CBD Bioavailability - The real story
Surprisingly, scientists still know only a relatively small amount about what happens to cannabidiol (CBD) once it enters your body. Often, consumers are provided with a simplified version of how it works; sometimes, this makes it easier to understand, but it can also be a tactic to market products and exaggerate the results.
In this article, you will get to see behind the usual story and gain an in-depth understanding of what is known and unknown about CBD absorption.
We’ll also take a closer look at some of the different product types, such as full-spectrum, broad-spectrum, isolate and even water-soluble, to discover how their differences can affect how they behave in your body.
Pharmacokinetics and Bioavailability of CBD
Pharmacokinetics is the movement of drugs within the body. Bioavailability refers to the amount of a substance that reaches your bloodstream and is able to have an active effect.
Any food, drug, or supplement that we consume is subject to numerous processes, systems and reactions. All the chemical reactions in your body that transform one substance into another are known collectively as the metabolism.
The complexity of the metabolism makes it hard to know exactly what is going on after you take CBD. Metabolic reactions either make new substance to be used in cells or detoxify them and remove them from the body. Both types of reactions are assisted and sped up by enzymes; metabolisis takes place anywhere enzymes are present in your body.
The Metabolites of Cannabidiol
For CBD, there are several ways to take it, and there are many different enzymes and reactions that can break it down or transform it into different substances. Across all the studies that have been conducted so far, scientists have found that it can be metabolised into over 100 different chemicals. In fact, many of the effects attributed to this cannabinoid may actually be produced by one of these new forms (metabolites) and not by the original molecule.
Not all of the CBD you take will reach your bloodstream or be used in your body. Some of it is metabolised or excreted before it can have any effect. Several studies have discovered that a significant amount is removed as a waste product completely intact before any metabolisis occurs.
CBD Follows Many Different Chemical Pathways
CBD in its natural form is fat-loving (lipophilic); this means that it can easily cross most cell membranes. Any that isn’t excreted will likely begin interacting with enzymes from the moment it enters your body. Some will be hydroxylated and slowly removed over time. Some will pass across membranes into blood vessels. A small amount will immediately enter nearby cells, and some will be polarised into a more water-soluble form.
Whichever way you take your CBD, the route it takes to your bloodstream and cells is exceptionally complex. Currently, there have been no human studies that were able to determine how it is distributed throughout your cells, tissues and organs after it’s been consumed. Some research with animals has indicated that it’s evenly distributed throughout brain tissue, but they were precisely focused on the presence of specific metabolites and certain organs.
Much more research is required for us to get an accurate picture of the many different chemical pathways that CBD follows.
What Happens When You Swallow CBD?
When CBD is swallowed, it’s immediately mixed with a range of enzymes in your mouth that begin the process of breaking down larger molecules. Once it reaches your stomach, even more fluids, including acids, are added, and muscular contractions mix everything into a liquid-like sludge. Some molecules can pass through the membranes in the stomach lining, but it’s minimal because there is a thick layer of protective mucus.
Once the CBD passes into the small intestine, it has better access to the gut wall, and some will begin to cross into the bloodstream. Also, at this point, pancreatic fluid and bile from the liver are introduced to further break down the molecules.
Because CBD is lipophilic (fat-loving), the molecules can move from an area of high concentration (the intestine) to an area of low concentration (the blood). We don’t know for sure what form it is in at this stage; it’s likely already been metabolised and changed to some degree to ease the passage into the blood.
The blood supply around the small intestine then passes through the liver, which uses numerous enzymes and chemicals to break down toxins. This is known as the ‘first pass system’ or ‘first pass metabolism’ and is where more CBD is changed, destroyed or excreted.
The reactions that occur from the point of placing the CBD in your mouth to when it passes out of your liver are known as phase 1 metabolism. Although we don’t know all of its new chemical forms, we do know that the most abundant substances (metabolites) created during this phase are 6alpha-hydroxycannabidiol (6 hydroxy CBD) and 7-hydroxycannabidiol (7 hydroxy CBD).
These are both made when CBD interacts with enzymes secreted by the liver, called CYP2C19 and CYP3A. Both 6 hydroxy CBD and 7 hydroxy CBD are thought to be active substances producing effects that are likely to be slightly milder than their parent molecule.
Having different forms of CBD present in your bloodstream will likely result in a more diverse range of effects. It also means that the non-polar, fat-loving (lipophilic) CBD molecules could break down into polarised, water-loving (hydrophilic) metabolites that are able to interact with your body in different ways. However, it may also mean that some of these metabolites may be inactive or have milder effects.
It’s also likely that different product types produced in different ways may result in different metabolites. For example, 6 hydroxy CBD and 7 hydroxy CBD will likely only be produced if the cannabidiol is eaten and passes through the liver in your bloodstream.
Taking CBD Under Your Tongue
The most popular method of taking CBD oil is to place it under your tongue so that it can be absorbed through the membrane into your sublingual blood vessels. This area has a denser network of blood vessels than the skin, making it ideal for absorption. It’s particularly well-suited for CBD because the molecules must pass through lipid (fatty) membranes.
This is easy for fat-loving substances like CBD but not so good for water-soluble substances. However, some experiments have revealed some parts of this membrane may have water-loving sections that will allow water-soluble substances to pass through.
Consuming CBD via this route results in a significantly higher bioavailability because absorption is easier, and it won’t have to pass through the liver. Blood flowing through your sublingual vessels goes on to visit your other organs and systems before it returns to your liver.
This quick journey into your blood and on to the rest of your body means that CBD taken under the tongue is also quick to take effect. You may feel results in as little as fifteen minutes.
By missing out your digestive system and liver, CBD taken in this way doesn’t have the same initial exposure to acids and enzymes. However, metabolic reactions will still be working to turn it into different chemicals in your mouth and blood vessels. It’s also likely that some will still be swallowed, so a small amount will still pass through the liver.
Vaping and Inhaling e-liquids
Inhaling vaporised e-liquid is another excellent way of taking CBD without it going through the first pass of your liver. When heated, the mixture of liquids (often vegetable glycerin and propylene glycol) vaporises and transports it through your airways into your lungs.
The lungs consist of many tiny sacs called alveoli. Alveoli are rich in blood vessels and have a mucous membrane. The CBD crosses the membrane into your blood, and it’s transported systemically to the rest of your body without passing through the liver.
As with the sublingual method, more CBD reaches the blood, and there are likely fewer enzymes present because there’s no direct secretion from the liver. However, it will still be broken down or converted to some extent by other enzymes present in your blood. Other metabolites will also be produced when it reaches different tissues and organs.
Full-Spectrum and Broad-Spectrum vs CBD Isolate
All CBD products contain some form of hemp extract; the type of extract used can affect the strength of the product and what effects it produces.
Full-spectrum – This is a CBD-rich extract with traces of all the other cannabinoids found naturally in the hemp plant, including THC, CBN and THCV.
Broad-spectrum – Sometimes known as ‘THC-free’, broad-spectrum extracts contain CBD and traces of all the other cannabinoids apart from THC/CBN and THCV. Out of broad-spectrum and full-spectrum, broad-spectrum products are the most likely to fall within the UK’s legal limit of 1mg of THC per container.
Isolate – This is a CBD only extract that has been processed until all the other cannabinoids have been removed.
Cannabinoids Taken Together Have a Better Absorption Rate
Recent research indicates that products made with full-spectrum or broad-spectrum extract may have an advantage when it comes to being absorbed into the bloodstream. This is because the presence of other cannabinoids may enhance the uptake and chemical interactions of CBD.
One study compared the blood concentrations of people who took isolate capsules compared to those who took raw extracts containing both CBDa and CBD. The results showed that the raw extract produced an average of up to four times as much CBD in the blood than with the isolate product.
Full-Spectrum CBD Increases in Potency in Large Measures
The entourage effect theory suggests that cannabinoids taken together will influence how they each interact with the body. The results could be stronger, more varied effects. One result of the entourage effect that’s been observed during research is that full-spectrum products produce more potent results the more you take. With isolate products, the benefits don’t continue to increase as the dose gets larger.
As you can see from this graph, once the serving size reaches a certain point, the effects of the isolate begin to reduce. Consequently, if you want more potent results or stronger products, full-spectrum (USA) or broad-spectrum (UK) are more likely to provide what you’re looking for.
What is Water-Soluble CBD?
Water-soluble CBD is cannabidiol that has been treated to allow it easily dissolves in water. This makes it easier to add flavour and makes products more pleasant to drink. Many brands also claim that it dramatically increases bioavailability.
In some cases, this claim is based on the fact that because our bodies consist of up to 60% water, it must be easier for drugs to move around them if they’re water-soluble. But, our body processes are never simple, and the transport of any substance around the body is complicated and features many different pathways and obstacles.
However, there is growing evidence that properly formulated water-soluble products can increase the amount of the active ingredient that reaches your bloodstream. A study conducted in 2020 found that water-soluble CBD powder was about 4.5 times more bioavailable than a similar, fat-soluble substance.
This increase in bioavailability is likely to be because the water-soluble particles prevent enzymes from breaking it down during the first phase of metabolism. Most water-soluble preparations will allow cannabinoids to travel into your gut and pass into the blood without needing to be broken down. It’s also likely that they may be able to reduce the amount of CBD that’s broken down as the blood passes through the liver.
What Are the Different Types of Water-Soluble CBD?
The majority of water-soluble CBD products are emulsified liquids. These are liquids that contains both oil and water, but the oil has been forced to form such tiny particles that it mixes with the water.
If you add oil into a bottle of water and then shake it vigorously, you’ll see that the oil forms tiny droplets in the water before joining back into a layer of oil. Water-soluble CBD manufacturers have been able to find ways to make those droplets even tinier and make them stay mixed with the water.
Different manufacturers use different methods and ingredients to create these products resulting in several different types. The most common are:
These are made when microscopic droplets of CBD oil are mixed into water. The droplets are often created by using sound waves to split the oil apart into tiny particles. Then small amounts of natural chemicals are used as ‘surfactants’ to prevent the drops from joining back together.
The droplets usually measure between 10 and 250 nanometres across. These are popular products and are likely to be the safest option because they don’t use high levels of chemical surfactants.
A surfactant is a substance that reduces the surface tension of a liquid allowing it to mix with some oil based products.
Using slightly larger droplets between 100 and 5000 nanometres, microemulsions require large amounts of chemical emulsifiers to split the oil into small parts and blend it onto the water.
These are simple to make and require less technology because they form when the ingredients are mixed together. However, the chemicals used are needed in large amounts and can sometimes cause side effects or even allergic reactions.
These are double-layered spheres of fats with a small amount of water trapped in the centre. The CBD molecules are encapsulated between the two layers of fats, so they’re not in contact with any water. The spheres usually measure between 50 and 5000 nanometres across. Because of the complex structure, these can be complicated to make and require lots of emulsifying chemicals to remain mixed into the water.
CBD Oil vs Water-Soluble CBD?
There is growing evidence to back up claims that carefully made water-soluble products are able to transport more CBD through your digestive system than oils can. If you swallow oil, some of the active ingredient is removed from your body unused, some of it is converted into other substances, and the rest enters your blood vessels, cells and tissues. Water-soluble preparations prevent enzymes from metabolising CBD in your digestive system and gut giving it a better bioavailability.
However, some of CBD’s metabolites provide benefits of their own. They may even contribute to results that regular users are looking for. Currently, most studies that compare oils with water-soluble products only look at how much CBD reaches the bloodstream intact. What is now needed is a detailed analysis of the effects and benefits of each product type. This would allow consumers to better ascertain which is right for them.
CBD oil is Best When Taken Under the Tongue
If you take CBD oil under your tongue, it avoids exposure to some digestive enzymes and doesn’t pass through the liver. This gives it enhanced bioavailability that may be similar to that of water-soluble CBD taken orally. This can also be taken under the tongue, but it may not pass through into your bloodstream as efficiently as the oil.
CBD Oil Contains Simple, Natural Ingredients
CBD oil is a simple, natural product with no need for additional chemicals. The process of making it water-soluble is more complicated and can involve several surfactants and emulsifiers. To ensure that the water-soluble products you use are as safe as CBD oils, it’s important to choose nanoemulsions with small levels of natural surfactants.
Water Soluble CBD Has Greater Bioavailability When Swallowed
When swallowed, a well-made water-soluble CBD product will be the most bioavailable option. However, the effects may vary, and some oils may match its effectiveness if you take them under your tongue.
The development of water-soluble CBD won’t remove the need for CBD oil, but it will provide another option that may work best for some people or for certain situations. As with any food supplement, it’s worth trying small amounts, increasing slowly and making notes of the effects to decide what works best for you.
It’s easy to get the impression that there is nothing left to learn about the human body, but this couldn’t be further from the truth. There are numerous systems and interactions that scientists still don’t understand, and many substances and structures yet to be discovered. When it comes to how CBD works, we know many of the effects it produces, and some of the systems it interacts with, but much more research is required before we can understand the complexities of how it’s absorbed.