herbal remedies to treat anxiety disorders · anxiety is a central nervous system disorder [1-2]....
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Uttaranchal University Journal of Research, (2019), 01(01)
72
HERBAL REMEDIES TO TREAT ANXIETY DISORDERS Pallavi Ghildiyal
1, Alok Bhatt*
2
Affiliation:
1. Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun,
Uttarakhand, India
2. Department of Pharmacognosy, Zee Himgiri University, Dehradun, India.
*Corresponding Author E-mail: [email protected]
ABSTRACT
Anxiety, fear and worry are all completely natural human feelings. If these feelings occur and
endure for an extended period, it affects both physical and mental health. This leads to clinical
anxiety disorders. Anxiety is an aversive emotional state, in which the feeling of fear is
disproportionate to the threat. Anxiety is implicated in a number of psychiatric disorders, such
as depression, panic attacks, phobias, generalized anxiety disorder, obsessive-compulsive
disorder and post-traumatic stress disorder. Anxiety disorders are the most common class of
neuropsychiatric disorders in USA and many other countries. The symptoms experienced
during an anxiety attack include: Rapid heartbeat and rapid breathing, Twitching or trembling,
Muscle tension, Headaches, Sweating, Dry mouth and difficulty in swallowing and Abdominal
pain. Herbs play a major role in the management of various Anxiety disorders. Herbal
medicines are in great demand in the developed as well as developing countries for primary
health care because of their wide biological and medicinal properties, higher safety margins,
and lesser costs. Passiflora incarnata, Kava kava (Piper methysticum), Valeriana
officinalis,Ginkgo biloba, Hypericum perforatum,Matricaria recutita, Terminalia arjuna, Citrus
aurantium. Linn, Astragalus membranaceus, Withania somnifera, Coriandrum sativum L,
Bacopa monnieri (Brahmi) etc have been used in poly-herbal formulations meant for treatment
of Anxiety diseases. These Anxiety drugs contain variety of phyto-constituents like alkaloid
achilleine, isovaleric acid, salicylic acid, asparagines, sterols, flavonoids, tannins, choline and
trigonelline and coumarins. Glycosides, quercitrin and isoquercitrin etc.
KEYWORDS: Anxiety, herbal drugs.
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INTRODUCTION
Anxiety disorders are one of the most prevalent and highly comorbid psychiatric conditions [1]
.
Since the past decade, many herbal medicines have been used in people with anxiety disorders [2]
. Due to the increasing popularity of herbal medications majority of the patients are
consulting herbalists, naturopaths, and other healers, in addition to physicians. A study reveals
that 44% of psychiatric patients with anxiety disorders had used herbal medicine (mainly for
psychiatric purposes) during the previous 12 months [3]
. There is however, a limited data
regarding the benefits and liability of herbal remedies. There have been few reports of serious
adverse effects from these medications and by and large these medications have been
considered safe and effective [4]
. This article reviews the literature on various herbal
medications in the treatment of anxiety disorders as well as anxiety in general.
Stress and anxiety are common psychiatric manifestations of the modern world and lifestyles.
In small quantities, stress and anxiety are good; they can motivate and help one be more
productive. However, too much stress, or a strong response to stress, is harmful. It can set up
for general poor health as well as specific physical or psychological illnesses like infection,
heart disease, or depression. Persistent and unrelenting stress often leads to anxiety and
unhealthy behaviors.
Anxiety is a Central Nervous System disorder [1-2]
. Anxiety is a common emotional
phenomenon in humans [3]
. Anxiety is an emotional state, unpleasant in nature and is
associated with uneasiness, discomfort and concern or fear about some defined or undefined
future threat [4]
. Anxiety is considered to be a normal reaction to stress and is characterized by
heart palpitations, fatigue, nausea and shortness of breath. Anxiety is the most common mental
illness affecting one eighth of the total population and has become a very important area of
research in
PSYCHOPHARMACOLOGY IN THE CURRENT DECADE [5]
.
Anxiety disorders are psychiatric disorders affecting nearly 25% of the adult population at
some point in their life. The prevalence of anxiety disorders is 30.5% and 19.2% in women
and men respectively. The prevalence of anxiety disorders is remarkably high in young people.
Children aged 7 to 11 years reported a 15.4% prevalence rate of anxiety disorders. A survey
has also stated that less than 14% of people with such psychiatric disorders receive treatment [6]
. Anxiety can aggravate many physical and mental ailments and also impede recovery from
any other problems.
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FORMS OF ANXIETY DISORDERS
Anxiety disorders comprise clinical conditions of Generalized Anxiety Disorder, Obsessive-
compulsive Disorder, Panic Disorder, Post-traumatic Stress Disorder, Social Anxiety Disorder
and Phobias.
GENERALIZED ANXIETY DISORDERS
Generalized Anxiety Disorder involves a broad presentation of anxiety. It is characterized by
long-lasting anxiety (for over 6 months) that is not focused on any one object or situation.
Those suffering from this disorder experience non-specific persistent fear and worry and
become overly concerned with everyday matters like health, work, money or family and
experience these symptoms even when there are no signs of trouble in their life [4,10]
.
OBSESSIVE-COMPULSIVE DISORDER
This is a particularly important form of anxiety disorder which is characterized by obsessions
i.e. recurrent thoughts that may not be about real-life problems and which the person fails to
ignore or suppress. Compulsions are repetitive behaviors that the person feels driven to
perform in response to an obsession. The compulsive behaviors attempt to reduce the distress
from the obsessions.
PANIC DISORDER
In this type of a disorder the person suffers from brief attacks of intense terror and
apprehension which is often characterized by trembling, shaking, confusion, dizziness, nausea,
and difficulty in breathing, lasting for a few minutes. The person also believes that he or she is
seriously ill or about to die and this feeling can leave the person depressed or shaken for quite
a while afterwards [4]
.
POST-TRAUMATIC STRESS DISORDER
Post-traumatic stress disorder is an anxiety disorder which results from a traumatic experience.
The symptoms include flashbacks or nightmares about what happened, hyper vigilance,
startling easily, withdrawing from others, and avoiding situations that remind the person of the
event. This disorder can continue for a sustained period of time with marked impairment in
function.
SOCIAL ANXIETY DISORDER
Is a marked and persistent fear of social or performance situations [4]
.
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PHOBIAS
A phobia is an unrealistic or exaggerated fear of a specific stimulus, such as heights, enclosed
places or other situations. The phobic individual may experience full panic attacks when
exposed to such stimuli. Phobias tend to be the most common form of anxiety disorder
whereas panic disorders are fairly rare in the general population [11]
.
PHYSIOLOGY OF ANXIETY
The human brain is the centre of human nervous system and is a highly complex organ. The
part of the brain that triggers a response to danger is the Locus ceruleus and the area of the
brain responsible for the acquisition and expression of fear conditioning is the Amygdala [12]
.
Once the neurotransmitters pick up over activity/hyperactivity in the locus ceruleus, the
amygdala senses danger and instructs us to run from danger. Hence, once the amygdala gets
activated it sends an alarm to the heart to beat faster, breathing to become rapid and in turn
activates all the biological components of fight/flight response. The symptoms experienced
during an anxiety attack include:
• Rapid heartbeat and rapid breathing
• Twitching or trembling
• Muscle tension
• Headaches
• Sweating
• Dry mouth and difficulty in swallowing
• Abdominal pain
Sometimes other symptoms accompany anxiety, such as:
• Blurred vision and Dizziness
• Diarrhoea or frequent need to urinate
• Irritability, including loss of temper
• Sleeping difficulties and nightmares
• Decreased concentration and
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• Sexual problems.
All these physical symptoms are felt when one is anxious or having a panic attack and are part
of a system that is designed to keep one safe and do not cause any harm. They cause a problem
only when they occur in response to situations where one is not physically threatened.
ANXIETY -MECHANISM OF ACTION
The primary mechanism of action involves modulation of neuronal communication, via
specific plant metabolites binding to neurotransmitter/neuromodulator receptors [5]
and via
alteration of neurotransmitter synthesis and general function [6]
. Other mechanisms involve
stimulating or sedating CNS activity, and regulating or supporting the healthy function of
endocrine system [5-7]
. Anxiety is recognised as one of the most important emotional processes
with firm neurobiological roots. The neurochemistry of anxiety although not well understood
has emerged to be a major area of research leading to new approaches in the treatment of
anxiety.
Anxiety is caused due to too many or too few neurotransmitters in the brain. Brain synthesizes
several neurotransmitters such as acetylcholine, adrenaline, dopamine, endorphins, serotonin,
gamma amino butyric acid, glutamate etc. Most information has come from studying the
action of anxiety-reducing or anxiolytic drugs. The evidences suggest anxiety to be caused by
dysfunction of one or more neurotransmitters and their receptors. The major thrusts of current
work dealing with anxiety disorders have centered around the gamma amino butyric acid
mechanisms, the serotonergic system, noradrenergic mechanisms and neuropeptides [10]
. New
evidences suggest a role for adenosine and cholecystokinin in the development of anxiety;
drugs interactions with these neurotransmitters also may have anxiolytic effects.
Gamma amino butyric acid (GABA) is one among the chief inhibitory neurotransmitters in the
mammalian brain and an increasing wealth of information suggests that GABAergic
mechanisms have a special role in the neurophysiology of anxiety [13]
. GABA works to
regulate the neuronal excitability and thereby serves as a „brake‟ on the neuronal circuitry
during stress and is the brain‟s natural stress reliever [14]
.
MANAGEMENT OF ANXIETY
Management of anxiety disorders varies and depends on the nature of the disorder and
individual patient characteristics [26]
. The treatment involves:
Medications
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Psychological treatment
Alternative therapy
Medication includes Selective Serotonin Reuptake Inhibitors (SSRIs) which may be the first
choice of medication for generalised social phobia. These drugs elevate the level of
neurotransmitter serotonin, among other effects. Ex. Fluoxetine, sertraline, paroxetine,
citalopram etc. Other medications commonly prescribed for anxiety disorders include
Benzodiazepines (ex: diazepam, chlordiazepoxide etc.) which facilitate inhibitory GABA
transmission. Monoamine Oxidase Inhibitors (MAOIs) (Phenelzine, Moclobemide) that
prevent the breakdown of serotonin and noradrenalin. Beta-blockers like propranolol, atenolol
which reduce the ability to produce adrenaline.
The common limitations of anxiety medications or drug therapy include comorbid psychiatric
disorders and increase in dose leading to unbearable side-effects [27- 28]
, such as allergic
reactions, drowsiness, coordination problems, fatigue, mental confusion, nausea and addiction
liability among others.
PSYCHOLOGICAL TREATMENT
Cognitive-Behavioural therapy and Exposure therapy are effectively used to treat anxiety
disorders. Cognitive therapy focuses on changing patterns of thinking and beliefs that are
associated with, and trigger, anxiety. The most important component of behaviour therapy is
exposure. Exposure therapy includes confronting your fears to desensitize yourself to such
dangers/fears that can trigger anxiety.
ALTERNATIVE TREATMENTS
Meditation – beneficial to patients with phobias and panic disorders.
Exercise – a natural stress buster and anxiety reliever.
Relaxation techniques (Yoga) – include progressive muscle relaxation and controlled
breathing which when practiced regularly attenuate anxiety.
Biofeedback – an effective method that uses sensors that measure physiological functions like
heart rate, breathing and muscle tension and help to recognise the body‟s anxiety response and
learn how to control them using relaxation techniques.
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Hypnotherapy – is sometimes used in combination with cognitive-behavioral therapy. The
hypnotherapist applies different therapeutic approaches to help you confront your fears while
in a state of deep relaxation.
Acupuncture – used in traditional Chinese medicine, helps alleviate anxiety [4]
.
TEST FOR ANXIETY
Studies related to the Central Nervous System and brain is accomplished using animals as
experimental models. Animal models form the backbone of preclinical research on the
neurobiology of psychiatric disorders, and are employed as screening tools in the search for
novel therapeutic agents.[39]
Rodents especially mice have proven to be helpful in research as
mice and humans share more than 90% of their genes in common. Furthermore, animal
models are particularly helpful in situations when the impact of stress cannot be studied in
humans because of ethical and other reasons [40]
. A variety of tests for anxiety have been
developed of which the commonly used ones include Elevated plus maze, Elevated zero maze,
Light/Dark test, Vogel‟s conflict test etc.
ELEVATED PLUS MAZE (EPM)
The Elevated plus maze is a simple method for assessing anxiety responses of rodents. The
EPM has four arms (two open and two enclosed) that are arranged to form a plus shape and
elevated 40-70 cm from the floor. The model is based on rodent‟s aversion of open spaces.
The assessment of anxiety behavior of rodents is done by using the ratio of time spent on the
open arms to the time spent on the enclosed arms. The elevated plus maze relies upon rodents
proclivity towards dark (enclosed spaces) and an unconditioned fear of heights (open spaces).
ELEVATED ZERO MAZE
Elevated zero maze, a modification of the EPM comprises an elevated annular platform with
two enclosed and two open quadrants, mounted on a base that raises the maze above the floor.
The Elevated Zero Maze does not have a centre compartment thereby allowing uninterrupted
exploration of the open and enclosed spaces and eliminating any ambiguity in interpretation of
the time spent in a centre compartment.
LIGHT/DARK TEST
The light/dark test in mice is based on the innate aversion to brightly illuminated areas and the
spontaneous exploratory activity of mice. The apparatus comprises of a light (brightly lit) and
a dark compartment separated with a partition. The distance traveled in each chamber, the total
number of transitions, the time spent in each chamber and the latency to enter the light
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chamber are noted. The anxiolytic compounds are known to increase the total duration of time
spent in the light compartment whereas the anxiogenic compounds work in the opposite way.
VOGEL’S CONFLICT TEST
The Vogel conflict test is based on the principle that the water deprived animal is placed in the
test cage with a special conductive floor grid and a drinking bottle with an electrically
conductive nipple. The animal licks are recorded and monitored by very low electrical currents
applied to the nipple that are below the animal's perception level. After a specified number of
licks an electric shock is applied to the nipple and the animal can escape the shock by
withdrawing from the drinking tube/nipple. The number of shocks received after treatment
with the anxiolytic drug is compared with the untreated animals. The anxiolytic drugs
significantly increase the number of licks and therefore the number of shocks applied.
OPEN FIELD TEST
It is generally used paradigm to assess/evaluate the locomotor, exploratory and anxiety-like
behaviour in laboratory animals. The open field area/arena usually consists of brightly lit
square or round area enclosed by walls with the animal usually being placed in the centre and
its behavior being recorded for a known period of time (3-15 minutes). It relies on the fact that
the rodent when anxious stays close to the enclosed walls and measures the degree to which
the rodent avoids the central area.
HERBAL ANXIOLYTES
Ayurveda (Ayur = life, Veda = knowledge), which is “Science of Life”, originated from the
Vedic times and is a part of holistic health care system. The chief source of ancient Indian
Aryan culture and medicine are the four Vedas that are traditionally believed to be revealed to
the sages by Brahma (the creator) some 6000 years before Christian era. Ayurveda‟s primary
emphasis is on preservation and promotion of health, it also provides treatment for disease.
Many undesirable constitutions (about eight) in the body are mentioned in “CharkaSamhita”,
an authentic source of Ayurveda. Hepatotoxicity is one among them. It is said that it is
comparatively easy to help an liver disorders person.
The Indian Traditional Medicine like Ayurveda, Siddha and Unani are predominantly based on
the use of plant materials. Herbal drugs have gained importance and popularity in recent years
because of their safety, efficacy and cost effectiveness. Several Indian medicinal plants have
been extensively used in the Indian traditional system of medicine for the management of liver
disorder. The use of natural remedies for the treatment of liver diseases has a long history and
medicinal plants and their derivatives are still used all over the world in one form or the other
for this purpose.
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Plants are known to have enormous potential to cure ailments from time immemorial.
Ayurveda and Unani are such inherited traditional systems of health and longevity that are
based on herbal medicines. The „World Health Organization‟ has approved that traditional
health and folk medicine systems have proved to be more effective in health problems
worldwide [42]
. Traditional medicines are used by about 60% of the world populations in rural
areas in the developing countries and is gaining acceptance in the developed countries where
modern medicines predominates [4]
. However, the major hurdle in the uninhibited exploitation
of herbal medicines into the regular practice of prescription is the lack of sufficient scientific
data and better understanding of efficacy and safety of the herbal products [43]
.
A number of plants have been scrutinized for their anxiolytic effects. Table 1 gives a list of
some of the widely studied plants for anxiolytic effects.
Table 1: List of plants with anxiolytic properties.
Plant name Family Active constituents
Abies pindrow Royle Pinaceae Dipentene (8.4%), l-bornyl acetate (15.7%) and l-
codinene (9.9%).
Achillea millefolium.
L.
Asteraceae Alkaloid achilleine, isovaleric acid, salicylic acid,
asparagines, sterols, flavonoids, tannins, choline
Albizzia julibrissin
Durazz
Fabaceae Two flavonol glycosides quercitrin and isoquercitrin.
Angelica sinensis
Oliv. Diels.
Apiaceae The essential oil contains lingustilide.
Apocynum venetum.
L.
Apocynace
ae
The chemical constituents of the leaves and flowers
include ionone glucosides named apocynoside I and
II, several compounds have been isolated and include
kaempferol, kaempferol 3-0-beta-D-glucoside, vanillic
acid, baimaside, daucosterol.
Azadirachta indica. Meliaceae The chemical compounds isolated from Neem oil
include nimbin, nimbinin, and nimbidin. The seeds
contain a complex secondary metabolite azadirachtin.
Cannabis sativa L. Cannabace
ae
Cannabidiol an cannabinoid exerts anti-anxiety effects
Citrus aurantium. L. Rutaceae Alkaloids, flavonoids, triterpenoids and steroids.
Coriandrum sativum
L.
Apiaceae β-phellandrene, citranellol, 1, 8-cineole and geranyl
acetate.
Crocus sativus L Iridaceae Saffron contains more than 150 volatile and aroma
yielding compounds.
Echium amoenum Boraginace
ae
flavonoids, saponins, unsaturated terpeniods and
sterols.
Ginkgo biloba L. Ginkgoace
ae
flavonoids, glycosides and terpenoids
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CONCLUSION
Thus, natural herbs/herbal mixtures that act synergistically promise to provide an effective
remedy for anxiety. However, only very few among these have been proved to be effective
anxiolytes with trials carried out on humans. Synthetic drugs and medications possess
enormous side effects, so these herbs with a wide therapeutic applicability promise to alleviate
anxiety with very few adverse effects.
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