In the previous article (Part 1), we discussed the basics of the endocannabinoid system (ECS). We talked about the two main endocannabinoids, cannabinoid receptors, and their role in maintaining physiological balance within the body. Here in Part 2, we look at a small selection of health conditions and the role our ECS plays.




Pain is both a general and common symptom of many diseases and even considered a condition itself.  Although chronic and/or severe pain is one of the worst things anyone can live with, there aren’t many safe pharmacological options available. In fact, one of the most prescribed classes of drugs (opioids) are notorious for there potential for abuse and corresponding death rate. The most promising approach, based on recent research, appears to be the ECS. Modifying the activity of the ECS with phytocannabinoids has shown to provide benefit to multiple forms of pain in a variety of clinical trials.


Since CB1 receptors are found throughout the nervous systems in areas associated with pain, and because CB2 receptors are also involved in blunting the sensation of pain, THC, CBD, and anandamide can effectively reduce pain through its action on the ECS. Further, these cannabinoids can also work synergistically with non-steroidal anti-inflammatory drugs (NSAIDs, such as acetaminophen) to enhance their effectiveness.


Obesity and Diabetes


Most people already know that smoking cannabis can often bring on the “munchies.” Many times, this well-known effect of cannabis is used therapeutically in cases of cachexia (muscle wasting syndrome seen with cancer) or anorexia. By interacting with various tissues (including fat, muscle, liver, and the pancreas), CB1 receptors encourage the body to store energy/calories as fat. It’s no wonder the dysfunction of the ECS is linked to obesity. CB1 receptors are up-regulated in the liver and fat tissues in various types of obesity, and this has been linked to weight gain.


Logically, most would think that inhibiting CB1 would counter this effect and even be exploited therapeutically as an anti-obesity strategy. In fact, this has been tried—with disastrous results. This is because CB1 receptors control a lot more than just weight, and as with biology in general, the deeper we go, we reveal a picture of increasing complexity, not simplicity. This is a perfect example, of the saying, “a little bit of knowledge is a dangerous thing.” Without a full understanding, you can arrive at the wrong conclusions, and studies have revealed that cannabis consumption—even with its CB1 activation—does not correlate with obesity.


In fact, a 2011 study found that obesity rates were about one-third lower in people who regularly smoked cannabis (at least three times per week) compared to those who did not use cannabis at all. This observation remained true even after other factors were accounted for, like age, sex, and cigarette smoking. Another study in 2013 found that current cannabis users (compared to non-users) had fasting insulin levels that were 16% lower, had higher HDL cholesterol levels (the “good” cholesterol), as well as a smaller waist circumference. Observations were even better among those who reported recent cannabis use.


This suggests that the ECS is involved in preventing metabolic syndrome, and there are numerous studies that confirm this. Metabolic syndrome involves glucose/insulin regulation, cholesterol and triglyceride levels, blood pressure, and obesity. When endocannabinoid concentrations or receptor activation is unbalanced, it can result in increased abdominal fat storage, and higher risk of atherosclerosis, and type 2 diabetes.


Cardiovascular Health


The ECS is extensively involved in cardiovascular regulation, and CB1 receptors mediate many cardiovascular processes, including the dilation of blood vessels, and functioning of the heart. Discussed below are a number of cardiovascular conditions that are known to be modulated by the ECS.


Ischemia: Ischemia is the term used when blood flow is restricted. Maintaining proper blood flow is critical and anyone who has experienced angina (chest pain from reduced blood flow), a heart attack (blood flow blockage in the heart), or stroke (blockage in the brain) will know just how important it is. In one study, researchers administered CBD prior to ischemia as well as reperfusion injury (which is a negative consequence of restoring blood flow after ischemia). Results showed that CBD enhanced anandamide signalling, which caused a reduction in cell death and reduced the number of irregular heartbeats.


Atherosclerosis: Atherosclerosis is a condition that can increase the risk of other more sinister conditions, including a heart attack or stroke, and is one precursor to ischemia. Less serious consequences, but no less desirable, are things like erectile dysfunction and dementia. It is characterized by plaques that inhibit blood flow. The ECS is known to be active in cases of atherosclerosis, and given the anti-inflammatory and antioxidant functions of cannabinoids (both phyto- and endocannabinoids), they may be useful for addressing the health of the vascular system.


The immune-related cells found in atherosclerotic plaque are known to express CB2 receptors. Even though THC predominantly binds to CB1, here it exerts an anti-inflammatory effect via CB2 activation—potentially slowing progression of the plaques. However, most of the benefits probably come from 2-AG since it has a much stronger affinity for CB2.


Hypertension: Known as the “silent killer” since it can go unnoticed until it’s too late, hypertension can cause significant damage to the heart, arteries, brain, eyes, and kidneys. While we discussed CB2 receptors in arterial plaque, it should be pointed out that CB1 receptors outnumber CB2 throughout the cardiovascular system. Activating CB1 receptors with anandamide or THC can lower blood pressure. In fact, the higher the blood pressure, the greater effect anandamide and THC have—just as we’d expect for a regulator of homeostasis. In other words, the individuals with the highest blood pressure would receive the most benefit.


Brain, Cognition, and Neurological Health


Studies have shown that the ECS is involved in protecting the nervous system and nerve cells in a wide variety of situations. From acute injuries to the brain or nerves, to chronic neurodegenerative disorders (like multiple sclerosis and Alzheimer’s disease), the ECS is constantly helping to bring a pathological state back to balance and health.


Traumatic Brain Injuries: The ECS also activates a number of other signalling pathways that protect cells. The ECS and cannabis have shown to be involved in modulating mitochondrial metabolic rate and oxygen demand. It allows cells to have greater survivability in the face of low oxygen levels or reduced blood flow. For example, both anandamide and 2-AG protect nerve cells in the cerebral cortex when deprived of oxygen and glucose (the brain’s main source of fuel). This is especially useful in cases of traumatic brain injury, and a recent study published in the latter part of 2014 revealed the incredible level of neuroprotection endowed by THC. In this study involving over 400 patients suffering from traumatic brain injury, researchers found that those testing positive for THC had an 80% lower probability of dying than patients who tested negative for THC.


Multiple Sclerosis: Multiple sclerosis (MS) is a disease where the body’s immune system attacks the its own cells (an autoimmune disease). In MS the immune system’s target is the myelin sheaths that surround and insulate the “arms and legs” of the nerve cells, which allow nerve signals and communication to proceed normally. As more and more neurons lose their myelin sheaths, nerve communication and signalling gets progressively worse. Two common symptoms of MS are spasticity and tremors, both of which appear to be helped by cannabis via activation of CB1 and CB2 receptors. A couple double-blind, placebo-controlled clinical trials have confirmed that both THC and CBD can improve many aspects of MS in humans, including spasticity, mobility issues, pain, and bladder problems.


Alzheimer’s Disease: While there are many forms of dementia, the most common form is Alzheimer’s disease, which is characterized by the accumulation of toxic proteins in the brain (called beta-amyloid). Although there are currently no conventional medical treatments for this disease, there are varying degrees of success being reported with specific dietary protocols and natural therapies—including cannabis. Here again, the CB1 receptor plays an important role, where its activation inhibits the toxic effects of beta-amyloid through a number of ways. CB2 receptors also play an important role here, where it can then help reduce inflammation.


Anxiety: Anxiety is a great example of the balancing act of the ECS, and also shows how the right substance in the right amounts (not too little, not too much) will bring about homeostasis in a person. Here, research has shown that small quantities of cannabinoids such as THC has an anti-anxiety effect. However, as many novice cannabis users can attest to, the same compounds can result in anxiety when taken in higher doses. Similarly, both blocking and overstimulating the CB1 receptor has the same effect of causing anxiety, which is a clear example of this fine balancing act.

Gastrointestinal Disorders


Even though most people associate the gastrointestinal (GI) system with digestion, in actual fact, it plays a major role in many body systems and functions. It is the throne of the immune system (with a estimated 70-80% of the immune system being located in the GI system), and plays a major role in health of the nervous system (including mood and cognition), cardiovascular health, skin health, etc. CB1 receptors, along with the endocannabinoids anandamide and 2-AG, are prominently distributed throughout the nerves that regulate the GI tract. CB2 receptors are also present, including on a type of white blood cell called a macrophage. The ECS is involved in many functions of the GI system, including stomach acid secretion and GI motility (the muscle contractions that move food through the GI tract).

Activation of CB1 and/or CB2 receptors inhibit GI motility. This would suggest phytocannabinoids would be useful in cases of diarrhoea, and a clinical trial has confirmed this. Further, numerous studies have shown anandamide protects against ulcerative colitis (a form of inflammatory bowel disease, or IBD). As with other conditions, the ECS is often up-regulated as a protective mechanism.


Other than ulcerative colitis, IBD can also refer to Crohn’s disease. A small pilot study in 2013 examined the effectiveness of cannabis therapy for Crohn’s disease. In this double-blind, placebo-controlled study, 5 of 11 subjects in the cannabis group achieved complete remission compared to only 1 in the placebo group. Almost all of the cannabis subjects (10 of 11) experienced significant therapeutic benefits—compared to 4 in the placebo group—as well as better appetite and sleep; all this with no significant side effects!


Immune System Modulation


As mentioned above, since the GI system houses about 70-80% of the immune system, it has a critical (and direct) role to play in helping to modulate our body’s immune response. Due to the presence of cannabinoid receptors on immune cells, and anecdotal and historical evidence suggesting that cannabis use has potent modulating effects on the immune system, there has been considerable research directed at understanding the function and role of these receptors within the context of immune response. Studies from chronic cannabis smokers have provided much of the human evidence for the immuno-modulatory effects of cannabis, and animal and laboratory studies on immune cells have also provided important evidence.


In fact, many may know that Echinacea has been used in traditional medicine for a very long time as an immune booster. Modern research has now shown that this herb’s traditional benefits are due to compounds called alkylamides, which activate CB2 receptors, which are plentiful on immune cells. A recent study published in 2015 compared the effectiveness of an Echinacea product to Tamiflu (oseltamivir), which is regarded as the first-line therapy for resolving flu symptoms among conventional medicine authorities. This study found that 50.2% of those in the Echinacea group recovered after 5 days, compared to 48.8% in the Tamiflu group (no statistically significant difference between groups, meaning Echinacea and Tamiflu were equally effective). Even more impressive, however, was that those in the Echinacea group reported far less adverse effects from the treatment, with the Tamiflu group reporting the usual nausea and vomiting associated with the drug. The study included over 400 patients, including children, which shows that Echinacea (and therefore, immune enhancement through ESC and CB2 activation) was also safe. This suggests a bright future for CBD or CBD-heavy cannabis strains in immune modulation.




As mentioned earlier, this is just a small sample of health conditions linked to a dysfunctional ECS. It’s incredibly exciting to see more research come out and I fully expect to see this turn into an avalanche of studies as prohibition comes to an end in Canada, which will further help legitimize cannabis as a powerful natural medicine and reduce its stigma globally.



Disclaimer: The information in this article is for educational purposes only, and not to be construed as medical advice. It is not meant to diagnose, or in any way replace qualified medical supervision. For diagnosing or treating any medical condition, consult with your health care provider.


Lee Know is a licensed naturopathic doctor, the recipient of several awards, and the author of Life: The Epic Story of Our Mitochondria (FriesenPress, 2014). He has previously held positions as a medical advisor, scientific evaluator, and director of research and development for major organizations, and currently heads up Scientific Affairs and Product Development at Cannanda.

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