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Double-blind, randomised, placebo-controlled study to evaluate the efficacy and safety of a fixed combination containing two plant extracts (Crataegus oxyacantha and Eschscholtzia californica) and magnesium in mild-to-moderate anxiety disorders
Abstract
To assess the clinical efficacy of a neurotonic component containing fixed quantities of two plant extracts (Crataegus oxyacantha and Eschscholtzia californica) and magnesium versus placebo in mild-to-moderate anxiety disorders with associated functional disturbances, under usual general practice prescription conditions.
A total of 264 patients (81% female; mean age: 44.6 years) presenting with generalised anxiety (DSM-III-R) of mild-to-moderate intensity (total Hamilton anxiety scale score between 16 and 28) were included in a double-blind, randomised, placebo-controlled trial. Patients were randomly assigned to two groups: 130 received the study drug (Sympathyl), and 134 a placebo (two tablets twice daily for 3 months). Efficacy and safety data were recorded before first administration and 7, 14, 30, 60 and 90 days after start of treatment.
Efficacy was assessed by (a) change in Hamilton anxiety scale total and somatic scores; (b) change in patient self-assessment; (c) number and percentage of responsive subjects (reduction of at least 50% in Hamilton or self-assessment score); and (d) the physician's clinical global impression. Tolerance was assessed by undesirable events spontaneously reported by the patients over the study period.
Total and somatic Hamilton scale scores and subjective patient-rated anxiety fell during treatment, indicating clinical improvement. The decrease was greater in the study drug than in the placebo group. End of treatment clinical improvement, as measured by the mean difference between final and pre-treatment scores, was, for the study drug and placebo groups respectively: -10.6 and -8.9 on the total anxiety score (p = 0.005); -6.5 and -5.7 on the somatic score (p = 0.054); and -38.5 and -29.2 for subjectively assessed anxiety (p = 0.005). The risk/benefit ratio as judged by the investigating physicians was also significantly greater in the study drug than in the placebo group. In all, 15 patients (11.5%) in the study drug group and 13 patients (9.7%) in the placebo group experienced 22 and 15 adverse events, respectively. Undesirable events were mainly mild or moderate digestive or psychopathological disorders.
The preparation containing fixed quantities of Crataegus oxyacantha, Eschscholtzia californica, and magnesium proved safe and more effective than placebo in treating mild-to-moderate anxiety disorders. Sympathyl is produced and marketed by Laboratoire Innotech International, Arcueil, France.
... The GABA A receptor and the NMDA receptor are involved in the anxiolytic activity of Mg in [20]. Treatment with 124 mg Mg oxide combined with plant extracts was more effective than placebo in patients with mild to moderate long-term generalised anxiety disorder [21]. In addition, a very recent study on depression showed that taking 248 mg of MgCl 2 for 6 weeks has a clinically significant beneficial effect on generalized anxiety disorder [22]. ...
... The primary endpoint of the study was to determine the percentage of patients who showed a decrease in their Ham-A score ≥ 50%, considered responders to treatment. Data from the literature show a response rate of 40% with placebo [21]. With an expected response rate of 60%, a two-sided alpha risk of 5% and a power of 90%, it was necessary to analyse 93 patients to be able to describe this rate with an accuracy of 10%. ...
... The total study population had quite similar characteristics to those of the Stress 2 study: mean age 43 years (18-68 years), 66.1% female, family-related stressors in 40.7%, occupational stressors in 29.6% and health-related stressors in 8.5% of patients. The mean Ham-A score at inclusion was 25.5 (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38), i.e., almost the same as in the Stress 2 study (25.6). ...
Anxiety is a high frequency disorder in the general population. It is usually treated with benzodiazepines, which cause side effects and a dependence that could make withdrawal difficult. Alternative treatments are therefore needed to reduce the use of anxiolytics, particularly for adjustment disorder with anxiety. An observational, multicentre, prospective, longitudinal study has been conducted by general practitioners and one gynaecologist to evaluate the efficacy of a dietary supplement on adjustment disorder with anxiety (Stress 2 study). Patients diagnosed as anxious with a score of ≥ 20 on the Hamilton Anxiety Rating Scale (Ham-A, first visit on Day 0 (V0)) were offered a 28-day treatment with a dietary supplement formulated with bioactive peptides from a fish protein hydrolysate (Gabolysat®), magnesium and vitamin B6. At the second visit (V1), the Ham-A Rating Scale, the Patient Global Impression scale (PGI) and the Clinical Global Impressions scale (CGI) were administered. A 50% reduction in the Ham-A score, was achieved for 41.9% of the patients. The mean Ham-A score decreased by 12.1 ± 5.7 points (p < 0.001) between V0 (25.6 ± 3.8) and V1 (13.6 ± 6.0). Furthermore, according to the CGI scale, the anxiety of 75.3% of patients improved significantly and very significantly, with limited side effects and a negligible rebound effect. In conclusion, adjustment disorder with anxiety seems to be effectively managed by an alternative and safer solution than benzodiazepines.
... Of the 7781 identified records (7734 electronic databases, 47 other sources) ( Fig. 1), 6693 nonduplicates were screened, 54 were retrieved in full-text and 22 were excluded (Supplementary eAppendix 1) resulting in 32 included RCTs (Fig. 1). Most trials (n = 18) evaluated biologically-based therapies [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46], i.e., oral herbal preparations with extracts of Kava Kava (Piper methysticum), Lavender (Lavandula angustifolia), Galphimia glauca and Chamomile (Matricaria chamomilla) evaluated in more than one trial (Fig. 1). Manipulative and body-based therapies were evaluated in eight [47][48][49][50][51][52][53][54] and alternative medical systems [55][56][57] and (Fig. 1). ...
... Analysis included the five Kava Kava trials (placebo and active-controlled) and a further five placebo-controlled trials of other biologically-based therapies (all with an overall low risk of bias) [36,39,41,43,45] (Table 1) (see Supplementary eTable 1 for data). It indicated (Fig. 2) that for end-study HAM-A score as well as for proportion of responders, Kava Kava-placebo differences estimated in direct comparisons largely overlapped with estimated Kava Kava-placebo differences from comparisons between: Kava arms from placebo-controlled Kava trials versus placebo arms from other (non-Kava) trials; Kava arms from all Fig. 2 Meta-analysis of RCTs comparing Kava Kava extracts (120 or 210 mg/day fixed or titrated to 240-280 mg/day) to placebo or active treatments. ...
... This product was evaluated in a moderately-sized 12-week placebo-controlled trial [41] (Table 1) with an overall low risk of bias and with ITT efficacy analysis which showed significantly lower end-study HAM-A scores and a higher response rate with the tested product (Table 4). Data show efficacy, but require confirmation. ...
Introduction:
The objective was to evaluate efficacy/safety of complementary and alternative medicine (CAM) methods for generalized anxiety disorder (GAD) based on randomized controlled trials in adults.
Methods:
Data sources. Six electronic databases ("generalized anxiety (disorder)" and "randomized trial") and reference lists of identified publications were searched to March 2017.
Study selection:
Eligibility: full-text publications (English, German language); CAM versus conventional treatment, placebo/sham or no treatment; GAD diagnosed according to standard criteria; and a validated scale for disease severity. Of the 6693 screened records, 32 were included (18 on biologically-based therapies, exclusively herbal preparations; eight on manipulative and body-based therapies; and three on alternative medical systems and three on mind-body therapies).
Data extraction:
Cochrane Collaboration methodology was used for quality assessment and data extraction.
Results:
Direct comparisons of Kava Kava (Piper methysticum) extracts to placebo (4 quality trials, n = 233) were highly heterogeneous. Network meta-regression reduced heterogeneity and suggested a modest Kava effect [end-of-treatment Hamilton Anxiety scale score difference adjusted for baseline scores and trial duration: - 3.24 (95% CI - 6.65, 0.17; P = 0.059), Kava Kava 4 arms, n = 139; placebo 5 arms, n = 359]. Lavender (Lavandula angustifolia) extract (1 quality trial, 10 weeks, n = 523) and a combination of extracts of C. oxycantha, E. californica and magnesium (1 quality trial, 12 weeks, n = 264) were superior to placebo and balneotherapy was superior to paroxetine (1 quality trial, 8 weeks, n = 237) indicating efficacy. All other trials were small and/or of modest/low quality and/or lacked assay sensitivity. Safety reporting was poor.
Conclusion:
Evidence about efficacy/safety of most CAM methods in GAD is limited. Apparent efficacy of certain herbal preparations and body-based therapies requires further confirmation.
... Hanus et al. [72] reported positive effects of 12 weeks intake of 75 mg Mg combined with Hawthorn (75 mg) and California poppy (20 mg) extracts vs. a placebo in individuals reporting mild anxiety or symptoms of general anxiety disorder. Consistent positive effects on three anxiety outcome measures were reported. ...
... No clear dose effect of Mg emerges from the reviewed studies. Positive effects of Mg intake on subjective anxiety outcomes are reported with both low (75 mg [72]) and higher (360 mg [88]) Mg doses. One study that systematically examined the potential dosing effects of Mg (administering 200, 350, and 500 mg) reported no effects of any dose [64]. ...
... One study that systematically examined the potential dosing effects of Mg (administering 200, 350, and 500 mg) reported no effects of any dose [64]. Examination of the effect of Mg dose is further complicated by a number of the studies reporting positive outcomes combining Mg with additional ingredients (e.g., Hawthorn extract [72]). Therefore, it is difficult to assess if it is Mg administered at a particular dose that is efficacious, or the additional ingredients acting in isolation or synergistically with Mg. ...
Background:
Anxiety related conditions are the most common affective disorders present in the general population with a lifetime prevalence of over 15%. Magnesium (Mg) status is associated with subjective anxiety, leading to the proposition that Mg supplementation may attenuate anxiety symptoms. This systematic review examines the available evidence for the efficacy of Mg supplementation in the alleviation of subjective measures of anxiety and stress.
Methods:
A systematic search of interventions with Mg alone or in combination (up to 5 additional ingredients) was performed in May 2016. Ovid Medline, PsychInfo, Embase, CINAHL and Cochrane databases were searched using equivalent search terms. A grey literature review of relevant sources was also undertaken.
Results:
18 studies were included in the review. All reviewed studies recruited samples based upon an existing vulnerability to anxiety: mildly anxious, premenstrual syndrome (PMS), postpartum status, and hypertension. Four/eight studies in anxious samples, four/seven studies in PMS samples, and one/two studies in hypertensive samples reported positive effects of Mg on subjective anxiety outcomes. Mg had no effect on postpartum anxiety. No study administered a validated measure of subjective stress as an outcome.
Conclusions:
Existing evidence is suggestive of a beneficial effect of Mg on subjective anxiety in anxiety vulnerable samples. However, the quality of the existing evidence is poor. Well-designed randomised controlled trials are required to further confirm the efficacy of Mg supplementation.
... Hanus et al. [72] reported positive effects of 12 weeks intake of 75 mg Mg combined with Hawthorn (75 mg) and California poppy (20 mg) extracts vs. a placebo in individuals reporting mild anxiety or symptoms of general anxiety disorder. Consistent positive effects on three anxiety outcome measures were reported. ...
... No clear dose effect of Mg emerges from the reviewed studies. Positive effects of Mg intake on subjective anxiety outcomes are reported with both low (75 mg [72]) and higher (360 mg [88]) Mg doses. One study that systematically examined the potential dosing effects of Mg (administering 200, 350, and 500 mg) reported no effects of any dose [64]. ...
... One study that systematically examined the potential dosing effects of Mg (administering 200, 350, and 500 mg) reported no effects of any dose [64]. Examination of the effect of Mg dose is further complicated by a number of the studies reporting positive outcomes combining Mg with additional ingredients (e.g., Hawthorn extract [72]). Therefore, it is difficult to assess if it is Mg administered at a particular dose that is efficacious, or the additional ingredients acting in isolation or synergistically with Mg. ...
Experimental studies of anxiety in animal models, and evidence of efficacious outcomes of magnesium (Mg) supplementation in the treatment of acute clinical affective disorders, has increased interest in Mg as a potential novel treatment for symptoms of mild/moderate subjective anxiety. This short review examines the existing evidence for the effects of Mg supplementation on subjective anxiety in humans. Additionally, evidence from three unpublished studies that examined Mg and vitamin B6 intake on subjective anxiety is summarised to supplement the existing literature.
CONCLUSIONS
The efficacy of Mg in the treatment of anxiety in the mildly anxious and those reporting premenstrual syndrome-related anxiety is suggestive of a beneficial effect of Mg intake. Further randomised controlled trials are warranted to further establish the efficacy of Mg as a novel treatment for subjective anxiety.
... Several pharmacological activities and properties of C. monogyna include hypotensive [81], hypolipidemic and antioxidant activity, [66,[82][83][84][85], angiotensin-converting enzyme (ACE) inhibition [86], cardioprotective effects [87,88], anti-anxiety and anti-depression [89], adverse chronotropic and cardiotonic effects [90], protection against myocardial infarction [91], free-radical-scavenging, anti-inflammatory, gastroprotective and antimicrobial activities [67], inhibition of thromboxane A2 [92] and immunological activity [93] (Table 1). One beneficial effect of C. monogyna is linked to bioflavonoids, which contribute to relaxation and dilation of the arteries, increasing the blood flow of the heart muscle and reducing the symptoms of angina and heart muscle contractions [112]. ...
... Interestingly, plant extract use was associated with anxiety improvement. These data were the basis of the commercial development of new pharmaceutical treatments against the effects of anxiety [89]. However, more research is needed before any recommendations to use hawthorn supplements as anti-anxiety can be made. ...
Hawthorn (Crataegus monogyna Jacq.) is a wild edible fruit tree of the genus Crataegus, one of the most interesting genera of the Rosaceae family. This review is the first to consider, all together, the pharmaceutical, phytochemical, functional and therapeutic properties of C. monogyna based on numerous valuable secondary metabolites, including flavonoids, vitamin C, glycoside, anthocyanin, saponin, tannin and antioxidants. Previous reviews dealt with the properties of all species of the entire genera. We highlight the multi-therapeutic role that C. monogyna extracts could have in the treatment of different chronic and degenerative diseases, mainly focusing on flavonoids. In the first part of this comprehensive review, we describe the main botanical characteristics and summarize the studies which have been performed on the morphological and genetic characterization of the C. monogyna germplasm. In the second part, the key metabolites and their nutritional and pharmaceutical properties are described. This work could be an essential resource for promoting future therapeutic formulations based on this natural and potent bioactive plant extract.
... Californidine is one of the alkaloids that can be isolated from Eschscholzia californica (California poppy) [130]. This traditional plant of Indians was used for its sedative, hypnotic and anxiolytic effects [131][132][133]. Such effects are mediated via the affinity of California poppy aqueous alcohol extract to GABA A receptors (via affinity to the allosteric-binding sites for benzodiazepines) [134]. ...
... A clinical study with californidine was carried out by Hanus et al. The study disclosed improvement in the clinical status of adult patients with anxiety after regular administration for 3 months of a fixed dose of extracts from E. californica and Crataegus oxycantha together with magnesium [131]. ...
Prolyl oligopeptidase (POP), also called prolyl endopeptidase, is a cytosolic enzyme investigated by several research groups. It has been proposed to play an important role in physiological processes such as modulation of the levels of several neuronal peptides and hormones containing a proline residue. Due to its proteolytic activity and physiological role in cell signaling pathways, inhibition of POP offers an emerging approach for the treatment of Alzheimer's and Parkinson's diseases as well as other diseases related to cognitive impairment. Furthermore, it may also represent an interesting target for treatment of neuropsychiatric disorders, and as an antiangiogenesis or antineoplastic agent. In this review paper, we summarized naturally occurring POP inhibitors together with peptide-like inhibitors and their biological effects. Some of them have shown promising results and interesting pharmacological profiles. However, to date, there is no POP inhibitor available on the market although several clinical trials have been undertaken.
... It was used as sedative, analgesic and antispasmodic. It is traditionally indicated for treating the various physical and psychological conditions including insomnia, bedwetting (incontinence), anxiety and nervous tension, particularly in children [28, [33][34][35][36]. Indians on the western coast used this herb as a general pain killer, and Indian women would also add this to the food of their (unreactive) mates if pregnancy was desired. ...
... Treatment produced a rapid and progressive fall in anxiety. There was a significant improvement in the total anxiety score (P = 0.005), somatic score (P = 0.054), and self-assessment (P = 0.005) in patients taking Sympathyl for 3 months [36]. ...
Phytochemical analysis of Eschscholzia californica showed that both aerial parts and roots contained alkaloids, the latter being richer than the former, it contained up to 1.6% alkaloids. The alkaloids most commonly reported in Eschscholzia californica included sanguinarine, dihydrosanguinarine chelirubine, macarpine,. The plant also contained a variety of colours including orange, red and yellow due to its different carotenoid composition. Six flavonol 3-O-glycosides were isolated from the aerial parts of Eschscholtzia californica. Flavonoids, in the Eschscholzia californica, occurred mainly as quercetin isorhamnetine glycosides. The previous pharmacological studies revealed that the plant possessed antifungal, analgesic, anxiolytic, sedative, behavioural activities and beneficial effect in vasomotor headache with an interesting mechanisms. This review was designed to discuss the chemical constituents and pharmacological effects of Eschscholzia californica.
... Hawthorn (Crataegus oxyacantha) has quite a long history for its cardioprotective utilization which was proceeded into an early clinical practice [15][16][17]. In addition to its well-known cardiotonic properties, C. oxyacantha has been also reported to have various other pharmacological activities such as anxiolytic [18], hypotensive [19], antihyperlipidemic [20], antioxidant [21], antihyperglycemic [22], immunomodulatory [23][24][25], and antimutagenic [26]. Besides, C. oxyacantha is considered as an official plant in homeopathic medicine to treat cardiovascular conditions [27,28]. ...
... The combined extract preparation (Sympathyl ® ) of C. oxyacantha and Eschscholtzia californica Cham. (Californian poppy) was investigated for its possible anxiolytic effect in a double-blind, randomized, and placebo-controlled clinical study on 264 patients (81% female) diagnosed with generalized anxiety disoerder versus placebo by giving 2 × 2 tablets daily for 3 months [23]. Efficacy of the extract was measured using several parameters including mainly Hamilton anxiety scale total and somatic scores. ...
Crataegus oxyacantha L. (syn. C. rhipidophylla Gand.) (Rosaceae) is one of two medicinally recognized hawthorn species in European Pharmacopeia. Standardization of the extract prepared from the berry and flowers of the plant is required according to its oligomeric procyanidins. C. oxyacantha is well-known for its use in the treatment of various heart problems particularly, including heart failure in cases of declining cardiac performance equivalent to stages I and II of the New York Heart Association classification, angina pectoris, hypertension with myocardial insufficiency, mild alterations of cardiac rhythm, and atherosclerosis. C. oxyacantha has been reported to exert several other pharmacological activities such as hypotensive, antihyperlipidemic, antihyperglycemic, anxiolytic, immunomodulatory, and antimutagenic. Oligomeric procyanidins and flavone/flavonol types of flavonoids, which are considered to be the chief groups of active substances, phenolic acids, triterpenes, fatty acids, and sterols are present in the plant. The present review aims mainly to outline cardiotonic effect of C. oxyacantha as well as its brief phytochemistry. Numerous experiments and clinical studies have underlined cardiovascular efficacy of the plant through various mechanisms including positive inotropic and negative chronotropic effects, escalation in coronary blood flow and exercise tolerance, inhibition of the enzymes such as angiotensin-converting enzyme (ACE) and phosphodiesterase, anti-inflammatory and antihyperlipidemic effects, improving status of antioxidant enzymes, etc., which support its cardioactive efficacy. The plant possesses several other bioactivities for human health usually concomitant to its rich polyphenolic content.
... In addition, C-glycosyl flavones in the structure of Crataegus species affect inflammation by limiting the formation of cytokines, nitric oxide, and prostaglandin E2 in tissues and increasing the level of anti-inflammatory cytokines [9]. Also, research on different plant parts of Crataegus species clarified that it has other biological effects such as antioxidant, antimicrobial, gastroprotective, cardioprotective, anti-anxiety, anti-depression, cardiotonic, anti-atherogenic, hypoglycemic, and diuretic effects [10][11][12][13][14][15][16][17][18]. Crataegus species are described as "Generally recognized as safe, GRAS" and registered as "Traditional herbal medicinal product" in the Commi ee for Herbal Medicinal Products of the European Medicines Agency (EMA, 2016) [19]. ...
Crataegus turcicus is a plant endemic to Türkiye. For the first time, this study aimed to comparatively assess its flower-bearing branches, leaves, and fruits with other well-known Crataegus species (C. monogyna, C. pentagyna, and C. orientalis) in terms of chemical composition and bioactivity studies to evaluate its potential use as a food supplement. Firstly, the contents of total phenolics (TPC), flavonoids (TFC), proanthocyanidin (TPAC), and anthocyanin (TAC) in different plant parts of Crataegus species were evaluated. The highest TPAC was found in the hydroalcoholic extract of C. turcicus flower-bearing branches. Moreover, all plant parts had comparatively higher amounts of TPC, TFC, and TAC compared to other Crataegus species. The chemical screening by high-performance thin-layer chromatography (HPTLC) resulted that C. turcicus parts were rich with chlorogenic acid, neochlorogenic acid, quercetin and vitexin derivatives, epicatechin, procyanidin, etc., and their quantities were evaluated by high-performance liquid chromatography (HPLC). In terms of several in vitro antioxidant activity outcomes, the flower-bearing branches of C. turcicus showed the highest antioxidant activity by a 2,2-diphenyl-1-picrylhydrazyl (DPPH) test among the assessed antioxidant assays. Additionally, hydroalcoholic extracts of C. turcicus significantly decreased LPS-induced nitric oxide, tumor necrosis factor-alpha, and interleukin-6 production more potently than indomethacin (positive control). In addition to its remarkable anti-inflammatory activity, C. turcicus showed analgesic activity by reducing prostaglandin E2 levels.
... In particular, the hawthorn has a relaxing muscular activity, especially on the heart, and stabilizes the physiological nerve transmission [11,12]. On the other hand, Melissa officinalis has potential activity on the gastrointestinal tract, reducing gas production and exerting spasmolytic activity on the smooth muscles of the gut. ...
Aims: distress disorders (DD) include psychological symptoms such as sleep disorders, fatigue and psychophysical exhaustion that are common to many mental diseases. DD is often associated with somatic symptoms such as abdominal pain or bowel dysfunction. The aim of this study was to evaluate in patients with DD the effectiveness of a nutraceutical containing Hawthorn, Lemon Balm, and Magnesium (Vagostabil®) on psychological and abdominal symptoms. For this purpose, a clinical survey was conducted by 7 Italian gastroenterologists. Methodology: 85 patients with DD (60 F, mean age 51,6 yrs), identified by a score > 18 based on the Hamilton Anxiety Rating Scale (HAM-A), were included in the study. All patients assumed Vagostabil®, three tablets a day for two months. The same HAM-A score and a VAS score for abdominal pain were used to measure clinical results. Results: the mean score of the HAM-A scale decreased from 28.61 to 18.22 after 1 month and to 11.46 after 2 months of treatment respectively (P = .001 for all comparisons). An overall reduction of HAM-A score by 59.94 % was observed at the end of the treatment (P = .001). Similarly, VAS score for abdominal pain decreased from 7.59 to 4.86 after 1 month, and to 2.41 at the end of the treatment (P = .001 for both comparisons). A global reduction of 68.25% in the VAS score was observed at the end of the survey (P = .001). Conclusion: this clinical survey showed that Vagostabil® can ameliorate psychological symptoms and associated abdominal pain in patients with DD. These preliminary data suggest that Vagostabil® could be utilized by gastroenterologists in functional gastrointestinal disorders. However, further studies are needed to confirm these data.
... Crataegus, yüksek antioksidan ve bağışıklık uyarıcı aktivite göstermetedir (51), ayrıca anksiyete ve hafif depresyon gibi rahatsızlıklarında da kullanılmaktadır (58). ...
Some plants distributed in wild can support daily nutrition and/or replace traditional pharmacological treatment. One of these herbs is the hawthorn (Crataegus spp), which belongs to the Rosaceae family, that has about 280 species. Hawthorn has a wide distribution range in our country and various parts of this species including the fruits, flowers and leaves is rich in bioactive compounds and have some properties such as anti-microbial, anti-inflammatory, antioxidant, anti-cancer, anti-diabetic, anti-hyperlipidemic anti-hyperglycemic, anticoagulant, anti-atherosclerosis, gastroprotective and neuroprotective.
In this review, previous studies on the health effects of the hawthorn plant are presented. As a result, it has been seen that the hawthorn plant plays an important role in many diseases, including the treatment of metabolic syndrome, cognitive disorders, intestinal microbial disorders, various heart diseases and hypertension. The vinegar form has been reported to be effective on lipid metabolism, lowering blood sugar, reducing cholesterol, lowering triglyceride levels and weight loss. As a result, it is thought that hawthorn has an important place in the context of a healthy diet. Thus, it is aimed to contribute to many multidisciplinary fields with this research, which is carried out to guide the treatment strategies that are being developed for diseases whose number is increasing day by day.
... Treatment produced a rapid and progressive fall in anxiety. There was a significant improvement in the total anxiety score (P = 0. 005), somatic score (P = 0. 054), and self-assessment (P = 0. 005) in patients taking Sympathyl for 3 months (173)(174) . ...
Plants are a valuable source of a wide range of secondary metabolites, which are used as pharmaceuticals, agrochemicals, flavours, fragrances, colours, biopesticides and food additives. In the current review, PubMed, Web Science, Science Direct, Researchgate, Academia. edu and Scopus were searched to determinethe medicinal plantswhich pass the clinical trials with documented efficacy and safety.
... The change in HAMD and HAMA total score from baseline at week 4 and week 12 were the response criterion. Responders were identified as those with a 50% or greater decrease in HAMD or HAMA score as previously described (42,43). While remission was defined as the absolute value of HAMD or HAMA score less than 8. ...
Background:
Omega-3 polyunsaturated fatty acids (n-3 PUFAs) augmentation of antidepressants has shown great potential in the prevention and treatment of major depressive disorders (MDD).
Objective:
To investigate the effect of n-3 PUFAs plus venlafaxine in patients with first-diagnosed, drug-naïve depression.
Method:
A total of 72 outpatients with first-diagnosed depression were recruited. The daily dose of 2.4 g/day n-3 PUFAs or placebo plus venlafaxine was used for over 12 weeks. The outcomes were assessed by the Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA), Beck depression inventory (BDI), and Self-rating anxiety scale (SAS).
Results:
Both groups exhibited improvement on clinical characteristics at week 4 and week 12 compared with baseline. The rate of responders for anxiety in n-3 PUFAs group (44.44%) was significantly higher than that in placebo group (21.21%) at week 4 (χ2 = 4.182, p = 0.041), while week 12 did not show a difference (χ2 = 0.900, p = 0.343). The rate of responders for depression at both week 4 (χ2 = 0.261, p = 0.609) and week 12 (χ2 = 1.443, p = 0.230) showed no significant difference between two groups. Further analysis found that Childhood Trauma Questionnaire (CTQ) had positive correlation with HAMA (r = 0.301, p = 0.012), SAS (r = 0.246, p = 0.015), HAMD (r = 0.252, p = 0.038) and BDI (r = 0.233, p = 0.022) with Pearson correlation analysis. Social Support Rating Scale (SSRS) had negative correlation with SAS (r = -0.244, p = 0.015) and BDI (r = -0.365, p = 0.000).
Conclusion:
This trial found that n-3 PUFAs supplementation in favor of venlafaxine alleviated the anxiety symptoms rather than depressive symptoms at the early stage of treatment (4 weeks) for first-diagnosed, drug-naïve depressed patients. However, the advantage disappeared in long-term treatment. Furthermore, childhood abuse and social support are closely related to the clinical and biological characteristics of depression. Both childhood trauma and lack of social support might be predictors of poor prognosis in depression.
Clinical trial registration:
[clinicaltrials.gov], identifier [NCT03295708].
... California poppy contains 0.5 % to 1.2 % of total alkaloids, with protopine, a phytochemical that is also present in several other herbal medicines [15], being one of the major compounds [16][17][18]. Extracts of California poppy have shown sedative and anxiolytic effects in vivo [10], and these properties have been attributed to the isoquinoline alkaloids [19]. Several in vitro studies suggest that protopine is a CNS-active compound. ...
The placental passage of protopine was investigated with a human ex vivo placental perfusion model. The model was first validated with diazepam and citalopram, two compounds known to cross the placental barrier, and antipyrine as a positive control. All compounds were quantified by partially validated U(H)PLC-MS/MS bioanalytical methods. Protopine was transferred from the maternal to the fetal circuit, with a steady-state reached after 90 min. This study compound did not affect placental viability or functionality, as glucose consumption, lactate production, and beta-human chorionic gonadotropin, and leptin release remained constant. Histopathological evaluation of all placental specimens showed unremarkable, age-appropriate parenchymal maturation with no pathologic findings.
... Treatment produced a rapid and progressive fall in anxiety. There was a significant improvement in the total anxiety score (P = 0.005), somatic score (P = 0.054), and selfassessment (P = 0.005) in patients taking Sympathyl for 3 months [75]. ...
Insomnia and anxiety are worldwide medical problems. Plant extracts possessed sedative and anxiolytic effect via different mechanisms included interactions with Na+ channels, γ-aminobutyric acid type A receptors, N-methyl-D-aspartate receptors and chatecholamines. In the current review, Web Science, PubMed, Scopus and Science Direct, were searched to investigate the plants with sedative and anxiolytic effects.
... California poppy contains 0.5 % to 1.2 % of total alkaloids, with protopine being one of the major compounds [21][22][23]. Extracts of California poppy have shown sedative and anxiolytic effects in vivo [17], and these properties have been attributed to the isoquinoline alkaloids [24]. Several in vitro studies suggest that protopine is a CNS-active compound. ...
The placental passage of humulone and protopine was investigated with a human ex vivo placental perfusion model. The model was first validated with diazepam and citalopram, 2 compounds known to cross the placental barrier, and antipyrine as a positive control. All compounds were quantified by partially validated U(H)PLC-MS/MS bioanalytical methods. Only a small portion of humulone initially present in the maternal circuit reached the fetal circuit. The humulone concentration in the maternal circuit rapidly decreased, likely due to metabolization in the placenta. Protopine was transferred from the maternal to the fetal circuit, with a steady-state reached after 90 min. None of the study compounds affected placental viability or functionality, as glucose consumption, lactate production, beta-human chorionic gonadotropin, and leptin release remained constant. Histopathological evaluation of all placental specimens showed unremarkable, age-appropriate parenchymal maturation with no pathologic findings.
... The findings from an in vivo study suggest that E. californica possesses anti-anxiety effects at a 25 mg/kg/mouse dose and sedative effects at doses above 100 mg/kg/mouse [54]. A double-blind, randomized, placebocontrolled study showed promising results with a fixed combination of plant extracts (Crataegus oxyacantha L. (synonym of Crataegus rhipidophylla Gand.) and E. californica) in the treatment of mild to moderate anxiety disorder in adult patients [55]. However, relevant evidence for using California poppy in children with anxiety or sleeplessness is still lacking [56]. ...
The pivotal role of childhood nutrition has always roused a growing interest from the scientific community. Plant extracts and bioactive dietary components play a significant role in the maintenance of human health and wellness, with the potential to modulate risk factors and manage symptoms for a large number of common childhood disorders such as memory impairment, respiratory illnesses, gastrointestinal disorders, metabolic derangements, and pathologies related to the oral cavity. This review is designed to highlight the health benefits of botanical extracts and bioactive dietary components in children as evidenced by clinical trials, considering their safety with regards to childhood sensibilities. The supplementation of children with the herbal extracts or bioactive components mentioned in this review leads to the conclusion that they are useful for treating various ailments, with no serious adverse events being reported. However, for the limited number of investigations specifically focused on the safety of such products in children, time is needed to expand the literature data covering the safety of childhood supplementation with botanical extract and bioactive food components.
... Its fruit has been used over the course of time as a diuretic, for dyspnea, and renal calculi. There are also studies that show its sedative and anxiolytic effects (18), and cardiotonic properties (19). So the antioxidant and the hypolipidemic activity of crataegus oxycantha was the aim of this study. ...
This study was carried out to investigate the protective effects of 70% ethanolic alcohol extract of hawthorn (crataegus oxycantha) on some physiological functions of male rats exposed to 1% H2O2. Fifteen mature male Newzeland rats were randomly divided into three groups:- control group (C) ,two groups treated with 1% H2O2 alone (G1) or 1%H2O2 with crude extract of hawthorn(G2) orally daily for 30 days .Blood samples were taken at zero time and 30 days of the experiment .The present study declared an alteration in the lipid profile of the treated group (G2) at the end of treatment (30 days) manifested by asignificant reduction (p<0.05) in serumTC,TAG,LDL-C, VLDL-C concentrations. And elevation (p<0.05) in serum, HDL-C, as compared to the treated group (G1). Antioxidant status also exhibited significant (p<0.05) changes characterized by an elevation of serum GSH in group (G2). Histological study revealed that oral treatment with 1% H2O2 caused congestion of blood vessels of the heart with infiltration of inflammatory cells and odema between muscle fibers. It is concluded that treatment with hawthorn showed no clear pathological lesions.
... Studies conducted on the use of Mg in chronic stress have shown satisfactory results [5]. Stressed subjects show a decrease in their level of stress following various oral supplements (192 mg Mg lactate over 3 and 6 weeks [7]; 300 mg Mg oxide over 4 and 8 weeks [11] and 75 mg Mg over 12 weeks [131]). In addition, Mg supplementation of 400 mg promotes a better physiological regulation of sympathetic and parasympathetic efferent as measured by a heart rate variability test in stressed subjects [132]. ...
Background:
Magnesium (Mg) is commonly used in clinical practice for acute and chronic pain and has been reported to reduce pain intensity and analgesics consumption in a number of studies. Results are, however, contested.
Objectives:
This review aims to investigate randomised clinical trials (RCTs) on the effectiveness of Mg treatment on pain and analgesics consumption in situations including post-operative pain, migraine, renal pain, chronic pain, neuropathic pain and fibromyalgia.
Results:
The literature search identified 81 RCTs (n = 5447 patients) on Mg treatment in pain (50 RCTs in post-operative pain, 18 RCTs in migraine, 5 RCTs in renal pain, 6 RCTs in chronic/neuropathic pain, 2 RCTs in fibromyalgia).
Conclusion:
The level of evidence for the efficacy of Mg in reducing pain and analgesics consumption is globally modest and studies are not very numerous in chronic pain. A number of gaps have been identified in the literature that need to be addressed especially in methodology, rheumatic disease, and cancer. Additional clinical trials are needed to achieve a sufficient level of evidence and to better optimize the use of Mg for pain and pain comorbidities in order to improve the quality of life of patients who are in pain.
... It is cardioprotective [176], antimicrobial and antioxidant [177]. In a clinical trial [178], patients were separated into two groups. One group was treated with a formulation containing Crataegus oxyacantha, and the other was a placebo group. ...
Exploration of new drugs targeting anxiety treatment is a major concern worldwide. Medicinal plants are being used as a potential source of novel drugs for anxiety disorders. The objective of this review is to provide information about the healing outcomes of anxiety treatment with natural products. Valeriana officinalis, Citrus aurantium, Commelina benghalensis, Achyranthes aspera, Mimosa pudica, Achillea millefolium, Nymphaea alba, Leonurus cardiac, Camellia sinensis, Turnera aphrodisiaca, Crataegus oxyacantha and Piper methysticum showed promising effects on anxiety in animal models. In clinical studies, passion flower, kava, valerian, St John's wort, and ashwagandha showed the most positive results. More studies are needed for the exploration of the anti-anxiety of medicinal plants. In drugs derived from natural sources have explored many components that are playing an essential role in curing anxiety disorders and associated complications.
... List of Medicinal Plants recommended in Ayurveda for the management of neuropsychiatric complications of PD. Bind to GABA receptor • Modulate monoamine neurotransmission • Acts on neuroendocrine system[260,261]. Inhibit protein kinase • Inhibit MAO-A • Modulation on neuroendocrine system • Modulation on monoaminergic neurotransmission[268,269,270]. ...
Parkinson’s disease (PD) is a progressive neurodegenerative disease which affects millions of population worldwide. It is characterized by motor symptoms such as excessive tremor, bradykinesia, rigidity, postural instability and non-motor symptoms include neuropsychiatric complications like anxiety, depression, insomnia and cognitive impairment, orthostatic hypotension, sexual dysfunction and gastrointestinal complications. Treatment of anxiety in PD poses extensive challenge to global healthcare which makes it urgent to develop innovative treatment for the better management of the disease. The gold standard treatment by Levodopa provides symptomatic relief and its effect on neuropsychiatric complications like anxiety is elusive. Presence of anxiety worsens the condition and challenges therapeutic management of the PD. The in-depth analysis and understanding the molecular mechanism and pathophysiological pathways associated with the onset of anxiety in PD is essential. The disturbances in serotonergic, adrenergic and GABAergic neurons and hypothalamic pituitary adrenal axis play a significant role in the pathophysiology of anxiety. The drugs like Selective Serotonin Reuptake Inhibitors, tricyclic antidepressants and benzodiazepines are useful in the management of anxiety but due to severe side effects and progression of the disease it results in the failure of treatment. The present review imparts an insight in the management of anxiety in PD by understanding molecular mechanism and application of alternative treatment options which can enlighten the perception of researchers towards better therapeutic management of the disease.
... are commonly eaten as edible food. In addition, fruits, leaves, and flowers have long been used as a traditional medicine to cure various diseases such as asthma, insomnia, flu, coughs, and bronchitis, and headache, respiratory, and cardiovascular problems [6,7]. Previous research has shown that hawthorn exerts a variety of pharmacological effects, including antioxidant, antidiabetic, antimicrobial, antiviral, anti-inflammatory, antithrombotic, antihyperlipidemic, cardioactive, hepatoprotective, and hypotensive activities [8]. ...
Polysaccharides from the pulps (CAP) and seeds (CAS) of Crataegus azarolus L. var. aronia were extracted by hot water method. Both polysaccharides were characterized by scanning electron microscopy (SEM), Congo red test, FT-IR spectroscopy, and their antioxidant, α-amylase, antiacetylcholinesterase, and antibacterial activities were evaluated. CAP showed the highest total carbohydrate (82.35%) and uronic acid (29.39%) contents. The Congo red test revealed the lack of triple-helical conformation for both polysaccharides. The comparison of both infrared spectra indicated similar patterns with the presence of typical bands of polysaccharides. However, the microstructure of both samples indicated differences when analyzed by SEM. CAP displayed higher antioxidant, α-amylase, and acetylcholinesterase inhibitory activities. Besides, CAP showed the strongest antimicrobial effects against seven microorganisms and, notably, the Gram-positive bacteria. Overall, the results suggest that polysaccharides from C. azarolus L. var. aronia may be considered as novel sources of antioxidants and recommended as enzyme inhibitory agents in food and pharmaceutical industries.
... 114 Magnesium intake along with other combination therapies was effective in treating anxiety and related disorders in 3 clinical trials. [115][116][117] One study found the combination of magnesium (200 mg/d) and vitamin B 6 (50 mg/d) had a small synergistic effect and reduced anxiety-related symptoms. 116 Another study showed that magnesium taurinate or glycinate (125-300 mg at each meal and bedtime) alleviated anxietylike symptoms in patients with magnesium deficiency. ...
Suboptimal nutrition has been implicated in the underlying pathology of behavioral health disorders and may impede treatment and recovery. Thus, optimizing nutritional status should be a treatment for these disorders and is likely important for prevention. The purpose of this narrative review is to describe the global burden and features of depression and anxiety, and summarize recent evidence regarding the role of diet and nutrition in the prevention and management of depression and anxiety. Current evidence suggests that healthy eating patterns that meet food-based dietary recommendations and nutrient requirements may assist in the prevention and treatment of depression and anxiety. Randomized controlled trials are needed to better understand how diet and nutrition-related biological mechanisms affect behavioral health disorders, to assist with the development of effective evidence-based nutrition interventions, to reduce the impact of these disorders, and promote well-being for affected individuals.
... A double-blind, randomized, placebo-controlled study with 264 subjects showed a reduction in total and somatic Hamilton scale scores for anxiety (p � 0.005) [52]. ...
Background. Sleep complaints are common health issues in the general population. These conditions are associated with poorer physical and psychological activity, and they may have important social, economic, and personal consequences. In the last years, several food supplements with different plant extracts have been developed and are currently taken for improving sleep. Study Objectives. The aim of this study is to systematically review recent literature on oral plant extracts acting on sleep disorders distinguishing their action on the different symptoms of sleep complaints: difficulty in initiating or maintaining sleep, waking up too early, and quality of sleep. Methods. We searched the PubMed database up to 05/03/2020 based on data from randomized, double-blind, placebo-controlled trials, noncontrolled trials, and cohort studies conducted in children and adult subjects. The search words used contained the following terms: oral food supplement and sleep disorders and the like. The most studied compounds were further analyzed with a second search using the following terms: name of the compound and sleep disorders. We selected 7 emerging compounds and 38 relevant reports. Results. Although nutraceutical natural products have been used for sleep empirically, there is a scarcity of evidence on the efficacy of each product in clinical studies. Valerian and lavender were the most frequently studied plant extracts, and their use has been associated (with conflicting results) with anxiolytic effects and improvements in quality and duration of sleep. Conclusions. Sleep aids based on plant extracts are generally safe and well tolerated by the population. More high-quality research is needed to confirm the effectiveness of food supplements containing plant extracts in sleep complaints; in particular, it would be interesting to evaluate the association between plant extracts and sleep hygiene guidelines and to identify the optimal products to be used in a specific symptom of sleep complaint, giving more appropriate tools to the medical doctor.
1. Introduction
Insomnia is defined as dissatisfaction with sleep quality or quantity in addition to at least one other symptom among difficulty initiating sleep, difficulty maintaining sleep, or early morning awakening with inability to return to sleep [1]. Occasional insomnia is a very common disturb that has been reported to be experienced by about 30% of the U.S. general population [1–3]. Sleep disorders have an important societal and economic impact, with a consequent reduction in labour productivity or increased risk of accidents [4–6]. Chronic insomnia is also a risk factor for a variety of significant health problems, such as cardiovascular disease [7, 8], diabetes [9], and obesity [10], as well as bad mood and cognitive dysfunction [11–13]. Almost half of the individuals with sleep problems had never taken any steps to resolve them, and the majority of respondents had not spoken with a physician about their problems. Of those individuals who had consulted a physician, drug prescriptions had been given to approximately 50% in Western Europe and the USA [14]. The commonly used sleep aids based on benzodiazepine and non-benzodiazepine hypnotic drugs are often related to negative side effects such as daytime drowsiness, dependency, depression, hypnotic-withdrawal insomnia, and even excess mortality [15]. Moreover, there are limited data on long-term efficacy of hypnotic drugs [16]. Given these concerns and an increasing patient preference for nonpharmacological treatments [17], it is important to offer patients with insomnia evidence-based nonpharmacologic alternatives that may improve their sleep.
As defined in the Dietary Supplement Health and Education Act of 1994 (DSHEA), a dietary supplement is “a product (other than tobacco) intended to supplement the diet that bears or contains one or more dietary ingredients, including a vitamin, a mineral, an herb or other botanical, an amino acid, a dietary substance for use by humans to supplement the diet by increasing the total dietary intake of any of the aforementioned ingredients [18].” A growing body of evidence has shown promising results for these compounds in supporting health and body functions [19]. In particular, several dietary supplements are popularly used for sleep disorders [20], also in addition to other remedies (e.g., sleep hygiene and mind-body therapies) [21]. Moreover, no golden standard therapy is recommended to treat mild sleep disorders related to specific sleep stages (starting, maintaining, and ending sleep) [22, 23].
Our aim in this study was to systematically review recent literature on plant extracts and nutraceuticals administered orally and acting on sleep-related disorders. In particular, we differentiated the interventions and the outcomes of the studies based on the different sleep disorders (difficulty in initiating or maintaining sleep, quality and quantity of sleep, and waking up too early) and reviewed the available clinical data of the 7 most studied natural products: valerian, lavender, chamomile, hop, St. John’s wort, hawthorn, and rosemary.
2. Materials and Methods
A literature search was performed using a primary medical search engine the PubMed database considering all articles published up to 05/03/2020; the registered review protocol can be found at: https://www.crd.york.ac.uk/PROSPEROFILES/126991_PROTOCOL_20190301.pdf. The review was registered on PROSPERO (international prospective register of systematic reviews in https://www.crd.york.ac.uk/prospero/), registration number CRD42019126991. The inclusion criteria were randomized, double-blind, placebo-controlled trials, noncontrolled trials, and cohort studies. We used the following search terms to search the PubMed register: (Oral food supplement) OR (Oral nutraceutical) OR (Oral natural products) AND (Sleep disorders) OR (Insomnia) AND “humans” [Filter] AND “English”[Filter]. The most studied compounds were singled out and further analyzed with a second search using the terms: (name of the compound) AND (Sleep disorders) OR (Insomnia) AND “humans”[Filter] AND “English”[Filter]. Only articles written in English and only studies conducted on humans were selected for this review. Additionally, the same research criteria were applied also for the Spanish language but no additional references were found. We contacted the study authors to retrieve the full article where only the abstract was available. We selected 7 emerging compounds and 35 relevant reports, excluding duplicates, nonrelevant articles, reviews, and works with no full article available (Figure 1). Information was extracted from each included trial in view of: (1) type of food supplement for sleep disorders (herbal component, dose, length of the treatment, and additional substances) and (2) clinical endpoints considering the different stages of sleep and sleep problems: sleep latency, sleep maintenance, quality of sleep, and quantity of sleep. Finally, the risk of bias of individual studies was considered both at study or outcome level, and the Jadad scale [24] for quality rating was used to assess the quality of works. Parameters considered were randomization, blinding, withdrawals, sample size, quality of data reported, and statistical analysis. Publication bias and selective reporting within studies are likely to be affecting the selected literature for this review.
... Popovic-Milenkovic et al. (2014) demostraron que los extractos etanólicos obtenidos de frutos de C. nigra tienen un efecto ansiolítico, presumiblemente causado por el elevado contenido de compuestos fenólicos, principalmente kaemferol-3-O-glucósido, quercetina-3-O-glucósido, rutinósido, hiperósido, epicatequina, ácido 5-O-cafeocólico, ácido protocatecuico y ácido quínico. Similarmente, Hanus et al. (2004) observaron una disminución de ansiedad en pacientes tratados con extractos de C. oxiacanta y Eschscholtzia californica. Bor et al. (2012) reportaron efectos antinociceptivos causados por extractos etanólicos de hojas de C. orientalis, los cuales se atribuyeron al alto contenido de algunos flavonoides (hiperósido) presente en los extractos. ...
El tejocote (Crataegus spp.) es un planta ampliamente distribuida en México, donde se le utiliza principalmente como alimento humano y para el ganado. Su uso en la medicina tradicional es bajo, comparado con el que se presenta en otros países. Históricamente, este fruto se ha utilizado para tratar un sinnúmero de padecimientos, que incluyen enfermedades cardiovasculares, las cuales representan una de las principales causas de muerte en México y el mundo. Los estudios científicos atribuyen algunos efectos benéficos del tejocote a los compuestos fenólicos. En la presente revisión, se analizan de manera crítica y sistemática los efectos benéficos atribuidos al tejocote y los mecanismos de acción involucrados, con la finalidad de promover su uso en el tratamiento de diversos padecimientos catalogados en México como problemas de salud pública.
... Three hundred mg/day Mg support was given to university students and the difference between anxiety scores between placebo and intervention groups was evaluated; however, no difference was found (Gendle & O'Hara, 2015). Hanus et al. (Hanus, Lafon, & Mathieu, 2004) in a double-blind randomized clinical trial of Mg support were found to cure anxiety. The reason why we obtained different results from this study was thought to be this study had been a cross-sectional study and the methodology of research while evaluating anxiety. ...
Research problem/Aim: Magnesium is an essential mineral for the organism. Magnesium which is necessary for the ability of more than three hundred enzymes to function found to be associated with many diseases. The aim of this study was to determine the intake of dietary Magnesium in university students and to define its relationship with depressive symptoms, anxiety and eating behaviors. Method: This study included 386 university students who were not diagnosed with any psychiatric disorder and were not using magnesium-containing nutritional supplements. A questionnaire of 6 sections including the general characteristics of participants like age, smoking, income status, Beck Depression Scale, Beck Anxiety Scale, 24-hour retrospective food consumption form, physical activity record form and Dutch Eating Behavior Questionnaire were applied face to face and anthropometric measurements were obtained. Statistical analyzes were performed using SPSS IBM© version 23. Findings: The average magnesium intake of participants in inadequate Mg intake group was 175,5±47,6 mg/day, and 353,4±107,23 mg/day in adequate Mg group. Dietary Mg intake was evaluated according to Turkey Food and Nutrition Guide. It was determined that Mg intake of inadequate Mg group were met only 48,2±12,09% of the requirement. The factors such as smoking, BMI and fiber intake were found different into groups (p <0.05). It was concluded that inadequate Mg intake was not a risk factor for depression (OR: 1.035, 95% CI: 0,543-1,975, p = 0.916). Anxiety, restricting eating and emotional behaviors had no relationship with dietary Mg intake (p>0.05), but external eating behavior scores was found to be related with Mg intake (r=0,110; p<0,05). Conclusions: According to this research, there is no relationship between adequate Mg intake and depression, anxiety and eating behaviors but further research is needed. [Abstract Text must be 12pt, Garamond, adjusted, single line space, at least 150 words. Proper translate from local language on the right column. If the study is a field research, all parts (see header-C below) of work must be mentioned here in abstract section.
... 19,20 In contrast, clinical data on eschscholtzia are very scarce. 22,23 The effects of E. californica result from its chemical composition and in particular the presence of specific alkaloids, such as californidine and eschscholtzine. 18 Eschscholtzia would act by binding to benzodiazepine receptors. ...
Eschscholtzia californica Cham. and Valeriana officinalis L. have long been used for the management of sleep disorders and anxiety. Use of a fixed combination of these two plant extracts (Phytostandard® d’Eschscholtzia et de Valériane, PiLeJe Laboratoire, France) was investigated in an observational study. Adults with adjustment insomnia according to the criteria of the International Classification of Sleep Disorders and with an insomnia severity index (ISI) score >7 enrolled by GPs took a maximum of four tablets of the eschscholtzia and valerian combination every night for four weeks. Within one month, ISI score decreased by approximately 30% (from 16.09 ± 3.67 at inclusion (V1) to 11.32 ± 4.78 at 4 weeks (V2); p < 0.0001). Night sleep duration significantly increased between the first and the fourth week of supplement intake, sleep efficiency increasing from 78.4% ± 12.5 to 84.6% ± 10.2 (p = 0.002). There was no improvement in sleep latency. The number of awakenings decreased by approximately 25% and their total duration by approximately 25 min. Anxiety score significantly decreased by 50% from 13.9 ± 7.3 at V1 to 6.7 ± 6.3 at V2 (p < 0.0001). The supplement was well tolerated. These results suggest that the tested combination of eschscholtzia and valerian extracts could be beneficial for the management of insomnia in adults and deserves further investigation.
... Chang et al. (2002) found that C. oxyacantha fruit extract was effective in treating indigestion with epigastric distension, diarrhea, abdominal pain, amenorrhea, as a diuretic, for dyspnea, and renal calculi. In addition, C.oxyacantha fruit extract displayed beneficial actions such as hypolipidemic (Shanthi et al. 1996), hypocholesterolemic, anti-arterosclerotic (Rajendran et al. 1996), sedative, anxiolytic (Hanus, Lafon, and Mathieu 2004), anti-inflammatory, gastroprotective, antimicrobial, and free-radical scavenging properties (Tadic et al. 2008). However, this plant is particularly useful in the treatment of various heart problems as a cardio-stimulant in heart failure, angina pectoris, hypertension with myocardial insufficiency, alterations of cardiac rhythm, and atherosclerosis (Degenring et al. 2003;Weihmayr and Ernst 1996;WHO 2002). ...
Crataegus oxyacantha L. (Rosaceae) is a medicinal plant with a long history of use in European, Chinese, and American. The majority of pharmacological activities associated with fruit extracts of C. oxyacantha L. are related to cardio-stimulant properties utilized in the treatment of atherosclerosis, hypertension with myocardic insufficiency, angina pectoris, cardiac rhythm alterations, and heart failure. Some other therapeutic uses for renal calculi, dyspnea, as well as a diuretic, sedative, and anxiolytic were also reported. Due to the beneficial potential of C. oxyacantha fruits extract but evidence in vitro of genetic toxicity, the aim of the present study was to examine the genotoxic potential of plant extract in vivo in mice. The extract was administered orally, daily by gavage at doses of 50, 100, and 200 mg/kg body weight for seven days. Data demonstrated that C. oxyacantha extract did not markedly induce DNA damage in leukocytes and bone marrow cells by the comet assay; however, the extract produced a significant rise in micronucleated polychromatic erythrocytes (PCE) at all tested doses in a non-dose dependent manner as evidenced by the micronucleus test. The PCE/normochromatic erythrocytes (NCE) ratio indicated no significant cytotoxicity. Under our experimental conditions, C. oxyacantha fruits extract exhibited weak clastogenic and/or aneugenic effects in bone marrow cells of male mice, confirming our previous in vitro findings that this plant extract induced genotoxicity suggesting that prolonged or high dose use needs to be undertaken with caution.
... Popovic-Milenkovic et al. (2014) demostraron que los extractos etanólicos obtenidos de frutos de C. nigra tienen un efecto ansiolítico, presumiblemente causado por el elevado contenido de compuestos fenólicos, principalmente kaemferol-3-O-glucósido, quercetina-3-O-glucósido, rutinósido, hiperósido, epicatequina, ácido 5-O-cafeocólico, ácido protocatecuico y ácido quínico. Similarmente, Hanus et al. (2004) observaron una disminución de ansiedad en pacientes tratados con extractos de C. oxiacanta y Eschscholtzia californica. Bor et al. (2012) reportaron efectos antinociceptivos causados por extractos etanólicos de hojas de C. orientalis, los cuales se atribuyeron al alto contenido de algunos flavonoides (hiperósido) presente en los extractos. ...
Hawthorn (Crataegus spp.) is a plant widely distributed in Mexico, where it is mainly used as food for humans and feed for livestock. Its use in traditional medicine is low, compared to that in other countries. Historically, the fruit has been used to treat many conditions, including cardiovascular diseases, which represent one of the leading causes of death in Mexico and the world. Scientific studies attribute some beneficial effects of hawthorn to phenolic compounds. In this review, the beneficial effects attributed to hawthorn and the mechanisms of action involved are analyzed in a critical and systematic way in order to promote its use in the treatment of various diseases considered in Mexico as public health problems.
... Three hundred mg/day Mg support was given to university students and the difference between anxiety scores between placebo and intervention groups was evaluated; however, no difference was found (Gendle & O'Hara, 2015). Hanus et al. (Hanus, Lafon, & Mathieu, 2004) in a double-blind randomized clinical trial of Mg support were found to cure anxiety. The reason why we obtained different results from this study was thought to be this study had been a cross-sectional study and the methodology of research while evaluating anxiety. ...
... In 2017, Boyle and Dye published a review on the available studies investigating the effects of magnesium, alone or in combination, on the experience of subjective anxiety or stress (i.e., mild anxiety, premenstrual syndrome, postpartum status, and hypertension) in adult populations [72]. Eight studies were reviewed which focused on the treatment of mild anxiety with magnesium alone [77], magnesium in combination with vitamin B 6 [78][79][80][81], magnesium with fermented cow's drink with protein hydrolysate [82], or magnesium in combination with Hawthorn extract and California poppy [83]. Modest evidence of the beneficial use of various forms of magnesium for treatment of mild to moderate anxiety was found. ...
Magnesium is well known for its diverse actions within the human body. From a neurological standpoint, magnesium plays an essential role in nerve transmission and neuromuscular conduction. It also functions in a protective role against excessive excitation that can lead to neuronal cell death (excitotoxicity), and has been implicated in multiple neurological disorders. Due to these important functions within the nervous system, magnesium is a mineral of intense interest for the potential prevention and treatment of neurological disorders. Current literature is reviewed for migraine, chronic pain, epilepsy, Alzheimer’s, Parkinson’s, and stroke, as well as the commonly comorbid conditions of anxiety and depression. Previous reviews and meta-analyses are used to set the scene for magnesium research across neurological conditions, while current research is reviewed in greater detail to update the literature and demonstrate the progress (or lack thereof) in the field. There is strong data to suggest a role for magnesium in migraine and depression, and emerging data to suggest a protective effect of magnesium for chronic pain, anxiety, and stroke. More research is needed on magnesium as an adjunct treatment in epilepsy, and to further clarify its role in Alzheimer’s and Parkinson’s. Overall, the mechanistic attributes of magnesium in neurological diseases connote the macromineral as a potential target for neurological disease prevention and treatment.
... The effect is due to its hypocholesteromic action and presence of vitamin C which strengthens and opens tiny capillaries resulting in more nutrients and oxygen supply to the brain. Hawthorn has been used to treat anxiety (Hanus et al. 2004;Tabach et al. 2008;Arora et al. 2011). Seed and pulp extract of Hawthorn showed central nervous system depressant and opioid related analgesic effect at a dose range of 10-1000 mg/kg (Can et al. 2010). ...
Treatment of cognitive disorders is a challenging task in neurology since long time. Crataegus oxyacantha, also known as hawthorn belongs to family Rosaceae grown in colder areas and is one of the most widely used herb for the treatment of heart disorders. Traditionally Crataegus oxyacantha has also been used to treat Alzheimer disease, nervousness, stress, pain, and sleep disorders. In this study nootropic activity of petroleum ether, chloroform and methanol extract of Crataegus oxyacantha leaves was assessed using elevated plus maze model. Scopolamine (1 mg/kg) was used as amnesia inducing agent and piracetam (120 mg/kg) as standard nootropic drug. On the last day of the experiment, biochemical parameters like acetylcholinesterase, lipid peroxidase and superoxide dismutase were measured in brain homogenate. Effect of Crataegus oxyacantha on monoamines mediated behaviour was assessed through lithium induced head twitches and haloperidol induced catalepsy model in rats. Among all three extracts, methanol extract of Crataegus oxyacantha caused highest reduction in transfer latency time significantly as measured on 7th and 14th day and on 8th and 15th day on elevated maze and also decreased acetylcholinesterase and lipid peroxidase level and increased super oxide dismutase content as compared to scopolamine group. Methanol extract of Crataegus oxyacantha (200 mg/kg and 400 mg/kg) decreased number of head twitches and duration of catalepsy in rats significantly compared to vehicle treated group. So our study showed promising effect of Crataegus oxyacantha in enhancing learning and memory due to the presence of certain phytoconstituents.
... Ruta graveolens[30][31][32]Arborinine, Evoxanthine, Rutacridone[33]Passiflora incarnate[34]Harmaline, Harmalol, Harmane, Harmine, Harmol, Norharmane[35]Escholtzia californiea[36]Caryachine, Escholtzina, NMethyllaurotetanine, oMethylcaryachine, Protopin,[37]Sanguinarine[38]Fumaria officinalis[39,40]Cheilanthifoline, Coridamine, Fumaricine, Fumariline, Fumaritine, Fumaropycine, methylFumariphycine, Sinactin, Stylopine[40]Piper nigrum[41]Dihydropiperlonguminine, Piperanine, Piperine, Piperlonguminine[42]Galega officinalis[43,44]Galegin, Peganin[45]Ginko biloba[46]Ginkgotoxin[47]Achillea millefolium[48]Betonicine, Stachydrine[49]Mentha piperita[50]Lasiocarpine N-oxide[17,51]Urtica dioica[52]Seneciphylline N-Oxide[17,51]Cinchona succirubra[52]Cinchonanine A, B, C, D, E, F[52]Plantago major[55]Indicain, Plantagonin[56]Salvia officinalis[57,58]Heimidine[59]Vaccinium myrtillus[60]Epimyrtine, Myrtin[61]Veratrum album Cevadine, Jervine, Pseudojervine[62]Glycyrrhiza glabra[63]Aconine, Mesaconine[64]Valeriana officinalis[65]Actinidine, Cathinine, Valerianine, Valerine[66]This article is protected by copyright. All rights reserved.Table 6: Summary of the untargeted Alk profile of 52 herbal infusion samples and 6 commercial blends, sorted by chemical/botanical groups.Tropane ...
Herbal infusions are consumed worldwide thanks to their “natural” beneficial effects, also due to the presence of alkaloids, although these compounds can have poisonous effects. A method combining online solid-phase purification with high resolution mass spectrometry was used to define the alkaloid profiles of 117 herbs and 7 commercial blends. 41 alkaloids were quantified in reference to analytical standards, while the presence of a further 116 was confirmed on the basis of accurate mass, retention time and fragmentation profile. The targeted study showed that 52% of herbs and 42% of commercial blends contained at least one alkaloid, and pyrrolizidines were the most commonly present (26% of samples), with concentrations generally ranging from the quantification limit to roughly 100 μg kg-1. Moreover, a homemade infusion was studied, finding on average 45% and 6% lower extraction for pyrrolizidine and steroidal alkaloids, respectively. Nevertheless, the migration of pyrrolizidines was confirmed. The study confirmed the frequent presence, natural or accidental, of alkaloids in commercial infusion herbs, highlighting the urgent need for routine and accurate controls.
... 200 mg Mg/day plus 50 mg vitamin B6/day were found to reduce anxiety-related premenstrual symptoms (De Souza et al., 2000). Also, a combined treatment of plant extracts of Crataegus oxyacantha and Eschscholtzia californica and magnesium has been shown to be more effective than placebo in patients with mild to moderate generalized anxiety disorder GAD (Hanus et al., 2004). Although Mg administration which induces anxiolytic-like activity led to an increase in serum magnesium concentration (Poleszak et al., 2004), no differences were found in either the erythrocyte or brain Mg levels following an increase in serum Mg concentration evoked by acute and subchronic i.p. injections of Mg-chloride in rats (Wlaz, Serefko, Szopa, & Poleszak, 2016). ...
Elements (bioelements) are necessary factors required for the physiological function of organisms. They are critically involved in fundamental processes of life. Extra- and intracellular message and metabolic pathway factors as well as structural components include one or many elements in their functional structure. Recent years have seen an intensification in terms of knowledge gained about the roles of elements in anxiety disorders. In this chapter we present a review of the most important current data concerning the involvement of zinc, magnesium, copper, lithium, iron, and manganese, and their deficiency, in the pathophysiology and treatment of anxiety.
... Supplemental magnesium has been shown to have a positive effect in 70% children with autism at a dose of 6mg/kg/d combined with vitamin B6 (0.6mg/kg/d) (Meletis 2007). Significant clinical improvement of anxiety symptoms has also been demonstrated using magnesium in combination with Crataegus oxyacantha and Eschscholtzia californica (Hanus 2004). ...
Crataegus oxyacantha is used in the treatment of cardiovascular diseases. The aim of this study was to evaluate the transplacental genotoxicity effect of aqueous (AE) and hydroalcoholic extract (HE) of leaves C. oxyacantha in a rat model and the quantification of malondialdehyde (MDA) in the liver. Three different doses of the AE and HE of the C. oxyacantha leaf were administered orally (500, 1000 and 2000 mg/kg) to Wistar rats during 5 days through the pregnancy term (16–21 days), and sampling in rats occurred every 24 h during the last 6 days of gestation, while only one sample was taken in neonates at birth. A sample of the mother’s and the neonate’s liver was taken for the determination of MDA. The results show that, at the hepatic level, the evaluated doses of extracts C. oxyacantha in pregnant rats and their pups did not show cytotoxicity. However, the AE and HE generated cytotoxic and genotoxic damage in the short term. On the other hand, only the AE showed a teratogenic effect. Based on these results, the AE and HE of the C. oxyacantha leaf should not be administered during pregnancy.
Neurological disorders are a significant cause of mortality and disability across the world. The current aging population and population expansion have seen an increase in the prevalence of neurological and psychiatric disorders such as anxiety, bipolar disorder, depression, epilepsy, multiple sclerosis and schizophrenia. These pose a significant societal burden, especially in low - and middle-income countries. Many neurological disorders have complex mechanisms and lack definitive cures; thus, improving our understanding of them is essential. The pathophysiology of neurological disorders often includes inflammation, mitochondrial dysfunction and oxidative stress. Oxidative stress processes, especially the generation of reactive oxygen species, are key mechanisms in the development of neurological disorders. Oxidative stress refers to an imbalance between the production of reactive oxygen species and antioxidants that can counteract them. Through their impacts on the pathophysiology of neurological disorders, nutrients with anti-inflammatory, neuroprotective and antioxidative properties have been suggested to prevent or mitigate these disorders. Certain vitamins, minerals, polyphenols and flavonoids may have therapeutic effects as adjuvant treatments for neurological disorders. Diet quality is also a risk factor for some neurological and psychiatric disorders and addressing nutritional deficiencies may alleviate symptoms. Therefore, optimizing nutritional intake may represent a potential treatment or prevention strategy. This review summarizes a selection of promising nutrients for the prevention and amelioration of neurological disorders to provide a summary for scientists, clinicians and patients, which may improve understanding of the potential benefits of nutrients in the treatment of neurological disorders.
Consideration and improvement for anxiety and depression are important during global pandemic diseases. Appropriate healthcare can be obtained by paying more attention to traditional medicinal sciences. The adverse effects of stress with its various symptoms can be managed by introducing plants that boost mental health. The most relevant psychological reactions in the general population related to global pandemic are pervasice anxiety, frustration and boredom, aspecific and uncontrolled fear, disabling loneliness, significant lifestyle changes, and psychiatric conditions. Ginseng, chamomile, passionflower, herbal tea, lavender, saffron, kava, rose, cardamom, Chinese date and some chief formula like yokukansan, Dan-zhi-xiao-yao-san, so-ochim-tang-gamiband, and saikokaryukotsuboreito are notable herbal treatments for mental health problems. The most common medicinal plants which have been used in Iran for the cure of stress and anxiety are Viper,s-buglosses, Dracocephalum, valerian, chamomile, common hop, Hawhorns, and Lavender. Medicinal plants and herbs can be used for treatment and alleviating negative effects of stress, anger and depression during the global pandemic.
Silver nanoparticles (AgNPs) of both biologically and chemically origins trigger various physiological and metabolic processes through interaction with plant cells, exerting positive, negative and inconsequential effects. However, their impacts on plant systems must be critically investigated to guarantee their safe application in food chain. In this study, the effects of chemically synthesized (synthetic) AgNPs (sAgNPs) and biologically synthesized (biogenic) AgNPs (bAgNPs) on physiological and biochemical features of Eschscholzia californica Cham were evaluated at different concentrations (0, 10, 25, 50 and 100 mg L-1). Plants exposed to bAgNPs (at 10 and 25 mg L-1) and sAgNPs (at 10 mg L-1) displayed relatively uniform deposition of AgNPs on leaf surface, however, the higher concentration (100 mg L-1) was accompanied by aggregation of AgNPs, resulting in anatomical and physiological disorders. Foliar application of both AgNPs at lower concentrations resulted in significant (P < 0.01) improve in the content of photosynthetic pigments (chlorophylls a, b, a+b, and carotenoids) and total phenolics over the control in a dose-related manner. Leaf relative water content decreased steadily with increasing both sAgNPs and bAgNPs concentrations-with sAgNPs being more inhibitive. Both types of AgNPs at 100 mg L-1 significantly (P < 0.05) increased electrolyte leakage index, level of lipid peroxidation product (malondialdehyde), and leaf soluble sugar content when compared to controls. No significant difference was found on cell membrane stability index among the plants exposed to bAgNPs and sAgNPs at the lowest concentration over the control. Californidine content was significantly (P < 0.01, by 45.1%) increased upon all the bAgNPs treatments (with a peak at 25 mg L-1) relative to control. The obtained extracts from plants treated with bAgNPs at lower concentrations revealed a significant induction of antioxidant capacity (based on DPPH˙ free radical scavenging and ferrous ions-chelating activities) with lower IC50 values compared to the other treatments. Conclusively, bAgNPs at lower concentrations are potent elicitors of pharmaceutically active compounds biosynthesis, which enhance physiological efficiency of E. californica, but at higher concentrations bAgNPs are equally toxic as sAgNPs.
Hawthorn (Crataegus oxycantha) is one of the best cardiovascular herbs because it is both cardiotonic and antiarrhythmic. Its medicinal properties come from its flowers, leaves, and berries. Hawthorn is also sedating, adaptogenic, antioxidant, vasodilating, diuretic, and hypotensive. It may be beneficial for hypertension, coronary artery disease, congestive heart failure, orthostatic hypotension, and nonalcoholic fatty liver disease. The oligomeric procyanidins in hawthorn have been shown to have antioxidant properties. This chapter examines some of the scientific research conducted on hawthorn, both alone and in combination formulas, for treating numerous health conditions. It summarizes results from several human studies of hawthorn’s use in treating cardiovascular disorders, including hypertension, coronary artery disease, congestive heart failure, and orthostatic hypotension, as well as gastrointestinal and psychiatric diseases. Finally, the chapter presents a list of hawthorn’s active constituents, different Commonly Used Preparations and Dosage, and a section on “Safety and Precaution” that examines side effects, toxicity, and disease and drug interactions.
Sleep disorders are common among the general population and can generate health problems such as insomnia and anxiety. In addition to standard drugs and psychological interventions, there are different complementary plant-based therapies used to treat insomnia and anxiety. This review aimed to find and examine the most recent research on the use of herbal medicines for treating anxiety and insomnia as compiled from clinical trials, as well as to assess the safety and efficacy of these medicines and to elucidate their possible mechanisms of action. The process entailed a search of PubMed, Scopus, and the Cochrane Library databases from 2010 to 2020. The search terms included “sleep disorder”, “insomnia”, “sedative”, “hypnotic”, “anxiety”, “anxiolytic”, and “clinical trial”, combined with the search terms “herbs” and “medicinal plants”, in addition to individual herbal medicines by both their common and scientific names. This updated review, which focuses mainly on clinical trials, includes research on 23 medicinal plants and their combinations. Essential oils and their associations have also been reviewed. The efficacy of medicinal plants depends on treatment duration, types of study subjects, administration route, and treatment method. More clinical trials with an adequate, standardized design are necessary, as are more preclinical studies to continue studying the mechanisms of action. As a result of our work, we can conclude that the 3 plants with the most potential are valerian, passionflower, and ashwagandha, with the combination of valerian with hops and passionflower giving the best results in the clinical tests.
Objective: To investigate self-reported practice, beliefs, and barriers regarding prescription of dietary change for mental health from a range of mental health practitioners across Australia.
Method: An online survey was completed by 193 Australian mental health practitioners.
Results: Over 50% of practitioners reported prescribing dietary change for stress, depression, and anxiety at least weekly in their practice. Over half the practitioners considered dietary change to be 60-100% useful for enhancing mental health outcomes. Approximately one-quarter of the practitioners considered dietary change to be less than 40% useful for treating mental health conditions. Thematic analysis revealed the most frequently reported higher-order barrier themes were practitioner barriers (43.8%) and client barriers (29.2%), with insufficient skills and knowledge (15.9%) and client adherence (12.8%) being commonly cited initial codes.
Conclusion: Mental health practitioners in Australia prescribe dietary change for mental health. However, barriers to prescription of dietary change for mental health need be addressed to overcome challenges associated with using it as a therapeutic intervention for mental health conditions. Universities and university training accreditation bodies should consider providing more extensive instruction in psycho-nutrition as part of mental health practitioners’ training. Likewise, further recognised professional development should be offered, and awarded, for already qualified practitioners.
Key Points
What is already known about this topic:
• Diet is becoming more accepted as having a substantial influence upon mental health.
• Improving diet quality has been acknowledged as serving a protective role in reducing the rate of cognitive decline.
• The importance of dietary change remains underestimated by mental health professionals for the treatment of mental health maladies.
What this research adds:
• Results demonstrated over 50% of the sample of mental health practitioners reported prescribing dietary change for stress, depression, and anxiety at least daily or weekly in their practice.
• Approximately a third of the mental health practitioners reported believing dietary change to be 80-100% useful for mental health outcomes.
• Most frequently reported barriers to the prescription of dietary change for mental health were practitioner barriers (43.8%) and client barriers (29.2%) higher-order themes, with insufficient skills and knowledge (15.9%) and client adherence (12.8%) being commonly cited initial codes.
Naturellement, le cheval n’est pas conditionné pour la compétition. Cependant, l’homme a vu en lui un outil de travail intéressant pour la chasse, le portage ou la traction. Ses capacités athlétiques ne sont pas restées inaperçues, c’est ainsi que l’homme utilisa le cheval pour le loisir. Le cheval passa alors du pré au box, et son régime alimentaire s’en est retrouvé changé et ses besoins augmentés. Les cavaliers deviennent de plus en plus exigeants vis à vis des performances mais souhaitent également maintenir leurs chevaux en bonne santé et privilégier leur bien-être. Cette thèse approfondie l’utilisation des aliments complémentaires dans l’objectif de pallier les déficits que le cheval peut rencontrer. C’est pourquoi nous allons étudier dans un premier temps la physiologie du cheval à l’effort afin de comprendre ses besoins et les risques d’une activité telle que le saut d’obstacles. Nous intéresserons ensuite à ses besoins alimentaires et enfin nous présenterons différentes formules d’aliments complémentaires disponibles à l’officine.
Anksiozni i depresivni poremećaji su psihijatrijska stanja koja karakterišu emotivne, kognitivne i bihejvioralne izmene, uz značajno narušeno funkcionisanje. Urađen je sistematski pregled literature u PubMedu koji se odnosio na magnezijum, anksioznost i depresiju. Na osnovu dosadašnjih studija,primećeno je da postoje minimalni dokazi da je magnezijum, verovatno deficit/hipomagnezijemija, uključen u razvoj poremećaja raspoloženja, ali da nema protektivnu ulogu; suplementacija magnezijumom smanjuje depresivne simptome kod depresije udružene sa deficitom magnezijuma; suplementacija magnezijumom smanjuje depresivne simptome kod blage/umerene depresije (i to Mg-hlorid); suplementacija magnezijumom smanjuje anksiozne simptome u kombinaciji sa drugim suplementima; nema dokaza da suplementacija magnezijumom utiče na ishode anksioznih poremećaja; suplementacija magnezijumom smanjuje pridružene anksiozne simptome samo kod blage/umerene depresije. Potrebna su nova istraživanja, kako bismo imali još jasnije preporuke za primenu suplementacije magnezijumom u kliničkim uslovima kod lečenja depresije i anksioznih poremećaja.
About one third of the world's population is affected by insomnia. Insomnia may be due to various reasons such as physiological, psychological, genetic etc. It affects the health as well as the professional and social life of the affected person. There are many treatment of insomnia, among them pharmacological treatment with benzodiazepine and related tricyclic antihistamines are quite popular. But due to several side effects of these drugs, non-pharmacological and herbal treatments of insomnia are becoming popular day by day. Many types of herbs are reported to have sedative properties in the ethnobotanical evidences around the world. Among them Valerian, Kava Kava, Ginseng, St. John's Wort are most common. Besides these plants there are several other plants which are also used in insomnia treatment. Though there are lot of work to be done on herbal treatment of insomnia due to scarcity of reliable data and lack of proper preclinical (using animal models) and/or clinical evidences.
This chapter will present evidence from human clinical trials regarding the efficacy of nutritional supplements which have emerged in recent years as viable treatments for anxiety disorders.
B vitamins
Magnesium
Lysine and Arginine
Myo-Inositol
N-Acetyl-cysteine
The well being of dogs can be affected by changes in human lifestyle, eating habits and increased stressors that lead to behavioral disorders including fear, hyperactivity and anxiety, followed by negative affective moods and poor welfare. Our randomized, controlled clinical evaluation involved 69 dogs, 38 males and 31 females, of different breeds, with behavioral disorders related to anxiety and chronic stress. They were fed a control diet (CD group) or a nutraceutical diet (ND group) for 45 days. Neuroendocrine (serotonin, dopamine, β-endorphins, noradrenaline and cortisol) and stress (dROMs and BAP) parameters related to behavioural disorders were evaluated at the beginning and end of the study period.
Results showed a significant increase in serotonin, dopamine and β-endorphins plasma concentrations (*p < 0.05, *p < 0.05 and **p < 0.01, respectively) and a significant decrease in noradrenaline and cortisol plasma concentrations in the ND group (*p < 0.05). dROMs significantly decreased in the ND group (*p < 0.05) while BAP was not affected. This study demonstrated for the first time that a specific diet significantly and positively affected neurendocrine parameters and dROMs. These results open significant perspectives concerning the use of diet and neutraceuticals in the treatment of behavioral disorders
Background: Complementary and alternative medicine (CAM) therapies have considerable patient appeal. Perceived as better, safer and more economical than conventional treatments, such as pharmacotherapy and psychotherapy, they are often used by patients to self-treat symptoms of depression and anxiety, usually in combination with existing medications and without medical supervision. CAM therapies include physical therapies (e.g. exercise), herbal remedies (e.g. St. John’s wort) and nutraceuticals/dietary supplements (e.g. omega-3 fatty acids). This chapter will review the published evidence for the use of herbal and dietary supplements as augmenting or adjunctive agents in depressive and anxiety disorders.
Studies consisted in carrying out a systematic series of extractions of active principles from Lavandula angustifolia Mill, Melissa officinalis L, Origanum vulgare L si Crataegus sp,.using different solvents and processing the extractive solutions to obtain fractions with 0.048-16.240% flavonoid aglycones expressed as quercetin; 0.100-33.940% flavonoid glycosides expressed as rutoside; 0.006-6.140% polyphenolic acids expressed as caffeic acid, 0.473-18.970% polysaccharides expressed in glucose, 1,040-1,299 % triterpenoid aglycones and 0,023-0,257% triterpenoid saponins expressed as ursolic acid as well as 0.380-19.5007% inorganic substances. The obtained fractions were pharmacologically tested using 2 methods and having in view the sedative activity. Some fractions turned out an obvious sedative action or a weak one while other proved no sedative action, the results depending on the vegetal species used and also on the processing method.
Euphytose (EUP) is a combination of six extracts: Crataegus, Ballota, Passiflora and Valeriana, which have mild sedative effects, and Cola and Paullinia, which mainly act as mild stimulants. This multicenter, double-blind, placebo-controlled general practice study was carried outpatients with adjustment disorder with anxious mood. The study was coordinated by psychiatrists. Ninety-one patients were included in the EUP group and 91 patients in the placebo group. They all received two tablets three times a day over 28 days (D). Evaluation using the Hamilton-anxiety (HAM-A) rating scale were carried out on D0, D7, D14 and on D28. Comparing the two groups, 42.9% of the patients (EUP group) had a HAM-A score of less than 10 at D28 versus 25.3% in the placebo group (P = 0.012). Changes in the HAM-A score between D0 and D28 were as follows: D0 (EUP: 26.12 +/- 4.0, placebo: 26.27 +/- 4.5), D7 (EUP: 19.65 +/- 5.7, placebo: 21.37 +/- 5.6), D14 (EUP: 15.36 +/- 5.7, placebo: 17.48 +/- 6.7), D28 (EUP: 12.63 +/- 7.3, placebo: 15.2 +/- 8.1). From D7 to D28 there was a statistically significant difference (P = 0.042) between the two treatments, indicating that EUP is better than placebo in the treatment of adjustment disorder with anxious mood.
Objective: This study, conducted in Aquitaine (Southwest France), was designed to assess both frequency and treatment of anxiety disorders in general practice patients. Method: The assessment was cross-sectional ; a random sample of 312 patients was chosen and evaluated during the last week of Mai 1993, by 55 general practitioners who usually collaborate in the Aquitaine Sentinel Network, supported by the Department of Medical Statistics and Public Health of the University of Bordeauxll. Anxiety disorders were assessed by the Composite International Diagnostic Interview and level of depression was self evaluated by the Beck Depression Inventory. The physicians reported current psychological and psychopharmacological treatments, and request for treatment of every patient tested. Results : Frequency of anxiety disorders is concordant with available epidemiological data in French general population. There is no sex difference for anxiety disorders in this study, in opposition to what is known in the general population (2 = 1.47, p > .05). Women are more treated than men drugs χ 2 = 7.31 p < .01; psychotherapies: χ 2 = 7.58 p <.04) although they don't request for more treatment (χ 2 .59 p < .05). Benzodiazepines and psychodynamic oriented therapies are the most used treatments for any anxiety disorders ; specific treatments (antidepressive drugs, behavioral therapies) of anxiety are very rarely prescribed. Conclusion: This study shows the difference between the current theoretical knowledge in anxiety disorders, and the management of these disorders by the general practitioner. It suggests that patient's request, in opposition to what is often found in the literature, is not a determinant factor in treatment.
The main actions of benzodiazepines (hypnotic, anxiolytic, anticonvulsant, myorelaxant and amnesic) confer a therapeutic value in a wide range of conditions. Rational use requires consideration of the large differences in potency and elimination rates between different benzodiazepines, as well as the requirements of individual patients.
As hypnotics, benzodiazepines are mainly indicated for transient or short term insomnia, for which prescriptions should if possible be limited to a few days, occasional or intermittent use, or courses not exceeding 2 weeks. Temazepam, loprazolam and lormetazepam, which have a medium duration of action are suitable. Diazepam is also effective in single or intermittent dosage. Potent, short-acting benzodiazepines such as triazolam appear to carry greater risks of adverse effects.
As anxiolytics, benzodiazepines should generally be used in conjunction with other measures (psychological treatments, antidepressants, other drugs) although such measures have a slower onset of action. Indications for benzodiazepines include acute stress reactions, episodic anxiety, fluctuations in generalised anxiety, and as initial treatment for severe panic and agoraphobia. Diazepam is usually the drug of choice, given in single doses, very short (1 to 7 days) or short (2 to 4 weeks) courses, and only rarely for longer term treatment. Alprazolam has been widely used, particularly in the US, but is not recommended in the UK, especially for long term use.
Benzodiazepines also have uses in epilepsy (diazepam, clonazepam, clobazam), anaesthesia (midazolam), some motor disorders and occasionally in acute psychoses.
The major clinical advantages of benzodiazepines are high efficacy, rapid onset of action and low toxicity. Adverse effects include psychomotor impairment, especially in the elderly, and occasionally paradoxical excitement. With long term use, tolerance, dependence and withdrawal effects can become major disadvantages. Unwanted effects can largely be prevented by keeping dosages minimal and courses short (ideally 4 weeks maximum), and by careful patient selection. Long term prescription is occasionally required for certain patients.
Anxiety occurs as a normal phenomenon and as a symptom of numerous psychiatric and physical illnesses, while it is the dominant feature of generalised anxiety, panic and phobic disorders. The relationship between these and other disorders is not as straightforward as diagnostic classifications suggest, and this is at least in part due to previous research having been carried out on atypical cases referred to hospital rather than patients in the real world of general practice and the general community. There are particular difficulties in distinguishing anxiety disorders from depressive illnesses, somatisation disorder and some cases of substance abuse and dependence. There may also be difficulty in deciding to what extent anxiety is related to stress or to the underlying personality of the patient. There are many reasons for these difficulties, including limitations in our basic knowledge of anxiety, preconceived notions of the clinician and the difficulty that some patients have in describing their experiences. Numerous different psychological and pharmacological treatments have been used throughout history. They include various forms of psychotherapy, behaviour and cognitive therapies and anti-anxiety drugs. Many patients receive supportive psychotherapy, while more specialised techniques currently being investigated include exposure therapy and cognitive therapy. By far the most widely used drugs are the benzodiazepines, but because of concern over dependence increasing interest is being shown in the use of alternatives, including antidepressants, and in the development of new compounds which, it is hoped, will turn out to be free from the problem of dependence.
A self-report questionnaire is described which records the main symptoms experienced during withdrawal from benzodiazepines in pharmacologically dependent patients. The questionnaire consists of 20 items; evidence is given that these are reasonably independent and are sensitive in detecting withdrawal symptoms from a study of 68 patients undergoing slow withdrawal from benzodiazepines.
Alpidem, an imidazo-pyridine compound, has been evaluated as an anxiolytic in comparison with placebo and lorazepam. In the first of our normal volunteer studies, we compared single doses of alpidem, 25, 50 and 100 mg with lorazepam 2 mg and placebo on a range of cognitive, psychomotor and EEG variables. Lorazepam and the highest (100 mg) dose of alpidem impaired performance on a range of psychomotor tasks, the effects of the benzodiazepine being more severe and more prolonged. No impairment of performance was observed with the 25 and 50 mg doses.
In the second study, the focus was on memory functions. Lorazepam, 2 mg, caused anterograde amnesia which was most apparent 1 h post-drug but persisted until 4 h: sedation was marked. By contrast, single doses (25, 50 mg) of alpidem had little effect on either memory or alertness.
The third study compared the effects of alpidem (25, 50 mg) and lorazepam (1 mg) with placebo, each given twice-daily for 8 days to normal volunteers. On the final day, a test dose of ethanol was given. Lorazepam impaired many tests of cognitive and psychomotor function, and this impairment was enhanced by ethanol. By contrast, alpidem produced less impairment with less interaction with alcohol.
In a fourth, clinical, study, 24 patients with a DSM III primary diagnosis of generalised anxiety disorder were treated, under double blind conditions, with doses adjusted according to clinical need of either alpidem 25 - 150 mg daily or lorazepam 1 - 6 mg daily. Alpidem was an effective anxiolytic producing no significant withdrawal syndrome after 4 weeks use in contrast to the problems encountered in using the comparison drug lorazepam. Physiological and psychological effects were similar to those of our normal subject studies.
Pooled data were analyzed for 367 female patients enrolled in a double-blind, placebo-controlled, multi-centre trial comparing buspirone, a non-benzodiazepine anxiolytic, and diazepam in the treatment of generalized anxiety disorder. After a 4 to 7-day wash-out period, patients were allocated at random to receive one or other of the trial medications or placebo over a 4-week period. Mean daily dosages were 24.5 mg for buspirone and 20.8 mg for diazepam (range 10 mg to 60 mg for both drugs). Patients were assessed on entry and at weekly intervals using the Hamilton Anxiety Rating Scale, and at the end of treatment both patients and physicians gave an overall opinion of response to treatment. Details of adverse events were also recorded. The results showed that both buspirone and diazepam were approximately equal in efficacy and superior to placebo. Menstruation and the occurrence of premenstrual tension did not alter the anxiolytic activity of either drug. Patients taking diazepam had significantly more adverse effects, i.e. drowsiness, weakness, fatigue, inco-ordination and depression, than did those in the buspirone group. In a separate commentary, the anxiety disorder and the data from the study are reviewed to place them in the overall perspective of gynaecological care.
The classification of psychoactive drugs into minor tranquilizers (i.e. antianxiety drugs) and major tranquilizers (i.e. antidepressants, antimaniacs and antipsychotics) is based on clinical symptom rating scales. The group of symptoms in these scales of anxiety, depression, mania and schizophrenia has a shared phenomenology in the sense that the symptoms can be ordered from less to more severe. The inter-observer agreement when using these scales is adequate as agreement is of 80% or higher. By use of rating scales it has been found in controlled clinical trials that minor psychiatric disorders such as anxiety states without depression have a good outcome of placebo in 60 to 65%. In depressive disorders placebo has a good outcome in 20-45%, but in the elderly depressed patient the placebo effect is poorest (25%). Antidepressants have a good outcome in 60-75%, but in the elderly depressed patients only in 50%. In other words the drug-placebo difference is around 25%. In the major psychiatric disorders such as mania and schizophrenia the drug-placebo difference is around 50%. The use of clinical symptom scales in evaluating side-effects of psychoactive drugs is increasing. However, also non-clinical or laboratory tests have an important role in measuring side-effects, especially in motor skills related to car driving. The use of mentally healthy volunteers in measuring side-effects of major tranquilizers seems inadequate. As yet no biological methods to measure clinical effects of the tranquilizers have been developed for practical use.
The main actions of benzodiazepines (hypnotic, anxiolytic, anticonvulsant, myorelaxant and amnesic) confer a therapeutic value in a wide range of conditions. Rational use requires consideration of the large differences in potency and elimination rates between different benzodiazepines, as well as the requirements of individual patients. As hypnotics, benzodiazepines are mainly indicated for transient or short term insomnia, for which prescriptions should if possible be limited to a few days, occasional or intermittent use, or courses not exceeding 2 weeks. Temazepam, loprazolam and lormetazepam, which have a medium duration of action are suitable. Diazepam is also effective in single or intermittent dosage. Potent, short-acting benzodiazepines such as triazolam appear to carry greater risks of adverse effects. As anxiolytics, benzodiazepines should generally be used in conjunction with other measures (psychological treatments, antidepressants, other drugs) although such measures have a slower onset of action. Indications for benzodiazepines include acute stress reactions, episodic anxiety, fluctuations in generalised anxiety, and as initial treatment for severe panic and agoraphobia. Diazepam is usually the drug of choice, given in single doses, very short (1 to 7 days) or short (2 to 4 weeks) courses, and only rarely for longer term treatment. Alprazolam has been widely used, particularly in the US, but is not recommended in the UK, especially for long term use. Benzodiazepines also have uses in epilepsy (diazepam, clonazepam, clobazam), anaesthesia (midazolam), some motor disorders and occasionally in acute psychoses. The major clinical advantages of benzodiazepines are high efficacy, rapid onset of action and low toxicity. Adverse effects include psychomotor impairment, especially in the elderly, and occasionally paradoxical excitement. With long term use, tolerance, dependence and withdrawal effects can become major disadvantages. Unwanted effects can largely be prevented by keeping dosages minimal and courses short (ideally 4 weeks maximum), and by careful patient selection. Long term prescription is occasionally required for certain patients.
The herbal drug Phytonoxon N (abbreviated as PN) is indicated in nervousness induced insomnia, agitation and/or anxiety. It is composed of alcoholic drug extracts of the plants Corydalis cava (20%) and Eschscholtzia californica (80%). Both plants are rich in isoquinoline alkaloids derived from tyrosine metabolism. Recent research shows that they may influence the neurotransmitter metabolism.
A higher anxiolytic and hypnotic consumption has been evidenced in France by recent international and national surveys. In an effort to counteract this pattern French Health authorities have enforced limitation to the prescription of these drugs. Understanding the causes of this overuse needs a careful analysis of the pattern of use of this medicine but also of the associated morbidity factors. In the last ten years several studies have attempted to address these issues. In the general population there were 25 to 30% of occasional or regular users with between 5 and 7% chronic users making french anxiolytic users two to three time superior to most industrialised countries. This high level of consumption is not the privilege of anxiolytic since the same pattern of use is observed for all medicine. Studies in primary care, in medical inpatients and psychiatric inpatients show as expected that anxiolytic use increase with the psychiatric morbidity and also with somatic disorder. The main risk factors for anxiolytic use are female sex, old age and psychic and somatic morbidity. Age seems to play a major role in subjects over 65: 17% are chronic users. Multiple factors might play a role in benzodiazepine use as medical care system, physician type of practice, cultural specific aspects but no proper simple explanation is available to explain the mechanism of the french high anxiolytic use. Given the poor global recognition of mental disorder observed in most countries it is suggested to privilege primary care physician training in psychiatry to optimize psychotropic drug use.
This study, conducted in Aquitaine (Southwest France), was designed to assess both frequency and treatment of anxiety disorders in general practice patients.
The assessment was cross-sectional; a random sample of 312 patients was chosen and evaluated during the last week of Mai 1993, by 55 general practitioners who usually collaborate in the Aquitaine Sentinel Network, supported by the Department of Medical Statistics and Public Health of the University of Bordeaux. Anxiety disorders were assessed by the Composite International Diagnostic Interview and level of depression was self evaluated by the Beck Depression Inventory. The physicians reported current psychological and psychopharmacological treatments, and request for treatment of every patient tested.
Frequency of anxiety disorders is concordant with available epidemiological data in French general population. There is no sex difference for anxiety disorders in this study, in opposition to what is known in the general population (2 = 1.47, p > .05). Women are more treated than men (drugs: chi(2) = 7.31 p < .01; psychotherapies: chi(2) = 7.58 p < .04) although they don't request for more treatment (chi(2) = .59 p M .05). Benzodiazepines and psychodynamic oriented therapies are the most used treatments for any anxiety disorders; specific treatments (antidepressive drugs, behavioral therapies) of anxiety are very rarely prescribed.
This study shows the difference between the current theoretical knowledge in anxiety disorders, and the management of these disorders by the general practitioner. It suggests that patient's request, in opposition to what is often found in the literature, is not a determinant factor in treatment.
The efficacy of hydroxyzine and buspirone, controlled by placebo, was investigated in a double-blind, parallel group, multicentre study conducted in France and the UK. A total of 244 patients with generalised anxiety disorder in primary care was allocated randomly to treatments with hydroxyzine (12.5 mg morning and mid-day, 25 mg evening), buspirone (5 mg morning and mid-day, 10 mg evening) or placebo (three capsules/day) for 4 weeks, preceded by a 1-week single-blind placebo run-in and followed by 1-week single-blind placebo administration. Rating scales were applied on days -7,0,7,14, 12,28 and 35. Seventy percent of the patients were female, the average age was 41 +/- 11 years, and the mean Hamilton Anxiety Score at day 0 was 26.5 +/- 4.2. Only 31 of the 244 patients dropped out, but equally in the three groups. Intention-to-treat LOCF analyses on the primary variable showed a significant difference only between hydroxyzine and placebo with respect to improvement on the Hamilton Anxiety Scale (10.75 versus 7.23 points, respectively). Secondary variables such as CGI and self-ratings (HAD scale) showed both hydroxyzine and buspirone to be more efficacious than placebo. Thus, hydroxyzine is a useful treatment for GAD.
Abecarnil, a novel anxiolytic beta-carboline, was investigated in five four-week double-blind, European multicentre studies. Overall 451 patients with generalised anxiety disorder were randomised to abecarnil, 461 to placebo and 464 to active controls.
Data includes inferential statistics based on individual studies and descriptive analysis of 323 patients in open-label abecarnil long-term continuation up to 52 weeks.
Abecarnil was safe, the most frequent adverse event being drowsiness. Onset of effect was at week 1. At week 4 the Hamilton Anxiety Scale score had improved by 12-13 points on average. Due to notably large and variable placebo effects abecarnil was not consistently superior to placebo. No rebound or withdrawal symptoms were observed after fast-tapered discontinuation. Safety, extent of efficacy and incidence of rebound or withdrawal did not change during long-term treatment.
Abecarnil is safe and effective. Further research into its therapeutic potential seems warranted.
Anxiety disorders are now defined by precise diagnostic criteria and their treatments are facilitated by the clinical and therapeutic studies undertaken during the past two decades with current classifications. However, their recognition in everyday clinical practice can be difficult because the patients do not always evoke their symptoms spontaneously, and the attention of the physician is generally attracted by other mental disorders, such as depressive syndromes. The high prevalence of anxiety disorders in the general population, and the handicap associated with severe forms, must incite to their systematic exploration, in order to propose specific therapeutic procedures to the patients. In addition to the clinical exploration of various anxiety syndromes, the clinician can be helped in this goal by assessment instruments, nowadays well validated and easily used, such as dimensional scales or structured diagnostic interviews.
This pilot study was aimed at investigating the hypotensive potential of hawthorn extract and magnesium dietary supplements individually and in combination, compared with a placebo. Thirty-six mildly hypertensive subjects completed the study. At baseline, anthropometric and dietary assessment, as well as blood pressure measurements were taken at rest, after exercise and after a computer 'stress' test. Volunteers were then randomly assigned to a daily supplement for 10 weeks of either: (a) 600 mg Mg, (b) 500 mg hawthorn extract, (c) a combination of (a) and (b), (d) placebo. Measurements were repeated at 5 and 10 weeks of intervention. There was a decline in both systolic and diastolic blood pressure in all treatment groups, including placebo, but ANOVA provided no evidence of difference between treatments. However, factorial contrast analysis in ANOVA showed a promising reduction (p = 0.081) in the resting diastolic blood pressure at week 10 in the 19 subjects who were assigned to the hawthorn extract, compared with the other groups. Furthermore, a trend towards a reduction in anxiety (p = 0.094) was also observed in those taking hawthorn compared with the other groups. These findings warrant further study, particularly in view of the low dose of hawthorn extract used.
Prior studies have suggested a common etiology involved in Tourette's syndrome and several comorbid conditions and symptomatology. Reportedly, current medications used in Tourette's syndrome have intolerable side-effects or are ineffective for many patients. After thoroughly researching the literature, I hypothesize that magnesium deficiency may be the central precipitating event and common pathway for the subsequent biochemical effects on substance P, kynurenine, NMDA receptors, and vitamin B6 that may result in the symptomatology of Tourette's syndrome and several reported comorbid conditions. These comorbid conditions and symptomatology include allergy, asthma, autism, attention deficit hyperactivity disorder, obsessive compulsive disorder, coprolalia, copropraxia, anxiety, depression, restless leg syndrome, migraine, self-injurious behavior, autoimmunity, rage, bruxism, seizure, heart arrhythmia, heightened sensitivity to sensory stimuli, and an exaggerated startle response. Common possible environmental and genetic factors are discussed, as well as biochemical mechanisms. Clinical studies to determine the medical efficacy for a comprehensive magnesium treatment option for Tourette's syndrome need to be conducted to make this relatively safe, low side-effect treatment option available to doctors and their patients.
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Venlafaxine and generalised anxiety disorder: new preparation. Minimise recourse to drugs
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Legrain M. Rapport du Groupe de Réflexion sur l'Utilisation des Hypnotiques et des Tranquillisants en France [French]. Paris: SNIP, 1990 © 2004 LIBRAPHARM LTD – Curr Med Res Opin 2004; 20(1) Efficacy and Safety of Two Plant Extracts and Mg in Anxiety Hanus et al. 71 CrossRef links are available in the online published version of this paper: http://www.cmrojournal.com Paper CMRO-2431, Accepted for publication: 22 September 2003 Published Online: 20 October 2003 doi:10.1185/030079903125002603 Curr Med Res Opin Downloaded from informahealthcare.com by University of Maastricht on 06/17/14 For personal use only. Curr Med Res Opin Downloaded from informahealthcare.com by University of Maastricht on 06/17/14 For personal use only.
In: A.P.A. Manuel diagnostique et statistique des troubles mentaux (DSM-III-R). Traduction Française [French
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Diagnosis and outpatient management of generalised anxiety disorder in adults
- Anaes Guidelines Department
Rapport du Groupe de Réflexion sur l’Utilisation des Hypnotiques et des Tranquillisants en France
- M Legrain