A study published in Cell Reports found that the brain’s amygdala releases endogenous cannabinoid molecules when a person experiences stress. These molecules mitigate the incoming stress alarm from the hippocampus, which regulates memory and emotion. These findings support the research team’s hypothesis that these endogenous cannabinoid molecules are the human body’s natural coping response to stress. This coping response offers valuable insights into minimizing stress and, subsequently, reducing the risk of psychiatric disorders such as generalized anxiety, major depression, and post-traumatic stress disorder (PTSD).
The brain releases cannabinoids, which activate the same brain receptors as tetrahydrocannabinol (THC) derived from the cannabis plant. THC acts as an agonist on the cannabinoid receptors. Examining the endogenous cannabinoid signaling system and how the brain adapts to stress at the molecular, cellular, and circuit level can lead to the discovery of novel therapeutic targets for treating stress-related disorders.
The researchers used a new protein sensor that can detect the presence of cannabinoid molecules at specific brain synapses. Observing cannabinoid molecules in real time helped them understand how specific high-frequency patterns of amygdala activity can generate these molecules. The sensor demonstrated that several different types of stress in the mice released cannabinoid molecules.
When researchers removed the target of these cannabinoids, known as the cannabinoid receptor type 1, the mice demonstrated a decreased ability to cope with stress and motivational deficits. When the research team removed the receptor target of these endogenous cannabinoids at hippocampal-amygdala synapses, mice showed more passive and immobile responses to stress. The mice also had less desire to drink sweetened sucrose water after stress exposure. The researchers believe this finding may relate to anhedonia (a decrease in pleasure), often experienced by patients with stress-related disorders.
The endocannabinoid system is one of the leading signaling systems considered a prominent drug-development candidate for stress-related psychiatric disorders. The researchers plan to investigate the effects of increased levels of endogenous cannabinoids as potential therapeutics for stress-related conditions in future studies.