The 2022 Stress in America survey reveals a population overwhelmed and fatigued by a “constant stream of crises” over the last two years. It’s not just Americans who are besieged by stress and anxiety. Since 2020, we’ve seen a 25% rise in anxiety across the globe, and according to the latest research, it’s taking a huge toll on our health.
Mounting evidence shows that chronic stress plays a crucial role in the development of IBS, and is a predictor of musculoskeletal disorders, nervous system diseases, endocrine and metabolic diseases, and mental disorders including depression. Stress has also been suggested to increase the risk of heart disease, Alzheimer’s, obesity, and tumor development.
As for treatment options, despite advances in the field, current pharmaceutical medications can take weeks to work, don’t work for everything, and are associated with a high risk of abuse, misuse, dependency, and withdrawal symptoms – not to mention the expansive list of side effects. Benzodiazepine, for instance, lists suicidal ideation as potential adverse effects, and a trial in 2021 confirmed that SSRIs raise the risk of suicidal thoughts and behaviors in children and teens.
Despite the need for safer effective solutions, pharmaceutical research programs for mental health have essentially stalled completely, with only one new FDA-approved development (a Ketamine nasal spray for depression) since the SSRI breakthrough in the 1980s. Therefore, researchers have turned to herbal medicine to seek effective, low-risk treatment options.
One of the more promising herbal compounds is an adaptogen called Ashwagandha, or Withania somnifera (SM), used traditionally in Ayurvedic medicine for stress, nervous exhaustion, insomnia and to improve cognitive function.
Here’s where the research currently stands.
Clinical Trials on Ashwagandha for Stress & Anxiety
In a 2013 trial, patients with Generalized Anxiety Disorder reported significant improvements after 2 months on Ashwagandha, with better moods, less tension, and less anxiety. Since then, considerable evidence has emerged to support Ashwagandha as a potential anti-anxiety treatment, with numerous clinical trials reporting a significant reduction in anxiety and stress levels compared to placebo.
More recently, a clinical trial in 2020 on participants with moderate stress scores found Ashwagandha improved scores on the Perceived Stress Scale, the Oxford Happiness Questionnaire, and improvement in cognitive function, sleep quality, cortisol levels, memory, focus, and psychological well-being. The natural treatment was found safe and well-tolerated.
It’s clear that Ashwagandha has a positive impact, but how exactly does it work to improve stress and anxiety?
Ashwagandha & the GABA Pathways
One of the ways Ashwagandha exerts anti-anxiety effects is through modulating Gamma-aminobutyric acid (GABA) pathways, which play a huge role in our body’s own regulation of anxiety and stress signals.
GABA neurons are the main inhibitory neurotransmitters (chemical messengers) in our central nervous system. They bind to the GABA receptors on our nerve cells, sending a signal to reduce nerve impulses and decrease the ability of that nerve cell to receive, produce or send out messages throughout the nervous system. By inhibiting chemical messages related to extreme moods, activating GABA receptors quite literally blocks our stress signals.
This process causes minimal sedation, relaxes the muscles, and slows brain activity, promoting calm and better sleep quality. You could liken the effect to how one feels after a yoga session. In fact, one study found that the relaxed, good mood felt by many after yoga is actually the result of GABA activation.
GABA Activation for Stress & IBS
There are two different receptor groups for GABA neurons: GABAA and GABAB. Decreased binding with both groups is linked to depressive and anxiety disorders. GABAA is actually the target of Benzodiazepines, commonly prescribed for Generalized Anxiety Disorders (GAD).
Ashwagandha also interacts with GABAA receptors, with some researchers claiming this makes it an anti-anxiety agent comparable to current pharmaceuticals. It’s also a strong GABAρ1 receptor agonist (an ‘agonist’ binds to a receptor to produce the same action as the chemical that normally binds to that receptor). GABAρ1 receptors are thought to be highly sensitive to GABA, and ‘exhibit little desensitization’, meaning they don’t show the decreased response that usually occurs with repeated exposure to an agonist.
Interestingly, studies show that IBS patients have a dysregulated GABAergic system, with lower levels of GABA neurons and receptors, rendering GABAA receptor activists a potential target for future IBS treatments.
Ashwagandha & Cortisol for Stress & IBS
Ashwagandha may be especially beneficial to those suffering anxiety and IBS due to its effect on the main stress hormones, glucocorticoids cortisol, and corticosterone. Both are elevated during stressful periods, and although this is part of the body’s normal stress response, consistently elevated cortisol levels can have a detrimental effect on our overall health – especially the digestive system.
Cortisol is a glucocorticoid hormone, and because all tissues in our body have glucocorticoid receptors, cortisol affects nearly every organ. Aside from impacting the nervous, immune, and reproductive systems, excess cortisol triggers inflammation in the digestive tract, throws off the gut bacteria balance, harms the intestinal muscles, and causes the colon to spasm. All this in turn causes stomach cramps and the worsening of abdominal IBS symptoms.
In the 2020 trial on Ashwagandha mentioned earlier, researchers measured the serum cortisol levels of participants with moderate stress scores. They found a significant decrease in serum cortisol levels in the Ashwagandha treatment groups compared to the placebo group, making Ashwagandha a very promising solution for those managing stress and IBS.
Ashwagandha & the Hypothalamic-Pituitary-Adrenal (HPA) Axis
Researchers believe the compounds within Ashwagandha may have an “an attenuating effect on the HPA axis activity”, meaning it might reduce the force of its activity. So, what is the HPA axis anyway, and why should we care?
The hypothalamus is a small, crucial part of the brain responsible for keeping the body in a stable state (homeostasis), mainly by managing hormone signals. The hypothalamus receives messages from nerve cells in the peripheral nervous system (which regulates involuntary processes including heart rate, blood pressure, respiration, digestion, and sexual arousal.)
The hypothalamus then reacts to these messages by sending signals (hormones) to the pituitary glands, which in turn release hormones out into the body, or send another signal to a different gland to release a hormone.
Here’s why this matters for IBS. When the hypothalamus releases the ‘corticotropin-releasing hormone’ (CRH), the pituitary gland receives this signal and sends out the andrecortiocotropic hormone (ACTH) to the adrenal glands, which in turn releases cortisol. The problem arises when the HPA axis over-activates, causing excess cortisol secretion, and, in IBS, a worsening of symptoms.
Research is ongoing, but HPA axis modulation is now regarded as a potential treatment target for depression and anxiety, and perhaps even IBS.
The Many Health Benefits of Ashwagandha
Aside from the benefits to mental and digestive health, Ashwagandha offers a well-rounded boost to the entire body, supporting heart health and joint inflammation. It can even help with joint pain in rheumatoid arthritis due to its ability to inhibit nerve signals. And for the menfolk reading, it may offer a boost to your testosterone levels, helping with libido, stamina, and general reproductive health.
Tessa Eskin
