The discovery of the endocannabinoid system has ignited debate on its implications in human health. Additionally, its ability to be targeted by various therapeutic agents in different disease states has been of particular interest for biomedical and clinical researchers.
In fact, some researchers have suggested that the endocannabinoid system plays a crucial role in cellular homeostasis. This means that the health of this system may be directly related to the health of the rest of the body.
But you may ask yourself, what is the endocannabinoid system and why does it seem to be so important?
The following sections in this article will review the basics of the endocannabinoid system and its potential role in cardiovascular and neurological health. More importantly, the article will focus on how endocannabinoid system deficiency may have adverse effects on the other systems mentioned above.
What is the Endocannabinoid system?
The endocannabinoid system is a system mainly comprised of two receptors and a series of endogenously produced compounds (or compounds produced inside of the body). The two main receptors associated with the endocannabinoid system are the CB1 and CB2 receptors.
The name “endocannabinoid” comes from the fact that cannabinoids from the cannabis plant interact with the receptors from the endocannabinoid system. Endocannabinoids are the compounds produced inside of the body that interact with these receptors as well. Although there exists many endocannabinoids, one of the most widely known and studied is N-arachidonoylethanolamine (AEA).
AEA has been found to increase during times of oxidative stress, inflammation or cell death. This prompts researchers to believe that it may be produced as a response to injury to counteract inflammatory activity. AEA’s activity may be evidence of the role of the endocannabinoid system in cellular homeostasis.
The CB1 and CB2 receptors are found all throughout the body. However, CB1 receptors are mainly found within the nervous system, while CB2 receptors are mainly found in gut epithelium and cells of the immune system.
CB1 receptors have been shown to predominantly interact with THC and other psychoactive compounds in the cannabis plant. The psychoactivity of THC is logical simply because CB1 receptors are found mostly in the nervous system. Therefore, the interaction between CB1 receptors and THC may cause certain changes in brain chemistry, leading to the “high effects” produced from recreational cannabis use.
On the other hand, CB2 receptors are mainly known to interact with cannabidiol (CBD) which is the second major compound in the cannabis. This is not to say that CBD does not interact at all with CB1 receptors, but rather these interactions are so uncommon they are almost negligible. Because CBD does not interact to a significant extent with CB1 receptors, it does not possess the same psychoactive effects that THC does.
Both of these cannabinoid compounds have been found to have some potential therapeutic properties. Specifically, in many studies they have been found to control chronic inflammation in the case of conditions such as IBS (irritable bowel syndrome).
The use of THC to modulate endocannabinoid system deficiency has been highly limited by its psychoactive properties. These infamous psychoactive properties have blacklisted THC in many states within the U.S, within the U.S federal government as well as in other relatively conservative countries around the world. Because of this, researchers and clinicians often refrain from either investigating its therapeutic properties or recommending it as an alternative form of medicine.
But that is not the end for cannabinoids…
CBD possesses the same therapeutic properties as THC, but without the psychoactive effects. For this reason, CBD has been under extensive research and scrutiny as a promising compound that can be used to improve the progression of various diseases. Some researchers have gone as far as to create synthetic compounds that mimic the structure of CBD and its interaction with CB2 receptors.
Targeting the endocannabinoid system in cardiovascular health and disease.
When it comes to cardiovascular health, endocannabinoid system activation may lead to beneficial or adverse effects depending on which receptors are involved.
For example, interaction with CB1 receptors has been linked to increased risk of cardiovascular disease or cardiovascular events. Cardiovascular events are things such as: myocardial infarction (heart attack), atherosclerosis (hardening of the inside of the blood vessels), stroke, kidney dysfunction and liver problems. This has been demonstrated in animal models as well as epidemiological retrospective studies.
In contrast, activation of the endocannabinoid system through CB2 receptors may have cardioprotective properties. Some animal studies have shown that the use of synthetic cannabinoids that interact with CB2 receptors may be beneficial in myocardial infarction. This is mainly because of their ability to limit infiltration of cells that cause inflammation through CB2 receptor activation.
How is this clinically significant?
Well, if you refer back to our conversation on the difference between CBD and THC, you would understand that using THC as a therapeutic agent may increase risk of cardiovascular events due to its interaction with CB1 receptors. On the other hand, CBD is known to interact with CB2 receptors and it is therefore possible that administration of CBD may lead to these cardioprotective effects mentioned above.
The endocannabinoid system in adult neurogenesis and brain health.
In several research reports, neural-progenitor cells (stem cells of the nervous system) have been shown to produce endocannabinoids during time of injury and stress. This ultimately stimulates cell proliferation (division) in the brain, specifically in areas such as the hippocampus and sub-ventricles.
This proliferation is thought to be produced by an interaction of endocannabinoids with CB1 receptors. More importantly, other reports have actually shown that CB1 deficient mice have an impaired ability for neural-progenitor cell proliferation in the event of nervous system injury. This may mean that CB1 deficient mice have less of a chance to recover from a stroke or other brain injury compared to mice whose CB1 receptors are at normal levels.
AEA, for example, has also been seen to induce astroglial proliferation in mice. Astroglia are star-shaped neurons that are thought to be extremely important for brain structure and protection. Hence, they are found in areas such as the blood brain barrier, which protects the brain from the external environment. Additionally, pharmacological stimulation of CB1 with synthetic cannabinoids often leads to neurogenesis (formation of new tissue in the brain).
Well, when can this idea of using synthetic cannabinoids be beneficial for brain health?
Synthetic cannabinoids may not only be beneficial in the case of brain injury such as a stroke, but could also be used as a possible antidepressant. In fact, the synthetic cannabinoid HU210 has been previously used for this purpose because of its ability to modulate the endocannabinoid system and subsequently neurogenesis.
Finally, recent studies have shown that CB1-deficient mice tend to suffer from early age-related cognitive impairment. This may simply be due to the fact that CB1-deficient mice are not able to properly regenerate cells in the nervous system, and succumb quicker to age-related cellular death. This is a prime example of endocannabinoid deficiencies that may lead to adverse effects in humans as well.