Cannabis Doctors of New York ©
What is the Endocannabinoid System?
Updated: Feb 1
Cannabis Doctors of New York presents Chief Medical Officer Dr. Kenneth R. Weinberg. In this video, he briefly explains what the endocannabinoid system is.
“The endocannabinoid system or the ECS is a system that, just like the endorphin system which mediates the effects of opiates, the ECS mediates the effects of cannabis. It is a master system that is involved with learning, with sleep, with reproduction, with behavior, with balance, and with memory, among many other effects.” - Kenneth R. Weinberg, M.D.
A Glimpse Into The Endocannabinoid System Gregory Sondrol 05/01/22 The endogenous cannabinoid system—named for the plant that led to its discovery—is one of the most important physiologic systems involved in establishing and maintaining human health. Endocannabinoids and their receptors are found throughout the body: in the brain, organs, connective tissues, glands, and immune cells. With its complex actions in our immune system, nervous system, and virtually all of the body’s organs, the endocannabinoids are literally a bridge between body and mind. By understanding this system, we begin to see a mechanism that could connect brain activity and states of physical health and disease. - Bradley E. Alger, PH.D. Despite how the ECS is extremely prevalent and necessary for all functions of life, the ECS is not mentioned in my 2000-page New Oxford Dictionary. So... let's dive into the world of the ECS. The endogenous cannabinoid system, AKA The endocannabinoid system, AKA the ECS, is present in our guts, our brains (almost all our synapses), our cells, and nearly everywhere in our nervous system. The ECS consists of endocannabinoids, their receptors, and the enzymes facilitating the synthesis and breaking down of endocannabinoids after use. Within our body, we classify cannabinoid receptors as either CB1 or CB2. These receptors receive signals from either endogenous (endocannabinoids made by our body) or exogenous cannabinoids (produced by cannabis or similar external derivatives). These cannabinoids interact with receptors that are highly concentrated in our brains. CB1 receptors reside heavily within the central nervous system (densely located in the hypothalamus, basal ganglia, amygdala, striatum, cerebellum, neocortex, and hippocampus). CB2s have almost no psycho-activity and are mostly found along the spinal column, immune cells, or in the bone marrow. It wasn't until scientists discovered exogenous cannabinoids in cannabis that we even began to look into and discover the Endogenous cannabinoids, the receptors that correlate, and even the whole ECS in our bodies. "Since the time exogenous cannabinoids revealed their existence, the entire natural complex came to be called the endogenous cannabinoid system or endocannabinoid system”9. Delta 9- Tetrahydrocannabinol (THC), CBD, CBN, and over 170 different cannabinoids are found in cannabis. How the ECS heals us and its recent practical application… Cannabinoids and the ECS, from birth to death, are necessary for life. From synaptogenesis and synaptic pruning in the head to the sensory functions in the tips of our toes, the endocannabinoid system is there supporting us. The ECS holds many secrets to unraveling the mysteries of disorders like Post Traumatic Stress Disorder, for example. This is why it is crucial to understand the mechanisms behind cannabinoid signaling so we can close the gap and give relief to PTSD patients who often neurochemically fail to extinguish exaggerated or unwanted fear responses. In one study Lab mice that were genetically engineered without CB1 receptors acquired fearful responses quicker and were unable to extinguish learned fearful responses even after redundant high costs. There is much research being done on how cannabis could help veterans and others suffering from PTSD. A novel therapy may soon include CBD in exposure therapy for those with phobias. Profoundly, CB1 receptors are integral for “extinction”, an important process for PTSD and chronic anxiety. “CB1 receptor stimulation with THC enhances fear extinction in humans, which warrants further investigation in post-traumatic stress disorders and chronic pain.”11 Chronic pain states are also neuronally interrelated with those of high stressed states and both can further benefit from cannabinoid therapy. We are learning that the perception of pain and the emotional response to a traumatic event are (synaptically) important, perhaps just as important as the actual pain or event itself. Anxiety, fear, and even states of depression are natural and healthy when they are proportionate to the event. When these states are chronic and disproportional with the event cannabis can help to “reprogram” how we interpret our reward processing, how we derive pleasure from interacting with stress, or how we emotionally encode our responses to them. Clinical data also suggests endocannabinoids and CB1 receptors may attenuate anxiety and depression. Increased endocannabinoid signaling has been found to decrease depression and anxiety symptoms. Deeper within this molecular system... There are two integral receptors that we have identified so far: the CB1 and the CB2 receptors. As Scientist Ruth Ross explains in her Ted Talk “Demystifying the Endocannabinoid System.” A cannabinoid such as THC or Cannabidiol, simply speaking, is like the key, and the CB1 and CB2 receptors in our body are like the locks. Unlocking certain receptors has certain effects. One endocannabinoid could target a CB1 receptor to alleviate pain from a slipped disc. Another exogenous cannabinoid, like a CBD extract, could reduce inflammation by binding to a CB2 receptor in your immune cells. Our pathology and physiology are influenced every day by our own body generating endocannabinoids. Scientists are beginning to postulate that the main role of the ECS is to maintain homeostasis. Depending on which endocannabinoids and receptors are used, your body can respond to a plethora of attacks or problems to maintain homeostasis. Learning about cannabis and the world of the endocannabinoid system has allowed us to understand diseases that are linked to this impressive system. We now understand more than ever about neurodegenerative diseases such as Alzheimer's and MS because we now better understand the ECS. This has come full circle as we now are beginning to witness cannabis helping with diseases that are related to the very system it helped discover. Recently scientists have linked neurodegenerative diseases to inflammatory diseases. Cannabis is renowned as inherently anti-inflammatory and has “been found to modulate analgesia and anti-inflammatory pathways and provide neuroprotection among other functions”2 The ability of cannabis to quell the “cytokine storm” is currently of extreme interest to scientists as cytokine suppression is very important for autoimmunity, and currently relevant to our urgent global health issues. We do know the CB2 receptor plays the starring role in cannabinoid regulation of the immune and inflammatory systems. Promising results are also developing for neurodegenerative diseases which result in millions of deaths worldwide and diminished quality of life for far too many. The neurodegenerative processes of these disorders take place in the central nervous system. When CB2 receptors are activated in microglial cells they produce anti-inflammatory cytokines and inhibit pro-inflammatory cytokines. This is huge evidence for utilizing cannabis to fight neurodegeneration. Decreasing inflammation actually protects your neurons. Being able to control the immune response with MS or AD is pivotal in treatment. Cannabinoids have also recently been attributed to decreasing oxidative stress and helping with the integrity of the blood-brain barrier, again crucial for neurological health. Cannabis can bring profound change to the health of countless individuals. The now-famous “Charlotte’s Web” cannabis strain was specifically cultivated by cannabis growers for a girl named Charlotte who suffered from constant seizures but found significant relief from the strain’s medicinal properties. This treatment is now a common cure for patients (who have access to the appropriate cannabis) suffering from epilepsy and demonstrates how the medical cannabis community can bring change by understanding the plant itself. Charlotte’s Web was grown to have a high CBD content relative to THC. Interestingly the plants that were grown purely as CBD plants did not offer the therapeutic effects as did Charlotte’s Web, which contained small amounts of THC. This points to the importance of the synergistic effects between THC and CBD… AKA the entourage effect. Expanding implications of endocannabinoids… There are even CB1 receptors located in the basal ganglia and hypothalamus, which when stimulated, help regulate appetite and gastric motility.1 The medical uses of this discovery have far-reaching implications. Appetite excitation has been exploited by drug companies to help cancer patients struggling with appetite, wasting syndrome and nausea. Appetite suppression via cannabinoids has constant attention considering obesity issues in the U.S. and globally. One drug, Rimonabant, blocked CB1 in the hypothalamus and effectively proved weight loss, however during clinical trials negative side effects resulted as CB1 was also blocked throughout the body “including those brain regions where the endocannabinoid system regulates emotion and vomiting reflexes, among others.”9 and the negative effects (e.g. nausea, depression, even suicidal ideation) caused the product to be halted. Unfortunately, the drug Rimonabant was not successful in the way it blocked CB1 receptors (general CB1 inverse agonism). This shows we must do more research and dial in the receptor’s activity and find more acute methods to get the results we need without such ancillary negatives. Studies are ongoing and many focus on THCV, a cannabinoid sought after for its satiation and anti-munchie effects. The hunt for the perfect “diet weed” is intense. The future is bright as further drugs are being developed and might hold promising results concerning obesity. Unfortunately, decades of detrimental misinformation and negative cultural stigmas have stagnated medical research and are still hampering our scientists and doctors today. Panic led to the misclassification of Cannabis as a schedule 1 drug. With the Controlled Substances Act of 1970, signed in by Richard Nixon, the Federal government categorized cannabis as a Schedule 1 substance, considering it to have no acceptable medical uses. Thankfully science has pushed us to the truth; Cannabis is extremely beneficial medicinally and has exponentially low to non-existent toxicity levels compared to other legal drugs (caffeine, tobacco, alcohol, etc.) “With the discovery of the ECS, scientists and researchers have been petitioning to remove the cannabis Schedule 1 drug restrictions so medical research can more easily be done. Current research is studying the effects of exogenous cannabinoids in treating symptoms of epilepsy, HIV neuropathy, chemotherapy-induced nausea, anorexia, multiple sclerosis spasticity, chronic and neuropathic pain, glaucoma intraocular pressures, and asthma-associated dyspnea. The FDA has recently approved a study on the effect of medical cannabis on treating military veterans with post-traumatic stress disorder."1 Self-checks, methods of consumption, and the future... As young cannabis connoisseurs, (before legalization and access to all the many different strains of cannabis we see today) friends and I noticed different types of herb had different effects. One particular strain with a lot of red hairs made us euphoric with a heavy body high while a potent yellow strain was very psychoactive, creative, and energizing. We also learned that this medicine wasn't for everybody. The interaction of cannabinoids and our ECS is individually unique and we are still learning how exactly certain strains and their terpene profiles affect us. Sometimes it is important to do a self-check. Ask yourself “how does this medicine affect my body, or alleviate this or that?” or “Does eating a THC edible provide better migraine relief than that transdermal patch?” for example. Our bodies and collected anecdotal evidence should not be ignored and can help point us to the right method of medication. What also affects us and the ECS are the methods of cannabis consumption. Primarily you have inhalation or some form of ingestion. Topicals, transdermals, suppositories, etc. are less common but of equal importance. Each method has varied uses and effects: Inhalation is better for self titrating THC to blood levels and can be better for those who need a fast onset, such as nausea. Inhalation is often easier to predict oncoming effects and gives the patient more control of how much is needed, kicking in usually takes 20-40 seconds, and effects only last 10-40 minutes. Not being dependent on how much you have eaten that day or how long it might take to fully enter your bloodstream, cannabis patients accustomed to inhalation often become good at detecting their correct dosage of THC. Ingestion can be a great method for slow onset and steady delivery of medication. With the perk of being more discreet, ingestion is a practicable option for those who enjoy not having to re-medicate more regularly. For some, edibles are a great way to keep constant relief from chronic pain or anxiety. For others, ingestion can be less predictable and too long-lasting (up to 8 hours). Contacting a qualified cannabis doctor to receive the best medicine for your needs is a great idea. A cannabis doctor will help ensure you are not taking contraindications and they will give you recommendations for the best strains and products. You may ask “why medicate with cannabis?” or “why modulate these receptors with cannabinoids if the ECS works perfectly fine on its own?” Well as humans we are genetically variating, none of us have identical brain chemistry and sometimes even our receptors are not working perfectly fine. We have developed medicine to improve our livelihoods. For many, modulating our ECS may enhance our quality of life, elevate our mood, and improve cognition or overall health, the list continues to grow into the future with our finding of the many keys hidden in this beautiful plant and the many amazing locks hidden within ourselves. Written By Gregory Sondrol© - Cannabis Contributor 05/01/22 References: 1. Jarvis, Sabrina; Rasmussen, Sean; and Winters, Blaine, “Role of the Endocannabinoid System and Medical Cannabis” 2016. Student Works. 192. 2. Aggarwal S, Carter G, Sullivan M, ZumBrunnen C, Morrill R, Mayer J. Medicinal use of cannabis in the United States: historical perspectives, current trends, and future directions. Journal of Opioid Management. May 2009;5(3):153-168 3. Di Marzo V, Bifulco M, De Petrocellis L. The endocannabinoid system and its therapeutic exploitation. Nature Reviews Drug Discovery. 2004;3(9):771-784. 4. Lu H, Mackie K. An introduction to the endogenous cannabinoid system. Biological Psychiatry. April 2016;79(7):516-525. 5. Charytoniuk T, Zywno H, Berk K, et al. The Endocannabinoid System and Physical Activity-A Robust Duo in the Novel Therapeutic Approach against Metabolic Disorders. Int J Mol Sci. 2022;23(6):3083. Published 2022 Mar 12. doi:10.3390/ijms23063083 6. Iannotti F.A., Di Marzo V. The gut microbiome, endocannabinoids and metabolic disorders. J. Endocrinol. 2021;248:R83–R97. Doi: 10.1530/JOE-20-0444. 7. Mayoral L.P.-C., Andrade G.B., Mayoral E.P.-C., Teresa H.H., Socorro P.C., Francisco J.R.C., Héctor A.C.-F., Cruz M.M., Santiago A.D.P., Alpuche J.J., et al. Obesity subtypes, related biomarkers & heterogeneity. Indian J. Med. Res. 2020;151:11–21. doi: 10.4103/ijmr.IJMR_1768_17. 8. Meccariello R. Endocannabinoid system in health and disease: Current situation and future perspectives. Int. J. Mol. Sci. 2020;21:3549. doi: 10.3390/ijms21103549. 9. Alger BE. Getting high on the endocannabinoid system. Cerebrum. 2013;2013:14. Published 2013 Nov 1. 10. Vasincu A, Rusu RN, Ababei DC, Larion M, Bild W, Stanciu GD, Solcan C, Bild V. Endocannabinoid Modulation in Neurodegenerative Diseases: In Pursuit of Certainty. Biology (Basel). 2022 Mar 14;11(3):440. doi: 10.3390/biology11030440. PMID: 35336814; PMCID: PMC8945712. 11. Zieglgänsberger, Walter & Brenneisen, Rudolf & Berthele, Achim & Wotjak, Carsten & Bandelow, Borwin & Toelle, Thomas & Lutz, Beat. (2022). Chronic Pain and the Endocannabinoid System: Smart Lipids – A Novel Therapeutic Option?. Medical Cannabis and Cannabinoids. 5. 61-75.