Endocannabinoid System

It’s not just our own endogenous opioid system that provides feel good benefits, we have an endogenous cannabinoid system that does as well. This system primarily influences neuronal synaptic communications in the brain and affects all our biological functions from mood, inflammation, pain, metabolism, reproduction, growth and development to other central and peripheral nervous actions that help regulate and maintain homeostasis within the body. And just like endorphins they increase after exercise, exerting analgesic effects similar to opioids. In fact the feel good “runners high” may have more to do with this system than our endogenous opioid one.

It’s pretty shocking to think we first identified this incredibly important system in the 1990’s. Especially since it is so critical to most of our bodily functions. Unlike classic neurotransmitters, the endocannabinoid (EC) system controls nociception at the neuronal synapses where pain is actually processed. They are not stored at these sites but instead produced on demand following neuronal activation. This puts them in the unique position to act as a brake in response to high activity. For pain pathways this means they can produce an analgesic or “antinociception” response- the act of blocking the detection of painful or harmful stimuli so pain is decreased. They also suppress pro inflammatory cytokines and enhance anti- inflammatory ones.

After a nerve is injured, repair mechanisms kick in, causing inflammation and hyperexciability within the damaged neurons. The ECS plays a crucial role by reducing inflammation, decreasing pain sensitivity, and blocking pain signals from reaching the brain. When naturally occurring inhibiting neurons are not able to shut the hyperexcilability down, a viscous cycle results that can lead to chronic, persistent pain, resistant to treatments.

Endogenous cannabinoids or endocannibinoids are naturally occurring lipid based neurotransmitters- chemical messengers within the body that send signals between nerve cells. We only produce what we need, when we need them.

Two main encannibinoids are:

• Anandamide
• 2- arachidonoyl glycerol (2AG)

There are two enzymes that both produce and break down endocannibinoids:

• Fatty acid amide hydro laser breaks down anandamide
• Monoaclyglycerol which breaks down 2AG.

There are two primary receptors:

• CB1 located in both the peripheral and central nervous system, but CNS expression is far greater. It acts as a gateway for noxious stimuli to pass from the peripheral to the central nervous system.
• CB2 is thought to reside primarily, but not exclusively, in the immune cells e.g. macrophages, lymphocytes and mast cells. When activated it inhibits inflammation.

The ECS is complicated, and experts haven’t yet determined exactly how it works or all of its potential functions. 

Research has made clear how widespread and important this system is to every aspect of the body-

• Appetite and metabolism. It modulates how we feel about foods by acting at specific areas of the brain, especially the Mesolimbic system. As well as regulating food intake, energy balance and lipid metabolism through both the peripheral and central pathways.
• Chronic pain. The ECS is now known to be key in modulating pain sensations at all stages of pain processing pathways.
• Mood. It’s known impact on the limbic system within the brain has shown how much the ECS can exert over emotional responses and mood. New research has shown deficits in endocannibinoid signaling appears to result in depression and anxiety.
• Learning. The ECS appears to play a critical role in fine tuning neural transmissions that ultimately regulate learning and memory processes.
• Sleep. Studies show a clear overlap between the brain’s endicannibinoid system and sleep- wake circuitry. ECBs promote both rapid and non rapid eye movements by interacting with melatonin concentrating hormone neurons in the lateral hypothalamus.
• Motor control. Studies have shown endocannibinoids play an important role in producing motion from not only current pathways but also for their ability to reconfigure networks to learn new motor skills. This opens up all sorts if excite possibilities for the treatment of Parkinson’s, MS, even dementia.
• Cardiovascular system. They appear to have both a beneficial and deleterious effect on the cardiovascular system. On one hand they decrease cardiac work and progression of atherosclerotic plaques as well as tissue damage and arrhythmias during a myocardial infarction, may reduce progression but they also appear to affect gene mutations that promote cardiac dysfunction.
• Muscle formation. Skeletal muscle is critical for whole body health and is the principal tissue responsible for insulin mediated glucose uptake. New evidence shows ECS disfunction may play an important role in peripheral insulin resistance.
• Bone growth and remodeling. Bones are constantly changing, with a fine balance between osteoclastic activity- bone absorption, and steoblastic activity- bone deposition. CB1 receptors have shown osteoclastogenic effects and CB2 stimulation exerts anti-osteclastogenuc ones
• Liver function. It regulates a wide array of glucose and lipid metabolism in the liver. Impairments in this interaction results in a variety of metabolic issues. The resultant accumulation of fat along with insulin resistance is the main cause fatty liver changes or NAFLD.
• Reproductive function. They impact both male spermatogenesis and the female oocyte and follicular maturation, implantation of the blastocyst, endometrial proliferation and transport of the embryo through the oviduct.
• Stress. The amygdala reacts to both real and perceived dangers that can trigger the fight or flight response. New research shows the ECS relays messages to other neurotransmitters involved in producing or preventing stress. In this way it can actually put on the brakes by decreasing activity within the amygdala that produces anxiety and stress in the absence of a real threat.
• Skin. This is where the two main endocannibinoid molecules – 2-AG and anandamide are produced depending on the health of our skin or “cannabinod tone.” They are created in the epidermis, hair follicles and sebaceous glands. This tone impacts all compartments of our skin and their healthy physiological functions.
• Nerve function. It is critical to every aspect of our moment to moment functioning by regulating and controlling many of our critical bodily functions. It does this by being the gate keeper of what nerve signals get through to the brain by determining the levels of other neurotransmitters. Through immediate feedback they turn up or down the activity of whatever system needs to be adjusted.
• Thermoregulation. Sensory receptors in the skin collect data from external stimuli and sends information to the hypothalamus where temperature regulation is monitored. The ECS works to modulate activity in both the neurons that send and receives that neurotransmitter information in order to fine tune body temperatures. Too much we get hypothermia, too little, hyperthermia.

The endogenous cannibinoid system has far reaching and amazing effects on how we feel and function. It’s the traffic cop that directs and modulates many of our bodily needs and sensations like pain. New and exciting data show it’s gate keeper properties that act at the site where signals come and go could lead to amazing new ways to treat chronic pain.

Until then, encouraging our own activation of this feel good system will have to suffice. Next week I’ll explain how we can all to this better.

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-https://www.sciencedirect.com/science/article/abs/pii/S0098299718300359?casa_token=0lGsx1O2Xx0AAAAA:XRuDHU0M0Ps3eyMOr3TmyAxrN-MY1-Ha3_qJtWMvjG3Bm4Vw0HMz75knHCS9z12_L65J3MQx

-https://www.health.harvard.edu/blog/the-endocannabinoid-system-essential-and-mysterious-202108112569

-https://pubmed.ncbi.nlm.nih.gov/25846617/#:~:text=The%20endocannabinoid%20(EC)%20system%20is,stages%20of%20pain%20processing%20pathways.

-https://journals.physiology.org/doi/full/10.1152/physiol.00007.2010

-https://www.healthline.com/health/endocannabinoid-system#deficiency

-https://www.medicalnewstoday.com/articles/endocannabinoid#therapeutic-use

-https://pubmed.ncbi.nlm.nih.gov/32619926/

-https://www.researchgate.net/publication/228657215_Peripheral_endocannabinoids_regulate_skeletal_muscle_development_and_maintenance

-https://www.everydayhealth.com/marijuana/can-cbd-really-relieve-anxiety-research-on-the-endocannabinoid-system-may-hold-the-answer/#:~:text=Researchers%20have%20discovered%20that%20when,real%20threat%2C”%20says%20Hill

-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481537/#:~:text=The%20endocannabinoid%20system%20(ECS)%20in,actions%20throughout%20the%20nervous%20system

-https://pubmed.ncbi.nlm.nih.gov/25715681/