How CBD Oil Works in the Body: Endocannabinoid System Guide

How CBD Oil Works in the Body

Science has unveiled the mechanisms by which CBD oil works in the body to provide its rich health benefits. The CBD compound in this oil is a cannabinoid capable of interacting with myriad receptors in the body.

CBD Oil Endocannabinoid System

These receptors exist in the body’s endocannabinoid system, immune system and other regions. Interestingly, CBD doesn’t just work on its own. It releases endocannabinoids from the endocannabinoid system, stimulating anti-inflammatory, analgesic and anxiety-reducing effects

Woman holding CBD oil

These effects all occur without causing intoxication or a ‘high’ because CBD is not psychoactive. Its safety is a significant factor behind the popularity of CBD oil in Australia and why more people than ever are using it. Let’s reveal how CBD oil works in the body through the endocannabinoid system. You’ll learn about the activity CBD has in different metabolic pathways, as well as the benefits and effects of endocannabinoids.

Background on the Endocannabinoid System

Endocannabinoid system

Understanding how CBD oil works requires some knowledge of the endocannabinoid system. It’s this system in the body that enables the therapeutic effects of CBD.

The endocannabinoid system (ECS) is considered a ‘signalling’ or regulatory system. In other words, unlike most organs, it has no direct biological functions in the body itself. Instead, it signals to other organs, glands, or tissues to modulate (change) how they function.

Endocannabinoid signalling

Scientists have known about the ECS for decades. It’s been thoroughly studied for its medical potential in sleep, pain, anxiety, inflammation, and more treatments. 

That’s because the ECS helps to regulate each of these health facets. It contains messenger proteins and enzymes that can alter how differing bodily processes are controlled. Researchers have yet to fully understand the biological mechanisms of the ECS. One core way it works is by balancing the body’s internal state and stabilising other bodily systems. This process is called homeostasis and is a vital way the body self-regulates for long-term health.


endocannabinoids in the body

Most signalling chemicals secreted by the endocannabinoid system are ‘endogenous’ or made by the body. This is why the system has the prefix ‘endo’ in the name, which means endogenous. The primary signalling chemicals it creates are ‘endocannabinoids’ or endogenous cannabinoids. Anandamide and 2-AG are the key endocannabinoids responsible for CBD’s health benefits. We’ll cover these in more detail below. 

Endocannabinoids are powerfully therapeutic and block ailments like pain, anxiety, and inflammation. Unlocking their powers in the body requires the consumption of cannabinoids like CBD. Cannabinoids bind to the endocannabinoid system in cannabinoid receptors. Once endocannabinoids are released, the body secretes other enzymes to break them down. Let’s take a look at each of these components of the ECS.

Cannabinoid Receptors

Cannabinoid receptors in the brain

Cannabinoid receptors are bioactive protein receptors in all body tissues, including the brain, CNS, gut, and organs. Cannabinoids like CBD or THC have an affinity for these receptors and bind to them when consumed. In turn, the endocannabinoid system ‘activates’ and releases endocannabinoids. Scientists have identified two cannabinoid receptor types, CB1 and CB2. Each has distinctive characteristics and locations in the body.

CB1 receptors attach to the brain (including its neurons and neurotransmitter receptors) and central nervous system (such as the spine). In contrast, CB2 receptors are ‘peripheral’ cannabinoid receptors. In other words, they are only found in peripheral organs like the skin, immune system (such as lymph nodes), peripheral nerves, tissues and specific organs. Because of their location in the immune system and nerves, CB2 receptors are the main pathway by which CBD modulates inflammation and pain.

Cannabinoid receptors activating

On the other hand, CBD’s interactions with CB1 receptors are responsible for most of its mental health and neurological benefits. CBD binds to these receptor types, which is how it calms anxiety, mitigates depression, and stabilises mood. Once endocannabinoids are released, homeostasis kicks in, and the body metabolises them. This is done by specific enzymes in the endocannabinoid system.


Woman holding CBD oil in Australia

Breaking down endocannabinoids and cannabinoids is vital in regulating the endocannabinoid system. Imbalances or deficiencies in endocannabinoids can cause adverse health consequences. For example, ‘endocannabinoid deficiency’ is a genuine clinical condition that can damage the body’s ability to regulate sleep, mood, pain, and digestion. 

It is essential to avoid this by keeping endocannabinoids in balance via homeostasis. Once endocannabinoids have served their purpose, the body secretes the FAAH and MAGL enzymes to clear them. Fatty acid amide hydrolase (FAAH) targets and metabolises the anandamide endocannabinoids. To clear it, the monoacylglycerol lipase (MAGL) enzyme reacts with the 2-AG endocannabinoids. 

Breaking down endocannabinoids prevents the endocannabinoid system from overstimulating or dysregulating other systems. It ensures the body is brought back to normality internally and optimal health is maintained.

How CBD Oil Works in the Body

How CBD Works in the body

Although CBD oil works in the body mainly through the endocannabinoid system, there are other pathways it also works on. Let’s take a look.

Inhibiting Endocannabinoid Breakdown

Inhibiting endocannabinoid breakdown

A critical way CBD acts in the body is by slowing the breakdown of endocannabinoids. Doing so extends the half-life of endocannabinoids and their overall therapeutic benefits. CBD inhibits FAAH to prevent anandamide from being cleared too quickly. Similarly, it slows MAGL from eliminating 2-AG. Through these mechanisms, CBD amplifies the ability of endocannabinoids to lower pain, improve mood, support sleep and reduce inflammation. More research is being conducted on these effects and how endocannabinoid enzymes might be targeted in future clinical treatment methodologies.

PPAR Receptors

Cannabis bud close up

In the body, CBD also stimulates non-endocannabinoid receptors. One example is the ‘PPAR’ or peroxisome proliferator-activated receptors. The PPAR receptors work in the cells to control their replication and metabolic regulation. Modulating them has profound immune and metabolic benefits. Through this pathway, CBD may help with metabolic function at the cellular level, helping cells replicate correctly to prevent cancer risk (anti-proliferative effects).

Multiple cannabis sativa plants

In addition, CBD has demonstrated abilities to modulate TRPV1 pain receptors and nociceptors in the nervous system. Each plays a role in how pain is transmitted in the body, experienced and regulated. Altering nervous system pain receptors within the body is one way CBD can dampen pain and lower its severity. Most research to date has shown these benefits are far more pronounced when CBD is combined with THC, however. These two cannabinoids are synergistic in their potential for pain alleviation and work more effectively in combination.

Effects of Endocannabinoids

girl holding cannabis leaf

When stimulated by cannabinoids like CBD, the body produces two main endocannabinoids. These are anandamide and 2-AG. 


Anandamide chemical

Anandamide is the ‘feel good’ endocannabinoid that provides mental calmness, stress alleviation and feelings of comfort. It is called the “bliss molecule” in cannabis culture because of these profoundly soothing effects on the mind. Some describe the sensation anandamide provides as similar to the endorphin high experienced from intense cardio. There are a few reasons anandamide causes this. In the brain, it has profound capacities to alter serotonin and neurotransmitter transmission. Correspondingly, this benefits neurological outcomes like improved learning, mood, anxiety alleviation and appetite control. 

Researcher studying anandamide

Anandamide has anxiolytic (anxiety-reducing) properties and displays antidepressant effects. In a 2019 study from the Journal of Neuroscience, it was shown to lower anxiety and stress in mice. These clinical outcomes were thought to result from anandamide’s capacity to modulate the serotonin neurotransmitter. Because serotonin controls mood, improving its transmission in the brain increases mood, feelings of well-being, and anxiety cessation. Importantly, these effects were clinically significant compared to a placebo control group in the rodent study.

Cannabis bud close up

A separate 2008 study showed that anxiety was reduced in rodents dosed with anandamide. This trial also observed the breakdown of anandamide by FAAH. During its bioactive period in the body, anandamide displayed antidepressant characteristics. Researchers are now targeting this endocannabinoid as a potential natural depression treatment. Its potent effects on serotonin regulation and mood improvement may prove to be a robust method by which depression can be mitigated.

Cannabinoids on hemp plant

Anandamide also has nociception-blocking properties through the CB1 receptors in the brain and CNS. In other words, it can alter pain perception. Specifically, anandamide reduces pain signalling in the nerve pathways that cause pain sensations. Mice studies have supported this claim. In a 2011 Pharmacology Journal study, using anandamide and FAAH inhibitors in mice substantially reduced pain symptoms in test subjects. This was theorised to result from both CB1 and CB2 receptor agonism. This means that anandamide blocks pain stimulated in nerve endings and reduces pain signals from being received in the brain.

Cannabinoids dripping

Another reason anandamide can lower pain is its powerful anti-inflammatory function. Anandamide down-regulates prostaglandin and cytokine production. These compounds form a crucial part of the body’s inflammatory response. When dysregulated, they cause chronic inflammation in the tissue. Chronic inflammation causes IBS, colitis, rheumatoid arthritis, and atherosclerosis. Controlling pro-inflammatory signalling compounds correspondingly provides immense inflammatory and immune benefits. 

Woman calm from endocannabinoids

These anti-inflammatory properties also extend to reducing brain inflammation. Inflammation in brain neurons contributes to cognitive decline, Alzheimer’s risk, and memory problems. In 2021, a clinical trial run by the Journal of CNS & Neurological Disorders studied anandamide for its ability to reduce neuronal inflammatory symptoms. It stimulated neuroinflammatory reductions in test subjects successfully, improving neuron function. Anandamide’s antioxidative properties also supported these brain health outcomes. As an antioxidant, it reduces oxidative stress in brain cells. This helps to protect these cells from damage or degradation over time. 


2-AG endocannabinoid chemical

2-Arachidonoylglycerol (2-AG) is the other important endocannabinoid. In contrast to anandamide’s mental affinities, it favours interactions with receptors in the body. 2-AG is renowned for its immunomodulating effects and cardiovascular benefits. It’s been linked to many beneficial outcomes for the cardiovascular system, cognition, hormone balance, and nerve function.

Liquid medical cannabis oil

2-AG is potently anti-inflammatory because it works as an immunomodulator. A 2015 study demonstrated these properties. This study highlighted the ability of 2-AG to alter the regulation of immune signalling proteins such as cytokines. Changing their body levels helped calm chronic inflammation symptoms and lower inflammatory markers.

Cannabis growing in laboratory

While it primarily functions in the body, 2-AG has also displayed anti-inflammatory benefits for brain neurons. A 2019 review highlighted these neuroinflammation-reducing properties. It elucidated that 2-AG worked to block excessive or ‘excitatory’ neuron firing, which can cause neurotoxicity (brain damage). In simple terms, it displayed neuroprotective effects.

Endocannabinoids in brain

It achieved this by blocking excess glutamate transmission. Glutamate is an excitatory brain chemical. Excessive production of it can damage neurons and cause cognitive dysregulation. Over time, this will degrade the brain and contribute to the risk of neurodegenerative disorders such as Alzheimer’s. Protecting brain cells is a fundamental way that 2-AG strengthens brain health. It’s also thought to be one of the main ways in which CBD works for epilepsy and related neurological disorders relating to neuron excitation.

Scientist researching endocannabinoids

Besides its neuroprotective properties, 2-AG has also been found to aid in appetite management. It helps reduce caloric intake and maintain a healthy weight by altering hunger hormone secretion. These hormones are controlled by the hypothalamus (a brain region), which 2-AG modulates via CB1 receptors in the brain. When this occurs, appetite can be suppressed and better controlled. Dysregulated hunger hormones are brought back into balance to prevent binge eating, overconsumption of food, and increased body fat.

A 2011 trial showed the appetite benefits of 2-AG in a rodent model. It discovered that 2-AG acted on the hypothalamus in the brains of 12 mice. The mice were then observed to consume less food and maintain better weight ranges. In other words, 2-AG stimulated feelings of being ‘full’ and not hungry for extended periods. It was also theorised to reduce hunger triggered by stress or stress-eating behaviour patterns. This occurred from the anxiolytic and calming effects of the endocannabinoid.


CBD Drops in bottle

In the body, CBD oil works in a range of complex, interrelated ways across the endocannabinoid system and bodily receptors. These effects are stimulated by CBD’s ability to bind with receptors in the endocannabinoid and metabolic systems. Importantly, it does so without causing addiction or intoxication like THC. When consumed, CBD acts on the CB1 and CB2 cannabinoid receptors. This stimulates the release of health-promoting endocannabinoids like anandamide and 2-AG. 

Additionally, CBD slows the rate at which these helpful compounds are cleared from the body to accentuate their benefits. In addition, CBD works more directly on PPAR receptors to improve cellular function. There is already a large body of research on how these interactions of CBD work to provide benefits like reduced pain, lower anxiety, anti-inflammatory effects and better metabolic markers. As more clinical studies are performed, our understanding of how CBD works in the body will deepen. It may yet yield new medical and therapeutic applications in the future for cannabinoids, as well as endocannabinoids.


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