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Decoded: How our body fights stress

Ever wondered how our body fights stress? Researchers, including one of Indian-origin, have found that during stress, our brain releases its own cannabinoid molecules to calm us down, activating the same brain receptors as THC derived from cannabis plants. 

But the brain activity patterns and neural circuits that are regulated by these brain-derived cannabinoid molecules were not well known.

A team from the Northwestern University in the US, in a mice study, 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. 

The study provides more support for 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). 

“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,” said Dr Sachi Patel, chair of psychiatry and behavioural sciences at Northwestern University-Feinberg’s School of Medicine.  

The study, published in the journal Cell Reports, 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, Patel said. 

For the study, the team 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 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 signalling systems that has been identified as a prominent drug-development candidate for stress-related psychiatric disorders is the endocannabinoid system, Patel said.

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