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CBD Role in Stress, Anxiety, and Fear Responses and The Endocannabinoid System

By Dan Putnam April 30, 2017 0 comments

During stress, glucocorticoid hormones (e.g. cortisol) are secreted from the cortex and can produce a variety of physiological changes that can prove beneficial in the short term. However, when confronted with repetitive exposure to stress, diminished glucocorticoid response is critical as continued glucocorticoid secretion could have harmful effects on metabolic, immune, cardiovascular, and neurobiological function. The hormones from the hypothalamus (a section of the brain), is responsible for key physiologic functions such as temperature regulation, thirst, hunger, sleep, mood, sex drive, or in essence, to maintain homeostasis, which is to maintain balance or equilibrium throughout the body. Endocannabinoid signaling in the hypothalamic-pituitary-adrenal (HPA) system reacts to and controls the activity of the hypothalamus that regulates the secretion of glucocorticoids and other hormones throughout the body. Current scientific evidence appears to suggest that in order to support a healthy stress response, the endocannabinoid system must remain balanced. Data also points to the cannabis compound cannabidiol as an agent for modulating emotional behaviors such as stress, fear, and anxiety.

The Potential Role of the Endocannabinoid System (ECS) in Tackling Stress, Fear, and Anxiety

Stress presents a challenge to homeostasis in the body and can disrupt an individual’s normal functioning day to day. Fear can be a factor either in acute stress response or a maladaptive response (inappropriate based on the situation) to a perceived threat. Anxiety is characterized by excessive fear and even avoidance of an object or situation that poses no real danger. While the hippocampus is often implicated in stress response, the amygdala also plays a crucial role in the mediation of anxiety and fear. Still, while much of the research on the subject has long focused on the role of the certain neurotransmitters such as monoamines(e.g. dopamine, serotonin, and norepinephrine) in controlling mood and anxiety, clinical intervention that targets those neurotransmitters have shown to be less than 100% effective in ameliorating stress, fear, and anxiety. Today, researchers are gradually making the case for the potential role of the endocannabinoid system (ECS) in stress and fear responses. Endocannabinoid signaling may be useful as a regulatory buffer system for emotional responses, by maintaining emotional homeostasis.

The ECS comprises of cannabinoid receptors, namely CB1 and CB2 that are located in the areas of the brain known to control emotional behaviors- mood, stress, and fear. There are endogenous cannabinoid compounds such as anandamide and 2- arachidonoyl glycerol fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) and their respective enzymes that have been demonstrated to have promising therapeutic effect. The cannabinoid receptors in the body are the primary targets of cannabis compounds such as tetrahydrocannabinol (THC) and cannabidiol (CBD). Researchers believe that CBD attenuates the neurofunctional engagement of the amygdala and cingulate cortex when confronted with fearful stimuli, and this effect is correlated with a reduction in the skin conductance response (marker for emotional response), consistent with behavioral evidence that it has anxiolytic (anxiety reducing) effects.

CBD and Fear, Stress, Anxiety Reduction

Since the endocannabinoid system is linked homeostatic balance, can be found throughout the body, and comprises of receptors that CBD can bind to and activate certain responses, it is not farfetched to consider the role that CBD could play in minimizing fear, stress, and anxiety. More compelling are the studies that show to some degree the extent of that relationship.

In one study, researchers investigated the potential involvement of hippocampal neurogenesis in the anxiolytic effect of CBD in mice subjected to 14 d chronic, unpredictable stress (CUS), and were administered CBD (30 mg/kg i.p., 2 h after each daily stressor), which increased hippocampal neurogenesis and prevented the anxiogenic (causes anxiety) effect of CUS. The study points to the facilitation of endocannabinoid-mediated signaling as a significant factor in CBD exerting its anxiety reduction effect.

Furthermore, human studies have also validated the possible anxiolytic effect of CBD. Researchers investigated the anxiolytic effects of CBD on pathological anxiety in 12 subjects with social anxiety disorder (SAD), who received CBD (600mg) and another 12 who received placebo; the results show that SAD group that received CBD presented lower levels of anxiety in the anticipatory and performance phases compared to the placebo group.

Research indicates that the endocannabinoid system (ECS) plays an essential role in maintaining homeostasis in the body, and that in order to achieve this equilibrium, there must be balance in the ECS. This in turn, creates a system that can support health stress, anxiety, or fear response. Furthermore, the ECS comprises of cannabinoid receptors that bind to CBD or THC, which can result in these compounds exerting therapeutic effects that can reduce negative emotional behaviors. There is much research to support the anxiolytic effects of CBD, but more investigation into the efficacy of CBD in treating stress and fear is warranted.


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