How Chronic Stress Impairs the Endocannabioid System

In general, research into the body’s endocannabinoid system proceeds via administering a substance like a cannabinoid or another drug, and recording the impact of that administration on a specific behavior or physiological process. However, few experiments consider the reverse question: how do our behaviors and environments affect the endocannabinoid system? This system, like most other neurological systems, is not made up of a rigidly fixed number of receptors or ligands. Instead, it constantly changes and adapts to best serve the body, ramping up and down receptor density and receptor affinity as the body deems appropriate. Stress is now understood to be one of the factors that can impact the endocannabinoid system. In general, exposure to stressful events can easily cause a diverse and lasting set of consequences in both humans and animals. In what is most likely the body’s attempt to overcome and live with chronic stress or the possibility of another stressful event, synapses, which are the paths of communication between individual neurons, re-wire themselves. One extreme example is the maladaptive change that can occur in soldiers put in life or death situations. Soldiers may, for instance, learn to associate sounds heard during such a stressful event with the occurrence of the event itself. Later, in non-hostile environments, these same sounds can then trigger the body and brain to re-live the event, with intense physiological changes, such as the release of adrenaline and increased aggression. This is a classic example of PTSD (Post Traumatic Stress Disorder). However, stress can…

Anandamide

Up to this point, we haven’t spoken much of the body’s own endocannabinoids. As a quick refresher, the endocannabinoid system consists of receptors and enzymes that metabolize any cannabinoids bonding to those receptors. However, our cannabinoid receptors do not exist for the purpose of consuming externally produced cannabinoids like those found in cannabis. These receptors exist because our bodies produce their own cannabinoids (endocannabinoids), which are used to signal and control various functions. Of all our naturally produced cannabinoids, one of the most important is anandamide (AN). Anandamide, like our other endocannabinoids, is produced on the spot, where needed. It primarily bonds to CB1 receptors, giving it an effect profile similar to THC, the well-known psychoactive ingredient of cannabis. FAAH (fatty acid amide hydrolase) then metabolizes the anandamide, clearing the receptor for re-activation. Because anandamide is produced locally where needed, while external cannabinoids, like THC, are supplied to any tissue, comparing effect differences may be comparing apples to oranges. However, an oversimplification would be that ananadmide is the body’s own THC with a shorter effect endurance. In fact, the name “anadamide” is actually based on the Sanskrit word “ananda”, meaning “joy” or “bliss”. Rimonabant, the failed weight-loss drug we often reference on the blog, blocked CB1 receptors from being activated by anandamide. From known research, we can now safely guess that many of the negative psychological effects of Rimonabant resulted from preventing the body from using its own anandamide. In other words, anandamide seems to hold at least one key…