Ashwagandha Withanolides: Uses, Side Effects, and Contraindications

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Ashwagandha, or Withania somnifera is an evergreen shrub that grows in hot, dry climates.  This herb is very popular in India and the Middle East.  The shrub produces small greenish-yellow flowers as well as fleshy fruit which is orange-red when ripe.  Ashwagandha is sometimes called “winter cherry”.

Ashwaghanda has been utilized in Ayurvedic medicine.  This “whole-body” healing system was developed in India more than 3000 years ago.  It is used as a Rasayana which is an herbal or metallic substance that increases happiness and helps promote a youthful mental and physical condition.  Withania is the most prominent ayurvedic Rasayana herb and is given to small children as well as middle-aged and elderly in hopes of increasing longevity. Ashwagandha supplements are most commonly recommended for energy enhancement and to boost exercise performance. 1

Withania somnifera contains a group of pharmaceutically active steroidal lactones known as withanolides.  These withanolides are believed to have many positive medical effects including antimicrobial, anti-inflammatory and anti-cancer properties. 2

The word ashwagandha translates to “smells like a horse”.   It not only smells like a horse but is also thought to give those who ingest it the power of a horse.  Ashwagandha is also known as Indian ginseng, even though it is generally used for its calming and anti-stress properties whereas ginseng supports energy and stamina. 3

Ashwagandha and Cognition

Cognition is a complicated process and is performed by our brain.  It includes thinking, communicating, problem solving, memory, judgement, processing information from our senses and more.   It is not surprising that many are interested in obtaining substances which improve cognition.  These substances are known as nootropics.  As we get older, our cognition tends to decline.  A study by Sing-Manoux found this decline often begins between 45 and 55 years of age. 4

A double-blind, placebo-controlled study was performed on a group of subjects with mild cognitive impairment (MCI).  This is a state between normal cognitive aging and dementia.  These people have memory deficits but not to the extent that activities of daily living are adversely affected.  A total of fifty adults were randomized to receive either 300 mg Ashwagandha root extract in capsule form, twice daily, for eight weeks or a placebo. 

The researchers concluded that “Ashwagandha (Withania somnifera) may be useful in enhancing immediate and general memory, executive function, attention, and information processing speed in people with MCI, with few adverse effects.” 5

The Anxiety Formula available in our Sunshine Store contains Ashwagandha.  This is a supplement I consume daily to keep me focused and to clear my mind.  I have had great success with this supplement and have had no adverse effects occurring with its use.  You can order this supplement by clicking the box shown below.

Ashwagandha and Obsessive Compulsive Disorder (OCD)

Obsessive compulsive disorder (OCD) is a mental illness where the patient to suffers from obsessive, intrusive thoughts.  These thoughts may lead the patient to clean continuously or constantly check light switches to be sure they are off, etc.  This disorder can cause distress to the point that it affects daily functioning.   Selective serotonin reuptake inhibitors (SSRIs) are the medications most commonly used for OCD.  Unfortunately, SSRIs are only mildly effective in treating OCD. 6




A study conducted in 2016 showed Ashwagandha was more effective than placebo in improving Y-BOCS scores in patients with a diagnosis of OCD.  Y-BOCS is the standard test for assessing the frequency and severity of OCD symptoms.  Thirty patients were randomized into two groups and Y-BOCS scores were evaluated in both groups at baseline and after six weeks of treatment.  The treatment group received an evaporated root extract of Ashwagandha obtained from Iran.  Each capsule contained either 30mg of root extract and lactose to a total weight of 250mg, or lactose only (placebo).  The treatment group had Y-BOCS scores improve by 8 units, whereas the placebo group only improved by 2 units.  This was a statistically significant difference. 10

Ashwagandha and Blood Sugar Levels in Schizophrenia

I work as a psychiatric pharmacist so I am concerned about the effects of antipsychotic agents on blood sugar.  A small study was published in the Indian Journal of Pharmacology in 2013.  This study was designed to assess the ability of Ashwagandha to decrease blood sugar levels in schizophrenic patients who were receiving second-generation antipsychotic medications.

This study found a significant improvement in both fasting blood glucose and serum triglyceride levels in the Withania group as compared to the placebo group.  More studies with a larger sample size are needed to establish safety and efficacy of this treatment option. 11

Ashwagandha for Pain and Inflammation

Pain relief has become more difficult in the wake of the opiate crisis.  Many physicians are not willing to prescribe opiates for chronic pain due to the recent guidelines which recommend against this practice.  Unfortunately, other drug classes, such as non-steroidal anti-inflammatory agents (NSAIDs), also can be detrimental, especially if taken over an extended period of time.  Pain can be debilitating for some. It can lead to problems sleeping, decreased mood, and reduced work performance.

A study was performed to see what effects a single 1000 mg dose of Withania somnifera would have on mechanical pain.   In this study a device was set up to measure pain threshold as well as pain tolerance force and time.  The researchers found Withania somnifera increased pain threshold and pain tolerance force and time as compared to placebo.  No adverse effects were reported in this study. 12

W. somnifera has also demonstrated analgesic and antipyretic effects in rat models. A study was done comparing Ashwagandha root powder to indomethacin. This study showed the root powder was able to curb the inflammatory response without causing damage to the GI tract of the rats. 13


Ashwagandha for Stress, Anxiety and Cortisol Levels

Ashwagandha is probably most known for its effects as an adaptogen.  These substances (adaptogens) are able to help the body combat physical, chemical, and biological stress.  A study published in 2012 included 64 people who had a history of chronic stress.  These subjects were randomly assigned to two groups.  The treatment group received 300mg Ashwagandha root extract in capsule form twice daily for 60 days.  The other group, placebos.

On day 60, the treatment group displayed a significant reduction in all stress assessment scales relative to the placebo group.   Serum cortisol levels were also substantially reduced in the treatment group.  Cortisol is the body’s main stress hormone.  Increased cortisol levels can be an indication of increased stress. 14

Ashwagandha as a Cancer Treatment

Scientists have been searching for a cure for cancer for many years.  Most of the medications available to treat various cancer types come with a long list of life-changing side effects.  Ashwagandha root extract was first shown to decrease cancer incidence experimentally in vivo in 1967. 15

This has led to an increasing interest in Withania for both cancer treatment as well as prevention.

We know that the carcinogenic process is prolonged.  Is there a way to prevent cancer?  In 1976, the idea of chemoprevention was presented by Michael Sporn. 16

The definition of chemoprevention is the use of natural, synthetic, biological or chemical agents to reverse, suppress, or prevent the process of carcinogenesis.  This has become an increasingly popular area of research.  Natural substances and nutraceuticals are getting a closer look.  Sulforaphane derived from vegetables such as broccoli for prostate cancer and turmeric for colorectal cancer prevention are examples of studies currently under way.

Breast Cancer

A study using mice that were predisposed to developing breast cancer showed a 33% reduction in tumor formation when being fed a diet containing 750mg/kg of Withania root extract for 10 months. 17

Hepatocellular Cancer

Cancer of the liver is aggressive and has a poor response rate to traditional cancer therapies. 18

A study, published in the Journal of International Medical Research in 2018, concluded the water extract of Withania somnifera is a powerful antioxidant and has anticancer effects on HepG2 cells.  They suggest it may be a favorable treatment for hepatocellular carcinoma and should be confirmed in animal studies. 19

There are barriers to using Withania for chemoprotection.  This plant only thrives under specific environmental conditions and is relatively slow growing.  There is also variability in the alkaloids and withanolides produced by each plant, as well as different parts of the plant (leaves vs roots).  This variability requires standardization of the active components of the preparation.  Care must also be taken to not over-utilize fertilizers and pesticides when growing Ashwagandha. 20

Ashwagandha Contraindications

Although Ashwagandha is considered safe for most individuals, there are three groups of people who should avoid it. 

  • Those with hormone-sensitive prostate cancer: Ashwagandha may increase testosterone levels, therefore, it should not be consumed by these patients. 21
  • Those who take benzodiazepines, barbiturates, or anticonvulsants: Ashwagandha may have a sedative effect, as well as effects on GABA, so it should not be used in these patients. 22
  • Pregnant women: Ashwagandha may induce abortion at higher doses. 23

Ashwagandha Side Effects

Ashwagandha has very few side effects when utilized in normal doses.  A study using Sprague-Dawley rats did show some sedation, ptosis and ataxia 15-20 minutes after administering Withania but this was a very large dose 1-2g/kg. 24

Michael Brown pictured with Final Thought written

Ashwaganda is one of the most prized herbs used in Ayurvedic medicine.  This herb contains many substances, including withanolides, which seem to be effective for a wide range of ailments. 

Ashwaganda has been shown to possess chemopreventive as well as chemotherapeutic properties.  Research is being done to assess its use for the prevention and treatment for certain types of cancer.  Ashwagandha has been used for thousands of years in India for its calming and anti-stress effects. 

There is also some evidence to suggest Ashwagandha can improve cognition, help with pain and inflammation and lower blood sugar levels.

This herb may also have a positive effect on certain neurogenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. 25I believe Ashwagandha is a valuable herb which will be more widely utilized as information from clinical trials becomes available.  This herb has few side effects and is well tolerated.  It is one of the ingredients in the Sunshine Sleep Aid as well as our Anxiety Formula, and I also have a single ingredient Ashwagandha product as well.

Please contact me with any questions.  This has been a complex subject to research and there is much more to learn.  It does give me hope for the future of cancer treatment in the United States.  As always, live a happy, healthy life and most of all, stay happy!

Michael Brown in Lab Coat with arms crossed

Michael J. Brown, RPh, BCPS, BCPP

Mr. Brown is a Clinical Pharmacist specializing in pharmacotherapy and psychiatry.

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