Endocannabinoid System


The endocannabinoid system (ECS) is a "homeostatic" mechanism. Homeostasis is the steady state of internal physical and chemical conditions within a living organism. The many interrelated systems in the human body (nervous system, immune system, digestive system, etc.) are in a particular stable balance and are adjusted to conditions which are best for the survival of the organism. Imbalance of homeostasis can lead to a variety of disease states and symptoms. The ECS is involved in regulating appetite, pain sensation, mood, digestive functions, memory, immune response, inflammatory responses and tumor suppression.

Your body produces cannabinoids, called endocannabinoids, just as it produces opiates, called endorphins. Research into the endocannabinoid system has paralleled the research into endorphins.

The endorphin system was discovered when the specific site of action where morphine exerts its effects, the receptor, was identified. Furtherer research then found naturally occurring opiates produced in the body and the receptors on which they had an effect. Our understanding of the endorphin system has led to the development to a variety of exogenous (form outside the body) drugs which are used to activate the opiate receptors present in the body. The endorphin system is primarily involved in pain perception, enhancement of immune response, modulating stress responses and causing euphoria by activation of "reward" centers in the brain.

Endocannabinoids are produced by the body. The best studied are anandamide (abbreviated AEA) and 2-arachidonoylglycerol (2-AG). The primary receptors on which they work are called, of course, cannabinoid receptors. Cannabinoid receptors are primarily the CB1 and CB2 types and are present throughout the body. It is the location and density of these receptors which determine the effects their activation produce. CB1 receptors are located in the highest density within the central nervous system (brain and spinal cord) and on peripheral nerves. The distribution of CB1 receptors correlates with its role in memory, thinking processes, movement functions and pain perception. AEA primarily activates the CB1 receptor. 2-AG is more activate the CB2 receptors which are most prominent in peripheral organs that have immune system function.

Endocannabinoids are produced when needed and released by the postsynaptic cell (the cell effected by the neurotransmitter) which then combine with cannabinoid receptors on the presynaptic cell (which released the neurotransmitter) to decrease the amount of neurotransmitter released by the presynaptic cell. They work as a negative feedback mechanism. The particular pathway these nerves are involved with can be inhibitory or excitatory, although the function of the cannabinoids is always the same: to "turn down" the activity of the particular pathway. Decreasing the activity of an excitatory pathway decreases the nerve processes associated with it while endocannabinoids function on inhibitory pathways is to increase the those processes.

The endocannabinoids, as are all neurotransmitters, are then disposed of after "delivering the message" to prevent continued activation of the receptor. They are moved into the presynaptic neuron for storage and metabolized by enzymes called FAAH and MAGL to inactive forms.

A basic understanding of the endocannabinoid system is necessary as it is the phytocannabinoids (cannabinoids produced by plants) which interact with the endocannabinoid system. Choosing the right combination of phytocannabinoids for your particular symptoms and conditions is the first step in achieving the best possible response in using medical cannabis.

Brian Nichol MD
Cannabis Expert