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Role of the Endocannabinoid System in Mood Homeostasis

From love to hate and from happiness to sadness, our lives are vastly defined by emotions. But how do we experience these emotions? And how do emotions contribute to our mood? The answer might just be found in the growing field of endocannabinoid sciences, which focuses some of its efforts on finding the role of the endocannabinoid system in mood homeostasis.

What is mood homeostasis

Homeostasis is the state in which a given system will be able to function sustainably and consistently. Aside from sugar levels, iron, water, blood pH, etc., the brain also needs to maintain balance in mood so we can continue to behave in a productive and sustainable way.

Unlike emotions, which are short-lived feelings that have an objective cause, mood is based on a pattern of longer-lasting feelings that have no clear cut cause, and are more indicative of one’s sense of well-being.

Mood is heavily influenced by environment (weather, lighting, people around us), physiology (what we’ve been eating, how much we’ve been exercising, how healthy we are in general), and current mental state (where our attention is focused, and our current emotional state.) Emotions are highly specific, like thoughts without words, while moods are generally either positive or negative, without a more specific nature.

What is the role of the Endocannabinoid System in Mood Homeostasis

Cannabis and its derivatives have a complex biphasic (having opposing effects at different doses) relationship with the physiology of the human body. With respect to mood, cannabinoid agonists in the brain elevate an organism’s mood by mitigating stress in low doses. To illustrate, in animal studies, scientists found that when given low doses of cannabinoids, animals have decreased anxiety or anxiolytic effects in acute restraint tests. However, at higher doses the opposite was true, with increased anxiogenic effects.

Cannabinoid CB1 Agonist CP 55,940 increased immunoreactivity in brain structures such as amygdala, hippocampus, anterior cingulate cortex, and prefrontal cortex. These regions are deeply involved in the emotional response to anxiety and fear, in particular the central nucleus of the amygdala.

We understand that the function of presynaptic cannabinoid receptors in the brain is to end a single firing of a neuron. When a neuron fires, chemical neurotransmitters travel from the presynaptic neuron to the postsynaptic neuron. When they interact with the postsynaptic neuron, it releases endocannabinoids, which travel retrograde to the presynaptic neuron and activate cannabinoid receptors there. These cannabinoid receptors are like an “off switch on the presynaptic neuron, causing the signal to cease. This whole process happens in less than a millisecond.

Scientists believe that the endocannabinoid system is implicated in regulation of aversive-stress related stimuli because the dysregulation of the ECS has been associated with deficits in behavioral flexibility which manifests into stress-related PTSD and depression. Just like the tonic (automated) release of endocannabinoids functions as the “end” of a single firing of a neuron, when the same endocannabinoids are released prior to a firing of that neuron, they can prevent it altogether. By regulating emotional processes in this way over a long-term period, mood is produced.

Endocannabinoids have been reported to act in a retrograde manner at the synaptic level, meaning they travel the opposite direction of the primary signal, providing a mechanism for positive and negative feedback. Though the number of roles of retrograde endocannabinoid signaling in vivo has not been clarified yet. According to one extensive research study, endocannabinoids “are synthesized “on demand” at the postsynaptic sites of neurons after an increase in neural activity and [concurrent] calcium ion influx, and are then released into the synaptic cleft. Their main function appears to be the suppression of neurotransmitter release from the presynapse. Thus, eCBs act as retrograde neurotransmitters, modulating other neurotransmitter systems” through inhibitory retrograde feedback.

Can endocannabinoid deficiency affect Mood

Through and through, scientists have conferred, based on pharmacological modulation, that the endocannabinoid system has therapeutic potential because of the negative effects caused by deficiency of this system. Because increased pain sensitivity, anxiety, panic disorders, depression, and psychosis are associated with dysregulation (or pharmacological antagonism) of the ECS, it is logical that maintaining the health and normal function of the endocannabinoid system could produce the opposite result. The endocannabinoid system is critical in the regulation of emotion and stress.

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