Document Detail

Dietary and botanical anxiolytics.
Jump to Full Text
MedLine Citation:
PMID:  22460105     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Drugs used to treat anxiety have many negative side effects including addiction, depression, suicide, seizures, sexual dysfunction, headaches and more. Anxiolytic medications do not restore normal levels of neurotransmitters but instead manipulate the brain chemistry. For example, selective serotonin reuptake inhibitors (SSRIs) prevent the reuptake of serotonin from the synapse allowing serotonin to remain in the area of activity for a longer period of time but does not correct the lack of serotonin production. Benzodiazepines, such as Valium and Xanax®, stimulate GABA receptors, thus mimicking the calming effects of GABA but again do not fix the lack of GABA production. Often, the brain becomes accustomed to these medications and they often lose their effectiveness, requiring higher doses or different drugs. In contrast to anxiolytic drugs, there are herbs and nutrients which can stimulates neurotransmitter synthesis and more naturally effect and even adjust brain chemistry in the absence of many of the side effects experienced with drugs. Therefore this paper explores several herbal and nutritional approaches to the treatment of anxiety.
Authors:
Elham Alramadhan; Mirna S Hanna; Mena S Hanna; Todd A Goldstein; Samantha M Avila; Benjamin S Weeks
Related Documents :
174765 - Occurrence and function of cyclic nucleotides in blood vessels.
22555085 - Risk evaluation and mitigation strategies: assessment of a medical center's policies an...
22712525 - Comparative study between atorvastatin and losartan on high fat diet-induced type 2 dia...
22573625 - The elusive biomarker for personalized medicine in multiple sclerosis: the search conti...
22632845 - Could treatment of iron deficiency both improve adhd and reduce cardiovascular risk dur...
3112935 - The regression line for erythromycin is not valid for beta-hemolytic streptococci group a.
Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Medical science monitor : international medical journal of experimental and clinical research     Volume:  18     ISSN:  1643-3750     ISO Abbreviation:  Med. Sci. Monit.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-03-30     Completed Date:  2012-08-07     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  9609063     Medline TA:  Med Sci Monit     Country:  Poland    
Other Details:
Languages:  eng     Pagination:  RA40-8     Citation Subset:  IM    
Affiliation:
Department of Biology Adelphi University, One South Avenue, Garden City, NY 11530, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Anxiety Agents / therapeutic use*
Dietary Supplements*
Herbal Medicine*
Hormones / metabolism
Humans
Chemical
Reg. No./Substance:
0/Anti-Anxiety Agents; 0/Hormones
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): Med Sci Monit
Journal ID (iso-abbrev): Med. Sci. Monit
Journal ID (publisher-id): Medical Science Monitor
ISSN: 1234-1010
ISSN: 1643-3750
Publisher: International Scientific Literature, Inc.
Article Information
Download PDF
© Med Sci Monit, 2012
License:
Received Day: 31 Month: 12 Year: 2011
Accepted Day: 13 Month: 1 Year: 2012
collection publication date: Year: 2012
Electronic publication date: Day: 01 Month: 4 Year: 2012
Volume: 18 Issue: 4
First Page: RA40 Last Page: RA48
PubMed Id: 22460105
ID: 3560823
Publisher Id: 882608

Dietary and botanical anxiolytics
Elham Alramadhan1
Mirna S. Hanna1
Mena S. Hanna3
Todd A. Goldstein1
Samantha M. Avila1
Benjamin S. Weeks12
1Department of Biology Adelphi University, One South Avenue, Garden City, NY, U.S.A.
2Environmental Studies Program, Adelphi University, One South Avenue, Garden City, NY, U.S.A.
3Department of Biological Sciences, Rutgers University, Newark, NJ, U.S.A.
Correspondence: Benjamin S. Weeks, Adelphi University, Department of Biology, One South Avenue, Garden City, NY 11530, U.S.A., e-mail: weeks@adelphi.edu

Background

Anxiety is a mood of fear, worry, and uneasiness resulting from the apprehension of something bad happening and has widespread deleterious social consequences. While anxiety can be a normal beneficial response to events that truly threaten ones security, chronic and irrational anxiety in response to normal life events in the absence of genuine threats can be debilitating and is considered to be an anxiety disorder. In developed countries, anxiety disorder rates range from 13.6% to 28.8% of the population. In the United States, anxiety disorders effect 40 million people above the age of 18 [1]. Further, in developed nations, women are between two and three times more likely to experience generalized anxiety disorder compared to men [16]. Anxiety can be the consequence of a variety of causes and arise in individuals through various different chemistries. For example, anxiety can be the consequence of dietary deficiency, hormonal changes, illness, traumatic experiences, bad habits, life stressors, aging, and genetics. In specific vitamin, mineral and amino acid deficiencies in the diet are associated with increased risk for anxiety disorder. Changes in hormonal balances, particularly associated with women during menstruation, pregnancy, post-partum periods, and menopause are all associated with increased frequencies of anxiety disorder. Further, a traumatic violent experience may lead to post-traumatic stress disorder in which a person will feel anxiety when the environment reminds them of the original violent experience. Bad habits can also lead to anxiety. For example, illicit drug abuse and even over consumption of caffeine or lifestyle choices can lead to anxiety. Hospitalization due to a diagnosis with a serious illness such as HIV/AIDS and cancer can increase the risk for anxiety. Moreover, often the stress and discomfort associate with the treatments that go along with these illnesses increase the risk for anxiety. With regard to an inherited genetic basis for anxiety, some studies suggest that variation in neurotransmitter receptor genes are associated with certain forms of anxiety. In addition anxiety often occurs in conjunction with other psychiatric or medical conditions, such as depression, chronic fatigue, cardiac disease, or respiratory compromise. Moreover, chronic anxiety is associated with greater risk of morbidity and mortality due to both cerebrovascular and cardiovascular diseases as well as a range of other neurological disorders [68]. Further, persons with anxiety disorders are at increased risk of suicidal behavior when faced with adverse life events such as divorce or financial difficulties [9]. Anxiety is also closely associated with other mental health conditions, especially depression. This relationship can work both ways causally. For example, anxiety can lead to depression and depression can lead to anxiety. In the National Co-morbidity Survey, the co-occurrence of anxiety and depression is in 58% of the cases. Interestingly, in this regard, anti-depressive medicines can be used to treat anxiety, even when there is no co-morbidity which is suggestive of common neurophysiologies and perhaps even common causes. Indeed the neurochemistry of anxiety and depression is similar, each sometimes involving imbalances of dopamine and serotonin making anxiety difficult to diagnose and treat effectively. In part, due to the overlapping chemistry and treatment between anxiety and depression, the use of diet, herbs and lifestyle changes is a valuable means both treat anxiety and depression and dissect the causes of anxiety from the causes of depression. There are five main types of anxiety disorder. They are generalized anxiety disorder (GAD), panic disorder, obsessive compulsive disorder, phobia and post-traumatic stress disorder. In all cases, central nervous system neurotransmitter levels are inappropriate and/or the HPA axis is imbalanced. Generalized anxiety disorder (GAD) is characterized by worry in the absence of a real threat or problem. People with GAD are constantly apprehensive and are unable to relax. People with GAD experience insomnia and fail to concentrate well. A person with mild GAD can manage to keep a career and a social life, however, severe GAD can lead to failure at work and an avoidance of social situations. Women are at a greater risk for GAD than are men and a diagnosis of GAD is made when an individual three or more of the above symptoms almost daily for six consecutive months [10,11]. Panic disorder is sudden attacks of fear and a sense of impending doom. This can cause elevated heart rate, sweating, and dizziness. During a panic attack the person experience shortness of breath, nausea and chest pain. Often these physical symptoms can feedback and make the panic attack worse. Panic attacks are unpredictable and sudden and are roughly 10 minutes long. A person with panic disorder will avoid places where past attacks have taken place and even conditions similar to those places. Panic disorder often leads to lost jobs. Panic disorder effect 6.0 million Americans, and is twice as common in women as it is in men [1,12]. Obsessive-compulsive disorder (OCD) is characterized by persistent thoughts (obsessions). The obsessions then cause anxiety and this anxiety leads to the use of ritualistic actions (compulsions) in an attempt to alleviate this anxiety [13,14]. A good example of OCD is an obsession with bacteria in the environment and a subsequent compulsion wash hands repeatedly. Approximately 2.2 million American adults suffer with OCD and OCD affects men and women equally [1]. Phobias are unjustifiable fears. There are specific and social phobias. Specific phobias are a fear of certain objects while social phobia is anxiety about everyday social situations. Social phobia is a chronic fear of being judged by others. A social phobia can last weeks prior to a scheduled encounter or social event. Social phobias affect a 15 million Americans [1,15,16]. Posttraumatic stress disorder (PTSD) is initiated through an experience of a traumatic or violent event. This could include a serious accident, a violent crime, or a natural disaster. People with PTSD relive this violent experience in nightmares or wakeful memories. Subsequent ordinary events can trigger “flashbacks” that cause the afflicted person to believe the event is happening again. Approximately 5.2 million Americans are affected by PTSD [1,17].

Screening tests for anxiety disorders are available to help determine the cause and severity of anxiety, however despite these tests, the diagnosis of anxiety disorders is partially subjective and based mostly on observation [18]. Once an anxiety disorder is diagnosed the treatments will usually involve several approaches that may including diet and lifestyle changes, relaxation and massage therapy, psychotherapy, behavioral therapy or cognitive-behavioral therapy, and drug intervention. Most recently Yoga and music have been used to treat anxiety disorder with some success. Cognitive-behavioral therapy requires the patient to consciously modification their thinking patterns regarding their own perceptions and sensations accompanying anxiety and fear. This form of therapy involves helping the patient to recognize cognitive distortions, or and inaccurate perceptions of everyday issues. Patients are then taught how their own distortions produce their anxiety and panic, and the patient learns to recognize when their thinking is distorted and taught methods to cognitively replace the distorted thoughts with more accurate ones. Cognitive-behavioral therapy is an effective first-line treatment for all forms of anxiety [19,20]. Behavior therapy uses several techniques to teach the patient how to modify their behavior which can contribute to the feelings of anxiety. For example, breathing exercises teaches people how to control the physical signs of anxiety by taking slow, deep breaths, which helps control hyperventilation. Further, exposure therapy relies on small and progressive exposures to whatever frightens them the patient such that the gradual, and safe exposures reveal to the patient that the cause of the anxiety is really not that threatening.

The neurochemistry of anxiety disorders can be distilled into two main categories. First, is an imbalance in neurotransmitter (GABA, serotonin and dopamine) function in the amygdale; an area of the brain involved with the perception and assessment of threats. Second is the hypothalamic-pituitary-adrenal axis (HPA-axis) which involves brain stimulation of the adrenal gland to release cortisol, DHEA, adrenaline and noradrenaline. Cortisol is the stress hormone and adrenaline and noradrenaline increase heart rate and breathing in what is known as the “fight or flight” response.

Anxiety disorders are treated with anxiolytic medicines that fall into four categories. First, are the benzodiazepams that include xanax (alprazolam), klonapin (clonazepam), valium (diazepam) and ativan (lorazepam). These work by acting on the receptor for the neurotransmitter, GABA. Second, are the anti-depression drugs, which increase serotonin and dopamine levels and are the selective serotonin reuptake inhibitors (SSRI’s) (Prozac, Zoloft, Paxil, Lexapro, and Celexa) and monoamine oxigenase inhibitors (MAOIs) (Nardil, Parnate, Marplan and Emsam) and tricylic antidepressants (TCAs). Third, are tranquilizers such as buspirone (BuSpar) which elevate serotonin and dopamine. Fourth are beta-blockers (blood pressure medications) which act on the HPA axis by blocking the effects of norepinephrine. In addition to being expensive, these medications, as mentioned above, can have harsh side effects such as, addiction, suicide, hallucinations, insomnia, headaches, loss of motor coordination, and can disrupt everyday activities such as driving, work and socializing.

Drug therapy targets two main circuitries in the body. The first is the amygdala and the second is the HPA axis. Recently, the HPA axis has been targeted for the treatment of anxiety using beta blockers which can affect the activity of norepinephrine, and cortisol (the stress hormone). The classic and well know anxiolytic medications target the activity of the neurotransmitters dopamine, serotonin, GABA. For example, benzodiazepines act by extending the life of gamma-aminobutyric acid (GABA), an inhibitory brain neurotransmitter within the synapses [21]. GABA is essential to limiting the excitation of neurons so that input signals are balanced and not overdone. Benzodiazepines relieve anxiety symptoms quickly. However, these drugs can become habit forming, and also, patients can develop a tolerance to them, which results in an increasing required dosage during treatment. After the use of benzodiazipenes, some individuals experience a variety of withdrawal symptoms which include seizures, confusion, memory loss, hyper-anxiety, and re-emergence of the original symptoms [22]. Commonly prescribed benzodiazepines include Valium® (diazepam), Xanax® (alprazolam), Klonopin® (clonazepam), and Ativan® (lorazapam). Tranquelizers such as azipirones are also anxiolytic medications that do not have the same tolerance and dependency issues as the benzodiazepines. These drugs are partial serotonin receptor agonists (promote receptor activity). BuSpar® (buspirone) is a member of the azipirone class prescribed to treat general anxiety disorder. Side effects include nausea, headaches, and dizziness. Antidepressant drugs can also be effective for treating anxiety, especially when the anxiety occurs in conjunction with depression. These drugs include the selective serotonin reuptake inhibitors (SSRIs) which increases the level of serotonin activity in the synapse and the less commonly used tricyclic antidepressants and monoamine oxidase inhibitors. These drugs are known to have potentially significant side effects. In 2004 the US Food and Drug Administration announced that the SSRIs must carry a strong warning advising patients of the increased risk of suicide among adolescents using these drugs. Popular SSRIs include Prozac® (fluoxetine), Zoloft® (sertraline), Luvox® (fluvoxamine), Paxil® (paroxetine), and Celexa® (citalopram). Recently, Beta-blockers include Inderal® (propranolol) and Tenormin® (atenolol) and are used primarily to treat heart conditions. However these drugs reduce heart palpitations and other physical HPA-related symptoms of anxiety and by controlling these feedback signals, the beta blockers offer a relatively new approach to treating some forms of anxiety. Potential side effects include sexual dysfunction, slow pulse, drowsiness, fatigue, dry mouth, numbness or tingling of fingers or toes, dizziness, diarrhea, nausea, weakness, and cold hands and feet [23].

In contrast to medicines, a number of nutrients and herbs have been identified which reduce anxiety by re-establishing a healthy diet and by altering both neurotransmitter levels and the HPA axis in the absence of the severe side effects. For example, vitamins C, D, and E, omega-3 fatty acids, and the green tea amino acid L-theanine are dietary supplements known to increase the production of dopamine. Further, supplementation with the amino acid L-tryptophan and its precursor, 5-HTP, and the B vitamins, vitamin D, selenium, and omega-3 fats increases serotonin production. These amino acid supplements are neurotransmitter building blocks and the vitamins act as cofactors in neurotransmitter biosynthesis pathways. This dietary approach can correct the underlying neurochemistry, unlike many of the drugs mentioned above which simply mask the problem.


Nutritional Approaches for Anxiety
Amino acids

The amino acid glutamate is the principle excitatory neurotransmitter and also used to make the neurotransmitter gamma-aminobutyric (GABA). L-tryptophan and L-tyrosine are precursors for the neurotransmitters, serotonin, dopamine, and norepinephrine. The ability of the body to produce these neurotransmitters is directly linked to the levels of these amino acids consumed in the diet [24].

L-tryptophan, L-tyrosine and L-phenylalanine

Dietary deficiency in L-tryptophan, L-phenylalanine, or L-tyrosine leads to low serotonin synthesis due to the lack of availability of these building blocks and this dietary deficiency is associated with anxiety [2528]. Dietary supplementation with increased L-tryptophan is known to increases serotonin synthesis in rats and humans [25,26,29] verifying a nutritional approach to the treatment of anxiety. 5-hydroxytryptophan (5-HTP), the tryptophan precursor, elevates the levels of serotonin synhtesized in humans [30,31] and 5-HTP and tryptophan elevate brain serotonin levels are known to enhance a sense of well being [3035]. Lastly, the increase in nutritional D, L-phenylalanine and L-tyrosine is known to increases synthesis of dopamine and norepinephrine [36] further supporting the role of nutrition in fighting anxiety.

L-lysine and L-arginine

Interestingly, L-lysine deficiency is known to increase the risk of anxiety in humans [37,38]. In clinical trials, supplementation of the diet with the amino acid nutrient arginine reduces synthesis of the stress hormone, cortical, in humans and may in this way be involved in the health of HPA-axis [39].

Minerals
Magnesium

In a placebo controlled clinical study, when magnesium was taken orally along with calcium supplements, anxiety in human subjects was decreased compared to placebo [40]. Similarly, supplementation with magnesium and vitamin B6 was shown to reduces premenstrual-related anxiety and GAD in women [41,42]. Animal research supports this observation with a mouse-model of magnesium deficiency that leads to anxiety behavior in mazes. Most interesting is that the anxiety in these mice is reversed with diazepam treatment, and with magnesium supplementation supporting the observation that nutrients can perform as well as anxiolytic drugs [43].

Selenium

In clinical trials people given daily oral supplementations of 100 mg of the nutrient, selenium, for 5 weeks reported less anxiety [4446]. Further, selenium added to the diet also reduced the anxiety in hospitalized patients who are elderly, cancer patients, and/or HIV patients [4749].

Fatty acids
Omega-3 fatty acids

Dietary omega-3 fatty acids has been shown to both improve mood and reduced the risk of anxiety [5052]. In one clinical study, students studying for exams were given 2.5 g/day of omega-3 (n-3) polyunsaturated fatty acids and the students receiving these supplements had a 20% reduced rate of in anxiety [53]. In a three month clinical study, omega-3 fatty acid supplementation reduced anxiety in patients who had been substance abusers suggesting a role for nutrition in managing hospital and withdrawal related anxiety [54].

Vitamins

Vitamin C is a cofactor for enzymes involved in biosynthesis and supplementation with this vitamin reduces anxiety by limiting the oxidative stress from metabolites and also by limiting cortisol [55]. One clinical study with humans showed that high dose vitamin C improves mood [56]. Vitamin E also reduces anxiety in humans [57] and vitamin D reduces anxiety in people with fibromyalgia-associated anxiety [58,59].


Herbs and Botanical Medicine for Anxiety

In addition to nutrients such as amino acids, minerals and vitamins, dietary supplementation with herbs and plant products have also been shown to be effective in treating anxiety [6064]. These herbs are not neurotransmitter building blocks or enzyme enhancers, but may have less harsh effects when compared to anxiolytic medicines.

St. John’s wort (Hypericum perforatum)

St. John’s wort is an aromatic perennial plant that is native to Europe and parts of Asia, North America, and South America and has been widely used as an anti-depressant. In fact the majority of clinical studies that compare it with antidepressant drugs found it superior to the placebo [6567]. St. John’s wort increases brain levels of serotonin [68,69] and also normalizes the HPA-axis by reducing inflammatory and oxidative stress [61]. Recently, two clinical studies show that dietary supplementation with St. John’s wort can reduce anxiety in women associated with premenstrual syndrome (PMS) [70,71]. However, St. John’s wort is should not be used during pregnancy, lactation, and exposure to strong sunlight and should not be taken along with antidepressant medication [72].

Ginkgo biloba

Animals given nutritional supplements of Ginkgo biloba demonstrated reduced anxiety [73,74]. Further in controlled clinical studies using MRI, Ginkgo biloba extracts were shown to activate GABA pathways and act like a benzodiazepine and reduce anxiety in patients with GAD [75,76].

Ashwagandha (Withania somnifera)

Ashwagandha, an herb with anti-inflammatory and rejuvenating qualities [77]. Rodents treated with ashwagandha showed reduced anxiety behavior compared to control treatment. This reduction matched the reduction in anxiety in these rodents when treated with several benzodiazepine drugs [7880], again supporting the concept than anutritional herbal supplement can act to replace the need for harsh drugs. In addition to rodents, Ashwagandha has also been shown in clinical studies to reduce anxiety in patients which were divided into two groups and were either provided psychotherapy or treated with ashwagandha [8183]. In this case, the ashwagandha treated group demonstrated a greater reduction in anxiety parameters compared to those receiving psychotherapy [84].

Kava kava

Kava is a preparation from the plant Piper methysticum which contains six psychoactive kavalactones that bind to GABA receptors, dopamine receptors and opiate receptors and work to uncouple the sodium potassium channels thereby reducing impulses to muscles and serves as a muscle relaxant [60]. Of all of the anxiolytic herbs, Kava is the most studied and also demonstrates the best results against mild anxiety and anxiety disorders in humans [8587]. In 1997, anxiety patients were given the kava extract for 25 weeks and compared to the placebo these patients had significantly reduced anxiety [88]. Subsequent clinical studies confirm that dietary kava is an effective treatment and benzodiezepam replacement and treatment for anxiety and PMS [8993].

Valerian (Valeriana officiaonalis)

Valerian is a temperate root and has been since the time of Hippocrates. Valerian root components have been shown to both increase GABA synthesis and decrease synaptic GABA reuptake [94]. Valerian root activates glutamic acid decarboxylase, an enzyme involved in the synthesis of GABA [95]. The active Valerian root extract known as valernic acid acts as a GABA agonist by binding to GABA receptors in cell culture systems [9698]. These Valerian root extracts have anxiolytic properties for rodents [99101] and in people when taken at doses of 400–900 mg daily valerian root was as effective as diazepam in the in reducing anxiety in psychiatric rating scales [102105]. Again, these studies show that dietary supplementation can be as effective as drugs in reducing anxiety.

GABA

GABA is a neurotransmitter and is found occurring naturally in herbs and plants. GABA is the main inhibitory neurotransmitter and works by reducing the excitability of a neural network thereby functioning as a brake on the neural circuitry during stress. Indeed, low GABA levels are associated with, restlessness, anxiety, insomnia and a poor mood state [106108]. Dietary GABA supplement in clinical studies relieves anxiety and increases alpha brain waves, which are associated with relaxation [109111].

Theanine

Theanine is an amino acid found in green tea. Theanine produces a calming effect on the brain [60,112,113]. Theanine crosses the blood-brain barrier and increased the production of both GABA and dopamine [114,115]. In a clinical study, healthy volunteers were given theanine and a benzodiazepine and subjected to experimentally induced anxiety. The people who received theanine had lower baseline anxiety throughout the trial [116].

Hops, Lemon Balm, Skullcap, Passionflower, Rosenroot and Chamomile

Extracts from skullcap (genus Scutellaria), hops (Humulus lupulus), dried passion flower (genus Passiflora), Chamomile (Matricaria recutita), and lemon balm (Melissa officinalis) are also all reported to reduce anxiety [105,117123]. Lemon balm increases synaptic GABA and reduced cortisol in animals [60]. Skullcap components, bacalin and bacalein, are GABA receptor agonists and promote GABA activity [60;95]. Magnolia and Phellondendron bark have beneficial anxiolytic effects in premenopausal women [124]. A clinical study showed that dietary supplementation with 340 mg of a Rosenroot for 10 weeks reduces generalized anxiety disorder [125].


Anxiety and Hormones

Anxiety disorders in general affect more women than men. Further, pregnant, postpartum, premenstrual and menopausal women also experience symptoms of anxiety to a greater extent than at other times in life. This general observation has lead scientists to investigate a hormone-anxiety link. By now, it is well known that most steroid hormones (e.g., pregnenolone, estrogen, progesterone, testosterone, and DHEA) are neurologically active. In fact, large quantities of DHEA, as well as estrogen and progesterone receptors, are found in the brain. These hormones have a number of effects within the brain, including regulation of mood. Accordingly, a number of studies have linked abnormalities in hormone levels to various anxiety disorders [126129]. Further, in the first week of menses with increases in estrogen, women produce more serotonin and have improved mood and decreased estrogen and serotonin is associated with the premenstrual period [130]. Further, the drop in estrogen during menopause is associated with reduced serotonin production. In this regard, the selective serotonin reuptake inhibitors (SSRIs) used to treat anxiety have also been shown to improve mood and cognitive function in menopausal women [131].

It is also important to examine the relationship between the stress hormone cortisol and DHEA (the metabolite building block for the sex the steroid hormones) During times of prolonged stress a greater proportion of cortisol is made compared to DHEA such that increased blood cortisol/DHEA ratios are a marker of stress and dysfunctions that lead to this state are associated with anxiety disorder [132]. In an animal study that compared normal mice to mice that lacked a progesterone receptor, researchers found that progesterone decreased anxiety behavior through a mechanism of action similar to that of benzodiazepines by acting on GABA receptors [133]. Another study found that a single dose of progesterone given to animals decreased anxiety indicators during stress tests, while the abrupt cessation of progesterone therapy increased measures of anxiety [134]. Clinical studies with DHEA supplementation has been found to be particularly helpful in relieving anxiety in females with low hormone levels [135].

Researchers have found in double blind randomized placebo controlled clinical trials, that St. John’s wort reduces the duration and severity of hot flashes in both premenstrual and premenopausal women [145]. In addition, the Central American plant, Piper hispidum Swingle, has been traditionally used to treat dysmenorhea and pain in Guatemala and contains molecules that bind to both the estrogen receptor and serotonin receptors in human cells [136]. Extracts of the Chinese herb, Fructus Sophorae has also been shown to ease anxiety in menopausal women [137] and reduced anxiety in postmenopausal women has been achieved in placebo controlled studies by supplementing with 80 mg/day for 90 days of red clover isoflavinones [138]. Vitex agnus-castus (chaste tree/berry) when taken over a 16 week period in combination with St. John’s wort also reduced anxiety associated with premenstrual syndrome and menopause [71]. A metabolite of the isoflavone daidzein from soy has also been shown to reduce anxiety in premenopausal, perimenopausal and postmenopausal women [139,140]. Lastly, in healthy cycling women of reproductive age, a preparation combining magnolia and Philondendron bark has been shown to reduce anxiety for women [124]. Nutritional supplements including calcium, vitamin D3, lycopene, bioflavoids and even the probiotic lactobacilli have been shown in various combinations to reduce anxiety symptoms including panic disorder associated with menopause [27,141]. Post-partum associated anxiety is significantly reduced in some cases with 100 mg/day selenium supplementation [46].

In addition to herbal and nutritional approaches to control and regulate the effects of decreasing estrogen on serotonin levels and anxiety, it is also important to examine the relationship between the stress hormone cortisol and DHEA (the metabolite building block for the sex the steroid hormones) During times of prolonged stress a greater proportion of cortisol is made compared to DHEA such that increased blood cortisol/DHEA ratios are a marker of stress and dysfunctions that lead to this state are associated with anxiety disorder [132]. In an animal study that compared normal mice to mice that lacked a progesterone receptor, researchers found that progesterone decreased anxiety behavior through a mechanism of action similar to that of benzodiazepines by acting on GABA receptors [133]. Another study found that a single dose of progesterone given to animals decreased anxiety indicators during stress tests, while the abrupt cessation of progesterone therapy increased measures of anxiety [134]. Clinical studies with DHEA supplementation has been found to be particularly helpful in relieving anxiety in females with low hormone levels [135].


Conclusions

Anxiety is a generalized mood of fear, worry and or uneasiness that results from an bad felling about something that happens or may happened. It can be stimulated from environment factors, or result from bad habits or social situations. There are different types of anxiety that could be mild or sever depending on the level of the disorders. Anxiety, as with other medical problems, can be diagnosed and treated by different therapies, such as cognitive-behavioral therapy, panic disorder, and drug therapy. Using drugs is a common but harsh way to treat anxiety disorders. However more natural treatments including amino acid, minerals, and fatty acids can reduce anxiety. Further, herbs and botanical medicine, such as St. John’s wort (Hypericum perforatum), Ginkgo biloba, Kava Kava, which have different roles to reduce many psychiatric disorders, also reduce anxiety. In this regard, anxiety may be managed without the harsh side effects of pharmaceuticals using nutritional and botanical treatment as well as life-style changes.


Notes

fn1-medscimonit-18-4-ra40Source of support: Self financing

References
1. Kessler RC,Ruscio AM,Shear K,Wittchen HU. Epidemiology of anxiety disordersCurr Top Behav NeurosciYear: 20102213521309104
2. Kessler RC,Berglund PA,Demler O,et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication (NCS-R)Arch Gen PsychiatryYear: 200562659360215939837
3. Kessler RC,Chiu WT,Demler O,Walters EE. Prevalence, severity, and comorbidity of twelve-month DSM-IV disorders in the National Comorbidity Survey Replication (NCS-R)Arch Gen PsychiatryYear: 20056266172715939839
4. Bulloch AG,Currie S,Guyn L,et al. Estimates of the treated prevalence of bipolar disorders by mental health services in the general population: comparison of results from administrative and health survey dataChronic Dis Inj CanYear: 20113131293421733350
5. Roberson-Nay R,Kendler KS. Panic disorder and its subtypes: a comprehensive analysis of panic symptom heterogeneity using epidemiological and treatment seeking samplesPsychol MedYear: 2011111
6. Culpepper L. Generalized anxiety disorder and medical illnessJ Clin PsychiatryYear: 200970Suppl 2202419371503
7. Goodwin RD,Davidson KW,Keyes K. Mental disorders and cardiovascular disease among adults in the United StatesJ Psychiatr ResYear: 20094332394618614179
8. Gureje O. Comorbidity of pain and anxiety disordersCurr Psychiatry RepYear: 20081043182218627670
9. Ringbäck Weitoft G,Rosén M. Is perceived nervousness and anxiety a predictor of premature mortality and severe morbidity? A longitudinal follow up of the Swedish survey of living conditionsJ Epidemiol Community HealthYear: 20055997949816100319
10. Weisberg RB. Overview of generalized anxiety disorder: epidemiology, presentation, and courseJ Clin PsychiatryYear: 200970Suppl 24919371500
11. Wyrwich KW,Harnam N,Revicki DA,et al. Assessment of quality of life enjoyment and satisfaction questionnaire-short form responder thresholds in generalized anxiety disorder and bipolar disorder studiesInt Clin PsychopharmacolYear: 20112631212921164351
12. Roy-Byrne PP,Wagner AW,Schraufnagel TJ. Understanding and treating panic disorder in the primary care settingJ Clin PsychiatryYear: 200566Suppl 4162215842183
13. Bienvenu OJ,Wuyek LA,Stein MB. Anxiety disorders diagnosis: some history and controversiesCurr Top Behav NeurosciYear: 2010231921309103
14. Merlo LJ,Storch EA. Obsessive-compulsive disorder: tools for recognizing its many expressionsJ Fam PractYear: 20065532172216510055
15. Machado-de-Sousa JP,Arrais KC,Alves NT,et al. Facial affect processing in social anxiety: tasks and stimuliJ Neurosci MethodsYear: 201019311620800619
16. Coelho CM,Gonçalves DC,Purkis H,et al. Specific phobias in older adults: characteristics and differential diagnosisInt PsychogeriatrYear: 20102257021120478098
17. Cantor C. Post-traumatic stress disorder: evolutionary perspectivesAust N Z J PsychiatryYear: 2009431110384820001399
18. Risbrough V. Behavioral correlates of anxietyCurr Top Behav NeurosciYear: 201022052821309111
19. Hunot V,Churchill R,Silva de Lima M,Teixeira V. Psychological therapies for generalised anxiety disorderCochrane Database Syst RevYear: 20071CD00184817253466
20. Tolin DF. Is cognitive-behavioral therapy more effective than other therapies? A meta-analytic reviewClin Psychol RevYear: 20103067102020547435
21. Durant C,Christmas D,Nutt D. The pharmacology of anxietyCurr Top Behav NeurosciYear: 201023033021309115
22. Cloos JM,Ferreira V. Current use of benzodiazepines in anxiety disordersCurr Opin PsychiatryYear: 2009221909519122540
23. Bourin M,Lambert O. Pharmacotherapy of anxious disordersHum PsychopharmacolYear: 200217838340012457374
24. Fernstrom JD,Fernstrom MH. Tyrosine, phenylalanine, and catecholamine synthesis and function in the brainJ NutrYear: 20071376 Suppl 11539S47S discussion 154–8S. 17513421
25. Hood SD,Hince DA,Davies SJ,et al. Effects of acute tryptophan depletion in serotonin reuptake inhibitor-remitted patients with generalized anxiety disorderPsychopharmacology (Berl)Year: 201020822233219936713
26. Toker L,Amar S,Bersudsky Y,et al. The biology of tryptophan depletion and mood disordersIsr J Psychiatry Relat SciYear: 2010471465520686199
27. Belcaro G,Cesarone MR,Cornelli U,Dugall M. MF Afragil® in the treatment of 34 menopause symptoms: a pilot studyPanminerva MedYear: 2010522 Suppl 1495420657535
28. Roiser JP,Levy J,Fromm SJ,et al. The effect of acute tryptophan depletion on the neural correlates of emotional processing in healthy volunteersNeuropsychopharmacologyYear: 20083381992200617882232
29. Feurté S,Gerozissis K,Regnault A,Paul FM. Plasma Trp/LNAA ratio increases during chronic ingestion of an alpha-lactalbumin diet in ratsNutr NeurosciYear: 2001454131811842917
30. Trachte GJ,Uncini T,Hinz M. Both stimulatory and inhibitory effects of dietary 5-hydroxytryptophan and tyrosine are found on urinary excretion of serotonin and dopamine in a large human populationNeuropsychiatr Dis TreatYear: 200952273519557117
31. Croonenberghs J,Verkerk R,Scharpe S,et al. Serotonergic disturbances in autistic disorder: L-5-hydroxytryptophan administration to autistic youngsters increases the blood concentrations of serotonin in patients but not in controlsLife SciYear: 2005761921718315733932
32. Ruhe HG,Mason NS,Schene AH. Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studiesMol PsychiatryYear: 2007123315917389902
33. Rot M,Mathew SJ,Charney DS. LinksNeurobiological mechanisms in major depressive disorderCMAJYear: 200918033051319188629
34. Young SN. How to increase serotonin in the human brain without drugsJ Psychiatry NeurosciYear: 20073263949918043762
35. Young SN,Leyton M. The role of serotonin in human mood and social interaction. Insight from altered tryptophan levelsPharmacol Biochem BehavYear: 20027148576511888576
36. Lakhan SE,Vieira KF. Nutritional therapies for mental disordersNutr JYear: 20087218208598
37. Ghosh S,Smriga M,Vuvor F,et al. Effect of lysine supplementation on health and morbidity in subjects belonging to poor peri-urban households in Accra, GhanaAm J Clin NutrYear: 20109249283920720257
38. Smriga M,Ghosh S,Mouneimne Y,et al. Lysine fortification reduces anxiety and lessens stress in family members in economically weak communities in Northwest SyriaProc Natl Acad Sci USAYear: 20041012282858815159538
39. Smriga M,Ando T,Akutsu M,et al. Oral treatment with L-lysine and L-arginine reduces anxiety and basal cortisol levels in healthy humansBiomed ResYear: 2007282859017510493
40. Carroll D,Ring C,Suter M,Willemsen G. The effects of an oral multivitamin combination with calcium, magnesium, and zinc on psychological well-being in healthy young male volunteers: a double-blind placebo-controlled trialPsychopharmacology (Berl)Year: 200015022202510907676
41. De Souza MC,Walker AF,Robinson PA,Bolland K. A synergistic effect of a daily supplement for 1 month of 200 mg magnesium plus 50 mg vitamin B6 for the relief of anxiety-related premenstrual symptoms: a randomized, double-blind, crossover studyJ Womens Health Gend Based MedYear: 2000921313910746516
42. Hanus M,Lafon J,Mathieu M. 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 disordersCurr Med Res OpinYear: 2004201637114741074
43. Sartori SB,Landgraf R,Singewald N. The clinical implications of mouse models of enhanced anxietyFuture NeurolYear: 2011645317121901080
44. Benton D,Cook R. Selenium supplementation improves mood in a double-blind crossover trialPsychopharmacology (Berl)Year: 19901024549502096413
45. Benton D,Cook R. The impact of selenium supplementation on moodBiol PsychiatryYear: 199129111092981873372
46. Mokhber N,Namjoo M,Tara F,et al. Effect of supplementation with selenium on postpartum depression: a randomized double-blind placebo-controlled trialJ Matern Fetal Neonatal MedYear: 2011241104820528216
47. Gosney MA,Hammond MF,Shenkin A,Allsup S. Effect of micronutrient supplementation on mood in nursing home residentsGerontologyYear: 20085452929918463429
48. Bargellini A,Piccinini L,De Palma M,et al. Trace elements, anxiety and immune parameters in patients affected by cancerJ Trace Elem Med BiolYear: 200317Suppl 13914650622
49. Shor-Posner G,Lecusay R,Miguez MJ,et al. Psychological burden in the era of HAART: impact of selenium therapyInt J Psychiatry MedYear: 2003331556912906343
50. Perica MM,Delas I. Essential Fatty acids and psychiatric disordersNutr Clin PractYear: 20112644092521775637
51. Ross BM. Omega-3 polyunsaturated fatty acids and anxiety disordersProstaglandins Leukot Essent Fatty AcidsYear: 2009815–63091219906519
52. Appleton KM,Rogers PJ,Ness AR. Is there a role for n-3 long-chain polyunsaturated fatty acids in the regulation of mood and behaviour? A review of the evidence to date from epidemiological studies, clinical studies and intervention trialsNutr Res RevYear: 2008211134119079852
53. Kiecolt-Glaser JK,Belury MA,Andridge R,et al. Omega-3 supplementation lowers inflammation and anxiety in medical students: A randomized controlled trialBrain Behav ImmunYear: 201125817253421784145
54. Buydens-Branchey L,Branchey M,Hibbeln JR. Associations between increases in plasma n-3 polyunsaturated fatty acids following supplementation and decreases in anger and anxiety in substance abusersProg Neuropsychopharmacol Biol PsychiatryYear: 20083225687518060675
55. Hughes RN,Lowther CL,van Nobelen M. Prolonged treatment with vitamins C and E separately and together decreases anxiety-related open-field behavior and acoustic startle in hooded ratsPharmacolBiochem BehavYear: 201197349499
56. Brody S. High-dose ascorbic acid increases intercourse frequency and improves mood: a randomized controlled clinical trialBiol PsychiatryYear: 20025243717412208645
57. Ambrogini P,Ciuffoli S,Lattanzi D,et al. Maternal dietary loads of α-tocopherol differentially influence fear conditioning and spatial learning in adult offspringPhysiol BehavYear: 201110458091521839761
58. Kalueff AV,Lou YR,Laaksi I,Tuohimaa P. Increased anxiety in mice lacking vitamin D receptor geneNeuroreportYear: 200415812717415167547
59. Armstrong DJ,Meenagh GK,Bickle I,et al. Vitamin D deficiency is associated with anxiety and depression in fibromyalgiaClin RheumatolYear: 20072645515416850115
60. Weeks BS. Formulations of dietary supplements and herbal extracts for relaxation and anxiolytic action: RelarianMed Sci MonitYear: 20091511RA2566219865069
61. Head KA,Kelly GS. Nutrients and botanicals for treatment of stress: adrenal fatigue, neurotransmitter imbalance, anxiety, and restless sleepAltern Med RevYear: 20091421144019594222
62. Chiappedi M,Bejor M. Herbals and natural dietary supplements in psychiatric practiceRecent Pat CNS Drug DiscovYear: 2010521647120030623
63. Saeed SA,Bloch RM,Antonacci DJ. Herbal and dietary supplements for treatment of anxiety disordersAm Fam PhysicianYear: 20077645495617853630
64. van der Watt G,Laugharne J,Janca A. Complementary and alternative medicine in the treatment of anxiety and depressionCurr Opin PsychiatryYear: 2008211374218281839
65. Sarris J,Kavanagh DJ. Kava and St. John’s Wort: current evidence for use in mood and anxiety disordersJ Altern Complement MedYear: 20091588273619614563
66. Linde K. St. John’s wort – an overviewForsch KomplementmedYear: 20091631465519657198
67. Linde K,Berner MM,Kriston L. St John’s wort for major depressionCochrane Database Syst RevYear: 20084CD00044818843608
68. Ara I,Bano S. St. John’s Wort modulates brain regional serotonin metabolism in swim stressed ratsPak J Pharm SciYear: 20092219410119168429
69. Tadros MG,Mohamed MR,Youssef AM,et al. Involvement of serotoninergic 5-HT1A/2A, alpha-adrenergic and dopaminergic D1 receptors in St. John’s wort-induced prepulse inhibition deficit: a possible role of hyperforinBehav Brain ResYear: 200919923343919136030
70. Canning S,Waterman M,Orsi N,et al. The efficacy of Hypericum perforatum (St John’s wort) for the treatment of premenstrual syndrome: a randomized, double-blind, placebo-controlled trialCNS DrugsYear: 20102432072520155996
71. van Die MD,Bone KM,Burger HG,et al. Effects of a combination of Hypericum perforatum and Vitex agnus-castus on PMS-like symptoms in late-perimenopausal women: findings from a subpopulation analysisJ Altern Complement MedYear: 200915910454819757982
72. Mannel M,Kuhn U,Schmidt U,et al. St. John’s wort extract LI160 for the treatment of depression with atypical features – a double-blind, randomized, and placebo-controlled trialJ Psychiatr ResYear: 201044127606720181361
73. Walesiuk A,Braszko JJ. Preventive action of Ginkgo biloba in stress- and corticosterone-induced impairment of spatial memory in ratsPhytomedicineYear: 2009161404617482446
74. Kuribara H,Weintraub ST,Yoshihama T,Maruyama Y. An anxiolytic-like effect of Ginkgo biloba extract and its constituent, ginkgolide-A, in miceJ Nat ProdYear: 2003661013333714575433
75. Woelk H,Arnoldt KH,Kieser M,Hoerr R. Ginkgo biloba special extract EGb 761 in generalized anxiety disorder and adjustment disorder with anxious mood: a randomized, double-blind, placebo-controlled trialJ Psychiatr ResYear: 20074164728016808927
76. Faustino TT,de Almeida RB,Andreatini R. Medicinal plants for the treatment of generalized anxiety disorder: a review of controlled clinical studiesRev Bras PsiquiatrYear: 20103244293621308265
77. Mishra LC,Singh BB,Dagenais S. Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a reviewAltern Med RevYear: 2000543344610956379
78. Mohan L,Rao US,Gopalakrishna HN,Nair V. Evaluation of the Anxiolytic Activity of NR-ANX-C (a Polyherbal Formulation) in Ethanol Withdrawal-Induced Anxiety Behavior in RatsEvid Based Complement Alternat MedYear: 20112011 pii. 32716020953426
79. Kulkarni SK,Singh K,Bishnoi M. Comparative behavioural profile of newer antianxiety drugs on different mazesIndian J Exp BiolYear: 20084696333818949892
80. Ramanathan M,Balaji B,Justin A. Behavioural and neurochemical evaluation of Perment an herbal formulation in chronic unpredictable mild stress induced depressive modelIndian J Exp BiolYear: 20114942697521614890
81. Andrade C. Ashwagandha for anxiety disordersWorld J Biol PsychiatryYear: 2009104 Pt 26868719363747
82. Bhattacharya SK,Bhattacharya A,Sairam K,Ghosal S. Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: an experimental studyPhytomedicineYear: 2000764636911194174
83. Cooley K,Szczurko O,Perri D,et al. Naturopathic care for anxiety: a randomized controlled trial ISRCTN78958974PLoS OneYear: 200948e662819718255
84. Saeed SA,Bloch RM,Antonacci DJ. Safety of kava for patients with mild anxiety disordersAm Fam PhysicianYear: 20087844333418756649
85. Sarris J,Kavanagh DJ,Byrne G,et al. The Kava Anxiety Depression Spectrum Study (KADSS): a randomized, placebo-controlled crossover trial using an aqueous extract of Piper methysticumPsychopharmacology (Berl)Year: 200920539940719430766
86. Sarris J,Kavanagh DJ,Deed G,Bone KM. St. John’s wort and Kava in treating major depressive disorder with comorbid anxiety: a randomised double-blind placebo-controlled pilot trialHum PsychopharmacolYear: 2009241414819090505
87. Scherer J. Kava-kava extract in anxiety disorders: an outpatient observational studyAdvances in TherapyYear: 1997152616910186945
88. Volz HP,Kieser M. Kava-kava extract WS 1490 versus placebo in anxiety disorders – a randomized placebo-controlled 25-week outpatient trialPharmacopsychiatryYear: 1997301159065962
89. Boerner RJ,Sommer H,Berger W,et al. Kava-Kava extract LI 150 is as effective as Opipramol and Buspirone in Generalised Anxiety Disorder – an 8-week randomized, double-blind multi-centre clinical trial in 129 out-patientsPhytomedicineYear: 200310384912807341
90. Watkins LL,Connor KM,Davidson JR. Effect of kava extract on vagal cardiac control in generalized anxiety disorder: preliminary findingsJ PsychopharmacolYear: 2001152838611769822
91. Malsch U,Kieser M. Efficacy of kava-kava in the treatment of non-psychotic anxiety, following pretreatment with benzodiazepinesPsychopharmacology (Berl)Year: 20011572778311605083
92. Cagnacci A,Arangino S,Renzi A,et al. Kava-Kava administration reduces anxiety in perimenopausal womenMaturitasYear: 200344103912590005
93. Boerner RJ. Kava kava in the treatment of generalized anxiety disorder, simple phobia and specific social phobiaPhytother ResYear: 2001156464711746854
94. Ortiz JG,Nieves-Natal J,Chavez P. Effects of Valeriana officinalis extractson [3H]fl unitrazepam binding, synaptosomal [3H]GABA uptake, and hippocampal [3H]GABA releaseNeurochem ResYear: 1999241113737810555777
95. Awad R,Levac D,Cybulska P,et al. Effects of traditionally used anxiolytic botanicals on enzymes of the gamma-aminobutyric acid (GABA) systemCan J Physiol PharmacolYear: 20078599334218066140
96. Yuan CS,Mehendale S,Xiao Y,et al. The gamma-aminobutyric acidergic effects of valerian and valerenic acid on rat brainstem neuronal activityAnesth AnalgYear: 20049723535814742369
97. Khom S,Baburin I,Timin E,et al. Valerenic acid potentiates and inhibits GABA(A) receptors: molecular mechanism and subunit specificityNeuropharmacologyYear: 20075311788717585957
98. Trauner G,Khom S,Baburin I,et al. Modulation of GABAA receptors by valerian extracts is related to the content of valerenic acidPlanta MedYear: 2008741192418095218
99. Benke D,Barberis A,Kopp S,et al. GABA A receptors as in vivo substrate for the anxiolytic action of valerenic acid, a major constituent of valerian root extractsNeuropharmacologyYear: 20095611748118602406
100. Hadjikhani R. Anxiolytic-like Effects of Dichloromethane Extracts of Valerian (DEV) in Adult Male Wistar RatsWorld Academy of Science, Engineering and TechnologyYear: 20095553236
101. Hattesohl M,Feistel B,Sievers H,et al. Extracts of Valeriana officinalis L.s.l. show anxiolytic and antidepressant effects but neither sedative nor myorelaxant propertiesPhytomedicineYear: 2008151–221518160026
102. Andreatini R,Sartori VA,Seabra ML,Leite JR. sEffect of valepotriates (valerian extract) in generalized anxiety disorder: a randomized placebo- controlled pilot studyPhytother ResYear: 20021676505412410546
103. Muller SF,Klement S. A combination of valerian and lemon balm is effective in the treatment of restlessness and dyssomnia in childrenPhytomedicineYear: 20061363838716487692
104. Bhattacharyya D,Jana U,Debnath PK,Sur TK. Initial exploratory observational pharmacology of Valeriana wallichii on stress management: a clinical reportNepal Med Coll JYear: 200791363917593676
105. Kennedy DO,Little W,Haskell CF,Scholey AB. Anxiolytic effects of a combination of Melissa officinalis and Valeriana officinalis during laboratory induced stressPhytother ResYear: 20062029610216444660
106. Nemeroff CB. The role of GABA in the pathophysiology and treatment of anxiety disordersPsychopharmacol BullYear: 2003371334615131523
107. Kendell SF,Krystal JH,Sanacora G. GABA and glutamate systems as therapeutic targets in depression and mood disordersExpert Opin Ther TargetsYear: 200591536815757488
108. Kugaya A,Sanacora G. Beyond monoamines: glutamatergic function in mood disordersCNS SpectrYear: 2005108081916400244
109. Bazil CW,Battista J,Basner RC. Gabapentinimproves sleep in the presence of alcoholJ Clin SleepMedYear: 2005128487
110. Abdou AM,Higashiguchi S,Horie K,et al. Relaxation and immunity enhancement effects of gamma aminobutyric acid (GABA) administration in humansBiofactorsYear: 2006263201816971751
111. Thorne Research, IncGamma-Aminobutyric Acid (GABA)Altern Med RevYear: 20071232747918072823
112. Heese T,Jenkinson J,Love C,et al. Anxiolytic effects of L-theanine – a component of green tea – when combined with midazolam, in the male Sprague-Dawley ratAANA JYear: 20097764454920108732
113. Rogers PJ,Smith JE,Heatherley SV,Pleydell-Pearce CW. Time for tea: mood, blood pressure and cognitive performance effects of caffeine and theanine administered alone and togetherPsychopharmacology (Berl)Year: 200819545697717891480
114. Kakuda T. Neuroprotective effects of theanine and its preventive effects on cognitive dysfunctionPharmacol ResYear: 20116421626821477654
115. Cho HS,Kim S,Lee SY,et al. Protective effect of the green tea component, L-theanine on environmental toxins-induced neuronal cell deathNeurotoxicologyYear: 20082946566218452993
116. Lu K,Gray MA,Oliver C,et al. The acute effects of L-theanine in comparison with alprazolam on anticipatory anxiety in humansHum PsychopharmacolYear: 20041974576515378679
117. Koetter U,Schrader E,Kaufeler R,Brattstrom A. A randomized, double blind, placebo-controlled, prospective clinical study to demonstrate clinical efficacy of a fixed valerian hops extract combination (Ze 91019) in patients suffering from non-organic sleep disorderPhytother ResYear: 20072198475117486686
118. Dimpfel W,Suter A. Sleep improving effects of a single dose administration of a valerian/hops fluid extract – a double blind, randomized, placebo-controlled sleep-EEG study in a parallel design using electrohypnogramsEur J Med ResYear: 2008135200418559301
119. Kennedy DO,Little W,Scholey AB. Attenuation of laboratory-induced stress in humans after acute administration of Melissa officinalis (Lemon Balm)Psychosom MedYear: 20046646071315272110
120. Dimpfel W,Pischel I,Lehnfeld R. Effects of lozenge containing lavender oil, extracts from hops, lemon balm and oat on electrical brain activityof volunteersEur J Med ResYear: 2004994233115546807
121. Wolfson P,Hoffmann DL. An investigation into the efficacy of Scutellaria lateriflora in healthy volunteersAltern Ther Health MedYear: 200392747812652886
122. Movafegh A,Alizadeh R,Hajimohamadi F,et al. Preoperative oral Passiflora incarnata reduces anxiety in ambulatory surgery patients: a double-blind, placebo-controlled studyAnesth AnalgYear: 2008106617283218499602
123. Amsterdam JD,Li Y,Soeller I,Rockwell K,et al. A randomized, double-blind, placebo-controlled trial of oral Matricaria recutita (chamomile) extract therapy for generalized anxiety disorderJ Clin PsychopharmacolYear: 20092943788219593179
124. Kalman DS,Feldman S,Feldman R,et al. Effect of a proprietary Magnolia and Phellodendron extract on stress levels in healthy women: a pilot, double-blind, placebo-controlled clinical trialNutr JYear: 200871118426577
125. Bystritsky A,Kerwin L,Feusner JD. A pilot study of Rhodiola rosea (Rhodax) for generalized anxiety disorder (GAD)J Altern Complement MedYear: 20081421758018307390
126. Cunningham J,Yonkers KA,O’Brien S,Eriksson E. Update on research and treatment of premenstrual dysphoric disorderHarv Rev PsychiatryYear: 20091721203719373620
127. Parcells DA. Women’s mental health nursing: depression, anxiety and stress during pregnancyJ Psychiatr Ment Health NursYear: 20101798132021040227
128. Bloch M,Azem F,Aharonov I,et al. GnRH-agonist induced depressive and anxiety symptoms during in vitro fertilization-embryo transfer cyclesFertil SterilYear: 2011951307920801439
129. Sundermann EE,Maki PM,Bishop JR. A review of estrogen receptor alpha gene (ESR1) polymorphisms, mood, and cognitionMenopauseYear: 20101748748620616674
130. Kikuchi H,Nakatani Y,Seki Y,et al. Decreased blood serotonin in the premenstrual phase enhances negative mood in healthy womenJ Psychosom Obstet GynaecolYear: 2010312838920384471
131. Cubeddu A,Giannini A,Bucci F,et al. Paroxetine increases brain-derived neurotrophic factor in postmenopausal womenMenopauseYear: 20101723384319934779
132. Jezova D,Hlavacova N. Endocrine factors in stress and psychiatric disorders: focus on anxiety and salivary steroidsAnn NY Acad SciYear: 2008114849550319120147
133. Froy O. Cytochrome P450 and the biological clock in mammalsCurr Drug MetabYear: 20091021041519275546
134. Saavedra M,Contreras CM,Azamar-Arizmendi G,Hernández-Lozano M. Differential progesterone effects on defensive burying and forced swimming tests depending upon a gradual decrease or an abrupt suppression schedulesPharmacol Biochem BehavYear: 20068311303516483644
135. Binder G,Weber S,Ehrismann M,et al. the South German Working Group for Pediatric EndocrinologyEffects of dehydroepiandrosterone therapy on pubic hair growth and psychological well-being in adolescent girls and young women with central adrenal insufficiency: a double-blind, randomized, placebo-controlled phase III trialJ Clin Endocrinol MetabYear: 200994411829019126625
136. Abdali K,Khajehei M,Tabatabaee HR. Effect of St John’s wort on severity, frequency, and duration of hot flashes in premenopausal, perimenopausal and postmenopausal women: a randomized, double-blind, placebo-controlled studyMenopauseYear: 20101723263120216274
137. Michel JL,Chen Y,Zhang H,et al. Estrogenic and serotonergic butenolides from the leaves of Piper hispidum Swingle (Piperaceae)J EthnopharmacolYear: 201012922202620304039
138. Lee J,Kim KW,Kim HK,et al. The effect of Rexflavone (Sophorae fructus extract) on menopausal symptoms in postmenopausal women: a randomized double-blind placebo controlled clinical trialArch Pharm ResYear: 20103345233020422360
139. Lipovac M,Chedraui P,Gruenhut C,et al. Improvement of postmenopausal depressive and anxiety symptoms after treatment with isoflavones derived from red clover extractsMaturitasYear: 20106532586119948385
140. Ishiwata N,Melby MK,Mizuno S,Watanabe S. New equol supplement for relieving menopausal symptoms: randomized, placebo-controlled trial of Japanese womenMenopauseYear: 20091611414819131846
141. Mucci M,Carraro C,Mancino P,et al. Soy isoflavones, lactobacilli, Magnolia bark extract, vitamin D3 and calcium. Controlled clinical study in menopauseMinerva GinecolYear: 20065843233416957676

Article Categories:
  • Review Article

Keywords: anxiolytic, anxiety, Kava Kava, nutrition, botanical medicine.

Previous Document:  Treatment of pulmonary hypertension.
Next Document:  Treatment of Gustilo grade III tibial fractures with unreamed intramedullary nailing versus external...