The hypothalamic-pituitary-adrenal (HPA) axis regulates our stress response through the hypothalamus, pituitary, and adrenal glands, inducing a fight-or-flight response to a perceived threat.

How CBD Can Support a Healthy HPA Axis

By Jenny Menzel, H.C.

You may not exactly know what a healthy HPA axis entails, but you probably know what chronic stress is — a state of continuous tension, earning names like burnout, work exhaustion, and adrenal fatigue.

More than 75% of American adults report symptoms like fatigue and sleep disturbances caused by physical or emotional stress, according to the American Psychological Association (APA). But what role does the HPA axis play? And can the hemp compound cannabidiol (CBD) help repair stress-induced adrenal fatigue? In this article, you’ll learn how stress is managed through the HPA axis and how it is influenced by the endocannabinoid system (ECS) through the use of CBD. First, let’s look at how the HPA axis creates a balanced state of health, free of disease. 

What is The HPA Axis?

Central to creating homeostasis, the hypothalamic-pituitary-adrenal (HPA) axis regulates our stress response through the hypothalamus, pituitary, and adrenal glands, inducing a fight-or-flight response under a perceived threat. This response is incredibly helpful when adrenaline is needed to avert danger. However, this protective reaction to prolonged stress can damage our health — affecting metabolism, sleep, appetite, and our ability to focus. 

When We Get Stressed Out

Responsible for processing emotions, the amygdala analyzes and interprets emotional signals from our five senses and alerts the hypothalamus, the region located just above the brainstem, of imminent danger. The hypothalamus secretes corticotropin-releasing hormone (CRH), which takes a short trip to the pituitary gland, stimulating the release of adrenocorticotropic hormone (ACTH), which then travels through the blood to the adrenals to stimulate the release of cortisol. Under normal circumstances, cortisol secretion is the sign to the hypothalamus that it is safe to stop the stress response. However, stress can override this negative feedback loop, falsely informing the hypothalamus that more cortisol is needed.

When The Adrenal Glands are Overworked

Resting on the kidneys like a hat, the adrenal glands are essentially two endocrine glands in one. At the very core of the adrenals is the adrenal medulla, the tissue responsible for organizing the fight-or-flight response. In fact, this tissue area operates more neurologically as a part of the sympathetic nervous system than as a classic endocrine gland. Within seconds of a perceived threat, preganglionic neurons from the brain incite the medulla to produce epinephrine and norepinephrine — otherwise known as adrenaline and noradrenaline, which work as both hormones and neurotransmitters.

Operating as a classic endocrine gland, the adrenal cortex consists of three tissue layers encapsulating the medulla and are responsible for a host of hormonal functions:

  • Zona glomerulosa. This outermost tissue layer produces mineralocorticoids like aldosterone to regulate sodium, potassium, and fluid volumes to maintain blood pressure. 
  • Zona fasciculata. The middle and largest layer of cortex tissue produces glucocorticoid hormones like cortisol to regulate glucose metabolism in a crisis. 
  • Zona reticularis. This lesser-understood layer of the cortex produces masculinizing androgens like DHEA (dehydroepiandrosterone) and precursors to hormones like estrogen. It’s unclear how this plays a role within the HPA axis, but it may explain how stress negatively impacts reproductive health.

Cortisol Follows a Circadian Rhythm

Made in the middle layer of the adrenal cortex, cortisol is a hormone chief regulating long-term stress. In optimal health, cortisol production follows our natural circadian rhythm — increasing production in the morning with sunrise, slowly declining throughout the day, and hitting a low after dark when the sleep hormone, melatonin, is secreted. People doing shift work or suffering from sleep deprivation interrupt their sleep cycle — throwing off cortisol production and impairing adrenal health over time.

The Fight-Or-Flight Stress Response 

Cortisol is also secreted under physical, mental, or emotional duress — coming along after the initial stress response to cleanup, like a clean up crew after a party. When the brain sounds the alarm to a problem, a swirl of adrenaline and inflammatory cytokines are released to prepare an immune defense. When stressors are short-lived, this stress response is healthy. However, if trauma turns chronic, more cortisol is produced to curb chronic inflammation and autoimmune diseases. This suppressive action of cortisol is why cortisone shots are used in autoimmune diseases like rheumatoid arthritis — and why too much cortisol can lower immunity.

6 Ways CBD Reduces Stress and Heals the HPA Axis

CBD can support the HPA axis and assist with managing stress.

As you can see, the HPA axis plays an essential role in managing stress — and our health. So, how can CBD support the health of our HPA axis? 

1. CBD Interrupts Cortisol to Regulate Sleep.

It’s no secret that adequate sleep helps in coping with stress and maintaining immune function. CBD assists us with this largely by interfering with cortisol secretion — especially at night when cortisol should be at its lowest levels. Researchers measured blood hormone levels in 11 volunteers and found CBD to have a sedating effect taken at high doses between 300-600 mg — helping you to get to sleep faster and stay asleep longer.

2. CBD May Reduce Stress by Calming Anxiety.

CBD is documented as a valuable calming agent in neuropsychiatric disorders like anxiety. In fact, an impressive study published in The Permanente Journal looked at 72 adults where anxiety and poor sleep were of primary concern. CBD decreased anxiety scores within the first month in 79% of the subjects, with a majority experiencing benefits after stopping CBD — showing CBD as a potential long-term solution for anxiety and stress reduction. 

3. CBD Regulates Appetite to Decrease Stress Eating. 

When people suffer from adrenal fatigue, the outer layer of the adrenals struggles to make aldosterone — depleting necessary minerals like magnesium, potassium, and sodium. Craving sugary or salty foods may be an indicator of stress that results in “stress-eating.” CBD may alleviate stress-eating by modulating the appetite through its interaction with the cannabinoid (CB) receptors in the gut, signaling satisfaction to the brain after you’ve eaten — curbing the desire to eat unhealthily in excess.

4. CBD Targets the Amygdala to Process Emotions.

Perhaps one of the most proactive ways to extinguish the vicious cycle of stress is to strengthen the center responsible for controlling emotions — the amygdala. This region of the brain is our first alert system, sending signals of danger to the hypothalamus to kick off fight-or-flight — even in the absence of an actual threat. CBD interacts with CB receptors in the brain to make emotional processing more accurate and less traumatic. 

5. CBD Inhibits Fear by Boosting Anandamide.

As chronic stress rises, the “bliss molecule” anandamide is drained — increasing our sensitivity to stress. Animal studies have shown when anandamide levels are elevated, anxiety and fear-based stress responses are reversed. CBD boosts anandamide in our system by inhibiting a catabolizing enzyme called FAAH. Scientists show evidence this can help mediate fear and better process our reaction to the threat by directly impacting the amygdala.

6. CBD Increases Blood Flow to the Hippocampus.

Past research suggests a link between an unhealthy HPA axis and those with psychiatric disorders, noting an association between stress and changes to the hippocampus. CBD may increase blood flow to the hippocampus, another area of the brain that assists in processing emotions. Further research is needed to confirm, but increased blood flow to the hippocampus may reverse cognitive decline and facilitate memory recall — allowing for more effective coping of stress. 

The Takeaway

As we all experience stress to varying degrees, our stress responses are quite individual — established as early as in utero. Someone with a history of abuse, neglect, poverty, or illness may react more severely to even minor emotional stressors when compared to someone who experienced a consistently comfortable upbringing — making the ability to predict individual stress responses difficult. Understanding how the HPA axis seeks to protect us from stress and how CBD can potentially help repattern a dysfunctional stress response is a great starting point to address stress-related disorders like fatigue, depression, anxiety, and other physical manifestations of disease. 

References:
  • Bluett RJ, Gamble-George JC, Hermanson DJ, Hartley ND, Marnett LJ, Patel S. Central anandamide deficiency predicts stress-induced anxiety: behavioral reversal through endocannabinoid augmentation. Transl Psychiatry2014;4(7):e408. Published 2014 Jul 8. doi:10.1038/tp.2014.53
  • Cohen S, Janicki-Deverts D, Doyle WJ, et al. Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk. Proc Natl Acad Sci U S A. 2012;109(16):5995-5999. doi:10.1073/pnas.1118355109
  • Gunduz-Cinar, O., MacPherson, K., Cinar, R., Gamble-George, J., Sugden, K., Williams, B., . . . Holmes, A. (2012, June 12). Convergent translational evidence of a role for anandamide in amygdala-mediated fear extinction, threat processing and stress-reactivity. Retrieved February 15, 2021, from https://www.nature.com/articles/mp201272
  • Miller WL. The Hypothalamic-Pituitary-Adrenal Axis: A Brief History. Horm Res Paediatr. 2018;89(4):212-223. doi:10.1159/000487755
  • Phillips LJ, McGorry PD, Garner B, et al. Stress, the hippocampus and the hypothalamic-pituitary-adrenal axis: implications for the development of psychotic disorders. Aust N Z J Psychiatry. 2006;40(9):725-741. doi:10.1080/j.1440-1614.2006.01877.x
  • Shannon S, Lewis N, Lee H, Hughes S. Cannabidiol in Anxiety and Sleep: A Large Case Series. Perm J. 2019;23:18-041. doi:10.7812/TPP/18-041
  • Urbinati, E. C., Zanuzzo, F. S., & Biller, J. D. (2020). Stress and immune system in fish. Biology and Physiology of Freshwater Neotropical Fish, 93-114. doi:10.1016/b978-0-12-815872-2.00005-1
  • Zuardi AW, Guimarães FS, Moreira AC. Effect of cannabidiol on plasma prolactin, growth hormone and cortisol in human volunteers. Braz J Med Biol Res. 1993 Feb;26(2) 213-217. PMID: 8257923

Jenny Menzel, H.C., is a Certified Health Coach and branding specialist for various alternative healthcare practices, and volunteers her design skills to the annual grassroots campaign, the Lyme Disease Challenge. Jenny was diagnosed with Lyme in 2010 after 8 years of undiagnosed chronic pain and fatigue, and continues to improve by employing multiple alternative therapies, including Āyurveda, Chinese Medicine and Bee Venom Therapy.

Leave a Reply

Your email address will not be published. Required fields are marked *