Key points:
- Researchers discovered that the amygdala releases endogenous cannabinoid molecules under stress.
- Stress exposure heightens risk for the development or worsening of psychiatric disorders from generalized anxiety and major depression to PTSD.
- The finding opens new avenues for drug development to treat psychiatric disorders.
A new Northwestern Medicine study in mice has discovered that a key emotional brain center—the amygdala—releases the body’s own cannabinoid molecules under stress, and these molecules dampen the incoming stress alarm from the hippocampus. These results provide more support for the hypothesis that these endogenous cannabinoid molecules are a body’s natural coping response to stress.
For the study, scientists used a new protein sensor that can detect the presence of these cannabinoid molecules at specific brain synapses in real-time to show that specific high-frequency patterns of amygdala activity can generate these molecules. The sensor also showed that these molecules were released as a result of several different types of stress in mice.
When scientists removed the target of these cannabinoids, the cannabinoid receptor type 1, it resulted in poorer ability to cope with stress and motivational deficits in the mice. Specifically, when the receptor target of these endogenous cannabinoids was removed at hippocampal-amygdala synapses, mice adopted more passive and immobile responses to stress and had a lower preference to drink a sweetened sucrose water after stress exposure. The latter finding may relate to anhedonia, or the decrease in pleasure, often experienced by patients with stress-related disorders, such as depression and PTSD.
One of the leading signaling systems that has been identified as a prominent drug development candidate for stress-related psychiatric disorders is the endocannabinoid system.
“Determining whether increasing levels of endogenous cannabinoids can be used as potential therapeutics for stress-related disorders is a next logical step from this study and our previous work,” said corresponding study author Sachi Patel, chair of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine and a Northwestern Medicine psychiatrist. “There are ongoing clinical trials in this area that may be able to answer this question in the near future.”