1. CRFR2 adapts in the limbic system to control homeostasis
  2. CRFR2 can maladapt, leading to lost homeostasis and chronic disease
  3. CRFR2 maladaptations are reversible

CRFR2=corticotropin-releasing factor receptor type 2

The Limbic System

Long relegated to an emotional role, it has become increasingly evident that the limbic system is at the core of maintaining homeostasis (steady state). It receives input from, and outputs to, the sensory, autonomic, endocrine, metabolic and immune systems (among others). It relies upon generating a specific serotonin signal (modulating other neurotransmitters as necessary) to control homeostasis.


In response to any threat to homeostasis, corticotropin-releasing factor (CRF) acts via 2 receptors (CRFR1 and CRFR2) to control serotonin in the limbic system and cord. When the threat subsides these receptors return to their basal configuration.

Intense or prolonged threats to homeostasis can permanently upregulate CRFR2. This disrupts serotonin, leading to a deregulation of body systems and processes, characteristic of many acquired chronic diseases.


Cortene’s treatment approach mimics a natural process that prevents neurons (or cells) from becoming over-excited. This process, called endocytosis or downregulation, overstimulates the receptors, causing them to leave the membrane and internalize in the neuron. Cortene’s proprietary CRFR2 agonist, CT38, has been shown to achieve downregulation

Cortene’s hypothesis, treatment approach and clinical trial are described more thoroughly in our recent publication.