The medical world has only recently begun learning about the human endocannabinoid system. In 1990 the cannabinoid receptor CB1 was first cloned. Cannabinoid receptor CB2 was discovered subsequently “in an endocannabinoid system that extends far and wide within the body as a physiologic modulator not only of the central nervous system but also of the autonomic nervous system, immune system, gastrointestinal tract, reproductive system, cardiovascular system, and endocrine network.” (Blurred Boundaries: The Therapeutics and Politics of Medical Marijuana, J. Michael Bostwick, Mayo Foundation for Medical Education and Research, February, 2012.)
Some government agencies do not officially recognize that an endocannabinoid system even exists. Several European nations, as well as Israel, have conducted research on it. And the opening paragraph in a 158-page manual published by the Federal Government of Canada entitled “Information for Health Care Professionals; Cannabis and the cannabinoids” states:
“The endocannabinoid system (Figure 1) is an ancient, evolutionarily conserved, and ubiquitous lipid signaling system found in all vertebrates, and which appears to have important regulatory functions throughout the human body. The endocannabinoid system has been implicated in a very broad number of physiological as well as pathophysiological processes including neural development, immune function, inflammation, appetite, metabolism and energy homeostasis, cardiovascular function, digestion, bone development and bone density, synaptic plasticity and learning, pain, reproduction, psychiatric disease, psychomotor behaviour, memory, wake/sleep cycles, and the regulation of stress and emotional state.”
Figure 1. The Endocannabinoid System in the Nervous System
(1) Endocannabinoids are manufactured “on -demand” in the post-synaptic terminals: anandamide (AEA) is generated from phospholipase-D (PLD)-mediated hydrolysis of the membrane lipid N-arachidonoylphosphatidylethanolamine (NAPE); 2-AG from the diacylglycerol lipase (DAGL)-mediated hydrolysis of the membrane lipid diacylglycerol (DAG); (2) These endocannabinoids (AEA and 2-AG) diffuse retrogradely towards the pre-synaptic terminals and like exogenous cannabinoids such as THC (from cannabis), dronabinol, and nabilone, they bind and activate the pre-synaptic G-protein-coupled CB1 receptors; (3) Binding of phytocannabinoids and endocannabinoids to the CB1 receptors triggers the activation and release of the Gi/Go proteins from the CB receptors and inhibits adenylyl cyclase, thus decreasing the formation of cyclic AMP and the activity of protein kinase A; (4) Release of the Gi/Go proteins also results in the opening of inwardly-rectifying K+ channels (depicted with a “+”) causing a hyperpolarization of the pre-synaptic terminals, and the closing of Ca2+ channels (depicted with a “-“), arresting the release of stored excitatory and inhibitory neurotransmitters (e.g. glutamate, GABA, 5-hydroxytryptamine (5-HT), acetylcholine, noradrenaline, dopamine, D-aspartate and cholecystokinin) which (5) once released, diffuse and bind to post-synaptic receptors; (6) Anandamide and 2-AG re-enter the post- or pre-synaptic nerve terminals (possibly through the actions of a specialized transporter depicted by a “dashed” line) where they are respectively catabolized by fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase (MAGL) to yield either arachidonic acid (AA) and ethanolamine (ETA), or arachidonic acid and glycerol. See text for additional details. Figure adapted.
The endocannabinoid system is believed to regulate neurotransmitter release at the synapse. Their locations within the human body, and their effects on human health are far too broad to be answered fully within the confines of this FAQ.