New findings related to how the body’s endocannabinoid system responds to stress could open a new avenue of drug development to treat psychiatric disorders, say researchers.
Scientists believe that when an individual is under stress the brain may release its own cannabinoid molecules to calm them down, activating the same brain receptors as THC derived from cannabis plants.
However, the brain activity patterns and neural circuits that are regulated by these brain-derived cannabinoid molecules are not well known.
A new study in mice has discovered that a key emotional brain centre, the amygdala, releases endogenous (the body’s own) cannabinoid molecules under stress, and these molecules dampen the incoming stress alarm from the hippocampus, a memory and emotion centre in the brain.
These results support the hypothesis that these endogenous cannabinoid molecules are a body’s natural coping response to stress.
Stress exposure heightens risk for the development or worsening of psychiatric disorders from generalised anxiety and major depression to post-traumatic stress disorder (PTSD).
For the study, scientists at Northwestern Medicine 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 (CB1), 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 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.
READ MORE: Understanding the endocannabinoid system
Corresponding author of the study, Dr Sachi Patel, chair of psychiatry and behavioural sciences at Northwestern University Feinberg School of Medicine and a Northwestern Medicine psychiatrist, said: “Understanding how the brain adapts to stress at the molecular, cellular and circuit level could provide critical insight into how stress is translated into mood disorders and may reveal novel therapeutic targets for the treatment of stress-related disorders.”
According to Dr Patel, the study could indicate that impairments in this endogenous cannabinoid signalling system in the brain could lead to a greater susceptibility to developing stress-related psychiatric disorders including depression and PTSD, although this remains to be determined in humans.
One of the leading signalling systems that has been identified as a prominent drug-development candidate for stress-related psychiatric disorders is the endocannabinoid system.
Dr Patel continued: “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.
“There are ongoing clinical trials in this area that may be able to answer this question in the near future.”
The research was supported by grants from the National Institute of Mental Health and the National Institute of Alcohol Abuse and Alcoholism, Integrative Neuroscience Initiative on Alcoholism, all of the National Institutes of Health.
Read more about the study here
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