In situations of excessive stress, the brain may produce its own cannabinoid substances that exert a soothing effect by stimulating the same receptors in the brain as THC from the cannabis plant. However, little is known about the neural networks and brain activity patterns regulated by these endocannabinoids.
A new study in mice from Northwestern Medicine found that the amygdala, a key emotional center of the brain, releases endogenous (the body's own) cannabinoid molecules during stress, and that these molecules suppress stress alarms from the hippocampus, the brain's memory and emotion center. These results further support the hypothesis that these endocannabinoid molecules are the body's natural response to stress.
From generalized anxiety disorder and major depressive disorder to post-traumatic stress disorder (PTSD), stress exposure can increase the risk of developing or worsening mental illness.
"Understanding how the brain adapts to stress at the molecular, cellular and circuit levels can provide insights into how stress translates into mood disorders and may reveal novel therapeutic targets for treating stress-related disorders," said Northwestern Medicine psychiatrist Dr. Sachi Patel, corresponding author of the study and chair of the Department of Psychiatry and Behavioral Sciences at Northwestern University Feinberg School of Medicine.
The study may suggest that damage to this endocannabinoid signaling system in the brain may make people more susceptible to stress-related mental illnesses, including depression and post-traumatic stress disorder, though this has yet to be determined in humans, Patel said.
The research will be published September 12 in Cell Reports.
In the study, Northwestern scientists used a new protein sensor that can detect the presence of these cannabinoid molecules in specific brain synapses in real time, showing that specific high-frequency patterns of amygdala activity produce these molecules. The sensor also showed that mice release these molecules under several different types of stress.
When scientists removed the type 1 cannabinoid receptors, the targets of these cannabinoids, the mice were less able to cope with stress and had deficits in motivation. Specifically, when receptor targets for these endocannabinoids were removed at hippocampal-amygdala synapses, mice adopted a more passive and immobile response to stress and had a reduced preference for drinking sugar-sweetened sucrose water after being stressed. The latter finding may be related to the amusia, or decreased sense of pleasure, that often occurs in people with stress-related disorders such as depression and post-traumatic stress disorder.
The endocannabinoid system is a major signaling system that has been identified as one of the leading candidate drug development systems for stress-related mental disorders, said Patel.
"Determining whether increasing endocannabinoid levels could serve as a potential therapy for stress-related disorders is the next logical step from this research and our previous work," said Patel, who is also the Lizzie Gilman Professor of Psychiatry and Behavioral Sciences. "Clinical trials in this area are ongoing and may answer this question in the near future."