How CBD Works – A Guide To Cannabinoids –

Cannabidiol is one of over a hundred chemical compounds found in the cannabis plant, collectively known as cannabinoids. Cannabinoids are defined based on their ability to impact the endocannabinoid system, a complex system of cells and chemical messengers responsible for everything from regulating cognitive processes and mood to maintaining homeostasis and regulating stress.

While an explanation of the process is relatively complex, you can imagine cannabinoids as acting like keys. Neurons, which are the cells that make up the nervous system, each have a membrane that separates their insides from the outside, much like how your skin keeps your muscles, bones, and organs inside. These membranes are lined with doors that allow certain compounds to come in and out of the cell. Like any good doors, they have locks. In this metaphor, the doors and locks are receptors and the keys are neurotransmitters. Cannabinoids are one type of neurotransmitter that interacts with cannabinoid receptors in your body. Collectively, the cannabinoid receptors and cannabinoids in your body are known as the endocannabinoid system. Endocannabinoids, the compound produced in your body, and phytocannabinoids, those produced in plants, can both activate your cannabinoid receptors and induce a cascade of reactions that have far-reaching implications. Since the endocannabinoid system is so expansive and responsible for so many different internal bodily and cognitive functions, altering the system can have equally pervasive effects and is the reason why cannabinoids have such wide-spanning recreational impacts.

CBD has been lauded for its effectiveness without getting the user “high”. As such, CBD has been categorized as non-psychoactive , meaning it doesn’t affect the mind. It is worthwhile to note that CBD may be a psychotropic, which affects a person’s mental state. This particular cannabinoid is not inebriating, unlike its famous counterpart THC. Understanding how CBD works without getting you high requires a slightly deeper understanding of the endocannabinoid system.

There are two main types of cannabinoid receptors: Cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2). CB1 receptors are critical for brain function and, depending on where they are found in the brain, will be responsible for modulating mood, memory, pain perception and more. CB1 receptors are also found throughout the body, just in less density than in the brain. CB2 receptors are found scattered throughout the body and partially in the brain. They are primarily involved in moderating the immune system and issuing inflammatory responses. THC and CBD both interact with CB1 and CB2 receptors. THC is functionally similar to the cannabinoid key discussed earlier, while CBD is slightly different. Instead of acting like a key to open the locks on cannabinoid receptor doors, CBD changes the shape of the lock itself, which subsequently alters the way that a THC key will interact with it. Simply put, CBD modifies CB1 and CB2 receptors and “antagonizes” them, meaning that when CBD is around, cannabinoids like Anandamide and THC will not be as potent. CBD can be thought of as a moderator of the endocannabinoid system, toning down the system in its responses to THC and other states of consciousness.

Given CB2’s role in affecting inflammation, it’s simple to see why CBD has been the subject of so much research. This same logic applies to CBD’s impact on CB1 receptors, potentially mitigating an overactive set of CB1 receptors and curbing high-energy cognitive states.

It should make a bit more sense now why CBD doesn’t get you high but THC does. THC triggers a response, whereas CBD mitigates it. The question remains, does CBD give you a body high? Similar to how a massage feels good for individuals who need relief from muscle tension, have an overactive immune system or muscle pain following weightlifting, CBD can make you feel “high” in the sense that it alters your current state and helps you transition to a more elevated quality of life.

Once in your bloodstream, CBD can do its job with relative ease; there are endocannabinoid receptors all over the body, so it can quickly get to work by modifying CB1 and CB2 receptors. Getting CBD into your bloodstream efficiently, however, is whole different story.

What is bioavailability?

The bioavailability of CBD is measured based on the proportion of ingested CBD that actually ends up having an effect on your endocannabinoid system. If you’re concerned with how to increase the effectiveness each CBD serving, your focus should be on maximizing bioavailability.

The most critical variable in determining a CBD product’s bioavailability is whether or not it goes through first-pass metabolism. First-pass metabolism of CBD is the absorption of CBD by the liver and gut wall. The liver helps to metabolize many drugs and other ingested items that may contain ingredients that are harmful to the body. Sometimes it does this to such an extent that only a small amount of the drug makes it into the bloodstream. As a result, first-pass metabolism can significantly reduce the bioavailability of CBD. Only one CBD ingestion method goes through first-pass metabolism: edibles. Edibles include anything that is swallowed, such as CBD cookies, crackers, coffee and oil. After the CBD is swallowed, it is absorbed by the digestive system before entering the liver.

First-pass metabolism also elongates the activation time of CBD; the process of moving an edible through your digestive system before the liver allows it into the bloodstream is lengthy and can be blamed for edibles always taking a bit longer to “hit”. This also answers the question of, “Why does CBD oil cause decreased absorption?” CBD oil has to go through first-pass metabolism, meaning it can’t be absorbed in high quantity without somehow sneaking past the liver. There are many ways to bypass first-pass metabolism and get CBD into your bloodstream much faster and more efficiently, including sublingual tinctures, which get absorbed by the mucous membranes under your tongue, and CBD vapor pens, which are absorbed by your lungs’ alveoli.

Did you also know that CBD oil can be absorbed through the skin? In what is known as transdermal absorption, taking CBD through a patch applied to the skin also bypasses first-pass metabolism and offers an extended period of effects.

CBD edibles and sublingual tinctures are two products that have skyrocketed in popularity alongside the rise of CBD itself. The decision of whether to consume sublingual vs. edible CBD is an important one that impacts serving size and the duration of effects. As a steadfast rule, CBD consumers looking to maximize bioavailability should look into products such as these that bypass first-pass metabolism. Epidiolex, the first CBD-based drug approved by the FDA for seizures, comes as a sublingual tincture oil form because of its bioavailability.


Many of the products featured on’s Best Seller Page are optimized for increased absorption. Specifically, the CBD vape juice, tincture oils and face masks all bypass first-pass metabolism. When reading the label of a CBD product, the total mg of CBD in the product is not always what will be made bioavailable. Importantly, a Cannabis DNA test can inform you if you are genetically predisposed to being an ultra-slow metabolizer of CBD, which may lead to cirrhosis if you consume too many edibles. All this being said, consumers looking for the quickest and most bioavailable CBD should look towards CBD vapes and sublingual tincture oils.


About the Author

Nicco Reggente earned a PhD in Cognitive Neuroscience from UCLA, where he focused on using machine learning to determine optimal, personalized treatment plans for individuals. Nicco is passionate about personalized medicine, especially as applied to the cannabis industry. He is the co-founder and CEO of Strain Genie—a cannabis DNA test that helps match users to the right cannabinoids and terpenes for their body.