HPA Axis Dysregulation

A disruption of the hypothalamic-pituitary-adrenal (HPA) axis - the system that regulates the body's stress response and cortisol rhythm. The HPA axis can be activated not only by physical stressors, but also by thoughts, emotions, fear, and anxiety. Inflammatory cytokines such as IL-1β, IL-6, and TNF-α also activate the HPA axis, forcing the body to release cortisol to suppress inflammation and protect tissues from immune overactivation.

The different branches of the HPA and stress-response system: The classical HPA axis follows the pathway hypothalamus → pituitary → adrenal glands → cortisol, which is activated by psychological stress, threat perception, inflammation, or metabolic instability. There is also an acute cortisol pathway, triggered by heavy exercise, hypoglycemia, or sudden physical stress, where cortisol rises rapidly to mobilize fuel. Another pathway directly activates the sympathetic nervous system, increasing heart rate, arousal, and blood pressure without psychological anxiety. This explains why some people experience elevated heart rate or "wired but tired" states after stress, fasting, or training even when they feel mentally calm—sympathetic activation bypasses the emotional centers but still stresses the system.

How walking repairs the HPA axis: Walking plays a unique role in restoring HPA balance because it strengthens the baroreflex and activates the vagus nerve. These effects lower sympathetic tone upstream of cortisol, allowing the hypothalamus to re-establish a normal rhythm. Unlike heavy exercise, walking remains below the sympathetic activation threshold and therefore retrains the body to return to baseline after stress. Over time, this consistent low-intensity movement reconditions the HPA axis to respond appropriately, reduces “false alarms” in stress circuitry, stabilizes resting heart rate, and restores normal diurnal cortisol patterns even in individuals with chronic dysregulation. Ancient humans routinely walked 6–10 km per day, meaning our stress systems evolved to expect this level of steady, rhythmic movement.

Chronic worry or trauma can keep the stress response active even in the absence of real danger. Inflammatory cytokines also chronically stimulate the HPA axis, as the body must continuously release cortisol to counter inflammation and prevent immune overactivation. Over time, these constant activations cause the system to become dysregulated, leading to either hyperactive (high cortisol) or hypoactive (low cortisol) patterns.

• High cortisol (hyperactive phase): Chronic stress keeps the hypothalamus and pituitary signaling the adrenals to release cortisol. Over time, cells become resistant to cortisol, similar to insulin resistance, forcing the body to produce even more. This leads to anxiety, irritability, and insomnia. Supportive interventions include Ashwagandha and phosphatidylserine (PS)—especially useful after training—which help lower excessive cortisol, calm the HPA response, and restore receptor sensitivity.
• Low cortisol (hypoactive phase): After prolonged overdrive, the system downregulates. The adrenals and brain reduce cortisol output, leading to fatigue, apathy, poor stress tolerance, and low motivation. Recovery focuses on rebuilding adrenal capacity and restoring rhythm. Ashwagandha can help normalize cortisol, improve resilience, and restore circadian stability, while nutrients such as vitamin C, B5, magnesium, and sea salt support adrenal hormone synthesis.

Psychedelics such as psilocybin or LSD appear to temporarily reset and retrain the HPA axis by disrupting rigid stress-response pathways and enhancing neuroplasticity, allowing the brain to form a calmer baseline stress response.

You must also remove the physiological cause of the dysregulation—such as chronic inflammation, nutrient deficiency, sleep deprivation, leaky gut, histamin or low blood sugar—otherwise the HPA axis will simply become dysregulated again even after psychedelics, adaptogens, or PS.