Cortene believes that ME/CFS and related diseases result from the upregulation of the corticotropin-releasing factor receptor subtype 2 (CRF2) in the limbic system. This deregulates serotonin, norepinephrine (and other neurotransmitters) and cortisol, leading to wide-ranging dysfunction.



In response to any threat to homeostasis (steady state), the neuroendocrine system releases corticotropin-releasing factor (CRF), which acts via 2 receptors (CRF1 and CRF2) in the limbic system, to control serotonin in the brain and cord.

Intense or prolonged departures from homeostasis can upregulate CRF2, changing the sensitivity of the system and resulting in a major response to a minor threat.


With CRF2 upregulated, the neuroendocrine system becomes sensitized, but being highly dynamic, cannot be blocked (with an antagonist or antibody).

Instead, Cortene’s treatment approach mimics the natural process that returns the system to homeostasis, once the threat diminishes. This involves, the release of an agonist (urocortin 1), which binds to CRF2, eventually internalizing and metabolizing the receptor. Cortene intends to dose CT38 (a CRF2 agonist) to internalize CRF2. This novel approach has not been tried in humans (in any disease).

Cortene’s theory of ME/CFS and treatment approach were the subject of a 3-part blog series (Part I, Part II and Part III). HealthRising is an independent blog that reports research in an easy-to-understand format.