Ashwagandha as a Nootropic – Experiment Begins

Ashwagandha, the 'Indian ginseng', shares some of the properties of Korean ginseng. (Photo by bartpogoda)

Ashwagandha is one of the plants used in Ayurvedic medicine. Also known as Indian ginseng, the scientific name of this nightshade family member is Withania somnifera. The latter part of the name means "sleep-inducing" in Latin, suggesting that the plant is used for its relaxing properties.

Ashwagandha is also said to be an adaptogen – a herb that increases the body's resistance to stress, anxiety and fatique by "normalizing" its functions. Before you dismiss the whole thing as new age garbage, let me point out that unlike some other Ayurvedic herbs, this one has been studied quite extensively. A pubmed search on 'ashwagandha' gives about 360 results.

Having browsed through the entire list, it appears that ashwagandha has a variety of effects on health. In this post, however, I will concentrate on the nootropic aspect of the herb. Bear in mind that I'm using the term in a very broad sense here: any paper examining the effect of the herb on cognition, mood, stress-relief, or motivation will be included. We'll save the studies on topics such as immune function for later.

The effect of ashwagandha on mood and libido

GABA, which is short for gamma-Aminobutyric acid, is the chief inhibitory neurotransmitter in mammals. GABA agonists – drugs that stimulate or increase the action at the GABA receptor – usually have a relaxing and stress-relieving effect. Alcohol is one such agonist. At least one paper has shown that ashwagandha contains an ingredient that activates the GABA receptor in a dose-dependent manner (link). Thus, the GABAergic activity may explain why many people report feeling more relaxed after taking ashwagandha.

GABA agonists are sometimes also used to treat psychostimulant addiction. Indeed, in animal models of drug addiction, ashwagandha apparently reduces alcohol intake and morphine tolerance (link). Ashwagandha itself appears to be well-tolerated: a review concluded that it has little or no risk of toxicity (link).

In a study that examined the role of stress in male infertility, 5 grams of ashwagandha root powder was given daily for 3 months to infertile men suffering from psychological stress (link). The treatment resulted in a decrease in stress levels and an increase in the level of antioxidants. At the same time, semen quality improved, which led to pregnancy in 14% of the subjects' partners.

Another study showed similar results, with reduced oxidative stress and improved sperm count and motility in infertile men (link). Testosterone levels increased significantly, while prolactin decreased. This is interesting, because prolactin counteracts the effect of dopamine. Dopamine is responsible for sexual arousal and motivation, while prolactin is thought to cause the sexual refractory period after an orgasm. High levels of prolactin cause impotence and loss of libido. The increase in testosterone and decrease in prolactin may therefore explain some of the claimed positive effects of ashwagandha on motivation and libido.

Some of the evidence on ashwagandha and libido is contradictory, however. When male rats were given 3,000 mg/kg of the root extract for 7 days, a marked impairment in libido, sexual performance, sexual vigour and penile function was seen (link). The authors state that since no change in testosterone levels was seen, the negative effects may be due to an increase in prolactin levels or the activity of GABA and serotonin. The increase in prolactin is interesting because it's opposite to what was seen in the study on humans. Note, however, that the dose used here was much higher than in the other rodent studies – perhaps the dose-response curve is U-shaped and more is not necessarily better.

Ashwagandha, stress and memory function

In mice, ashwagandha improves retention of a passive avoidance task (link). In this task, the mouse learns to refrain from stepping through a door to an apparently safer but previously punished compartment, which allows their memory to be assessed. The dosages used were 50, 100 and 200 mg/kg orally. The treatment also reversed the negative effects of scopolamine and electroconvulsive shocks on memory. Furthermore, mice and rats seem to do better on a forced swimming test when treated with ashwagandha (link, link).

Korean red ginseng, also known as Panax ginseng, is also called an adaptogen and shown to be helpful in treating stress. In a study comparing the two, both Panax ginseng and ashwagandha alleviated stress-related conditions such as sexual dysfunction, cognitive deficits and depression in mice subjected to footshocks (link). Ashwagandha was given orally in a dose of 25 or 50 mg/kg and was apparently more effective than Panax ginseng.

Acetylcholinesterase (AChE) is an enzyme that degrades the neurotransmitter acetylcholine, which is a facilitator of memory formation. AChE inhibitors increase the availability of acetylcholine, presumably leading to an improvement in memory. They can be extremely harmful in high doses: AChE inhibitors occur in natural venoms and poisons and are also used in nerve gases. However, AChE inhibitors are also used for medicinal purposes, for example to treat Alzheimer's disease. Huperzine A and galantamine, which are used for memory support and as nootropics, inhibit acetylcholinesterase. Ashwagandha appears to be an AChE inhibitor as well, with methanol extracts being more potent than water extracts (link).

In memory-deficient mice with neuronal atrophy and synaptic loss in the brain, withanolide A – an extract of ashwagandha – induced significant regeneration of nerve fibers and dendrites, as well as a reconstruction of pre- and postsynapses in the neurons (link). Treatment with the extract resulted in a reversal of the memory deficit. Two other extracts, withanoside IV and withanoside VI, appear to have similar effects (link). Ashwagandha or its extracts could thus be used to reconstruct neuronal networks.

Methanol extracts and withanolides are not the only useful part of ashwagandha, however. One study showed that even a withanolide-free water extract of ashwagandha roots had significant antistress activity (link).

Conclusion & my self-experiment

The evidence supports the claims that ashwagandha is an adaptogen and a nootropic. While there are no studies showing that ashwagandha improves mood per se, it does have a range of benefits.

The relaxing and anti-stress effect can be at least partly attributed to the fact that ashwagandha acts as a GABA agonist. It also improves stress-related memory problems by acting as a AChE inhibitor, and has the ability to prevent cognitive degeneration and even reconstruct neuronal networks.

Ashwagandha also seems to correct hormonal imbalances and reduced libido in men by increasing testosterone and decreasing prolactin. Very high doses may have the opposite effect, however.

For the purposes of my own human experiment, I have a bottle of NOW Foods' Ashwagandha extract. The bottle contains 90 capsules with 450 mg of root extract standardized to a minimum of 4.5% total withanolides. Once again, the measuring stick will be my own subjective evaluation of my mood, stress level and libido. Stay tuned for a conclusion of the experiment once I've finished the bottle.

Meanwhile, if you've tried ashwagandha, feel free to drop a comment about your experience. For more information on cognition, stress, mood and libido, see these posts:

Nootropic Battle Conclusion: Acetyl-L-Carnitine vs. Ginkgo Biloba vs. Taurine
Green Tea Protects from the Psychological Effects of Stress in Rats
The Effect of Maca Root on Energy and Libido – Experiment Conclusion
Caloric Restriction Improves Memory in the Elderly