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Adrenal Fatigue: What It Really Means

How Adaptogens and Cannabinoids Support A Healthy Stress Response
Fatigue is a normal part of life, and the second most common complaint heard by primary care physicians (after cough).[1] But if you’re constantly tired, if your energy keeps ‘crashing’, have you ever wondered if you suffer from “adrenal fatigue” or “adrenal exhaustion”?[2]
Google those phrases and you’ll end up at innumerable websites asking if adrenal fatigue is even real or just a myth. In fact, adrenal fatigue is a phrase most people, and many functional medicine physicians, use to describe feeling achy and tired, suffering from sleep disturbances, low libido, brain fog and digestive problems. It is thought that stress, along with poor diet and inadequate sleep, burdens the adrenal glands. Someone might feel wired at night yet tired in the morning. A mid-afternoon energy crash is not uncommon.
Your tiny adrenal glands are remarkable powerhouses, perched above the kidneys and produce or regulate many important hormones like cortisol (the stress hormone) and adrenaline (the fight-or-flight hormone), and have an impact as well on estrogen, progesterone.  In fact, because of the strong connection between the adrenals and our sex hormones, optimal adrenal function is necessary for women going through menopause.[3] The adrenal glands produce precursors to estrogen, testosterone, DHEA and progesterone, and a smooth menopause is far likelier if the adrenals are functioning well.
Above all, we think of cortisol when we consider the adrenals. Whenever the body is faced with a demand or threat, the adrenals release cortisol.[4] Cortisol plays a role in managing stress, as well as regulating metabolism, sleep, blood sugar and even inflammation.
But What is Adrenal Fatigue, Really?
Adrenal fatigue can be a confusing phrase. Do adrenal glands actually get “tired”? Does too much stress just wear down the adrenal glands? The answer is actually a bit more complex, and illuminates the intricate symphony of our glandular system and our response to stress. Once we understand this symphony, we can understand why adaptogenic herbs are so well suited to so-called adrenal fatigue.
The adrenals do not exist in isolation. They are part of a tightly bound triad called the hypothalamic–pituitary–adrenal (HPA) axis. The HPA axis is our central stress response system, and it offers a highly dynamic dance between the central nervous system and endocrine system. The central players are:

  • The hypothalamus: a region of the brain that coordinates your autonomic nervous system and the activity of your pituitary gland. It helps regulate body temperature, thirst, hunger, sleep and emotions.
  • The pituitary gland: though it is merely the size of a pea, the pituitary has been called the body’s master gland, because it regulates the function of the other endocrine glands.
  • The adrenal glands: as described above, release many important hormones, such as cortisol and adrenaline, along with hormone precursors.

Stress activates the HPA axis and triggers an avalanche of neuroendocrine signals that stimulate a cascade of hormones and neurotransmitters such as cortisol, noradrenaline and adrenaline. The HPA axis impacts nearly every bodily system—the brain, gut, thyroid, and reproductive systems.[5] Childhood trauma or profound early-life stress can permanently derail the smooth function of the HPA axis.[6] The HPA axis may be intimately involved in depression and neurodegenerative conditions, as well as post-traumatic stress disorder.[7],[8]
When we talk of “adrenal fatigue” we are actually talking about HPA axis dysregulation. If our cortisol production is low, it is usually not because adrenals are “fatigued” or innately low in the hormone. Cortisol production is regulated upstream, by the nervous system, by the entire HPA axis.[9] A dysregulated HPA axis tends to include mild low-cortisol levels, a dysregulated daily cycle (leading to a wired-at-night and tired-by-day syndrome), and inadequate or blunted responsiveness of the HPA axis.
There are potentially many reasons the HPA axis can become dysregulated, but inevitably it is due to the demands of chronic stress, whether they be emotional, physical, infectious, or toxic. The entire HPA system becomes less responsive.[10] A dysregulated HPA axis and the resulting disruptions in cortisol have been linked to autoimmune disease, hypertension, mood disorders, and fatigue.[11],[12]
Adaptogens to the Rescue: Botanicals Uniquely Supportive of the HPA Axis
            Botanicals known as adaptogens help us adapt to stress. They offer a sort of “non-specific” resistance to stress, and support our response and adaptation to situations of high demand. Adaptogens possess a broad-spectrum ability to balance the hypothalamic-pituitary-adrenal (HPA) axis. The stress—protective activity of adaptogens is linked specifically with homeostasis and balance in the responses of the HPA axis.[13]
As long ago as the 1950’s, scientists first came up with the idea of using herbal medicinal plants to increase stamina and improve resistance to stress. The concept of “adaptogens” was introduced back then.
Classic energy-supporting adaptogenic herbs such as Ashwaganda, American Ginseng, Licorice, Peruvian maca and Rhodiola roots have an age-old reputation for increasing the resilience to stress.[14]
For women, female-specific botanicals that support the entire endocrine system, such as Chaste Tree (Vitex agnus-castus) and Shatavari as well as Angelica archangelica can aid and assist the reproductive organs and healthy flow of sex hormones. In fact, shatavari (Asparagus racemosus) is a revered Ayurvedic herb taken through all phases of a woman’s life, gently supporting normal hormonal function. Dong quai (Angelica sinensis) has been shown to support menstrual regularity.[15]
For men, herbs such as Tribulus and Epimedium are reputed to enhance vigor and support male hormones such as androgens and testosterone.[16]
Ideally, mutually supportive adaptogens are blended into a global resonance formula with subtle but profound harmonics and interactions, offering help through all seasons and situations.
Cannabinoids Also Support Balance in the HPA Axis
            Evidence suggests that cannabinoids are neuromodulatory and stimulating to the HPA axis.[17] We discovered the balancing potential of cannabis in Xinjiang, China, back in 500 BC. Cannabinoids offer a deep and basic communication system for life on this planet and are present in all plants and animals. They support bioregulation and homeostasis throughout our body and brain. Our built-in endocannabinoid system (ECS), regulates inflammation, pain, appetite, sleep, mood, insulin sensitivity, fat and energy metabolism. Cannabinoid receptors, called CB1 and CB2, are highly expressed in the hippocampus and central nervous system (CNS), the immune system, and peripheral nervous system.[18]
With a nuanced understanding of “adrenal fatigue” as a consequence of HPA axis dysregulation, we can wisely make informed decisions about supporting our response to stress. Adaptogenic botanicals and cannabinoids are two tried and true gifts of the plant world.

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[1]Hamilton W. Investigating fatigue in primary care. BMJ 2010; 341.
[2]Wilson JL: Adrenal Fatigue: the 21st Century Stress Syndrome, Petaluma, 2001, Smart Publications.
[3]Genazzani AD et al. Long-term low-dose dehydroepiandrosterone oral supplementation in early and late postmenopausal women modulates endocrine parameters and synthesis of neuroactive steroids. Fertil Steril Dec;80(6):1495-501, 2003.
[4]Gozansky WS et al: Salivary cortisol determined by enzyme immunoassay is preferable to serum total cortisol for assessment of dynamic hypothalamic-pituitary-adrenal axis activity, Clin Endocrinol (Oxf) 63(3):336-41, 2005.
[5]Zhu LJ, Liu MJ et al. The different roles of glucocorticoids in the hippocampus and hypothalamus in chronic stress-induced HPA axis hyperactivity. PLoS One. 2014 May 15;9(5):e97689
[6]Kuhlman KR, Vargas I. Age of Trauma Onset and HPA Axis Dysregulation Among Trauma-Exposed Youth. J Trauma Stress. 2015 Dec;28(6):572-9.
[7]Du X, Pang TY.  Is Dysregulation of the HPA-Axis a Core Pathophysiology Mediating Co-Morbid Depression in Neurodegenerative Diseases? Front Psychiatry. 2015 Mar 9;6:32. doi: 10.3389/fpsyt.2015.00032. eCollection 2015. Review.
[8]Klaassens ER, Giltay EJ et al. Adulthood trauma and HPA-axis functioning in healthy subjects and PTSD patients: a meta-analysis. Psychoneuroendocrinology. 2012 Mar;37(3):317-3
[9]Papadopoulos AS, Cleare AJ. Hypothalamic-pituitary-adrenal axis dysfunction in chronic fatigue syndrome. Nat Rev Endocrinol. 2011 Sep 27;8(1):22-32
[10]Gadek-Michalska A, Spyrka J et al. Influence of chronic stress on brain corticosteroid receptors and HPA axis activity.Pharmacol Rep. 2013;65(5):1163-75.
[11]Harbuz MS, Richards LJ et al. Stress in autoimmune disease models. Ann N Y Acad Sci. 2006 Jun;1069:51-61
[12]del Rey A, Besedovsky HO. The cytokine-HPA axis circuit contributes to prevent or moderate autoimmune processes. Z Rheumatol. 2000;59 Suppl 2:II/31-5
[13]Panossian A, WIkman G. Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress—Protective Activity. Pharmaceuticals (Basel). 2010 Jan; 3(1): 188–224.
[14]Yuan D, Wang H e al. Protective effects of total flavonoids from Epimedium on the male mouse reproductive system against cyclophosphamide-induced oxidative injury by up-regulating the expressions of SOD3 and GPX1. Phytother Res. 2014 Jan;28(1):88-9
[15]Samy RP, Pushparaj PN et al. A compilation of Bioactive Compounds from Ayurveda. Bioinformation. 2008; 3(3): 100–110
[16]Yuan D, Wang H e al. Protective effects of total flavonoids from Epimedium on the male mouse reproductive system against cyclophosphamide-induced oxidative injury by up-regulating the expressions of SOD3 and GPX1. Phytother Res. 2014 Jan;28(1):88-9
[17]Cota D. The role of the endocannabinoid system in the regulation of hypothalamic-pituitary-adrenal axis activity. J Neuroendocrinol. 2008 May;20 Suppl 1:35-8.
[18]Pertwee RG, Howlett AC, Abood ME et al. Cannabinoid receptors and their ligands: beyond CB₁ and CB₂.Pharmacol Rev. 2010 Dec;62(4):588-631
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