Endocannabinoid System Immune System Science

Immunity and the ECS, Part 3: Homeostasis

ECS effect on baseline immune cell activity

The complexities of the human immune system have been studied for centuries, but only recently has the existence of the endocannabinoid system become a subject of intrigue. In immune cells, there are around 100 times more CB2 receptors than CB1 receptors. CB2 is involved in negative feedback of ATP, which is the body’s primary source of cellular energy. This receptor also regulates the cellular presence of cAMP, which is the precursor to most of the enzymes that our bodies use, and more cAMP = more activity.

Interestingly, anandamide and 2-AG, the body’s primary endocannabinoids, are never synthesized simultaneously in the same cell, suggesting contradictory effects, namely, 2-AG induces cAMP production and anandamide induces cAMP degradation.

More specific mechanisms of ECS immune activity

Activation of cannabinoid receptors also up regulates MAPK pathways, which are essential for the initial cell response to any stimuli. In immune cells, this increases the amount of those surface antigens that bind to enemy bodies, so they can be eradicated more efficiently. It also promotes chemotaxis, which is the movement of a cell in the direction of a specific chemical stimulus, i.e. inflammatory hormones released at the site of an injury or infection.

In promoting the migration of immune cells toward a stimulus, activation of cannabinoid receptors indirectly reduces the production of inflammatory factors because their purpose (to attract immune cells to the site) has been carried out faster than usual. This contrasting modulation of two of the most vital pathways in immune cells is evident of the homeostatic effect that the ECS has on immune activity.

Homeostasis as a product of the ECS

In addition to antigens from foreign organisms, our bodies also produce alarm antigens whenever there is an injury, and this process is generally referred to as the inflammatory response. In the environment of an inflammatory response, CB2 receptor activation by either endocannabinoid actually mediates a negative feedback reversal of cAMP levels, which serves to balance out the inflammatory response in a hormone-level-dependent manner.

This means that if an injury is really bad, then more of the inflammatory hormones will be released, and therefore more CB2 receptors will be activated, reducing the cellular activity level to combat the overwhelming effect of proinflammatory hormones, in a textbook negative feedback loop.

In this way, the ECS is a very potent homeostatic modulator of the immune system. Supplementing our own endocannabinoid system with CBD-rich phytocannabinoid oil has consistently demonstrated an increase in immunity to novel pathogens, suggesting that augmenting our ECS has a positive effect on baseline immune system activity.