Hypothalamic-pituitary-adrenal (HPA) axis

The hypothalamic-pituitary-adrenal axis is the hormonal chain linking the brain to the adrenal glands that controls the body's stress response and the daily rhythm of cortisol.

When the brain perceives a threat, the hypothalamus releases corticotropin-releasing hormone, which prompts the pituitary gland to release adrenocorticotropic hormone, which in turn tells the adrenal glands to release cortisol. Cortisol mobilizes energy, sharpens attention and dampens inflammation, and it feeds back on the brain to shut the response off once the threat passes. The same axis produces a daily rhythm, with cortisol highest shortly after waking and lowest around midnight.

Prolonged activation, as in chronic stress, poor sleep or persistent pain, is associated with altered cortisol rhythms, and disturbances of the axis are seen in depression, post-traumatic stress disorder and some sleep disorders. Clinicians measure cortisol in blood, saliva, urine or hair, and in research the axis is often probed with a controlled stress task. The endocannabinoid system helps restrain the axis, and cannabinoids have been studied for effects on cortisol and stress responses in early human and animal work with mixed findings.