Today we will talk about an adaptogen, ashwaganda.
We will also focus on how it could help us with stress management, anxiety and memory.

The origin in Ayurvedic medicine

Ashwagandha is a compound word from the Sanskrit language; Ashwa means horse and Gandha means smell.
According to some sources, a first meaning would explain the characteristic horse smell of the plant, while a second would interpret it as a substance capable of reproducing the strength of a horse.

Withania somnifera, such is the scientific name for ashwaganda, is commonly used in Ayurveda and other types of traditional Eastern medicine.
This plant has seen a global increase in use due to its reputation as an adaptogen.
This popularity has sparked further scientific study of its biological effects, including a possible application for neuropsychiatric and neurodegenerative disorders.

Ashwaganda belongs to the nightshade family, is widely known and enjoys a formidable reputation in Ayurvedic medicine as a rasayana herb, that is, it has properties capable of rejuvenating the body and promoting the health of all tissues.
By classifying it as an adaptogen, we mean that it would behave as an agent that promotes homeostasis throughout the body not only through a specific pharmacological mechanism, but also by provoking other types of more complex responses. Recognized properties include the ability to improve concentration, memory, and mood, as well as providing resistance against some pathogens and certain diseases.

Stress management

The widespread and growing use of ashwaganda by the general public highlights the need for a greater understanding of its biological properties and active ingredients in order to validate and optimize its use.
Fortunately, it is one of the most studied medicinal herbs.
A review of around 140 reported compounds from the plant was conducted in 2021.
Among them, the most well-known are a complex group of steroid lactones known as withanolides, which also occur as glycosides (withanosides).
More than 70 individual withanolide derivatives have been reported in ashwaganda leaves and roots, with higher levels in the leaves than in the roots.

The study also determined that it contains four sitoindosides of which sitoindosides IX and X are glycosylated derivatives of withanolide, withaferin A, while sitoindosides VII and VIII are long-chain acylsterylglycosides.
Multiple alkaloids, phenolic compounds, and organic acids have also been reported in ashwaganda.
Withanolide derivatives are the most common group that has been examined individually for biological activities.
In fact, some withanolides contain electrophilic sites that confer reactivity to the thiol group, which may play an important role in mediating biological activity associated with antioxidant activity and/or target other electrophilic sensors that modulate transcriptional or post-transcriptional responses.
DOI: 10.1016/j.jep.2020.113469

According to a systematic review that included 12 articles with a total sample of 1002 participants and an age range between 25 and 48 years, it was found that supplementation with ashwaganda significantly reduced anxiety and stress level compared to placebo.
In addition, dose-response analysis indicated a favorable effect of plant supplementation on anxiety at doses up to 12,000 mg/day and stress at doses of 300 to 600 mg/day.
https://doi.org/10.1002/ptr.7598

Another study attempted to determine the effects on stress and some stress-related neuropsychiatric disorders: anxiety, depression, and insomnia. Ashwaganda root and leaf extracts exhibited remarkable anti-stress and anxiolytic activity in animal and human studies.
Symptoms of depression and insomnia also improved. Ashwaganda was able to alleviate these conditions predominantly by modulating the hypothalamic-pituitary-adrenal and sympathetic-adrenal medullary axes, as well as through the gabaergic and serotonergic pathways.
While some studies link specific components of withanolide to its neuropsychiatric benefits, there is evidence of the presence of additional active compounds not yet identified in the plant.
DOI: 10.2174/1570159X19666210712151556

Six human studies evaluated the use of ashwaganda for anti-stress activity in adults aged 18 to 75 years.
Study populations included healthy, stressed, overweight, or obese participants.
They experienced chronic work stress, had a diagnosis of anxiety and/or schizophrenia and/or schizoaffective disorder.
The number of participants in each study ranged from 52 to 130 participants.
Each study administered the plant in extract form, through capsules.
All presentations were commercial preparations.
The daily dose of extract ranged from 240 mg to 1000 mg, and two of the studies used more than one dose in the intervention group.
The treatment period was variable, with three studies lasting 8.5 weeks, two lasting 8 weeks, and one lasting 12 weeks.
Stress was assessed using serum cortisol levels and three questionnaires: the Stress, Anxiety and Depression Scale, the Perceived Stress Scale and a General Health Questionnaire. Ashwaganda supplementation improved stress markers and symptoms in most trials, as well as decreased serum cortisol levels compared to placebo. DOI: 10.4103/0253-7176.106022

Reduced anxiety

Anxiolytic effects were observed for ashwaganda root extracts, leaf extracts, and isolated compounds, including withaferin A and a mixture of sitoindosdos VII-X.
Extracts produced from the leaves or roots and with various solvents (water, ethanol, methanol, hydroalcoholic), solvent ratios, and different extraction methods produced anxiolytic effects, suggesting the possibility of multiple bioactive compounds.

In addition, the extracts enhanced the effects of well-known anxiolytics.
A subtherapeutic dose of the root extract potentiated the anxiolytic effect of a subtherapeutic dose of diazepam in a rat model of social isolation.
In a model of alcohol withdrawal also observed in rats, a subtherapeutic dose of an ethanolic root extract of ashwaganda potentiated the anxiolytic action of a subtherapeutic dose of ethanol.
Of note, in a mouse model of obsessive-compulsive disorder, a subtherapeutic dose of aqueous and methanolic root extract potentiated the inhibitory action of the disorder exerted by fluoxetine.
DOI: 10.2174/1570159X19666210712151556

In humans, the anxiolytic effect of ashwaganda was evaluated in ten trials in adults aged 18 to 75 years.
The study populations included participants described as healthy, stressed, diagnosed with general anxiety disorder or a related condition, with insomnia, or with schizophrenia or schizoaffective disorder.
Sample sizes ranged from 39 participants to 130 participants, and most studies included between 60 and 80 participants.
All studies administered ashwaganda in capsule or tablet form, except one, in which dried root granules were used.
Daily doses were variable, ranging from 125 to 1000 mg in studies using capsules or tablets and up to 12 g in the form of dried root granules. An improvement in anxiety was observed in most studies after ashwaganda supplementation, as measured by changes in anxiety scores.
DOI: 10.7759/cureus.6466

In another study of adults who reported a high level of stress, daily administration of 240 mg for 60 days was found to significantly decrease Hamilton scale scores compared to placebo.
In those with general anxiety disorder, administration of 12 g of a dry root preparation from or placebo was found to decrease all measured anxiety scores from baseline.
DOI: 10.1097/MD.00000000000017186

How does Ashwaganda work?

GABA is the most important inhibitory neurotransmitter of the central nervous system and GABAergic neurotransmission is thought to play a key role in the regulation of anxiety.
GABA-A receptors are the main site of action of GABA agonist drugs, which stimulate GABAergic activity and are commonly used in the treatment of anxiety disorders.
There is substantial evidence to suggest that compounds found in ashwaganda interact with and modulate these receptors, which may partly explain its anxiolytic effect.

In 1991, a group of researchers demonstrated for the first time evidence of ashwaganda’s direct mimetic activity on the receptors mentioned above.
There, a methanolic extract of the root was found to increase the entry of chloride ions into mammalian spinal cord neurons in the absence of GABA and also inhibit GABA binding in a manner similar to GABA-A receptor agonists.
Receptor-binding assays have shown that components of ashwaganda methanolic root extracts show a high affinity for GABA-A receptors, with a significantly lower affinity for GABA-B, glutamatergic, and opioid receptors.
DOI: 10.1016/j.phymed.2013.10.021

The stimulating actions of morphine and ethanol on dopaminergic neurons of the ventral tegmental area in rats were suppressed by a methanolic root extract of the plant through a mechanism mediated by GABA-A, but not mediated by GABA-B.
On the other hand, attempts to identify which specific ashwaganda compound is responsible for its activity in the GABA-A receptor have been unsuccessful so far.

Is Ashwaganda safe to use?

The widespread use of ashwaganda as a traditional medicine and dietary supplement, as well as the current scientific literature, supports its overall safety. In a review of clinical trials using plant root preparations for a wide variety of conditions, one research group noted that good safety outcomes were observed with no serious adverse events or changes in vital signs, hematologic or biochemical parameters.

Some studies reported mild to moderate transient adverse events such as drowsiness, dizziness, and vertigo, while other studies involving adults and children reported no adverse events.
Similarly, a 2012 review reported that ashwaganda has been used in all age groups and in both sexes, including during pregnancy, with no side effects reported. https://doi.org/10.1007/s11101-011-9221-5

Another study formally measured the tolerance of a root extract using the patient’s global assessment of tolerance to therapy and found that it had a high score.
DOI: 10.7759/cureus.7083

Ashwaganda extracts have also been shown to be safe in animal toxicity studies.
The acute and subacute toxicity of a hydroalcoholic root extract was investigated in female rats and no signs of behavioural toxicity or serious pathological changes were observed at acute doses up to 2000 mg/kg.
Similarly, no signs of subacute toxicity were observed in rats that received 500, 1000, or 2000 mg/kg of the extract daily for 28 days.
Still, and despite all the evidence, more studies are needed to examine the safety of extracts using other extraction methods and plant parts.

While these studies suggest that the plant under study does not cause significant toxicity, the possibility of adverse events stemming from interactions between some herbs and drugs should be considered.
DOI: 10.1016/j.pbj.00000000000000015

This is because there may be pharmacodynamic interactions between ashwaganda and some groups of drugs, as evidenced by the additive effects observed in studies with rodents treated with imipramine, diazepam, and fluoxetine.
The gabamimetic and serotonergic activities observed with the extracts in rodents would suggest caution when co-administering it with drugs that work through similar mechanisms.
Pharmacokinetic interactions can also occur when the activity of enzymes that metabolize some drugs is altered.
Several ashwaganda root extracts had high reactive values for the CYP3A4, CYP2D6, CYP1A2, and CYP2C9 isoenzymes of cytochrome P450 in human liver microsomes.
DOI: 10.1016/j.cbi.2019.108825

Active Sweet Dreams by Salengei

Active Sweet Dreams contains in its formula some plants of traditional use such as valerian, hops, passionflower and lemon balm, recognized for their anxiolytic properties.
This formulation is completed by rhodiola and ashwaganda extracts (KSM-66), which promote relaxation.
In turn, minerals such as magnesium, zinc, and vitamin B6 are added, which are necessary for the normal functioning of the nervous system.

Ashwaganda KSM66 is a full-spectrum brand extract with the highest concentration available on the market today.
It is produced using a unique proprietary extraction process, based on the principles of “Green Chemistry”, without using alcohol or any other chemical solvents.
KSM-66 uses only the roots of the ashwaganda plant with absolutely no leaf addition.

Conclusion

Since time immemorial, ashwaganda has been used as a tonic in Ayurvedic medicine.
Today, with many studies in favor, its high power in the treatment of anxiety, stress and in improving memory has been demonstrated.