Scripps Research Institute (TSRI) researchers have described how two important molecules in the brain work together to trigger a condition commonly known as post-traumatic stress disorder (PTSD). The brain’s endocannabinoid (eCB) system, which is part of the Endocrine System, includes natural lipid signaling molecules that bind to cannabinoid receptors in the brain. These cannabinoid (type 1) receptors control stress-mediating circuits by inhibiting neurotransmitter release to keep anxiety in check. In contrast, a peptide molecule called corticotropin-releasing factor (CRF) activates the stress response and promotes increased sensitivity to stress and anxiety when activated over and over again. Researchers study the interaction between the stress-promoting (CRF) and stress-constraining (eCBs) mechanisms in the central nucleus of the amygdala, a critical brain region involved in mediating emotional reactions. Their findings reveal that overactive CRF signaling in this region produces a wide range of effects that override the stress-reducing capabilities of a major eCB called N-arachidonoylethanolamine (anandamide). Without anandamide to balance out the system, the brain is primed to react to stress.