Ashwagandha Effects on Depression

Ashwagandha And Depression: Is Ashwagandha Better Than Anti-Depressants?

Millions of people suffer from depression every year, and many of them turn to prescription medications for relief. While anti-depressants can be effective for some people, they can also cause various side effects. In recent years, there has been growing interest in the use of ashwagandha for depression. Ashwagandha is a plant used in traditional Indian medicine for many centuries, and evidence suggests that it may help treat depression. 

Ashwagandha differs from conventional anti-depressants in health benefits, mechanisms of action, and nutritional components. Ashwagandha or the Withania somnifera Dunal plant is not only an anti-depressant; it has anti-inflammatory, anti-stress, anti-cancer, immunomodulatory, antioxidant, blood-producing, and rejuvenating properties. Cognitive disorders, rheumatic pain, joint inflammation, male infertility, and poor physical performance are treated with extracts derived from its roots and leaves. Aside from these, ashwagandha can safely treat concomitant anxiety, insomnia, and stress. This benefit contrasts with conventional anti-depressants, whose dosages need to be adjusted for these three different usages. Some anti-depressants also can affect sleep and are regulated for this purpose. 

Ashwagandha’s long tuberous roots, short stems, oblong leaves, and greenish axillary and bisexual flowers characterize this erect, grey evergreen shrub. The plant parts used include roots, leaves, fruits, and flowers containing differing compounds that contribute to its health effects. The leaves and root extracts bear 29 common metabolites. The most pharmacologically and medicinally significant components in ashwagandha are withanolides, sitoindosides, and other alkaloids. 

More specifically, the roots have the most medicinally-beneficial phytochemicals with about 200 pharmacological activities. These compounds are alkaloids, steroidal lactones, and saponins. They also contain amino acids, starch, steroids, volatile oil, reducing sugars, glycosides, dulcitol, hentriacontane, and withaniol. These compounds shield the body’s cells against oxidative stress and illness, are cytotoxic to cancer cells, and possess immune system modulation and brain-protecting qualities. The plant’s fruits have proteolytic enzymes, condensed tannins,  amino acids, and flavonoids. Other metabolites are phenolic, fatty, organic, aliphatic, aromatic acids, polyols, sterols, tocopherols, sugars, squalene, and withanamides. The leaves contain withanolides and are reported to contain unidentified alkaloids, condensed tannins, glycosides, chlorogenic acid, glucose, and flavonoids. 

Ashwagandha has rich all-natural nutritional components and an alkaloidal content between 0.13% and 0.31%. It is representative of the alkaloids withanine, withasomnine, and visamine and contains the free amino acids tyrosine, tryptophan, alanine, proline, glutamic acid, glycine, aspartic acid, and cystine. In contrast, anti-depressants are composed of genetically-engineered neurotransmitters or chemical messengers that mimic those present in the brain. 

Ashwagandha extracts from the root, leaves, or a mixture are available in various forms as supplements, most commonly pills and capsules. Anti-depressants are also commonly available in pill forms, but patch and intravenous preparations are also available. There are no standard dosages of ashwagandha extract. Studies have shown that it is non-toxic even at 2,000 mg/kg body weight doses. Anti-depressants, on the other hand, are controlled medications due to their narrow therapeutic index and high risk for misuse and abuse.

Ashwagandha is a mood stabilizer in clinical anxiety and depression cases. There are four mechanisms for these effects. It modulates the neurotransmitters dopamine and serotonin, expresses GABAmimetic actions, promotes the creation of new brain cells, and reduces excessive cortisol production. All of these mechanisms play a role in relieving depression. Aside from this, the extracts can be used in comorbid anxiety disorders and reduce the stress that aggravates depressive symptoms. Because of these vast benefits, there is an increase in demand and production of ashwagandha in dietary supplement form. 

However, safety studies are limited. Therefore, precaution is necessary, especially in pregnant and lactating mothers, persons with diabetes or thyroid problems, and those taking sedating, blood pressure-lowering, and immunosuppressant medications. 

This article will discuss the research on ashwagandha and depression and explore whether ashwagandha is a better option than anti-depressants.

What Is The Relationship Between Ashwagandha And Depression?

Depression is linked to normal feelings of sadness and grief, but when feelings persist after the external cause is eliminated, it becomes dysfunctional. According to Liu, Liu, Wang, Wang, Li, & Li, depression has been labeled “major depression” since the 1960s, including symptoms such as anxiety and insomnia. For the diagnosis of major depressive disorder, The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) requires a distinct change in mood, characterized by sadness or irritability and accompanied by several psychophysiological changes such as sleep, appetite, or sexual desire disturbances, constipation, loss of ability to experience pleasure at work or with friends, crying, suicidal thoughts, and slowing of speech and action. These feelings must endure for at least two weeks and cause significant work and family life disruption.

Depressive disorders are one of the most common types of mental disease and significantly impact individuals and society. People in today’s culture often suffer from psychological problems, including sadness, anxiety, and sleeplessness. According to the World Health Organization (WHO), major depressive disorders (MDD) will be the second most common ailment by 2020. In the Global Burden of Disease Study by Murray and Lopez, MDD was identified as a pivotal contributor to the incidence of suicide and ischemic heart disease and was listed as the second-largest cause of disability worldwide. Psychiatric disorders like MDD impact people’s jobs, quality of life, and sense of well-being. According to Belmaker & Agam, depression affects more than 12% of men and 20% of women in the United States over their lifetime.

Ashwagandha, botanically known as Withania somnifera Dunal, belongs to the Solanaceae family. The herb is synonymously called “Winter Cherry” or “Indian Ginseng.” Ashwagandha means the “Smell of horse,” derived for two reasons. First, the herb’s raw roots have a horse-like odor. Second, it is believed that by taking extracts of the herb, a person can achieve strength and vigor equivalent to that of a horse. According to Chandrasekhar, Kapoor & Anishetty, the herb is essential in Ayurvedic therapy. Because of its numerous rejuvenating properties on the human body, ashwagandha is known as a “royal herb.” It is a versatile plant that affects the nervous, energy-producing, immunological, endocrine, and reproductive systems.

There are few evidence-based therapy options for psychiatric diseases. According to Liu, Liu, Wang, Wang, Li, & Li, currently, pharmacological therapy is the most widely utilized treatment for mood disorders. However, research shows that complementary and alternative medicine (CAM) is frequent among those suffering from psychiatric disorders, particularly depression and anxiety. For example, in the past year, 53.6% of people with self–reported depression and 4.5% of non–institutionalized adults with insomnia used various forms of CAM to treat their psychiatric disorders, according to a nationally representative study conducted in the United States. In addition, many studies have shown the value of CAM in treating mental diseases. Herbal medicine is the most often utilized complementary and alternative medicine therapy.

Adaptogens are herbs that help people cope with stress more effectively. These herbs help the body adapt to changes by normalizing its physiological processes during increased tension. According to Chandrasekhar, Kapoor, & Anishetty, an adaptogen regulates an organism’s ability to adapt to environmental factors that can cause stress and avoid bodily damage derived from such elements. Ideally, an adaptogen should reduce damage induced by stress, be safe for consumption, have no adverse side effects or withdrawal symptoms, and not interfere with normal bodily processes more than what is essential. Ashwagandha possessing these qualities is one of the most common herbal medicines used in CAM to treat psychiatric diseases like depression. 

Over 50 known chemical compounds are found in various amounts of the ashwagandha plant, with steroidal alkaloids and lactones, together known as withanolides, being the most important, according to Zahiruddin, Basist, Parveen, Parveen, Khan, Gaurav & Ahmad. There are human and animal studies that support this. In the study by Lopresti, Smith, Malvi, & Kodgule, the brain’s antioxidants are modulated to prevent excessive damage to neurons. After using ashwagandha root extracts, brain cell growth was observed, suggesting that it may have a role in neural regeneration. On the other hand, Manjunath & Muralidhara also explains that the ashwagandha plant can offset neurotoxicity, regulate perturbations in the neurotransmitter system, and normalize dopamine levels which are implicated in depression.

 

Ashwagandha And Depression Content Image 1

 

What Are The Unique Benefits Of Ashwagandha When Compared To Anti-Depressants?

The unique benefits of ashwagandha compared to anti-depressants are listed below:

  • Alternative anti-depressant for patients who experience side effects from conventional drugs
  • Alternative for those who do not benefit from standard anti-depressants.
  • Helpful therapeutic agents in areas where conventional drugs cannot be supplied 
  • Useful therapeutic agents for those who can not afford conventional anti-depressants 
  • Considered to be safe and affordable
  • Devoid of any toxic effect in acute and sub-acute toxicity studies
  • Little to no side effects, no changes in behavior, body weight, liver function tests, or any gross pathological lesions in the liver, adrenals, spleen, kidneys, lungs, thymus, heart, testes, and uterus
  • Withanolides, its main components, are clinically proven to be a safe, effective treatment for autoimmune/inflammatory illnesses, cancer, neurodegenerative diseases, and neurobehavioral/psychiatric diseases across numerous disease pathways.
  • Unlike conventional anti-depressants, there are no severe reactions following administration of large doses, even at an amount of 2,000 mg/kg body weight.
  • Not associated with misuse or abuse potentials
  • It works as an anti-depressant and helps enhance vigor by promoting muscle strength, endurance, and overall health.
  • Has anti-anxiety properties

What Are The Unique Side Effects Of Ashwagandha When Compared To Anti-Depressants?

The unique side effects of ashwagandha compared to anti-depressants are listed below:

  • Nasal congestion (rhinitis)
  • Cough and cold
  • Drowsiness
  • Decreased appetite
  • Headache
  • Gastrointestinal disturbances
  • More safety studies must be performed in pregnant or breastfeeding mother
  • Not FDA approved as a drug
  • It is unsafe to use simultaneously with glucose-lowering medications.
  • It boosts the action of the immune system, thus, could interfere with immunosuppressant medications. Consult your health care provider if you are taking cyclosporine, prednisone, mycophenolate, tacrolimus, or other corticosteroids.
  • It interacts with sedative-hypnotic drugs. 
  • It also can lower blood pressure levels, so caution must be taken in persons who take drugs to treat high blood pressure.
  • It can increase thyroid hormone levels, so people with hyperthyroid problems should be carefully monitored.

How Does Ashwagandha Work As An Anti-Depressant?

In the investigation by Bhattacharya, Bhattacharya, Sairam, & Ghosal, ashwagandha exhibited an anxiolytic-anti-depressant effect among psychiatric patients. This was attributed to the plant’s bioactive component, glycowithanolides. These compounds are further elaborated as sitoindosides VII to X and withaferin A, which prevented acute and chronic stress-induced anxiety and depression in rats. In their study using two conventional tests, the forced swim-induced “behavioral despair” and “learned helplessness” tests, ashwagandha showed an effect comparable to the anti-depressant drug imipramine. The research generally tells of ashwagandha’s mood-stabilizing properties in clinical anxiety and depression cases.

To further understand how ashwagandha works as an anti-depressant, it is essential to examine the hypotheses of how depression is produced. Belmaker & Agam cite that the monoamine-deficiency hypothesis is a key theory of depression. This theory proposes that a decrease in serotonin, dopamine, or norepinephrine levels in the central nervous system represents the fundamental pathophysiologic foundation of depression. These neurotransmitter systems begin deep in the brain and spread throughout, implying they can influence various emotions, thoughts, and behaviors. The mechanism of action of anti-depressants appears to support this anticipated pathophysiology. Medications that raise the levels of these neurotransmitters in the brain have been proven to alleviate depressive symptoms. 

In an experimental study by Suganya, levels of the neurotransmitter dopamine were increased in animals given ashwagandha. Glycowithanolides are bioactive chemical compounds that may function in neurotransmitter secretion by avoiding neuronal degeneration.

On the other hand, according to Belmaker & Agam, cortisol and its key releasing component, corticotropin-releasing hormone (CRH), are implicated in depression. Cortisol levels in the blood, CRH levels in the cerebrospinal fluid, and CRH messenger RNA and protein levels in limbic brain regions may all be higher in patients with depression. This happens because the brain’s cortex detects stress and transmits it to the hypothalamus, releasing corticotropin-releasing hormone (CRH) onto the pituitary. This stimulus causes corticotropin to be secreted into the bloodstream, stimulating its receptors. Cortisol is then released into the bloodstream. 

In the study by Salve, Pate, Debnath, & Langade, in adults given ashwagandha root extracts, the treatment groups had significantly lower serum cortisol levels at the end of the 8-week trial. The study also used two different dosages of ashwagandha and implies that while ashwagandha 250 mg/day helps lower cortisol levels, 600 mg/day is more effective.

According to Belmaker & Agam, the peptide called brain-derived neurotrophic factor (BDNF) is important for axonal growth, neuronal survival, and synaptic plasticity. Its levels are also influenced by stress and cortisol. In a postmortem study of patients with depression who had committed suicide, BDNF levels were found to be lower in the hippocampus. There are also studies that link depletion of BDNF to stress and hippocampal atrophy in depression. 

Konar, Shah, Singh, Saxena, Kaul, Wadhwa, & Thakur stated that ashwagandha protects against neural damage. It reverses neuron loss and plasticity, essential factors for producing and maintaining healthy neurons. In the study, ashwagandha alcoholic extracts also upregulate the expression of proteins that make BDNF. 

There is mounting evidence that gamma-aminobutyric acid (GABA) also plays a role in depression. According to Fogaça & Duman, GABAergic system malfunction is linked to the pathophysiology of depression, and GABA normalization results in the remission of depressive symptoms.

Candelario et al. found that ashwagandha’s aqueous and methanolic extracts cause GABAmimetic effects. It mimics the action of GABA on the receptors to regulate its production, suggesting that at least one of the withanolide derivatives is responsible for this effect. They also conclude that their findings imply that ashwagandha may have additional brain-protecting properties through activating GABA receptor channels.

These mechanisms may not be present in all types of depression cases. Thus, the usage of ashwagandha for these different physiologies may not work for everyone. This is because the physiology of depression is multifactorial. 

For example, in children, the annual incidence of depression is 1% to 2% at age 13 and 3% to 7% at age 15. In this age group, depression may be caused by hereditary factors, personality disorders, and psychosocial factors like bullying, adverse childhood experiences, or trauma from family separation. Middle-aged or elderly patients may attribute their depression as a disorder stemming from cardiovascular disease or endothelial dysfunction. Also, acute depression is thought to have a different etiology than recurring or chronic depression, marked by long-term deficits in function and cognition. Thus, the usage necessities of ashwagandha for treatment of depression may vary from one person to another. 

Does Ashwagandha Supplement Show Anti-Depressant Effects?

Ashwagandha supplements show anti-depressant effects. These supplements are in the form of pills, capsules, and powdered extracts. According to Mukherjee, Banerjee, Biswas, Das, Kar, & Katiyar, the plant’s roots contain the most active components necessary for pharmacological activity, like its anti-depressant properties. Ashwagandha supplement forms containing ample amounts of withanolides give off the same benefits. 

The research by Bhattacharya, Bhattacharya, Sairam, & Ghosal tells of ashwagandha’s use as a mood stabilizer in clinical anxiety and depression cases. It promotes neurogenesis, downregulates excessive cortisol, and modulates neurotransmitters like dopamine, serotonin, and GABA. All of these mechanisms play a role in the development of depression. 

Is Ashwagandha Included In Some Of The Anti-Depressant Pills?

No. Ashwagandha is not included in some of the conventional anti-depressant pills. The four classes of anti-depressants are Tricyclic anti-depressants (TCAs), Selective serotonin reuptake inhibitors (SSRIs), Monoamine oxidase inhibitors (MAOIs), Serotonin-norepinephrine reuptake inhibitor (SNRI), and atypical anti-depressants. Ashwagandha is not incorporated into these anti-depressant medications due to unknown drug interactions. Ashwagandha exists as a supplement form.

How To Use Ashwagandha For Anxiety?

There are no standard doses of ashwagandha for anxiety. Pratte, Nanavati, Young, & Morley, summarized clinical trials conducted on this herb. Ashwagandha can be used for anxiety in the following ways:

For ethanolic extracts of ashwagandha, use a 500 mg dose twice a day, or 1,000 mg/day for six weeks.

For ashwagandha root and leaf extract standardized to a minimum of 8% withanolide glycosides, 32% oligosaccharides, and maximum withaferin A (prepared as 125 mg and 250 mg hard-gelatin capsules): Take one 125-mg capsule once to twice a day for 60 days. 

For ashwagandha made from the root standardized to 1.5% withanolides (prepared as 300 mg supplements): Use one 300 mg supplement twice a day or 600 mg/day for 12 weeks. 

For high-concentration full-spectrum root extract capsules standardized to contain at least 5% withanolide content (prepared as 300 mg capsules): Use one 300 mg capsule twice a day or 600 mg/day for 60 days. This extract is obtained from the roots of the ashwagandha plant and produced without using alcohol or any synthetic solvents.

For granules made from dried root powder (prepared as 4 g granules): Use one 4 g granule three times a day or 12,000 mg/day for 60 days​​. This preparation is made with 1 part ashwagandha roots to 1 part sugar and water. First, the dried roots are pulverized into fine powder. Equal amounts of sugar syrup are made by adding enough water to a gentle flame and constantly stirring until the syrup reaches the tantumatvam or thread-like stage. The powder is then added to the sugar syrup and thoroughly mixed to get a homogeneous mixture.

The blended mixture is placed through a sieve to produce granules then dried at room temperature.

Can Ashwagandha Really Help To Treat Depression?

Yes, ashwagandha is among the herbs implicated in the treatment of depression. It targets four proposed mechanisms for the development of depression. First, it stabilizes the amounts of neurotransmitters. In an experimental study by Suganya, levels of the neurotransmitter serotonin were increased in animals given ashwagandha, which targets the first and widely accepted hypothesis in depression, the monoamine deficiency hypothesis. 

Second, it regulates the amount of cortisol and its key releasing component, corticotropin-releasing hormone (CRH), which is implicated in depression. Cortisol is a marker of dysregulation in the hypothalamic-pituitary-adrenal (HPA) axis due to stress, which can cause downstream anxiety and depressive symptoms. According to Luscher, Shen & Sahir, depression and anxiety are comorbid illnesses, and treating one disorder benefits the other. About 50% of depressed patients report a history of anxiety disorders, and patients with anxiety disorders manifest a history of depression treatment.

Third, it regulates the brain-derived neurotrophic factor (BDNF), an important factor for axonal growth, neuronal survival, and synaptic plasticity. The link between depletion of BDNF to stress and hippocampal atrophy is also implicated as a physiologic process that arises in depression. Ashwagandha maintains adequate BDNF levels.

Fourth, it functions as a GABAmimetic. A malfunction in the GABAergic system is linked to the pathophysiology of depression, and GABA normalization is associated with the remission of depressive symptoms. Ashwagandha works similarly to GABA by strengthening its effects on the receptor. 

How Long Before Ashwagandha Starts To Take Effect?

There is no definite duration of treatment before ashwagandha is known to take effect. In a study done by Fuladi, Emami, Mohammadpour, Karimani, Manteghi, & Sahebkar, statistically effective treatment with 1 g per day of ashwagandha root extracts was noticed after two weeks of treatment. This was supported by the study of Andrade, Aswath, Chaturvedi, Srinivasa &  Raguram, which used ethanolic extracts. Ashwagandha started to show anxiolytic effects beginning at two weeks of administration. In another study by Auddy, Hazra, & Mitra, there was an improvement in the well-being of participants given ashwagandha starting at 30 days. Naturopathic care, including ashwagandha root extracts, was given for eight weeks in the study participants of Cooley, Szczurko, Perri, Mills,  Bernhardt, Zhoun & Seely before improvements in concentration, mental health, fatigue, vitality, social functioning, and overall quality of life were noticed. Chandrasekhar, Kapoor & Anishetty also saw a reduction in depression anxiety scales among participants given ashwagandha at 600 mg/day for 60 days. 

What Are The Other Herbs That Help For Depression?

Some other herbs that help in treating depression are:

  1. Ginseng

Ginseng has been used as a herb in traditional Chinese medicine for ages to enhance mood and keep people healthy. Lee & Rhee’s review states the metabolite of ginseng called 20(S)-protopanaxadiol is the compound responsible for the anti-depressant activity of ginseng. This works by increasing the levels of norepinephrine and serotonin through the inhibition of monoamine reuptake. The authors add that depression has been linked to memory loss because it causes nerve cells to deteriorate over time. This neuronal cell injury, combined with a decline in neurogenesis caused by inflammation, can lead to hippocampus cell death, a process that can be halted by ginseng. These two processes are also possessed by ashwagandha, except the herb has additional GABAmimetic and HPA axis regulatory effects.

           2. Peony

The root part of Paeonia lactiflora Pall. (Ranunculaceae) is frequently used in Chinese herbal remedies to treat depression-like conditions. Paeonol has been identified as the active component among peony’s secondary metabolites. It works almost similarly to ashwagandha. According to Mao, Ip, Xian, Hu, & Che, it works by mediating multiple targets. First, it inhibits monoamine oxidases, increasing the levels of norepinephrine and dopamine. Second, it reduces oxidative stress in the mouse brain. Excess oxygen reactive species are known to damage the brain, causing dysfunction leading to depression. Third, it has neurotrophic and neuroprotective effects. These are the neuron’s ability to alleviate deficiencies in cellular plasticity and resilience that underpin the pathophysiology of major depressive disorders. It increases the amount of neurotrophins proteins to prevent neuron cell death cascades and promote cell survival proteins. 

         3. Epicedium

Epicedium is a Chinese herbal medicine with many benefits, including cancer and cardiovascular disease treatment and immunological suppression. According to Dong et al., Epicedium extract called icariin can successfully induce peripheral nerve regeneration and repair impaired nerve function. This herb primarily acts through its neuroprotective properties, unlike ashwagandha, which works by multiple mechanisms. Kaempferol, luteolin, and quercetin are the compounds scientist think are responsible for their anti-depressant properties. Luteolin-regulated genes, for example, may operate as anti-depressant receptors in the central nervous system. In the treatment of neurological illnesses, quercetin contains antioxidant and anti-inflammatory properties. By shielding neurons from oxidation and inflammation, quercetin reduced anxiety and depression in persistently stressed mice. It also works by modulating the estrogen receptor. The estrogen receptor can be stimulated to increase the production of dopamine, serotonin, and other neurotransmitters. 

       4. Perilla frutescens

Perilla frutescens (Perilla leaf) has been used as a traditional Chinese medicinal plant to cure various ailments, including depression. Lee, Ko, Huang, Chu, & Huang stated that poly-unsaturated fatty acids (PUFA), such as n-3 ALA, are abundant in Perilla frutescens seed oil, which positively affects the vascular and neurological systems. This PUFA is responsible for the plant’s anti-depressant properties. It has anti-inflammatory qualities to lower oxidative stress in the brain. It can also lower cortisol levels, which, as stated earlier, dysregulation can cause increased cortisol that can contribute to depression. It can also improve tryptophan conversion to serotonin, increasing serotonin levels to prevent depression. PUFA supplementation’s anti-depressant-like effects are also due to the increase in production of BDNF for neurogenesis. 

       5. Yueju

Yueju is a traditional herbal medication made of five plants created 800 years ago to treat depression-related illnesses. The five herbs include: Cyperus rotundus L. (Xiang Fu), Ligusticum chuanxiong Hort. (Chuan Xiong), Gardenia jasminoides Ellis. (Zhi Zi), Atractylodes lancea (Thunb.) DC. (Chang Zu), and Massa Fermentata (Shen Qu). Yueju is still commonly used for stomach problems and depression. Ren & Chen states that Yueju has recently been found in clinical and preclinical investigations to produce a fast-onset anti-depressant effect, similar to ketamine. The compound responsible for this rapid anti-depressant response is Gardenia jasminoides J.Ellis (GJ). This herb has a fast onset of action in increasing the expression of BDNF in the hippocampus, which is a factor responsible for neuronal plasticity and regeneration.  

Is It Safe To Take Ashwagandha With Any Type Of Anti-Depressant?

No studies found in the literature examine the safety profiles of simultaneous ashwagandha and anti-depressants. However, there are also no known drug interactions between the two.

  1. Tricyclic anti-depressants (TCAs) are sedating. Combining these with ashwagandha, which has hypnotic effects, could cause serious risks for falls and accidents, especially in the elderly.
  2. Selective serotonin-reuptake inhibitors (SSRIs) can also cause drowsiness and fatigue. At the same time, ashwagandha can cause sedative effects, which could enhance SSRI’s actions.
  3. Monoamine oxidase inhibitors (MAOIs). Orthostatic hypotension, drowsiness, dizziness, insomnia, and nausea are the most common side effects of MAOIs. They may cause synergistic actions when given concurrently with ashwagandha.
  4. Serotonin-norepinephrine reuptake inhibitor (SNRI). The side effects associated with SNRIs include tremors, sedation or insomnia, and dizziness, which may pose problems when added to the sedative effects of ashwagandha.
  5. Atypical anti-depressants. Most atypical anti-depressants also report dizziness or lightheadedness as side effects, which may potentially be deleterious when combined with ashwagandha. 

Can Depression Heal Naturally?

Depression can heal naturally. However, the clinical diagnosis and severity need to be determined to find the appropriate intervention for each type of depression. There are natural ways to heal depression. For example, depression, anxiety, and self-concept improved dramatically among depressed people who participated in a fitness program, according to Craft & Perna. Running had the same effect as psychotherapy in treating symptoms of depression. Thirty minutes of moderate aerobic exercise three times a week was as helpful as psychotherapy or anti-depressant medication. Relaxation techniques are also effective treatments. Research has backed up Yoga practice as a natural remedy for depression. Its roots in Indian culture consist of a complex system of spiritual, moral, and physical activities to achieve “self-awareness” in its original form.

A well-balanced diet helps to treat depression. For example, according to the Mayo Clinic, a 1,000 mg EPA capsule is useful in treating depression. Vitamin B also helps neurotransmission, and adequate intake can prevent dysregulated transmitter systems. Low folate levels, especially in alcoholics, were seen in a study by Coppen & Bolander-Gouaille to stop effective neurotransmission. Vitamin D also helps treat depressive symptoms. According to the National Institutes for Health, magnesium is a precursor for the production of serotonin; thus, adequate intake can help. Processed foods also contribute to inflammation in the body, and consumption has been linked to depression. Other culprits of inflammation are gluten, sugars, dairy, caffeine, and alcohol. 

The two most significant variables for aggravating depression are persistent stress and interrupted sleep cycles. Thus, adequate sleep and stress relief are intertwined with relief from depression. Light therapy or phototherapy has also been studied in depression treatment. It modulates the circadian rhythm responsible for the proper function of specific brain areas.

Is Ashwagandha A Good Anti-Depressant?

Yes, ashwagandha is a good anti-depressant. It is a popular adaptogen used in complementary and alternative medicine to treat depression. It not only prevents depression but can also help cure it. It is an ideal adaptogen that helps the body adapt to stress by normalizing its physiological processes. Ideally, it reduces damage induced by stress, is safe for consumption, has no adverse side effects and withdrawal symptoms, and does not interfere with normal bodily processes. 

It also cures depression should it occur. The research by Bhattacharya, Bhattacharya, Sairam, & Ghosal tells of ashwagandha’s use as a mood stabilizer in clinical anxiety and depression cases. It also works by four mechanisms compiled from scientific studies. It promotes neurogenesis, downregulates excessive cortisol, and modulates neurotransmitters like dopamine and GABA. All of these mechanisms play a role in the development of depression. 

 

Ashwagandha And Depression Content Image 2

 

Is It Safe To Take Ashwagandha For Long-Term Use?

No, the long-term use of ashwagandha has not been evaluated in scientific research. It is noteworthy that cases of acute liver injury have been reported by the National Institute Of Diabetes And Digestive And Kidney Diseases. It presented as jaundice and pruritus 2 to 12 weeks after the start of ashwagandha intake.

Despite its widespread use, ashwagandha is thought to be largely safe and free of severe adverse effects. There have been no reports of blood enzyme increases throughout medication use in clinical trials, and there has been no mention of significant side events or hepatotoxicity. Recently, however, multiple incidences of clinically evident liver impairment in patients taking commercial herbal preparations containing ashwagandha have been recorded. Jaundice resolved on its own after a long course, but it never resulted in death or long-term harm. Because commercial herbal preparations are frequently mixes of herbs and nutritional items, it’s not always apparent if the reported cases were caused by ashwagandha or one of its components or by a contaminant. However, in numerous recorded instances, the commercial product was analyzed and confirmed to contain only ashwagandha and no additional impurities. As a result, clinically visible liver impairment caused by ashwagandha appeared to occur but is rare.

On another point of view, the study by Verma, Gupta, Tiwari, & Mishrawas notes that an 8-week administration of ashwagandha root extract does not have any toxic effects in healthy volunteers when compared to a placebo. Long-term studies must be performed in the future.

What Are The Advantages Of Using Ashwagandha?

The advantages of using ashwagandha in depression are the following:

  1. Safe and with little or no side effects
  2. Effective
  3. Better tolerated
  4. Non-toxic
  5. No potential for abuse or misuse

Its other advantages are:

  • Increased energy levels
  • Improved concentration
  • Reduced stress and anxiety
  • Has cognition-promoting effect and is helpful in children and elderly with memory deficits
  • Useful in neurodegenerative diseases such as Parkinson’s, Huntington’s, and Alzheimer’s diseases
  • Improved sleep
  • Enhanced athletic performance
  • An anti-inflammatory and anti-arthritic agent
  • Improved immune system activity against disease 
  • Has potent antioxidant properties to protect cells against damage caused by free radicals
  • Revitalizes the body during debility
  • Increased testosterone levels and fertility in men
  • May lower blood sugar levels
  • Supports heart health
  • Has anti-tumor and anti-cancer activity
  • Provides neuroprotection

Withania somnifera (ashwagandha) is a rejuvenator and highly regarded herb in the Indian Ayurvedic medical system. It’s used for various ailments, most notably as a nervine tonic. 

What Are The Disadvantages Of Using Ashwagandha?

The disadvantages of using ashwagandha are listed below:

  1. It can produce extreme sleepiness.
  2. It may further decrease blood sugar levels in diabetic patients with maintenance medications.
  3. It can cause low blood pressure.
  4. It can affect thyroid function.
  5. It can aggravate auto-immune disorders.

Although ashwagandha’s efficacy has been recognized and validated, its safety may raise concerns due to a lack of relevant safety literature. Despite this, there has been very little research on ashwagandha’s safety.

What Are The Advantages Of Using Anti-Depressants?

Anti-depressants help alleviate the symptoms of depression by affecting the chemical balance of neurotransmitters in the brain. Chemical imbalance is the cause of the shift in mood and behavior. The Food and Drug Administration has authorized all anti-depressants. This indicates they have undergone extensive testing and clinical studies.

According to Khushboo, anti-depressants help with depressive symptoms while also targetting other symptoms such as anxiety, nervousness, major depression, obsessive-compulsive and manic-depressive disorders, and childhood bedwetting. Other disorders like diabetic peripheral neuropathy pain, social anxiety, and post-traumatic stress can also be treated with anti-depressants. According to studies, the benefit derived from anti-depressants is proportional to the degree of depression. The worse the depression, the greater the benefit. Anti-depressants are effective against chronic, moderate, and severe depression and prevent relapses.

The different types of anti-depressants are the following:

  1. Tricyclic anti-depressants (TCAs). TCAs, like amitriptyline, prevent norepinephrine and serotonin from being reabsorbed at the presynaptic neuronal membrane. They are beneficial in persons with primary depression, improvement of mood in the evening, previous positive response to a tricyclic anti-depressant, motor retardation, loss of appetite, early morning awakening, weight loss, loss of interest in work or hobbies, sadness or depressed feelings, and loss of interest in sex. For agitated depressions, amitriptyline was favored, whereas imipramine was preferred for retarded depressions.
  2. Selective serotonin-reuptake inhibitors (SSRIs) are the first-line treatment for depression. The reuptake of serotonin into presynaptic terminals is the primary process for its action to be terminated. SSRIs block this reuptake and enhance and prolong serotonergic neurotransmission. With continuous administration of SSRIs, there is an increase in the expression of BDNF and neurogenesis.
  3. Monoamine oxidase inhibitors (MAOIs) inhibit the monoamine oxidase enzyme. These enzymes break down serotonin, norepinephrine, and dopamine, causing lower levels of these neurotransmitters. This class of anti-depressants was the first to be discovered. Depending on the usage, they are also available in oral and patch forms.
  4. Serotonin-norepinephrine reuptake inhibitors (SNRI) are more selective than SSRIs. They prevent serotonin and norepinephrine from being reabsorbed in the synapse, increasing their levels. In patients with more severe depression, SNRIs are more superior for use.
  5. Atypical anti-depressants and other newer classes of anti-depressants vary according to their mechanisms of action. They are advantageous for use in very refractory cases of depression or persons with intolerable side effects to the above medications.

What Are The Disadvantages Of Using Anti-Depressants?

According to Liu, Liu, Wang, Wang, Li & Li, most synthetic anti-depressants have serious disadvantages, such as a narrow anti-depressant spectrum, unpleasant effects, high drug prices, and recurrences with abrupt drug discontinuation. They also have a narrow therapeutic index, and side effects are troublesome. Side effects are common in the first few weeks of treatment and become less common over time. Some of these adverse effects are thought to result directly from the medication’s action on the brain, and they are consistent across different medicines in the same class. Dry mouth, headaches, dizziness, restlessness, and sexual issues are just a few examples.

Also, not every anti-depressant will be effective for everyone. Some people may experience several weeks or months of trial anti-depressant therapy before the health care provider can be sure which fits a particular condition. 

  1. Tricyclic anti-depressants (TCAs): These can cause constipation, vision problems, trembling, dizziness, dry mouth, and difficult urination. These can cause risks for falls and accidents, especially in the elderly.
  2. Selective serotonin-reuptake inhibitors (SSRIs): Gastrointestinal upset, like nausea, is the most commonly reported side effect. Other adverse reactions are anxiety, agitation, weight gain, sexual dysfunction, and sleep disturbance. There are reports of increased risk for suicide ideation in children and adolescents.
  3. Monoamine oxidase inhibitors (MAOIs): Orthostatic hypotension, drowsiness, dizziness, insomnia, and nausea are the most common side effects of oral MAO inhibitors. More prolonged use can cause weight gain, paresthesias, edema, muscle pain, sexual dysfunction, myoclonus, and liver toxicity. Transient hypertension episodes have been described within 2 hours after administration of MAO inhibitors. The hypertensive episodes are usually self-limited but culminate in hypertensive crisis in rare circumstances. MAO inhibitor monotherapy can result in serotonin syndrome. Serotonin syndrome is a medical emergency characterized by restlessness, mental status changes, heightened reflexes, diaphoresis, or evidence of autonomic hyperactivity.
  4. Serotonin-norepinephrine reuptake inhibitor (SNRI): The side effects associated with intake are gastrointestinal disturbances, weight gain or weight loss, headaches, restlessness or nervousness, anxiety, agitation, tremors, sedation, dizziness, sleep disturbances, diaphoresis, and sexual difficulties
  5. Atypical anti-depressants: The most common side effects are dizziness, constipation, insomnia, lightheadedness, and constipation.

Sullivan & Evans state that anti-depressants can also be abused in large amounts through the intranasal and intravenous routes. Seizures, confusion, and psychotic-like symptoms have all been reported as adverse side effects, which vary depending on the anti-depressant class.

Does Ashwagandha Really Work For Calming Anxiety, Insomnia, And Stress?

Yes, ashwagandha works to calm anxious behaviors, treat insomnia, and reduce stress. It targets the following mechanisms of anxiety, stress, and insomnia. Anxiety disorders have an unknown mechanism of action. The neurological basis of anxiety, according to current data, is linked to the disruption of the neurotransmitters serotonin, norepinephrine, glutamine, and GABA. Some of the most significant psychiatric research findings have also pointed to a role for Corticotropin-Releasing Factor (CRF) and noradrenergic system dysfunction in anxiety disorders. The CRF system, whose product is cortisol, is a key regulator of anxiety and stress-related behavioral responses. Many conditions, including anxiety, are thought to be caused by dysregulation of the CRF system. 

In depression, Candelario et al. note that aqueous and methanolic extracts cause GABAmimetic effects, which mimic the action of GABA on the receptors. GABA works as an inhibitor that causes drowsiness, induces sleep, calms the mood, and relieves anxious behaviors. On the other hand, adults given ashwagandha root extracts had significantly lower serum cortisol levels at the end of the 8-week trial by Salve, Pate, Debnath, & Langade. This regulation of cortisol levels also plays a role in regulating CRF.

Insomnia is the most common sleep disorder and is often treated with various medicinal plants. Anomalies cause sleep disorders in the brain’s neurotransmitters and other pathways. These include the GABA receptors, cortisol level, cytokines, circadian rhythm, and excitatory amino acid receptors (glutamate and aspartate). 

In the study by Langade, Kanchi, Salve, Debnath, & Ambegaokar, quality and quantity of sleep were observed. The sleep parameters evaluated are sleep onset latency (SOL), total sleep time (TST), sleep efficiency (SE), and waking following sleep onset. Adults’ sleep quality and disruptions were also assessed using a self-reported questionnaire, such as the Pittsburgh Sleep Quality Index (PSQI). Ashwagandha extracts improved all of these parameters. The ashwagandha product contained root extracts at a dose of  300 mg given twice daily for ten weeks.

Cheah, Norhayati, Husniati Yaacob, & Abdul Rahman propose that this ability to sleep was formerly assumed to be due to ashwagandha’s GABAmimetic action. However, current evidence states the principal physiologically active element that induces sleep is attributed to triethylene glycol (TEG) in water extracts of ashwagandha. TEG promotes sleep by increasing the amount of non-rapid eye movements (NREM) episodes and shortening the waking episode. NREM is the stage of sleep that helps to achieve deep sleep and attains a feeling of restfulness.

Ashwagandha is an adaptogen that relieves stress. Stress is assumed to be channeled through the hypothalamic-pituitary-adrenal (HPA) axis’s dynamic responsiveness, resulting in increased cortisol released by the adrenal cortex in reaction to stressors. Ashwagandha modulates this activity and regulates the production of cortisol. Gopukumar, Thanawala, Somepalli, Rao, Thamatam, & Chauhan proves this in their study where ashwagandha root extract in a sustained-release capsule of 300 mg reduced stress after administering it for 90 days.

 

Ashwagandha And Depression Content Image 3

 

Do Anti-Depressants Really Work For Calming Anxiety, Insomnia, And Stress?

The anti-depressants in the class of SSRIs, designed to treat depression, are generally effective for many different types of anxiety disorders. The study by Cassano, Rossi, & Pini stated these drugs are the most frequently prescribed therapy for generalized anxiety disorder (GAD). Drowsiness, side effects, and toxicity have made tricyclic anti-depressants (TCAs) less favorable, despite their usefulness in treating anxiety disorders. Monoamine oxidase inhibitors are also beneficial for anxiety, but their use is limited due to dietary restrictions and adverse effects. Tricyclic anti-depressants and MAOIs treat panic disorder, another type of anxiety disorder. MAOIs are also efficacious for the treatment of social anxiety disorder. For post-traumatic stress disorder, TCAs, MAOIs, and SSRIs are effective. Obsessive-compulsive disorders are also treated with SSRIs. 

Both SSRIs and SNRIs work by affecting chemical messengers or neurotransmitters in the brain, such as serotonin and norepinephrine, which may affect anxiety, mood, sleep, and general well-being. The provider starts with the lowest dosage for therapeutic effect and gradually increases it. It also takes about 2 to 6 weeks for these SSRIs to reduce anxiety symptoms. If an SSRI is helpful, it is suggested to continue taking it for another 6 to 12 months before gradually lowering the dose. However, according to the limited evidence available, most patients (90%) relapse when effective medication is discontinued. As a result, the current practice is to continue successful pharmacotherapy for at least 1 to 2 years, if not indefinitely.

On the other hand, anti-depressants are frequently given for insomnia. Anti-depressants are not approved for use in insomnia, and there is a lack of evidence for this. If not contraindicated, the American Academy of Sleep Medicine suggests adding a low-dose, sedating anti-depressant to treat individuals with depression and accompanying insomnia. This is a two-edged sword. In the long run, all anti-depressants with clinical efficacy promote sleep due to improved mood and activity during the day. However, some types may disrupt sleep in the short term due to their stimulating effects.

In stress, anti-depressants inhibit the hormonal stress response system, allowing cortisol levels to return to normal. As a result, they rescue the brain cells from the effects of too much stress. Anti-depressants help with the treatment of current depression and the prevention of future depression due to stress.

How Do Anti-Depressants Function In The Brain?

Because the brain is the center of emotional experiences and regulation, it’s no surprise that anti-depressants work there. The widely held belief is anti-depressants work by restoring the activity of endogenous chemicals that mediate brain function (known as “neurotransmitters” or chemical messengers) that are reduced in activity during depressive disorders. As a result, restoring neurotransmitter activity has many positive side effects that help the brain cope with stress and deal with challenging emotional situations. First, they restore balance in understanding and recalling experiences. In depression, there is a tendency to perceive and remember events that occur to us as more destructive than they are. Second, they help depressed persons deal with stress by regulating the HPA axis and avoiding excess cortisol levels, which could damage the brain, leading to a vicious cycle ending in brain atrophy or loss of function. Third, they also work by increasing neurogenesis, the process of producing new and healthy brain cells. 

What Are The Other Alternatives Aside From Anti-Depressants?

  • Cognitive Behavioral Therapy 
  • Counseling
  • Interpersonal therapies
  • Electric shock treatment
  • Self-help groups
  • Natural anti-depressants (SAM-e, St John’s wort, Lavender, 5-Dehydroepiandrosterone, 5-hydroxytryptophan, Omega 3 Fatty acids)
  • Some herbal medicines (saffron, ginseng, chamomile)

The proper diagnosis of depression is crucial before starting anti-depressants. Some show positive effects to anti-depressants, but no one-size-fits-all drug can cure all depressive symptoms. According to Informed Health.org, 40%–60% of those who take prescription anti-depressants see improvement in their symptoms within 6–8 weeks, compared to only 20%–40% of those who don’t. Because anti-depressant effects vary in different persons, these alternative treatments may be useful. It is best to contact a health care provider for correct diagnosis and treatment. 

References:

  1. Liu, L., Liu, C., Wang, Y., Wang, P., Li, Y., & Li, B. (2015). Herbal Medicine for Anxiety, Depression and Insomnia. Current Neuropharmacology, 13(4), 481-493. doi: 10.2174/1570159×1304150831122734
  2. Table 9, DSM-IV to DSM-5 Major Depressive Episode/Disorder Comparison – DSM-5 Changes – NCBI Bookshelf. (2022). Retrieved 17 February 2022, from https://www.ncbi.nlm.nih.gov/books/NBK519712/table/ch3.t5/
  3. Belmaker, R., & Agam, G. (2008). Major Depressive Disorder. New England Journal Of Medicine, 358(1), 55-68. doi: 10.1056/nejmra073096
  4. Chandrasekhar, K., Kapoor, J., & Anishetty, S. (2012). A Prospective, Randomized Double-Blind, Placebo-Controlled Study of Safety and Efficacy of a High-Concentration Full-Spectrum Extract of Ashwagandha Root in Reducing Stress and Anxiety in Adults. Indian Journal Of Psychological Medicine, 34(3), 255-262. doi: 10.4103/0253-7176.106022
  5. Murray, C., & Lopez, A. (1997). Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study. The Lancet, 349(9064), 1498-1504. doi: 10.1016/s0140-6736(96)07492-2
  6. Zahiruddin, S., Basist, P., Parveen, A., Parveen, R., Khan, W., Gaurav, & Ahmad, S. (2020). Ashwagandha in brain disorders: A review of recent developments. Journal Of Ethnopharmacology, 257, 112876. doi: 10.1016/j.jep.2020.112876
  7. Lopresti, A., Smith, S., Malvi, H., & Kodgule, R. (2019). An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract. Medicine, 98(37), e17186. doi: 10.1097/md.0000000000017186
  8. Manjunath, M., & Muralidhara. (2013). Standardized extract of Withania somnifera (Ashwagandha) markedly offsets rotenone-induced locomotor deficits, oxidative impairments and neurotoxicity in Drosophila melanogaster. Journal Of Food Science And Technology, 52(4), 1971-1981. doi: 10.1007/s13197-013-1219-0
  9. Millan, Mark. (2004). The role of monoamines in the actions of established and “novel” antidepressant agents: A critical review. European journal of pharmacology. 500. 371-84. 10.1016/j.ejphar.2004.07.038. 
  10. Mukherjee, P., Banerjee, S., Biswas, S., Das, B., Kar, A., & Katiyar, C. (2021). Withania somnifera (L.) Dunal – Modern perspectives of an ancient Rasayana from Ayurveda. Journal Of Ethnopharmacology, 264, 113157. doi: 10.1016/j.jep.2020.113157
  11. Bhattacharya, S., Bhattacharya, A., Sairam, K., & Ghosal, S. (2000). Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: an experimental study. Phytomedicine, 7(6), 463-469. doi: 10.1016/s0944-7113(00)80030-6
  12. Luscher, B., Shen, Q., & Sahir, N. (2010). The GABAergic deficit hypothesis of major depressive disorder. Molecular Psychiatry, 16(4), 383-406. doi: 10.1038/mp.2010.120
  13. Delgado, P. (2000). Depression: the case for a monoamine deficiency. The Journal Of Clinical Psychiatry, 61 Suppl 6. Retrieved from https://pubmed.ncbi.nlm.nih.gov/10775018/
  14. Suganya, K. (2020). Effect of Withania Somnifera on the antioxidant and neurotransmitter status in sleep deprivation induced Wistar rats. Bioinformation, 16(8), 631-637. doi: 10.6026/97320630016631
  15. Salve, J., Pate, S., Debnath, K., & Langade, D. (2019). Adaptogenic and Anxiolytic Effects of Ashwagandha Root Extract in Healthy Adults: A Double-blind, Randomized, Placebo-controlled Clinical Study. Cureus. doi: 10.7759/cureus.6466
  16. Langade, D., Kanchi, S., Salve, J., Debnath, K., & Ambegaokar, D. (2019). Efficacy and Safety of Ashwagandha (Withania somnifera) Root Extract in Insomnia and Anxiety: A Double-blind, Randomized, Placebo-controlled Study. Cureus. doi: 10.7759/cureus.579
  17. Konar, A., Shah, N., Singh, R., Saxena, N., Kaul, S., Wadhwa, R., & Thakur, M. (2011). Protective Role of Ashwagandha Leaf Extract and Its Component Withanone on Scopolamine-Induced Changes in the Brain and Brain-Derived Cells. Plos ONE, 6(11), e27265. doi: 10.1371/journal.pone.0027265
  18. Fogaça, M., & Duman, R. (2019). Cortical GABAergic Dysfunction in Stress and Depression: New Insights for Therapeutic Interventions. Frontiers In Cellular Neuroscience, 13. doi: 10.3389/fncel.2019.00087
  19. Candelario, M., Cuellar, E., Reyes-Ruiz, J., Darabedian, N., Feimeng, Z., & Miledi, R. et al. (2015). Direct evidence for GABAergic activity of Withania somnifera on mammalian ionotropic GABAA and GABAρ receptors. Journal Of Ethnopharmacology, 171, 264-272. doi: 10.1016/j.jep.2015.05.058
  20. Fuladi, S., Emami, S., Mohammadpour, A., Karimani, A., Manteghi, A., & Sahebkar, A. (2021). Assessment of the Efficacy of Withania somnifera Root Extract in Patients with Generalized Anxiety Disorder: A Randomized Double-blind Placebo- Controlled Trial. Current Reviews In Clinical And Experimental Pharmacology, 16(2), 191-196. doi: 10.2174/1574884715666200413120413
  21. Khushboo, S. (2017). Antidepressants: Mechanism of Action, Toxicity and Possible Amelioration. Journal Of Applied Biotechnology & Bioengineering, 3(5). doi: 10.15406/jabb.2017.03.00082
  22. Sheffler, Z., & Abdijadid, S. (2021). Antidepressants. Statpearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK538182/
  23. Informed Health.org. (2020). Depression: How effective are antidepressants?. Institute For Quality And Efficiency In Health Care (Iqwig). Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK361016/
  24. Goldberg, S., Tilley, D., Friedel, R., Hamer, R., Ban, T., Brockett, C., Bale, P., & Stephens, V. (1988). Who benefits from tricyclic antidepressants: a survey. The Journal Of Clinical Psychiatry, 49(6). Retrieved from https://pubmed.ncbi.nlm.nih.gov/3379027/
  25. Wimbiscus, M., Kostenko, O., & Malone, D. (2010). MAO inhibitors: Risks, benefits, and lore. Cleveland Clinic Journal Of Medicine, 77(12), 859-882. doi: 10.3949/ccjm.77a.09103
  26. Sullivan, M., & Evans, E. (2014). Abuse and misuse of antidepressants. Substance Abuse And Rehabilitation, 107. doi: 10.2147/sar.s37917
  27. Pratte, M., Nanavati, K., Young, V., & Morley, C. (2014). An Alternative Treatment for Anxiety: A Systematic Review of Human Trial Results Reported for the Ayurvedic Herb Ashwagandha (Withania somnifera). The Journal Of Alternative And Complementary Medicine, 20(12), 901-908. doi: 10.1089/acm.2014.0177
  28. Dutta, R., Khalil, R., Green, R., Mohapatra, S., & Mohapatra, S. (2019). Withania Somnifera (Ashwagandha) and Withaferin A: Potential in Integrative Oncology. International Journal Of Molecular Sciences, 20(21), 5310. doi: 10.3390/ijms20215310
  29. Andrade, C., Aswath, A., Chaturvedi, S., Srinivasa, M., & Raguram, R. (2000). A double-blind, placebo-controlled evaluation of the anxiolytic efficacy ff an ethanolic extract of withania somnifera. Indian Journal Of Psychiatry, 42(3). Retrieved from https://pubmed.ncbi.nlm.nih.gov/21407960/
  30. Auddy, B., Hazra, J., & Mitra, A. (2022). A Standardized Withania Somnifera Extract Significantly Reduces Stress-Related Parameters in Chronically Stressed Humans: A Double-Blind, Randomized, Placebo-Controlled Study. Retrieved 18 February 2022, from https://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.324.8921
  31. Cooley, K., Szczurko, O., Perri, D., Mills, E., Bernhardt, B., Zhou, Q., & Seely, D. (2009). Naturopathic Care for Anxiety: A Randomized Controlled Trial ISRCTN78958974. Plos ONE, 4(8), e6628. doi: 10.1371/journal.pone.0006628
  32. Mao, Q., Ip, S., Xian, Y., Hu, Z., & Che, C. (2011). Anti-depressant-like effect of peony: a mini-review. Pharmaceutical Biology, 50(1), 72-77. doi: 10.3109/13880209.2011.602696
  33. Lee, S., & Rhee, D. (2017). Effects of ginseng on stress-related depression, anxiety, and the hypothalamic–pituitary–adrenal axis. Journal Of Ginseng Research, 41(4), 589-594. doi: 10.1016/j.jgr.2017.01.010
  34. Dong, Y., Tao, B., Xue, X., Feng, C., Ren, Y., & Ma, H. et al. (2021). Molecular mechanism of Epicedium treatment for depression based on network pharmacology and molecular docking technology. BMC Complementary Medicine And Therapies, 21(1). doi: 10.1186/s12906-021-03389-w
  35. Lee, H., Ko, H., Huang, B., Chu, Y., & Huang, S. (2014). Antidepressant-like effects of Perilla frutescens seed oil during a forced swimming test. Food & Function, 5(5), 990. doi: 10.1039/c3fo60717h
  36. Ren, L., & Chen, G. (2017). Rapid antidepressant effects of Yueju: A new look at the function and mechanism of an old herbal medicine. Journal Of Ethnopharmacology, 203, 226-232. doi: 10.1016/j.jep.2017.03.042
  37. Craft, L., & Perna, F. (2004). The Benefits of Exercise for the Clinically Depressed. The Primary Care Companion To The Journal Of Clinical Psychiatry, 06(03), 104-111. doi: 10.4088/pcc.v06n0301
  38. Coppen, A., & Bolander-Gouaille, C. (2005). Treatment of depression: time to consider folic acid and vitamin B12. Journal Of Psychopharmacology, 19(1), 59-65. doi: 10.1177/0269881105048899
  39. Prabu, P., Panchapakesan, S., & Raj, C. (2012). Acute and Sub-Acute Oral Toxicity Assessment of the Hydroalcoholic Extract of Withania somnifera Roots in Wistar Rats. Phytotherapy Research, 27(8), 1169-1178. doi: 10.1002/ptr.4854
  40. Ashwagandha. (2019). National Institute Of Diabetes And Digestive And Kidney Diseases. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK548536/
  41. Verma, N., Gupta, S., Tiwari, S., & Mishra, A. (2021). Safety of Ashwagandha Root Extract: A Randomized, Placebo-Controlled, study in Healthy Volunteers. Complementary Therapies In Medicine, 57, 102642. doi: 10.1016/j.ctim.2020.102642
  42. Cheah, K., Norhayati, M., Husniati Yaacob, L., & Abdul Rahman, R. (2021). Effect of Ashwagandha (Withania somnifera) extract on sleep: A systematic review and meta-analysis. PLOS ONE, 16(9), e0257843. doi: 10.1371/journal.pone.0257843
  43. Gopukumar, K., Thanawala, S., Somepalli, V., Rao, T., Thamatam, V., & Chauhan, S. (2021). Efficacy and Safety of Ashwagandha Root Extract on Cognitive Functions in Healthy, Stressed Adults: A Randomized, Double-Blind, Placebo-Controlled Study. Evidence-Based Complementary And Alternative Medicine, 2021, 1-10. doi: 10.1155/2021/8254344
  44. Cassano, G., Rossi, N., &  Pini, S. Psychopharmacology of anxiety disorders. (2002). Cerebral Aging, 4(3), 271-285. doi: 10.31887/dcns.2002.4.3/gcassano
  45. Clark, M., Smith, P., & Jamieson, B. (2011). Antidepressants for the Treatment of Insomnia in Patients with Depression. American Family Physician, 84(9), 1. Retrieved from https://www.aafp.org/afp/2011/1101/od1.html
  46. Wichniak, A., Wierzbicka, A., Walęcka, M., & Jernajczyk, W. (2017). Effects of Antidepressants on Sleep. Current Psychiatry Reports, 19(9). doi: 10.1007/s11920-017-0816-4

 

Leave a Comment

Your email address will not be published. Required fields are marked *

Scroll to Top