The Endocannabinoid System

In case you didn’t know, most of the recommendations made in medicine today are based on what we call Evidence-based Practice. Usually that comes in the form of heavily regulated clinical research and multi-phase clinical trials, which can take many, many years to complete. Currently, marijuana is still categorized by the federal government as a Schedule I controlled substance which requires that the Drug Enforcement Agency, or DEA, also be involved with any research. Having spent almost a year working with an interventional cardiologist who is also a world-renowned expert in cardiac research and clinical trials, let me just say in a nutshell, that’s a lot of hoops to jump through. So, with regard to cannabis and its medicinal uses most of the research we have today is conducted on lab animals with sparse human research, mainly based on peoples’ anecdotal accounts. At this point you might ask yourself, “Why should I care if they do research on cannabis?” Because there is so much more to cannabis then just getting high. Let’s delve in. Stay with me here, we’re gonna talk science.

In the 1990s scientist discovered this thing call the endocannabinoid system, or ECS, in humans and animals. Turns out the ECS is an integral part of homeostasis – the body’s way of regulating and trying to stay healthy despite constant internal and external changes. The ECS helps regulate appetite, sleep, mood, stress, memory, energy levels and even reproduction through receptor sites located throughout the body, in places like the brain, liver, kidneys, spleen, gonads, and heart.

Receptors are kind of like on-off switches in the body – broadly termed receptor agonist or antagonists. When a chemical substance sits on the receptor site it can either turn on (agonist) or turn off (antagonist) a response. This is how many over the counter and prescription medications work. For instance, opioids, like morphine, oxycodone, and fentanyl work by sitting on the opioid receptor site and block, or turn off, the pain signal to the brain, but also turn on the feeling of euphoria. Another example would be the commonly prescribed class of drugs called beta blockers, like metoprolol or propranolol, which sit on the receptor and help block the body’s natural ability to raise blood pressure and heart rate. The over-the-counter medication Famotidine, or Pepcid, blocks a receptor in the body resulting in reduced acid production in the stomach.

The two ECS receptors are called, CB1 and CB2. CB1 receptors are found in the brain and central nervous system, and primarily affect motor and cognitive function. They also play an important role in regulating the release of other neurotransmitters, like serotonin, dopamine, and glutamate, which are important in regulating mood and, in particular, depression. CB2 receptors are found on immune cells and on neurons in a few select brain regions and are involved in pain relief, inflammation reduction, and neuroprotection.

The human body produces two endocannabinoids (internal cannabinoids) naturally, named by scientist anandamide and 2-arachidonoylglycerol (2-AG). Anandamide primarily interacts with CB1, and plays a role in mood regulation, boosting happiness, reducing pain, managing stress, and regulating sleep. Anandamide gives us the feeling of bliss or a natural high. A good example of this is the “runner’s high” which scientist now readily attribute to endocannabinoids rather than endorphin release. 2-arachidonoylglycerol (2-AG) is thought to more readily target CB2 receptors which help regulate immune responses like inflammation and has also been linked to research suggesting it may reduce stroke symptoms. Low levels of naturally occurring anandamide and/or 2-AG have also been attributed to increased inflammatory response, osteoporosis, migraines, fibromyalgia, irritable bowel syndrome, and possibly autism.

In the same way medications enter the body and sit on receptor sites producing a specific effect – like reducing pain or lowering blood pressure – different cultivars of cannabis, when ingested in various forms, have the ability to sit on the CB1 and/or CB2 receptor sites and have an agonist or antagonist affect. Currently, according to the National Institute of Health’s National Center for Complementary and Integrative Health, the cannabis plant contains about 540 chemical substances. Cannabinoids, or more specifically phytocannaninoids (phyto means plant), are included in this long list of substances, with the most commonly known being tetrahydrocannabinol, or THC, and cannabidiol, or CBD. Whether inhaled or ingested, THC acts a lot like anandamide causing the feeling of high most associated with cannabis use. CBD, on the other hand, does not have the “high” effect of THC, but for many people does have the ability to reduce pain and stress.

Even though research is still scarce there are some positive preliminary results, and researchers are hopeful that the abundance of chemical compounds found in cannabis can play an important role in treating and relieving symptoms for conditions like depression, anxiety, PTSD, insomnia, multiple sclerosis, irritable bowel disease, HIV/AIDS symptoms, glaucoma, epilepsy, neuropathy, chronic pain, opioid dependence, and so much more.

These statements have not been evaluated by the FDA and are not intended to treat, cure, or diagnose any disease. This website contains general information about diet, health and nutrition. The information is not advice and is not a substitute for advice from a healthcare professional. You should always get your medical advice from a healthcare professional (HCP) knowledgeable about your individual needs. A competent healthcare professional will provide a comprehensive intake meeting where you review the conditions you want to treat and assess your prescription medications to identify potential contraindications with cannabis.


American Cannabis Nurses Association. What is the endocannabinoid system and what is its role?

Blesching, Uwe. Cannabis Health Index


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