HERBAL REMEDIES TO TREAT ANXIETY DISORDERS · Anxiety is a Central Nervous System disorder [1-2]. Anxiety is a common emotional phenomenon in humans [3]. Anxiety is an emotional state,

Uttaranchal University Journal of Research, (2019), 01(01)

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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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HERBAL REMEDIES TO TREAT ANXIETY DISORDERS · Anxiety is a Central Nervous System disorder [1-2]. Anxiety is a common emotional phenomenon in humans [3]. Anxiety is an emotional state,