How Can Medical Marijuana and CBD Improve Your Health

   How Can Medical Marijuana and CBD Improve Your Health:  The Nitty-Gritty Details of Endocannabinoids and Their Receptors


The two identified cannabinoid receptors are the CB-1 receptor and the CB-2 receptor.  A third receptor the GPR-55 receptor is suspected of being the CB-3 receptor, but there is much confusion and disagreement about this at present.  Both receptor types exist in the brain and the body, and both are activated by the endocannabinoid neurotransmitters, AEA (anandamide), and 2-AG.  CB-1 receptors are more prominent than CB-2 receptors in the brain and central nervous system, while CB-2 receptors are more prominent in peripheral tissues. 


For a receptor to be activated, it must have a substance (ligand) that attaches to it and alters chemical and/or electrical activity in the affected cell or tissue.  In the brain, this can involve nerve cell transmission or activation of the other cells that make up 90% of brain tissue, called glial cells. In the brain, the CB-1 receptors are quite involved in nerve cell signaling, while CB-2 receptors are involved in local inflammatory and anti-inflammatory responses.


Nerve signaling in the brain involves the structure and function of nerve cells.  Nerve cells have several components.  Most basically, they include nerve cell bodies, long projections from the central body called axons, and multiple, tentacle extensions called dendrites.  Electrical impulses travel from the body of the neuron, down the axon, and trigger neurotransmitter release from the end of the cell at the dendrites.


Axons are coated with insulation known as myelin of are left bare.  Myelinated nerves conduct electrical signals faster than unmyelinated nerves, which affects the speed at which electrical signals reach their targets.  The nerve cells are “connected” to each other at nerve endings, where there are small gaps where the neurotransmitter is released from the dendrites.  The chemical neurotransmitters then cross the gap to bind specific receptors on the body of the receiving neurons - and cascades of signals are sent along in this manner like railway car connections. 


This system allows nerves to transmit signals at variable speed, frequency, and intensity, creating an infinitely adjustable movement of information throughout the brain.  This, in turn, allows the brain to respond to the information in a nuanced fashion, instructing the body precisely how to change. 


Endocannabinoid receptors are located on presynaptic nerve endings.  Signaling in a retrograde (backwards) manner, endocannabinoid neurotransmitters are largely nonexistent until constructed in the synapse on demand.  As this happens, the brain constantly adjusts to signals coming form the body and from itself, shifting its patterns.  The temptation to treat the brain as if tis made up one one hundred billion nerve cells that determine how it functions is compelling, but it would be a hug underestimate of brain function.  There are nine times more glial cells in the brain than there are neurons.  For a long time, these cells were considered to only hold the nerve cells in place, but we now know they do much more.  These functions include nutrition, energy production, network coordination, protection, immunity, and synaptic plasticity.  To accomplish these tests, glial cells must communicate with nerve cells.  They achieve this through CB-1 receptors located on both nerve and glial cells.  The brain does more than receive information, sending out signals to the body that cause changes in the way we experience our surroundings, the way we behave, the way we mature and age, and the way we deal with illness or injury.  These brain changes, in response to incoming signals, are a basic aspect of neuroplasticity.


Neuroplasticity is a hug topic in and of itself.  It is an important thing to understand, because it determines a great deal about how people function and behave.  The brain constantly changes according to input from the body and constantly changes the body in return.  As the brain receives signals, it adjusts its own perception and makes changes to the connective tissue system, musculoskeletal system, neuroimmune system, autoimmune system, cardiovascular system, metabolic system, and all the organs in the body.  These are used on the brain’s perception of danger and safety.  Unfortunately, in many chronic conditions, the brain’s neuroplastic adaptations can be counterproductive and even destructive to the body.  There is a constant struggle throughout the lives of individuals between building up systems and breaking them down.  Everything living dies, and so the body deteriorates over time.  The brain makes micro-adjustments to itself and the body, to delay death as long as possible.  In the process, the individual person may suffer from various chronic conditions, all of which are attempts to forestall the inevitability of the end of life. These chronic illnesses often miss the mark and hasten death rather than put it off.  They almost always add more misery and discomfort.


We have developed treatments from surgery to medication and non-medical approaches to try to alter these processes, and have had great success in helping people live with their chronic conditions with less discomfort and greater resilience.  We have even been able to put off death in many cases, almost doubling life expectancies.


As we use these powerful approaches, there are often tradeoffs.  We can help spinal dysfunction with surgery, but the mechanical compensations often lead to further breakdown of the spine.  Antipsychotic medications are effective at toning down psychosis, depression and anxiety, but cause unpleasant flattening of affect in many people, who cannot tolerate this loss of emotional experience.  Opioids are very helpful in suppressing pain, but the side effects of tolerance, dependency, and addiction may be a terrible price to pay for pain relief when these treatments go on for any length of time.


The endocannabinoid system is critical to the micro-adjustments the body makes to right itself when things go awry and to maintain itself when things are normal.  The constant struggle in our bodies between breakdown and buildup requires innumerable adjustments throughout a person’s life.  Fortunately, we have multiple systems built into our being, creating minute changes that add up to prolonged comfort and longevity.  The endocannabinoid system doesn’t just put off death, but makes the act of living more comfortable, pleasurable, and adaptable. Since the endocannabinoid system is so newly discovered and so little involved in modern medical interventions or current clinical care, it offers remarkable potential to improve function, longevity, wellbeing, and comfort.  This built-in system, dedicated to restoring balance where it has been lost and stimulating pleasure s a guiding principle of all living things, is a major contributor to health and happiness.


CB-1 receptors are located mostly in the nerve endings in the brain and body, where neurotransmitters are released.  They are activated by both anandamide and 2-AG, the known endocannabinoids.  Their location in the brain affects pain, pleasure, mood, memory, cognition, and motor function.  CB-1 receptors affect other systems in the brain by changing energy metabolism, decreasing cellular nerve firing, and deceasing inflammation.  They also form with other receptors to modify their activity.  CB-1 receptors also exist in immune cells in the brain and body, inhibiting inflammation by slowing down inflammatory cascades.


CB-2 receptors are also located in the brain and peripheral body tissue - mostly in the immune system.  Here the substances that act as neurotransmitters in the brain work as immune cell modulators.  CB-2 receptors are also located on nerve tissue in the brain, but their use there remains unknown at present.  When an inflammatory process begins, they are on glial cells in the brain.  Anandamide then activates them, starting the resolution of brain inflammation.  CB-2 receptors on bone-forming cells activate bone formation when stimulated.


The CB-1 and CB-2 receptors belong to a family of receptors know as G-protein coupled receptors.  This is important because receptors in this family, including the endocannabinoid receptors, have to be created and replaced every two to three days. This dynamic receptor population allows for increases or decreases in these receptors in response to what is happening in the body.  Activated CB-1 receptors influence the activation of AEA and 2-AG, but also other neurotransmitters, including norepinephrine, serotonin, dopamine, orexin, histamine, GAGA, and endorphins.   They are most frequently located on nerve endings in the autonomic nervous system.  As a result, they affect many of the automatic functions in brain and body, fine-tuning everything from breathing and heart rate to connective tissue health and metabolic rate.  CB-2 receptors increase during bone resorption and decrease during bone development in direct relationship to the amount of another receptor, the TRPV-1 receptor, which causes breakdown of bone, chronic inflammation, and pain.  CB-1 and CB-2 receptors have  a profound effect on the gut, both in healthy states and in illness.  Virtually all due functions are controlled by the endocannabinoid system.  Stimulating CB-1 receptors in the gut increases gut motility in healthy states, but stimulation of CB-1 and CB-1 decreases excessive abnormal motility in GI illness.  CB-2 stimulation restores normal but motility.  Cannabinoid receptors are usually absent in the liver, but when the liver becomes fatty, they are expressed in multiple cell types.


The receptors frequently have opposite effects, which is how they are able to adapt to changing conditions within the body.  For instance, CB-1 activation promotes increased blood lipid levels and liver fibrosis, but CB-2 receptors decrease blood lipid level, fibrosis, and liver inflammation.  Typically, such conflict appears to happen in illness-related conditions rather than in normal states.  Another example of this coccus during cardiac disease.  Then, activation of CB-1 receptors may make heart health deteriorate, while activation of CB-2 receptors promotes cardiac health.  The CB-2 receptor is highly active in the immune system and lowers inflammation.  In muscle tissue, activation of CB-1 may either promote or inhibit energy use, leading to muscle formation or destruction.  In obese individuals, the endocannabinoid system gets more active with CB-1 activation, decreasing the effect of insulin in driving sugar out of the bloodstream and into the muscle cells.  On the other hand, activated CB-1 receptors are instrumental in bone formation and can prevent osteroporosis.  It appears that CB-2 receptors do the opposite. 


The endocannabinoid system highly regulates nervous system and brain health.  This includes the development and specialization of both nerve and glial cells.  CB-1 and CB-2 receptors are also present on the various glial cells that make up 90% of brain cells, and are involved in embryonic placement of nerve cells, structural and nutritional support of nerve cells, the function of the neuroimmune system, development and maintenance of the blood-brain barrier, myelination of nerve axons, regulation of neurotransmitter release, amount and spread, regulation of synaptic growth and development, reading and adjusting circulating molecules in the capillaries, activating inflammatory pathways in brain and specific body areas, and coordinating intellectual function of nerve cells.  The endocannabinoid system and particularly the CB-2 receptor are also involved in new nerve cell formation in the adult brain.  Hence, the endocannabinoid system is highly involved in regulation of adult neuroplasticity throughout life.


Dr. Allison Kendrick

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