How Does CBD Oil Work? Guide to the Endocannabinoid System

Most of CBD oil’s powerful therapeutic effects don’t come from CBD itself, but rather the biological responses it stimulates from the endocannabinoid system. This unique system in the body is responsible for the health-promoting properties of cannabinoids like inflammation reduction, lowered anxiety, better sleep and strengthened immunity. It has metabolic links and signalling pathways to many other critical areas of the body such as the brain, nervous system, immune system, cardiovascular system and even cells themselves. Only cannabinoids and terpenes from cannabis can interact, bind with and activate it. Unlocking its activity by using CBD oil may be the ideal pathway for many to boost their health, and recovery and mitigate symptoms of many issues like arthritis or anxiety. Let’s understand how the endocannabinoid system works, how to activate it, what endocannabinoids are, plus why this matters for your health.

What is the Endocannabinoid System (ECS)?

It’s a physiological system that is found in all mammals including humans and plays a key regulatory role in supporting homeostasis, and immune and nervous system function. The ECS was only discovered in the 1990s but has since been studied in-depth due to its therapeutic potential in mitigating or treating many chronic diseases. It consists of three biological elements: cannabinoid receptors, enzymes and endocannabinoids. Each of these plays a distinct role in the functioning of the endocannabinoid system and its interactions or modulation of other bodily processes. In combination, they work to primarily support the body and mind in maintaining homeostasis or the internal stability of the body’s natural systems. Some endocannabinoids also help to produce prostanoids which are pain-mitigating enzymes. Prostanoids lower the acute pain response and help to reduce inflammation occurring from tissue damage.

Cannabinoid Receptors

Cannabinoid receptors are present in all humans and are specifically designed by the body to bind and react with cannabinoids like CBD or CBG. The receptors are dispersed across the body. There are two receptor types. CB1 receptors are located primarily in the brain, spine and nervous system. These can modulate certain neurotransmitters and provide CBD with neurological and mental benefits. CB2 receptors are found in the cells, tissues, glands, organs and immune system. You can even find them in the peripheral tissue such as the skin. Predominantly this receptor type aids with lowering pain, reducing inflammation and helping to promote immune function.

A second type of cannabinoid receptor, the CB2 receptor, exists mostly in our immune tissues and is critical to helping control our immune functioning, and it plays a role in modulating intestinal inflammation, contraction, and pain in inflammatory bowel conditions. CB2 receptors are particularly exciting targets of drug development because they don’t cause the high associated with cannabis that stimulating the CB1 receptors does (which is often an unwanted side effect).


Receptors of the ECS bind with cannabinoids when they’re consumed from cannabis. This could be THC, CBD or other cannabinoids like CBN and CBG. Cannabinoids make their way into the bloodstream and are eventually transported to the receptors in the brain and body. They bind at the receptor sites causing them to activate. When activated, cannabinoid receptors release endogenous compounds known as endocannabinoids which are lipid-based signalling molecules. ‘Endogenous’ refers to these compounds being produced by the body itself. In other words, the presence of cannabinoids causes the body to produce its form of cannabinoid which have potent health benefits. While there is a range of endocannabinoids produced through this mechanism, the two most important and well-studied are anandamide and 2-arachidonoylglycerol.


After endocannabinoids are produced and act on the body, they are metabolized and broken down. The endocannabinoid system also plays a part in this metabolic process through specific enzymes. Fatty acid amide hydrolase (FAAH) works in breaking down anandamide in the body. 2-AG on the other hand is metabolized through the monoacylglycerol lipase (MAGL) enzyme. While less powerful than endocannabinoids, both of these enzymes have some beneficial health effects. They both may play a role in mitigating pain, suppressing depression, improving mood, supporting focus and fighting inflammation. More studies are exploring their capacity as antidepressant agents and homeostatic reinforcing molecules.

Benefits of Endocannabinoids

Endocannabinoids offer a swathe of health benefits as important modulators of many important bodily systems and signalling pathways. Their benefits are so wide-reaching and varied because they act on both physiological and neurological processes in the brain and body.

Anandamide (AEA)

In Sanskrit, the word ‘ananda’ translates to ‘bliss’. The endocannabinoid anandamide was coined after this word, as it can directly provide acute feelings of bliss, calm and reduced anxiety. But it also offers pain relieving and neuroprotective effects for users.

Anandamide has anxiolytic properties and displays antidepressant effects in users. In mice studies from 2019 in the Journal of Neuroscience, it was shown to lower anxiety and stress in mice. It was shown to improve mood and suppress anxious behaviour in the mice subjects that were dosed with cannabinoid solutions versus a control placebo group. A separate study from 2007 showed anxiety responses in rodents were mitigated by anandamide and its subsequent breakdown into FAAH which provided supplementary effects. The endocannabinoid displayed similar effects and characteristics to certain antidepressant chemicals.

Through the CB1 receptors in the brain and CNS, it also aids in lowering nociception or pain perception. It can suppress pain signalling in the nerve pathways that cause the sensation of pain. Mice studies have supported this effect in mammals. In a Pharmacology Journal study from 2011, the use of anandamide and FAAH inhibitors in mice produced a strong reduction in pain symptoms in test subjects. This was theorised to be the result of both CB1 and CB2 receptor agonism. 

Part of its capacity to lower pain is from anandamide’s anti-inflammatory properties. Like other endocannabinoids, it helps in down-regulating cytokine production. Cytokines are pro-inflammatory compounds the body produces that cause chronic inflammation in the tissue or cells. This also applies to inflammation occurring in the gut, brain or nerves – known as neuroinflammation. Inflammation in neurons contributes to cognitive decline, Alzheimer’s risk and memory problems. Anandamide was studied in 2014 during a clinical trial run by the Journal of CNS & Neurological Disorders for its ability to fight this form of inflammation. It provided targeted inflammatory improvements in the test subjects, both preventing and reversing symptoms. Part of this was also due to anandamide’s antioxidative capacities in mitigating oxidative stress which can exacerbate inflammatory symptoms. 

2-Arachidonoylglycerol (2-AG)

While not as effective as anandamide, 2-AG is the other primary therapeutic endocannabinoid the ECS generates in response to cannabinoid activity. 2-AG has strong effects in supporting better immunity and lowered inflammation. A 2015 study in the Journal of Leukocyte Biology showed that 2-AG could reduce the production of pro-inflammatory cytokines, similarly to anandamide. It also theorised to demonstrate similar neuroprotective benefits. An example of this lies in a 2012 study published in the journal PLoS One. This study found that 2-AG protected neurons from excitotoxicity, a degenerative process which is responsible for neurodegenerative diseases like Dementia and Alzheimer’s. Much of the neuron degeneration that is caused by ageing and neuroinflammation is due to glutamate. This is a neurotoxic chemical that inhibits the calcium channels and signalling between neurons, causing their misfiring or even death. Endocannabinoids like 2-AG are antioxidative and can help to prevent the damage caused by glutamate. 

2-AG may also aid in weight loss by inhibiting feelings of hunger and modulating hunger hormone activity through the CB1 receptors. It can stimulate the opposite effect of THC which is renowned for causing the ‘munchies’ through increased CB1 receptor activity. 2-AG blocks this receptor, lowering hunger via the same pathway. The journal Nature Neuroscience published a study in 2011 which concluded this effect was stimulated in mice administered with 2-AG. It was able to bind with these receptors in the hypothalamus to promote feelings of fullness for longer and better appetite control. The stress and anxiety-suppressing effects of 2-AG may also play a role in this phenomenon by aiding the user in avoiding stress-eating and inhibiting hunger triggers.

Neurotransmitter Activity of Endocannabinoids

Outside of interacting with the brain and CNS’ CB1 receptors, endocannabinoids also modulate neurotransmitters – specifically GABA and serotonin. Anandamide can increase the brain’s ability to produce serotonin and GABA. A 2011 study demonstrated its capacity to modulate GABA which has profound implications for the abilities of cannabinoids like CBD to stimulate the improved mood. This is because GABA is one of the primary inhibiting neurotransmitters in the CNS and plays an important part in mood regulation plus anxiety.

Serotonin is the other primary neurotransmitter influencing mood. But it also regulates memory, sleep patterns, appetite and cognition. Endocannabinoids like anandamide act on the serotonin receptors, helping mitigate symptoms of anxiety and depression while lifting mood. For example in a study from the Annals of General Psychiatry in 2023, a test group of depressed patients were found to have lower levels of 2-AG and anandamide. Dosing them with CBD helped to replenish their endocannabinoid levels and subsequently lift serotonin levels while reinforcing mood. The clinical evidence is strongly indicating endocannabinoids act similarly to antidepressant drugs which perform similarly in modulating serotonin.


While cannabinoids themselves offer some inflammatory-reducing and pain-mitigating benefits, their main purpose in the body therapeutically is activating the endocannabinoid system. CBD, CBN, THC, CBG and other cannabinoids can achieve this activation by binding with the distributed network of CB1 and CB2 receptors found throughout the brain and body. When endocannabinoids are released from this activity like 2-AG and anandamide, powerful health-promoting effects are unlocked. Endocannabinoids are potent at aiding with better mood, suppressing depression, boosting sleep and lowering inflammation throughout the body’s systems. They’re increasingly the focus of scientific research and may offer new, natural means of treating many chronic health conditions.