A natural molecule produced by the brain activates endocannabinoid receptors, protecting against stress by reducing the anxiety-producing connections between the amygdala and the prefrontal cortex. The results may help explain why people turn to marijuana when they feel anxious or stressed.
The finding, published in Neuron, may help explain why some people use cannabis when they feel anxious or stressed. It could also mean that pharmacological treatments that increase levels of this molecule, known as “2-AG”, in the brain could regulate anxiety and depressive symptoms in people with stress-related anxiety disorders, potentially avoiding dependence on medical marijuana or similar treatments.
Basically a brain-produced molecule that activates the same endocannabinoid receptors reduces the anxiety-causing connections between two brain regions, report researchers at Vanderbilt University Medical Center.
Generally , the collapse of endocannabinoid signaling contributes to stress-induced tonsil-cortical strengthening.
The circuit between the amygdala and the frontal cortex is therefore stronger in people with certain types of anxiety disorders. when people or animals experience stress and become more anxious. These 2 areas of the brain stick together and become more active together,” said Sachin Patel, MD, Ph.D., the journal’s corresponding author and director of the Division of General Psychiatry at Vanderbilt. University Medical Center.
When mice are exposed to acute stress, a disruption in the anxiety-generating connection between the amygdala and frontal cortex caused by 2-AG temporarily disappears, leading to the emergence of anxiety-related behaviors.
Indeed we could predict that there is a collapse of the endocannabinoid system, which includes 2-AG, in patients who continue to develop a disorder. But not everyone develops a psychiatric disorder after exposure to trauma, so maybe people who don’t develop a disorder can maintain that system in some way. Those are the things we want to test next.
The study also revealed that signaling between the amygdala and the frontal cortex can be enhanced by genetic manipulations that compromise endogenous cannabinoid signaling in this pathway, making mice anxious even without stress exposure in some cases. In short , this discovery demonstrates that the cannabinoid signaling system that suppresses the flow of information between these two brain regions is essential for setting the level of anxiety in animals.
We don’t know how or why this cannabinoid signaling system disappears or disintegrates in response to stress, but it does result in a stronger connection between these two regions and an increase in anxiety behaviors in mice. Understanding what causes this compromise, what causes the signaling system to return after a few days, and many other questions about the molecular mechanisms by which this happens are things we want to follow,” said Patel, who is also James G Professor Blakemore of Psychiatry and Behavioral Sciences, Molecular Physiology and Biophysics and Pharmacology.
David Marcus, a graduate student in neuroscience and first author of the article, and S. Patel are also interested in how the system responds to more chronic forms of stress and whether other environmental exposures compromise or enhance this system to regulate behavior.
cannabis short circuits brain connections related to stress and anxiety disorders
In general in Scientific Terms: Functional coupling between the amygdala and the dorsomedial prefrontal cortex (dmPFC) has been implicated in the generation of negative emotional states; however, the mechanisms by which stress increases the synaptic strength of the amygdala-dmPFC and generates anxiety-like behaviors are not well understood. So, we show that the circuit of the prefrontal pre-limbic cortex of the mouse basolateral amygdala (BLA) (plPFC) is engaged by stress and activation of this pathway in the anxiogenic. Besides, we demonstrate that exposure to acute stress leads to a sustained increase in synaptic strength within a reciprocal BLA-plPFC-BLA subcircuit.
Most important, we identify endocannabinoid signaling mediated by 2-arachidonoyl glycerol (2-AG) as a key mechanism limiting glutamate release at BLA-plPFC synapses and the functional collapse of multimodal 2-AG signaling as a molecular mechanism leading to the circuit-specific persistent synaptic enhancement and anxiety-like behaviors after stress exposure. So these data suggest that a circuit-specific alteration in 2-AG signaling may facilitate the functional coupling between BLA and plPFC and the translation of environmental stress into affective pathology.
- The BLA-pl PFC circuit is engaged by exposure to stress and its activation is anxiety-provoking.
- Stress enhances glutamate release in a reciprocal BLA-plPFC-BLA subcircuit
- The glutamatergic BLA-plPFC drive is constrained by multimodal 2-AG signaling
- The collapse of 2-AG signaling contributes to stress-induced circuit reinforcement and anxiety.
Although many users swear by the soothing effects of weed, research such as the new Vanderbilt study should help the drug obtain the official seal of approval for the treatment of additional conditions.
Especially, their study explains why weed might actually be a key to reducing anxiety.