Monoamines are neurotransmitters, such as serotonin, epinephrine, and dopamine, that play vital roles in regulating anxiety and mood. However, the vast majority of conventional drug-based therapies that target these monoaminergic systems have a limited efficacy.
Recently, there has been more research into the role of the endocannabinoid system (ECS) and cannabinoids for maintaining healthy stress levels.
The Role of the ECS in the Human Body
We have established in past articles that the ECS is a complex network within the human body made up of cannabinoid receptors (CB1 & CB2). Balance within the system is maintained by endogenous endocannabinoids (cannabinoids made within the body) such as 2-AG and anandamide. Enzymes act to regulate the use and the degradation of the active endocannabinoids.
It is not surprising that the biochemical machinery and cannabinoid receptors necessary to generate cannabinoids are equally located within the brain regions that control mood, stress, fear, and emotional behavior. These sub-organs include the amygdala, the prefrontal cortex, periaqueductal gray region of the midbrain, and the hippocampus.
Endocannabinoid Receptors Activated in the Brain
Studies conducted in mice have shown that activation of endocannabinoid receptors within the periaqueductal gray region, for instance, through the direct injection of anandamide, minimizes anxiety behavior and panic behavior, or the fight or flight response. Similar animal studies have shown reduced fear-avoidant and conditioned responses to punishment or pain.
However, before we jump to the conclusion that we have anxiety, fear, stress, and all emotional responses figured out, it isn’t as simple as activating the receptors via administration of the cannabinoids. Animal studies making use of systemic injections of THC have shown mixed responses–either reducing or increasing anxiety.
This paradoxical and bidirectional response appears to be dependent on dosage, where reduced doses seem to lower panic, stress, and anxiety. These counter effects may occur as a result of the involvement of other neurotransmitter circuits within the brain region that, when inhibited, will result in a hyper-excitable response including stress, fear, and anxiety.
Cannabinoids and Maintaining Healthy Stress Levels
The theory exists that 2-AG and anandamide act as gatekeepers to maintain stress response and keep high emotional loads at bay while improving recovery to pre-stress levels upon reduction of the stress burden to baseline. Moreover, preliminary human studies have shown that interrupting endocannabinoid signaling and regulation greatly impacts on the hypothalamic-pituitary-adrenal axis by raising the signs of anxiety and depression.
There is an emerging role in the interaction between the neuroendocrine system and the immune system, such that within the last five years, there has been intense research in the field of psychoneuroimmunology. The interaction between cytokine signaling, the immune system, and the nervous system influencing anxiety, mood and behavior have been proposed by a number of preclinical studies. Studies conducted recently have tried to highlight the role of CB2 receptors linked with the immune system in depression and anxiety-related behavior in human clinical trials and animal models.
It is interesting to note, in this context, that a balanced ECS appears to play an important role in healthy stress response, mitigation of fear and anxiety, and panic that tend to accumulate with dysfunctional stress responses.
Constant stress, whether emotional, psychological, or physical, raises the level of cortisol in the blood, thus causing inflammation. As a matter of fact, high-stress levels correlate with an inability of the body to regulate inflammation. When the immune cells lose their sensitivity to the regulatory effects of cortisol, then inflammation results which promotes the development of a number of chronic ailments.
Therefore, to minimize the impact of stress, inflammation must be addressed. Industrial hemp-derived cannabinoids, most especially cannabidiol (CBD), has potent effects on inflammatory processes. The body synthesizes its own cannabinoids in the body’s ECS, and this system plays a critical role in body homeostasis.
Studies have shown that cannabinoids influence inflammation. The endocannabinoid receptors are present in all body cells and are expressed in very high levels in the immune and nervous system. Cannabinoids influence the activities of at least a thousand different genes. These may help boost the cellular antioxidant defenses while downregulating a number of pro-inflammatory mediators.
CBD: A Tonic for the Brain
It should also be noted that cannabinoids stimulate the development of new neurons within the brain, thus inhibiting depression. They equally modulate the actions of receptors linked with symptoms of anxiety. Cannabinoids appear to function as a tonic for the brain, safeguarding against chronic stress, which can inhibit the growth and density of new neurons on certain parts of the brain.
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