We already know that humans have our own endocannabinoid systems, made to regulate a number of bodily functions with a number of cannabinoid receptors that interact with compounds like THC and CBD in cannabis.
Brain activity patterns and neural circuits regulated by these cannabinoids derived in the brain were not well known, but new research has revealed our bodies may actually release their own cannabinoid molecules in specific circumstances, independent of external cannabinoid use.
According to a new mice study from Northwestern Medicine published in the journal Cell Reports, the brain’s key emotional center, the amygdala, releases its own cannabinoid molecules under stress. When released, these molecules work to decrease incoming stress alarms from the hippocampus, which controls memory and emotions in the brain.
The study results add further evidence to the assertion that the brain contains innate cannabinoid molecules, key to our body’s natural coping response to stress. Further, the study may indicate that impairments to this endogenous (the body’s own) cannabinoid signaling system in the brain could result in higher susceptibility to developing psychiatric disorders related to stress, like depression and post-traumatic stress disorder (PTSD).
Still, further research is needed to determine exactly how these mechanisms work in the human brain, said corresponding study author Dr. Sachin Patel.
The Human Body’s Self-Made Cannabinoids and Understanding Stress
“Stress exposure confers risk for the development or exacerbation of psychiatric disorders: from generalized anxiety and major depression to post-traumatic stress disorder,” authors state in the introduction. “Understanding stress-induced molecular-, cellular-, and circuit-level adaptations could provide critical insight into how stress is translated into affective pathology and may reveal novel therapeutic targets for the treatment of stress-related disorders.”
Scientists at Northwestern Medicine used a new protein sensor that can detect the presence of these cannabinoid molecules in real time at specific brain synapses, which show that specific high-frequency patterns of amygdala activity can generate the molecules. Additionally, the sensor showed that mice brains released these molecules in response to several different types of stress.
Scientists also removed the target of these cannabinoids, the cannabinoid receptor type 1, which resulted in a worsened ability to cope with stress and motivational deficits in mice. After scientists removed the receptor target of the endogenous cannabinoids at hippocampal-amygdala synapses, mice adopted more passive and immobile responses to stress. They also had a lower preference to drink sweetened sucrose water after stress exposure.
“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 Patel and Lizzie Gilman, Professor of Psychiatry and Behavioral Sciences and a Northwestern Medicine psychiatrist.
The endocannabinoid system is one of the leading signaling systems identified as a prominent drug-development candidate for stress-related psychiatric disorders, Patel said. This system is an active, complex cell signaling network, involving a combination of endocannabinoids, enzymes and cannabinoid receptors helping to regulate a number of biological functions — like eating, anxiety, learning, memory, reproduction, metabolism, growth and development — through an array of actions across the nervous system.
This hypothesis is crucial in determining where future research guides this continued conversation, Patel said.
“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,” Patel said. “There are ongoing clinical trials in this area that may be able to answer this question in the near future.”