Ashwagandha or withania somnifera is a plant from the nightshade family that has a wide range of health benefits. 

As an adaptogen, ashwagandha is able to prevent and even reverse the physical effects of stress on the body.

It is a popular herb in Aryuvedic medicine where it is taken to reduce fatigue and increase endurance.

Recent evidence has revealed that ashwagandha elicits these effects at least partially by reducing the stress hormone cortisol, and also immunosuppression.

As a nootropic, ashwaganda is mostly used for its anti-anxiety effects, which seem to be considerably effective along with some additional sleep promoting and antidepressant effects.

Contents

Ashwagandha Root Infographic
Biochemical Composition

Neurological Mechanisms

          GABAergic Mechanisms

          Dopaminergic Mechanisms

          Serotonergic Mechanisms

          Cholinergic Mechanisms

          Melatonergic Mechanisms

How to Take

          Standardisation

          Ashwagandha Root Dosage

          Synergistic Compounds

Conclusion

 Biochemical Composition

There are a large number of compounds present in ashwagandha, and slightly different compounds in the plant as compared to the root. There are two main classes of compounds in the roots, which are:

Alkaloids (tropine and cuscohygdrine)

Steroidal lactones / withanolides (withaferin A, withanone, withanolide A, withanoside IV and sominone)

Neurological Mechanisms

Neuroprotection

The steroidal lactones in ashwagandha appear to enhance antioxidant enzymes in the frontal cortex and striatum following oral ingestion. [R]

Ashwagandha also has neuroprotective effect relating to serotonin receptors as described in the section of serotonergic mechanisms.

GABAergic Mechanisms

Ashwagandha root extracts appear to enhance the signalling of GABAA receptors considerably (as a positive allosteric modulator), but this effect is more pronounced in the presence of another GABAA agonist. [R]

These effects appear to be due to the steroidal lactones, particularly withaferin A and withanoside IV.

This mechanism is what mediates the anti-anxiety and sleep enhancing properties of ashwagandha. 

Dopaminergic Mechanisms

Ashwagandha root extracts do not possess any significant dopaminergic effects.

Serotonergic Mechanicisms

Ashwagandha appears to re-partition serotonin signalling away from the 5-HT1A receptor to the 5-HT2 receptor. [R]

This effect does not seem to elicit an antidepressant effect, but is responsible for some of ashwagandha's neuroprotective effects. This is because activation of the 5-HT2 receptor inhibits the production of nitric oxide, which in turn inhibits the production of the hormone corticosterone and this can reduce memory loss.

Cholinergic Mechanisms

Withanolide A appears to be able to increase acetylcholine concentrations via inhibition of acetylcholinesterase. However, this effect is rather weak and is probably not relevant to oral supplementation.

Furthermore, ashwagandha root extracts appear have modality as positive modulators at the M1 and M2 receptors, but again, these effects are probably not relevant to oral supplementation, though more research is still required.

Neurogenesis

Withanolide A, withanoside IV and sominone (and likely some other isolates) appear to be able to increase neurogenesis at a level relevant to oral supplementation. This appears to be through at least two mechanisms.

First, the neuroprotective effects of ashwagandha root seem to prevent neurotoxins from suppressing neurogenesis. [R]

Particularly, sominone appears to enhance neuron growth, including the axonal length of neurons and dendrites, by directly stimulating a neurological growth factor target called the RET receptor. [R]

Second, ashwagandha has been found to be able to increase brain-derived neurotrophic factor (BDNF) to 130% of control levels within one week. [R]

How to Take

Standardisation

Ashwagandha root extracts should be standardised to contain 5% withanolides (steroidal lactones) and 2% alkaloids.

This is usually a 10:1 root extract, rather than a leaf extract, where 10 kg of raw ashwagandha root gives 1 kg of the concentrated extract.

Ashwagandha root extract should be taken with a small meal, preferably at breakfast.

Ashwagandha Root Dosage

When using for anxiety, 300mg taken 2 to 3 times a day seems to be sufficient.

As an adaptogen and for anti-stress purposes, doses up to 2,000mg taken 2 to 3 times seem to be optimal.

Synergistic Compounds

As a positive GABAA modulator, ashwagandha root is synergistic with GABAA agonists. 

In regards to supplementation, this is relevant to Chinese skullcap (scutellaria baicalensis).

For neuroprotective effects, ashwagandha root is synergistic with curcumin.

If you want to find more supplements similar to valerian root extract, you can read this article on the best supplements for anxiety.