ATrain Education


Continuing Education for Health Professionals

Cannabis (Marijuana) for Medical Use

Module 3

The Endocannabinoid System

An evolving body of science about our physiology was not available to us in school (and unfortunately this information is still absent in most nursing and medical schools). All animals except for insects have an endogenous (made within the body) cannabinoid system, or endocannabinoid system (ECS) (Richmond, 2010). It has been found that we make our own cannabinoids, and they are similar in structure to those of the cannabis plant; further, we have receptors for these molecules. This newly discovered molecular signaling system is essential for life and helps keep us in balance as we deal with daily stressors. Some researchers are suggesting that a weak or overstressed ECS may be the underlying cause of a variety of ailments, such as fibromyalgia or migraine headaches as well as auto-immune diseases. Russo has suggested naming such a problem a clinical endocannabinoid deficiency, or CECD (2004).

In 1988 American researcher Allyn Howlett and her graduate student William Devane discovered cannabinoid receptors in the brain and called them cannabinoid 1 receptors (CB1) (Devane et al., 1988). In 1992 researchers in Israel discovered an endogenous cannabinoid and called it N-arachidonoyl ethanolamine or anandamide (“ananda” means bliss in Sanskrit) (Devane et al., 1992). By 1993 another group of scientists found cannabinoid receptors in the immune system (CB2), followed by the discovery of a second endocannabinoid called 2-arachidonoyl glycerol or 2-AG (Munro et al., 1993).

The CB1 receptors are found mainly on neurons in the brain, spinal cord, and peripheral nervous system, but are also present in other organs and tissues including immune cells, the spleen, adrenal and pituitary glands, heart, lungs, and parts of the reproductive, urinary, and gastrointestinal tracts. The CB1 receptors are abundant in the cerebral cortex, basal ganglia (substantia nigra pars reticulata, globus pallidus, nucleus caudatus and putamen), cerebellum, hippocampus, peri-aqueductal grey, rostral ventromedial medulla, certain nuclei of the thalamus and amygdala, and dorsal primary afferent spinal cord regions, which helps explain the role of cannabinoids in motor control, memory processing, and pain modulation. The low number of CB1 receptors in the brain stem may help explain the absence of cannabis overdoses due to the depression of respirations. The CB2 receptors are primarily found in immune cells, among them leukocytes, the spleen, and tonsils. There are cannabinoid receptors throughout our bodies, and we have more receptors for cannabinoids than for any other substance (Grotenhermen, 2005).

The endocannabinoids bind with the cannabinoid receptors in a fashion similar to other neurotransmitters and can exert various effects depending upon the lock-and-key mechanisms. They can activate the receptors as full agonists or partial agonists, or they can dock in a receptor and act as a neutral antagonist, which does not activate the receptor, or as an inverse agonist, in which case it deactivates the receptor.

The endocannabinoids are not stored in the body, but are synthesized and released on demand. The activation of these endocannabinoids influences other chemical reactions, producing a cascade effect. The ECS helps in maintaining homeostasis and has the ability to move back and forth across the synapses between cells and may exert either an excitation or inhibition of activity (McPartland, 2008).

Robert Melemede calls the ECS the “oil of life” because it keeps numerous physiologic processes running smoothly (Melamede, 2006). Endocannabinoids serve as neurotransmitters or neuromodulators. Italian researcher Vincenzo DiMarzo noted that the ECS helps us eat, sleep, relax, protect, and forget (1998). The existence of this molecular system may explain why cannabis is helpful for such a wide array of conditions.

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