What is Addison’s disease?
Addison’s disease, also known as Primary Adrenal Insufficiency, refers to general idiopathic (of unknown origin) dysfunction of the adrenal cortex, which consists of two glandular organs located on the roof of the kidneys. It’s relatively rare, affecting only .07% of the population. In addition, it is one of the more common disorders humans share with other mammals; dogs have a higher rate of addison’s disease than their human counterparts (.3%).
Symptoms include fatigue, weight loss/lack of appetite, mood instability, and in certain cases adrenal crisis. Adrenal crisis is noted by an acute drop in blood pressure and subsequent dizziness, pain in the lower extremities, and sometimes fainting. It can be fatal if not handled immediately.
What is the HPA, and how does it work?
The HPA, or Hypothalamic-Pituitary-Adrenal axis, is at the intersection of our endocrine system and central nervous system. The endocrine system controls all of the hormones and signalling molecules that initiate the various chemical cascades that facilitate everything from mood to blood pressure. The adrenal system is a part of the endocrine system, and it controls our biological response to stress, including mental/emotional stress. It is made up of the adrenal glands, located on top of the kidneys, and the pituitary gland, located in the brain near the hypothalamus.
The pituitary gland is called the master gland, as it controls all of the other glands in the body; the adrenal glands are two of these. The adrenal cortex is the outer layer of the adrenal glands, which produces mineralocorticoids and glucocorticoids.
Mineralocorticoids are steroid hormones that regulate salt levels in the body. They cause potassium concentrations to be increased as a result of a decrease in sodium levels. This is hugely important for ion signalling systems in our brain and muscles. The primary mineralocorticoid is aldosterone, and the adrenal glands produce it with or without signalling from the pituitary gland. Aldosterone released by the adrenal glands enters the kidneys and facilitates the removal of minerals from the blood, hence the name mineralocorticoid.
Glucocorticoids are steroid hormones that have a plethora of roles in the body. They control the synthesis and metabolization of carbohydrates and proteins, and they provide a negative feedback loop that regulates adrenal activity, including mineralocorticoid activity as well as glucocorticoids. They also downregulate inflammatory activities and passively inhibit COX-1 and COX-2 gene transcription, acting as a buffer for the catalysis of inflammatory cascades. Glucocorticoid insufficiency can lead to hypotension and insulin sensitivity, as well as several other more subtle effects. The primary glucocorticoid is cortisol; it can be medically administered as cortisone or hydrocortisone.
When the adrenal cortex undergoes an autoimmune assault, or it atrophies for unknown reasons, primary adrenal insufficiency occurs because it can no longer produce the hormones that our bodies need to function properly.
When the pituitary gland releases ACTH, or adrenocorticotropic hormone, it activates the adrenal cortex to produce more cortisol. Without ACTH, negligible cortisol is produced, but levels of aldosterone remain unchanged; this is secondary adrenal insufficiency.
Treatments of both kinds of adrenal insufficiency consist almost entirely of palliative hormone replacement therapy, while the underlying issue remains largely untouched.
How can CBD help?
While it’s rare, Addison’s disease shares many characteristics with other conditions or disorders which have been attenuated with CBD. CBD inhibits the inflammatory autoimmune reaction that initiates Addison’s disease. However, Addison’s doesn’t usually become symptomatic until more than 90% of the adrenal cortex has become nonfunctional. For this reason, CBD may help to prevent primary adrenal insufficiency with as much or more efficacy than it can ease the symptoms once the disease has progressed.
Outside of the causality of this condition, CBD is also able to relieve many of the symptoms, including lack of appetite, fatigue, mood instability, and vascular issues stemming from a lack of cortisol. Cannabidiol, in addition to other phytocannabinoids, is a powerful anti-inflammatory agent that works on several signalling pathways. One of these pathways is the Cytochrome P450 enzymes that catalyze a majority of the chemical reactions that take place with a metabotropic goal.
One of these CYP450 enzymes, 21-hydroxylase, is involved in the pathology of Addison’s disease in over 80% of cases. In these instances, the immune system attacks this enzyme and prevents it from synthesizing both cortisol and aldosterone. Without this enzyme, these hormones can’t be produced, and the symptomatology of Addison’s presents itself.
CBD has been shown to block the autoimmune response to this vital enzyme, but the exact mechanism of this action hasn’t been elucidated.