Mental Health Crisis: Stress, Anxiety, Poor Sleep & COVID

What Does the Endocannabinoid System Have to Do With It?

Photo by Nik Shuliahin on Unsplash

This interview was originally published on WholeFoods Magazine

During this unprecedented time, the vast majority of people have been rightfully concerned and preoccupied with this invisible viral enemy called COVID-19. Most of us have been focusing on maintaining overall health and strengthening our immune system using supplements to best deal with the current pandemic as a means to protect ourselves nutritionally. The role the endocannabinoid system (ECS) plays in strengthening the immune system must not be ignored, as it orchestrates numerous physiological processes to maintain immune resilience. 

Other than the elderly, immuno-compromised, and those with respiratory conditions who are at risk, diabetics, hypertensives, and the obese top the list of those who suffer the ravages of the COVID disease the most. While the COVID-19 pandemic has placed the world on hold, we continue to seek the appropriate and efficacious medical protocol to treat this new invader. Nutritionally, while we have the standard vitamins, minerals, and herbs that we have all been accustomed to for supporting immunity, we cannot ignore the most obvious issues plaguing everyone that suppress immune health—stress, anxiety, depression, fear, and isolation—requiring nutritional support above and beyond vitamin C through zinc! 

From the daily news reports to social media, we are bombarded every waking moment about the consequences of the COVID-19 pandemic and our lives are being transformed in every way. Defined as “headline stress disorder” by clinical psychologist Dr. Steven Stosny, the unmitigated media chaos with non-stop coverage of the pandemic has resulted in 24/7 stress that can cause functional anxiety disorders (anxiety, depression), cardiovascular issues (palpitations, chest tightness), insomnia, endocrine disorders, and hypertension. All of these conditions set the stage for increased susceptibility to the disease! This “high anxiety” state has been confirmed by the recent reports from Express Scripts showing anti-anxiety medication scripts (Xanax, Valium, Klonopin, etc.) that have skyrocketed since February 2020—a complete 180 from the downward trend over the past 5 years.

There is no doubt that the negative impact of the outbreak has significantly increased the level of fear, anxiety, and depression, which has been unprecedented worldwide. Unfortunately, the frontline medical personnel are suffering the most. The increasing stress to take care of the infected coupled with uncertainty about contracting the disease has put medical personnel at an even greater risk of stress-related disorders. Studies in China point to more than 70% of healthcare workers suffering psychological distress, including insomnia, anxiety, and depression. 

For the rest of society here in the U.S., anxiety and its related conditions have been equally as infectious as the coronavirus itself. Fueled by the medical consequences of the disease, financial losses, insomnia, social distancing, and isolation, many have succumbed to the complexity of the pandemic of anxiety and its own consequences: a suppressed immune system and increased inflammation.

In addition to the anxiety syndromes plaguing most, social distancing and isolation have untold consequences directed at increased inflammatory processes and decreased antiviral activity in the body. Mandated social distancing is one thing, but to lower risk of COVID exposure, many are resorting to socially isolating themselves to avoid infecting family members. Several studies have reviewed the effects of social isolation on reduced immune resilience and increased inflammatory processes while healthy social contact increases antiviral immunity. 

The rates of COVID anxiety and depression reported in several studies are significant. Unfortunately, while the epidemic will eventually subside, many clinicians feel that the physiological and psychological toll of these consequences associated with stress, anxiety, and depression will remain for some time.

It is well established that psychological stress downregulates immune response, including decreasing white blood cells called lymphocytes that help fight off infection. The lower your lymphocyte level, the more at risk you are for viral and bacterial infections. While immune response is coordinated via tri-directional communication between the brain, gut, and immune system, stress disrupts the homeostasis of this communication, resulting in altered immune function. The expression of anxiety and its negative impact on the body involves complex interaction among many physiological systems—especially the neuroendocrine, immune, and our microbiome. When our immune system is challenged, it must gather information and convey it to the brain for appropriate physiological response, including the release of inflammatory components as a first line of defense. These destructive inflammatory components not only work on the pathogen that initiates activity, but also direct themselves to the brain to elicit responses including fever, pain response, etc. Of particular interest, elevated destructive immune inflammatory markers are reported in a variety of psychological disorders, including anxiety and depression where the GUT-brain-immune connection is intimately involved.

The societal consequences of the COVID outbreak, with mandated social isolation and distancing, furthers the detrimental effects on the immune system. Being forced to home confinement, reducing social interaction, trying to work while occupying children, etc., provides for a breeding ground of psychological distress that impacts sleep as well. Studies investigating stressful emotional life events in humans clearly show how they contribute to the development of sleep disturbances and deprivation, including insomnia. Diwakar Balachandran, M.D., Director of the Sleep Center at the University of Texas M.D. Anderson Cancer Center in Houston, confirms the notion that if you don’t sleep well, you will get sick. Other than poor sleep and its role linked to anxiety and stress, an impaired immune system is included. This trifecta of poor sleep, anxiety, and stress sets the stage for decreased ability of our immune system to do its job and fails to adequately protect us from pathogens. Lowered immune response, reduced immune cells (T cells, antibodies, etc.), and elevated inflammatory components (C-reactive protein) are just a few of the consequences of anxiety and poor sleep that leave us at a greater risk of developing colds, flu, or infections.

Obviously, with the spread of the COVID virus, effective strategies towards alleviating stress, anxiety, and poor sleep should be the front-line defense to strengthen the immune system and to optimally prepare our best defense. With vitamins A through zinc, elderberry and echinacea being the focus of nutritional supplementation at present, we must address the best strategy to alleviate stress and anxiety via nutritional therapies. The goal here is to assist in immune resilience and homeostasis. Enter the Endocannabinoid System!

The Stress Response and the ECS

When we are exposed to threats, the stress/anxiety response is a coordinated series of events to help adapt and balance the body (homeostasis). The synchronized activity of physiological systems and biochemical events are all focused on survival. Of all the physiological systems in the body, the endocannabinoid system (ECS) has been shown to be the major modulator of how we perceive internal and external stimulus and how it influences anxiety, fear, and stress. 

It is intimately able to help us adapt to our changing environment and the stressors we are exposed to with the sole purpose of putting us back into balance. Essentially, the ECS helps us maintain long-term adaptability and provides for improved stress and immune resilience. While the ECS exerts its authority globally throughout the body, it employs specific regulatory roles localized throughout the central nervous system, GUT, and immune system that are all involved with coping and responding to stress. It performs this vital function by controlling several regions of the brain that help to orchestrate communication with key organ systems involved in regulating stress response, including the HPA axis (hypothalamic-pituitary-adrenal axis). In animal studies where the ECS is disrupted, increased anxiety via activation of the HPA axis has been demonstrated. There are excellent human studies suggesting that the ECS is an important regulator of various aspects of the stress response and that phytocannabinoid use results in relaxation and dampening anxiety. These effects are mediated by activating both CB1 and CB2 cannabinoid receptors in the body and require full support of the ECS to buffer overactive or chronic stress responses via control of the HPA axis.

The HPA Axis

The stress response begins in the brain where the hypothalamus acts as the command center and communicates with other key organs (pituitary and adrenal glands that activate stress processes). Other than the obvious triggering of the “fight or flight” reaction for immediate response, when chronically activated the axis contributes to the outpouring of certain compounds, such as cortisol, that can have deleterious effects on the immune system when overly expressed. In addition, when a stressor is always present, the “fight or flight” reactions are constantly turned on, resulting in overexposure to cortisol and disruption of many body processes. With exposure to chronic stress conditions, HPA axis dysfunction has been verified in numerous disease conditions and can place you at risk of anxiety, depression, digestive, neurological, and cardiovascular illnesses. For many facing this COVID pandemic, the presence of chronic stress, anxiety, fear, and sleeplessness encumbers the stress response system, and its ability to overcome the physiological and psychological demands placed on it. While activation of the HPA axis is a necessary function for survival, modulating its activity rests on the ECS. Data has revealed this key role for the ECS in addressing stress/anxiety related disorders, and preclinical studies have validated its ability to reduce anxiety by inhibiting chronic stress-induced HPA activation.

The Role of the ECS

With COVID pandemic anxiety and its related conditions being a major contributing factor in reducing immune resilience and making us more susceptible to disease, we look to augment current medical treatment (not replace it) with health strategies that can address immune homeostasis in the body. The ECS has been shown in several studies to be a promising anti-anxiety target owing to its role in the anxiety response modulation under the HPA axis. With 100+ phytocannabinoids found in true industrial hemp, cannabidiol (CBD) and others are being studied for their supportive roles in nourishing and feeding our ECS. With CBD being the most dominant phytocannabinoid in hemp, it has been shown to have several therapeutic effects to help alleviate stress and anxiety. CBD’s direct and indirect influence on both cannabinoid receptors (CB1, CB2) and on 5-HT1a receptors is believed to be key to its antianxiety effects. In addition, CBD was found to exert a significant effect on increased brain activity in various sections involved in the processing of emotional information. These anti-anxiety effects of CBD have been extensively studied in animals and a review of many human studies conclude that it is an effective treatment for generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, and post-traumatic disorder. In addition, several excellent studies have reported positive effects of CBD in treating post traumatic stress disorders (PTSD) and symptoms commonly associated with it including chronic anxiety, fear memories, and panic attacks in stressful environments. 

The major objective is to institute a variety of natural remedies (meditation, acupuncture, chiropractic, yoga, etc.) and diet/supplement regimens aimed at relaxing an overstressed, overactive, and immune-suppressed path most are following today. From a diet perspective, elimination of allergic and inflammatory foods (such as gluten, sugar, and alcohol) and a focus on a more plant-based regimen is essential. When it comes to supplements, one can make the case that vitamin A to the mineral zinc are all important for a healthy immune system. Current focus on vitamin C, vitamin D, zinc, and the herbs elderberry, astragalus, echinacea—while key players—may be short sighted when ignoring the modulator of stress, anxiety, and immune homeostasis: the endocannabinoid system! 


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Carl Germano

Carl Germano, CNS, CDN, NY Board Certified Clinical Nutritionist with a master’s degree in clinical nutrition from New York University, Vice President for Verdant Oasis, and has over 40 years’ experience in product development for several of the largest dietary supplement companies in the U.S. For the past three decades, he has been instrumental in bringing innovative nutritional ingredients and finished products – including dietary supplements, medical foods, and functional beverages – to a variety of markets. He continues to lead the industry in research and product development as it relates to next generation clinically relevant nutraceutical ingredients and recently published his 9th book called Road To Ananda: The Simple Guide To The Endocannabinoid System, Phytocannabinoids & Hemp.

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