.067). Kava-treated women had a significant increase in sex drive (P = 0.04).
The authors conclude that kava has no deleterious effects on sexual function and pleasure, has no addictive qualities or withdrawal issues, and is safe for patients with GAD when taken for 6 weeks. Patients with GAD would require treatment for longer than 6 weeks, so a longer-term study is needed to confirm the findings. Nonetheless, this study contributes to the growing body of evidence that water-soluble, standardized formulations of kava from noble cultivars are safe. The authors conclude that these data may assist in the reintroduction of kava in restricted markets. This study uses a medicinal dose of kava, and the results cannot be extrapolated to traditional recreational use.
—Heather S. Oliff, PhD
Source : American Botanical Council via
Sarris J, Stough C, Teschke R, et al. Kava for the treatment of generalized anxiety disorder RCT: Analysis of adverse reactions, liver function, addiction, and sexual effects. Phytother Res. January 24, 2013; [epub ahead of print]. doi: 10.1002/ptr.4916.
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Anxiety, Depression Identify Heart Disease Patients at Increased Risk of Dying
Heart disease patients who have anxiety have twice the risk of dying from any cause compared to those without anxiety, according to new research in the Journal of the American Heart Association.
Patients with both anxiety and depression have triple the risk of dying, researchers said.
"Many studies have linked depression to an increased risk of death in heart disease patients," said Lana Watkins, Ph.D., lead author of the study and an associate professor in Psychiatry and Behavioral Sciences at Duke University Medical Center in Durham, N.C. "However, anxiety hasn't received as much attention."
Studies show that depression is about three times more common in heart attack patients. The American Heart Association recommends that heart patients be screened for depression and treated if necessary.
Depressed heart disease patients often also have anxiety, suggesting it may underlie the risk previously attributed solely to depression, Watkins said. "It's now time for anxiety to be considered as important as depression, and for it to be examined carefully."
In the study, 934 heart disease patients, average age 62, completed a questionnaire measuring their level of anxiety and depression immediately before or after a cardiac catheterization procedure at Duke University Medical Center. Patients had anxiety if they scored 8 or higher on a scale composed of seven common characteristics of anxiety, with each item rated from 0 to 3 (range of possible scores: 0-21). Depression was measured using a similar scale composed of seven symptoms of depression.
Researchers, after accounting for age, congestive heart failure, kidney disease and other factors that affect death risk, found:
- 90 of the 934 patients experienced anxiety only, 65 experienced depression only and 99 suffered anxiety and depression.
- Among 133 patients who died during three years of follow-up, 55 had anxiety, depression or both. The majority of deaths (93 of 133) were heart-related.
Anxiety and depression each influence risk of death in unique ways. Anxiety, for example, increases activity of the sympathetic (adrenaline-producing) nervous system that controls blood pressure.
"People who worry a lot are more likely to have difficulty sleeping and to develop high blood pressure," Watkins said.
The link between depression and mortality is more related to behavioral risk factors, she said. "Depression results in lack of adherence to medical advice and treatments, along with behaviors like smoking and being sedentary."
Future studies should test strategies to manage anxiety alone and with depression in heart disease patients, Watkins said.
"Anxiety reducing medications combined with stress management could improve outcome for patients with just anxiety, whereas patients with anxiety and depression may need a stronger intervention involving more frequent outpatient monitoring and incentives to improve adherence," she said.
Source : Science Daily
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Anxiety About Relationships May Lower Immunity, Increase Vulnerability to Illness
Concerns and anxieties about one’s close relationships appear to function as a chronic stressor that can compromise immunity, according to new research.
In the study, researchers asked married couples to complete questionnaires about their relationships and collected saliva and blood samples to test participants’ levels of a key stress-related hormone and numbers of certain immune cells.The research focused on attachment anxiety. Those who are on the high end of the attachment anxiety spectrum are excessively concerned about being rejected, have a tendency to constantly seek reassurance that they are loved, and are more likely to interpret ambiguous events in a relationship as negative.
Married partners who were more anxiously attached produced higher levels of cortisol, a steroid hormone that is released in response to stress, and had fewer T cells – important components of the immune system’s defense against infection – than did participants who were less anxiously attached.
“Everyone has these types of concerns now and again in their relationships, but a high level of attachment anxiety refers to people who have these worries fairly constantly in most of their relationships,” said Lisa Jaremka, lead author of the study and a postdoctoral fellow in Ohio State University’s Institute for Behavioral Medicine Research (IBMR).
Though some scientists theorize that attachment anxiety can be traced to inconsistent care during one’s infancy, Jaremka noted that there is also research-based evidence that people with attachment anxiety can change.
“It’s not necessarily a permanent state of existence,” she said.
The study appears online and is scheduled for future print publication in the journal Psychological Science.
Jaremka and colleagues tested the health effects of attachment anxiety on 85 couples who had been married for an average of more than 12 years. Most participants were white, and their average age was 39 years.
The participants completed a questionnaire called The Experiences in Close Relationships scale. They also reported general anxiety symptoms and their sleep quality. Researchers collected saliva samples over three days and blood samples over two days.
Participants with higher attachment anxiety produced, on average, 11 percent more cortisol than did those with lower attachment anxiety. The more anxiously attached participants also had between 11 percent and 22 percent fewer T cells than did less anxiously attached partners. Four T-cell markers were analyzed in the study.
The combined findings make sense and are likely related, Jaremka said, because cortisol can have immunosuppressive effects – meaning it can inhibit production of these very same T cells. Previous research has suggested that reduced T-cell levels can impair the immune response to vaccines and that low levels of the cells are a hallmark of an aging immune system.
Attachment anxiety is considered a phenomenon related to childhood development, Jaremka explained. At a very young age, children learn whether or not their primary caregivers will respond when the children are in distress. If caregivers are responsive, children learn they can rely on other people. If care is inconsistent or neglectful, children can develop feelings of insecurity that might manifest as attachment anxiety later in life.
Though she knows of no research-based advice about how to shed these feelings of insecurity, Jaremka said it is clear that people can change.
“Most research that does exist in this area supports the idea that being in very caring, loving, close relationships might be a catalyst to change from being very anxious to not,” she said.
Jaremka’s research focuses on the physiological effects of dissatisfaction in relationships, or the feeling of being disconnected from other people. She also recently published a paper suggesting that loneliness can tax the immune system.
She works in the lab of Jan Kiecolt-Glaser, a professor of psychiatry and psychology at Ohio State, who was the principal investigator on a larger study in which the married couples participated. Kiecolt-Glaser, Jaremka and colleagues are continuing studies of links between health and close relationships, and are currently seeking participants for a study exploring connections between fast food and the immune system in married couples. More information is available online here: http://pni.osumc.edu/jkg/stressandhealth/couples.html.
Source : Newswise
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Black Cohosh Reduces Physiological and Psychological Stress Responses
Nadaoka I, Yasue M, Sami M, Kitagawa Y, Koga Y. Oral administration of Cimicifuga racemosa extract attenuates psychological and physiological stress responses. Biomed Res. June 2012;33(3):145-152.
Black cohosh (BC; Actaea racemosa syn. Cimicifuga racemosa) dietary supplements are most commonly used to reduce negative menopausal symptoms. In Native American traditional medicine, BC was used as a tonic, analgesic, and fatigue treatment, in addition to its prevalent usage in childbirth and the treatment of menstrual problems. Pharmacological studies have confirmed that BC exerts dopaminergic and serotonergic effects, rather than estrogen-like activities. In vitro, BC is an agonist of serotonin receptors, a competitive ligand and partial agonist of opiate receptors, and a positive modulator of gamma-aminobutyric acid (GABA) receptors. In vivo, BC has also been shown to attenuate the hypothalamic-pituitary-adrenal axis (HPA axis) stress response by decreasing corticosterone levels and modulating the sympathetic adrenomedullary (SAM) system stress-induced changes in dopamine (DA), serotonin (5-hydroxytryptamine [5-HT]), and norepinephrine (NE) metabolism. However, the anxiolytic effects of BC have not been evaluated in humans. This randomized, double-blind, placebo-controlled, crossover trial investigated the effects of BC on stress via the measurement of chromogranin-A (CgA; a protein used as a stress marker), cortisol, perceived stress intensity, and brainwave patterns.
This study consisted of 2 experiments with healthy adults. Twenty men (n=20) were enrolled in experiment 1, while both men (n=6) and women (n=5) were enrolled in experiment 2 (n=11). All subjects were free from a history of or current mental illness and drug use. They were instructed to continue normal sleep and other general routines, and to refrain from heavy physical exercise, tobacco use, and stimulant consumption (e.g., alcohol, caffeine, etc.) the day prior to each test. Subjects were randomized to receive either 200 mg/day of encapsulated BC extract (supplied by Nippon Funmatsu Yakuhin; Osaka, Japan) or identical placebo capsules containing 200 mg of lactose. [Note: No information on the extract preparation, concentration, or standardization was given.] Statistical significance was designated at P-values <0.05.
The first experiment consisted of 2 test sessions conducted a week apart. On the test day, baseline psychological measurements and saliva samples were collected before the subjects took the study medication. One hour following ingestion, the Uchida-Kraepelin (U-K) test, a math-related questionnaire testing for speed and accuracy, was administered in such a way as to impede subjects' successful completion. At the end of the U-K test (time 0) and 60 minutes later, saliva and psychological parameters were again assessed. The procedure was repeated 1 week later with the subjects taking the alternate medication.
The psychological measures were a visual analog scale (VAS) of perceived stress intensity and the State-Trait Anxiety Inventory (STAI). With the BC treatment, the mean VAS score was significantly lower at time 0 compared to placebo (P<0.01). No significant differences in the STAI scores were observed.
The saliva samples were analyzed to determine the concentration of the physiological stress markers CgA and cortisol. CgA is an indicator of the stress response mediated by the SAM system, while cortisol is an indicator of the response mediated by the HPA axis.
The BC treatment attenuated the SAM system-mediated stress response, significantly lowering CgA concentrations midway through the U-K test (P=0.05), at time 0 (P=0.01), and 60 minutes after completing the test (P<0.05). No significant differences were seen in cortisol concentrations.
In experiment 2, a modified U-K test requiring oral answers was conducted 60 minutes after ingestion of the study medication. Electroencephalography (EEG) was used to measure alpha waveband brain activity prior to the U-K test (baseline), mid-test, at time 0 (end of test), and 60 minutes after the test. The test was repeated 7 days later with subjects taking the alternate treatment.
The left and right occipital EEG data was analyzed for temporal variations in the alpha waveband. A recovery trend was observed from time 0 to 60 minutes after the test but the differences were not statistically significant (P=0.06 and P=0.07, respectively).
In summary, BC significantly reduced the VAS measure of psychological stress but not the STAI. It significantly reduced the concentration of the SAM system stress response indicator, CgA, but did not affect the concentration of the HPA axis stress response indicator, cortisol. In light of the in vitro and in vivo data and the limitations of this study, the authors maintain that BC affects both the HPA axis and SAM system stress responses and they suggest that BC may be suitable for the prevention and treatment of stress-related disorders.
This study suffers from a few major problems. The results cannot be generalized to other BC extracts nor can other researchers repeat the experiments because no information regarding the BC extract preparation, concentration, or standardization is provided. Inclusion criteria are not described and exclusion criteria are limited. The testing was done in the morning, when cortisol levels are high – a flaw in the study design. In this case, the salivary CgA would have been a better indicator of psychological stress. It reflects psychological stress more rapidly and is considered more sensitive than cortisol. The sample size was also very small. Nonetheless, the balance of the evidence indicates that further studies of BC's anxiolytic mechanism of action and clinical efficacy are warranted.
by Amy C. Keller, PhD
Source : American Botanical Council
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Chronic Anxiety Speeds Ageing
Chronic panic, phobia, and similar anxiety disorders may contribute to premature aging by shortening telomeres, an observational study suggested.
Women with the most severe phobic anxiety had telomere length 0.09 standardized units below average (P=0.02 versus less phobic women), Olivia I. Okereke, MD, of Brigham and Women's Hospital and Harvard in Boston, and colleagues reported online in PLoS ONE.
"The magnitude of this difference was comparable to that for women 6 years apart in age," they noted.
While lesser degrees of chronic anxiety showed a trend for shorter telomeres as well, the researchers called it primarily a threshold effect.
Shortening of telomeres -- a gradual process of loss of the repetitive DNA sequences capping off chromosomes that occurs when cells divide -- isn't reversible.
Prior studies have suggested that oxidative stress and inflammation accelerates the process, leading to DNA damage linked to cancer, cardiovascular disease, cognitive decline, and dementia.
However, "phobic anxiety is treatable; thus, any potential impacts on telomere shortening may be amenable to prevention through early identification and treatment," the researchers explained.
They used phobic anxiety as a typically chronic form of anxiety to look for correlation with telomere length in peripheral blood leukocytes among 5,243 women from the Nurses' Health Study, controls in prior case-control studies of telomeres and disease, and a random group of healthy women in a cognitive function sub-study.
Higher levels of long-term general anxiety as measured on the Crown-Crisp phobic index, which focuses on 'fear' disorders like panic and agoraphobia, showed a trend for lower age-adjusted relative telomere length z-scores (P=0.09).
But the more anxious women tended to be less healthy on a wide range of characteristics. After adjustment for significant factors -- paternal age at birth, smoking, body mass index, and physical activity -- the trend was further attenuated (P=0.15).
Women with a high anxiety score of 6 points or greater (range up to 16) appeared to account for the effect.
Whereas women with scores under 6 had an adjusted mean telomere length z-score of 0.02 standard units, the mean was -0.09 for women with higher scores, yielding a significant 0.10 standard-unit difference between groups (P=0.02).
By comparison, 1 additional year of age was associated with a -0.015 lower mean relative telomere length z-score.
The impact of high chronic anxiety levels appeared to be particularly strong among nonsmokers, which the researchers called counterintuitive, although smokers had shorter telomeres to start with.
The difference in telomere length among nonsmokers with a score of 6 or more versus 5 or less was -0.25 standard units (P<0.001).
Excluding women with cardiovascular disease, diabetes or obstructive airway diseases -- "chronic diseases that may act as intermediates ... and also may be associated with telomere shortening" -- attenuated the difference for high anxiety levels to a nonsignificant trend, at a mean of -0.07 standard units (P=0.12).
This finding suggested that the "findings may be partly explained by influences of phobic anxiety on risk of development of serious chronic diseases," Okereke's group noted.
They cautioned that women in the highest phobic symptom category that was linked to telomere shortening wouldn't necessarily meet diagnostic criteria for an anxiety disorder, "although this appears plausible."
Another limitation was that the study design didn't allow for determining whether the phobic anxiety predated the telomere shortening.
Causality is possible in either direction, the group pointed out.
Lack of data on anxiety duration and treatments, depression, or other residual confounders as well as the predominantly white population studied were also limitations.
The study was supported by National Institutes of Health grants.
The researchers reported having no conflicts of interest to disclose.
Primary source: PLoS ONE
Okereke OI, et al "High phobic anxiety is related to lower leukocyte telomere length in women" PLoS ONE 2012;7: DOI: 0.1371/journal.pone.0040516.
Source : Medical News Today
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Anxiety Can Burn Out Women's Brains
The brains of anxious women work much harder than those of men, new research shows.
The finding stems from an experiment in which college students performed a relatively simple task while their brain activity was measured by an electrode cap. Only women who identified themselves as particularly anxious or big worriers recorded high brain activity when they made mistakes during the task.
Jason Moser, lead investigator on the project, says the findings may ultimately help mental health professionals determine when females at a younger age are prone to anxiety problems such as obsessive compulsive disorder or generalized anxiety disorder.
“This may help predict the development of anxiety issues later in life for girls,” says Moser, assistant professor of psychology at Michigan State University. “It’s one more piece of the puzzle for us to figure out why women in general have more anxiety disorders.”
The study, reported in the International Journal of Psychophysiology, is the first to measure the correlation between worrying and error-related brain responses in the sexes using a scientifically viable sample (79 female students, 70 males).
Participants were asked to identify the middle letter in a series of five-letter groups on a computer screen. Sometimes the middle letter was the same as the other four (“FFFFF”) while sometimes it was different (“EEFEE”). Afterward they filled out questionnaires about how much they worry.
Although the worrisome female subjects performed about the same as the males on simple portions of the task, their brains had to work harder at it. Then, as the test became more difficult, the anxious females performed worse, suggesting worrying got in the way of completing the task, Moser says.
“Anxious girls’ brains have to work harder to perform tasks because they have distracting thoughts and worries,” Moser explains. “As a result their brains are being kind of burned out by thinking so much, which might set them up for difficulties in school. We already know that anxious kids—and especially anxious girls—have a harder time in some academic subjects such as math.”
Currently Moser and colleagues are investigating whether estrogen, a hormone more common in women, may be responsible for the increased brain response. Estrogen is known to affect the release of dopamine, a neurotransmitter that plays a key role in learning and processing mistakes in the front part of the brain.
“This may end up reflecting hormone differences between men and women,” Moser says.
In addition to traditional therapies for anxiety, Moser says other ways to potentially reduce worry and improve focus include journaling—or “writing your worries down in a journal rather than letting them stick in your head”—and doing “brain games” designed to improve memory and concentration.
Source : Futurity
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Effects of Yoga Versus Walking on Mood, Anxiety, and Brain GABA Levels: A Randomized Controlled MRS Study
Chris C. Streeter, MD,1 Theodore H. Whitfield, ScD,2 Liz Owen, BArch,3 Tasha Rein, BA,1 Surya K. Karri, MD, MPH,4 Aleksandra Yakhkind, MS,5 Ruth Perlmutter, MA,6 Andrew Prescot, PhD,7 Perry F. Renshaw, MD, PhD,8 Domenic A. Ciraulo, MD,1 and J. Eric Jensen, PhD9
1Division of Psychiatry, Boston University School of Medicine, Boston, MA.
2Division of Actuarial Science, Boston University, Boston, MA.
3Liz Owen Yoga, Arlington, MA.
4Department of Neurosurgery, Harvard University, Boston, MA.
5Medicine/Hematology-Oncology, Children's Hospital Boston, Boston, MA.
6School of Medicine, University of Massachusetts, Boston, MA.
7Department of Radiology, University of Utah, Salt Lake City, UT.
8Department of Psychiatry, University of Utah, Salt Lake City, UT.
9Department of Psychiatry, Harvard University, Belmont, MA.
Objectives: Yoga and exercise have beneficial effects on mood and anxiety. γ-Aminobutyric acid (GABA)-ergic activity is reduced in mood and anxiety disorders. The practice of yoga postures is associated with increased brain GABA levels. This study addresses the question of whether changes in mood, anxiety, and GABA levels are specific to yoga or related to physical activity.
Methods: Healthy subjects with no significant medical/psychiatric disorders were randomized to yoga or a metabolically matched walking intervention for 60 minutes 3 times a week for 12 weeks. Mood and anxiety scales were taken at weeks 0, 4, 8, 12, and before each magnetic resonance spectroscopy scan. Scan 1 was at baseline. Scan 2, obtained after the 12-week intervention, was followed by a 60-minute yoga or walking intervention, which was immediately followed by Scan 3.
Results: The yoga subjects (n = 19) reported greater improvement in mood and greater decreases in anxiety than the walking group (n = 15). There were positive correlations between improved mood and decreased anxiety and thalamic GABA levels. The yoga group had positive correlations between changes in mood scales and changes in GABA levels.
Conclusions: The 12-week yoga intervention was associated with greater improvements in mood and anxiety than a metabolically matched walking exercise. This is the first study to demonstrate that increased thalamic GABA levels are associated with improved mood and decreased anxiety. It is also the first time that a behavioral intervention (i.e., yoga postures) has been associated with a positive correlation between acute increases in thalamic GABA levels and improvements in mood and anxiety scales. Given that pharmacologic agents that increase the activity of the GABA system are prescribed to improve mood and decrease anxiety, the reported correlations are in the expected direction. The possible role of GABA in mediating the beneficial effects of yoga on mood and anxiety warrants further study.
Source : The Journal of Complementary and Alternative Medicine
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Antidepressant-Like Activity of 10-Hydroxy-Trans-2-Decenoic Acid, a Unique Unsaturated Fatty Acid of Royal Jelly, in Stress-Inducible Depression-Like Mouse Model
Symptoms of depression and anxiety appeared in mice after they had been subjected to a combination of forced swimming for 15 min followed by being kept in cages that were sequentially subjected to leaning, drenching, and rotation within 1-2 days for a total of 3 weeks. The animals were then evaluated by the tail-suspension test, elevated plus-maze test, and open-field test at 1 day after the end of stress exposure. Using these experimental systems, we found that 10-hydroxy-trans-2-decenoic acid (HDEA), an unsaturated fatty acid unique to royal jelly (RJ), protected against the depression and anxiety when intraperitoneally administered once a day for 3 weeks simultaneously with the stress loading. Intraperitoneally administered RJ, a rich source of HDEA, was also protective against the depression, but RJ given by the oral route was less effective. Our present results demonstrate that HDEA and RJ, a natural source of it, were effective in ameliorating the stress-inducible symptoms of depression and anxiety.
Source : Evidence-Based Complementary and Alternative Medicine Volume 2012 (2012), Article ID 139140
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Study Shows Chamomile Capsules Ease Anxiety Symptoms
Generalized anxiety disorder (GAD) has a wide array of psychological and physical symptoms. Although prescription drugs can help, they often have undesirable side effects. Many people experiencing symptoms of anxiety do not seek medical attention, turning instead to alternatives. One traditional remedy in widespread use is the herb chamomile. However, scientific evidence to support the use of chamomile for anxiety has been lacking.
NCCAM-funded researchers at the University of Pennsylvania recently conducted a randomized, double-blind, placebo-controlled trial to test the effects of chamomile extract in patients diagnosed with mild to moderate GAD. For 8 weeks, the 57 participants received either chamomile capsules containing 220 mg of pharmaceutical-grade extract from Matricaria recutita (German chamomile), standardized to 1.2 percent of the constituent apigenin; or chamomile-scented placebo capsules containing lactose. The initial dose of one capsule daily was increased to two capsules daily at week 2; dosages were then adjusted incrementally (up to five capsules) in some participants. Researchers used the Hamilton Anxiety Rating (HAM-A) and other tests to measure changes in anxiety symptoms over the course of the study; dosage adjustments were based on HAM-A scores.
Compared with placebo, chamomile was associated with a greater reduction in mean HAM-A scores—the study's primary outcome measure. The difference was clinically meaningful and statistically significant. Chamomile also compared favorably with placebo on other outcome measures (although the differences were not statistically significant), and was well tolerated by participants.
These results suggest that chamomile may have modest benefits for some people with mild to moderate GAD. As this was the first controlled trial of chamomile extract for anxiety, the researchers note that additional studies using larger samples and studying effects for longer periods of time would be helpful. They also point out that other chamomile species, preparations (e.g., extracts standardized to constituents other than apigenin), and formulations (e.g., oil or tea) might produce different results.
- Amsterdam JD, Yimei L, Soeller I, et al. A randomized, double-blind, placebo-controlled trial of oral Matricaria recutita (chamomile) extract therapy for generalized anxiety disorder. Journal of Clinical Psychopharmacology. 2009 Aug;29(4):378–382.
Source : NCCAM
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