Bioavailability & CBD

Bioavailability & CBD - What is it and why it matters

 

As the popularity of medical cannabis and hemp-infused products increases, so too are the different ways in which you can take it - from oils and tinctures, to gummies, creams, vapes, teas, and even toothpicks. 

 

No wonder then that an increasing number of people are starting to question the efficacy if what many consider more gimmicky products. But also, what IS the best and most effective way to take medical cannabis and hemp products?

 

The answer to this question pretty much depends on something known as bioavailability, which in turn, is influenced and controlled by the type of medical cannabis or CBD product used as well as how the product is taken.

 

This is because, not only do these two factors determine how much of the therapeutically active compounds like cannabinoids (e.g., cannabidiol (CBD) and Tetrahydrocannabinol (THC)) and terpenes (e.g., beta-caryophyllene and myrcene) are absorbed into the bloodstream, but also how quickly.

 

In this article we will take a look at what bioavailability is, how different methods of administration influence different levels of uptake and rates of onset and then explore how the way in which a product is formulated can increase its bioavailability.

 

 

What Is Bioavailability?

Bioavailability refers to the fraction (or percentage) of an administered substance that reaches systemic circulation.  In other words, bioavailability is simply a fancy way of referring to the how much of the substance is absorbed into the bloodstream (i.e., “level of uptake”), and how quickly it takes effect (i.e., “onset of action”) when taken in a specific way.

 

For instance, when a pharmaceutical substance of medicine is injected, it is considered to have a 100% bioavailability.  That is because all of that active compound enters directly into the bloodstream, making it immediately available for use by the body, and allowing for a fast onset of action. 

 

In contrast, say that very same substance is rubbed onto the skin, its bioavailability will decrease.  This is because less of it will be absorbed more slowly (level of uptake), and it will take longer before it works (rate of onset of action).

 

The reason why the bioavailability of a substance is important is because it not only determines the best type, but also the dosage and the best way of taking a particular therapeutic compound.  Simply put, the bioavailability of a compound will govern how, and how much of it should be taken for it to reach a high enough concentration in the blood stream for it work.

 

 

Bioavailability of CBD, Cannabis & Hemp Extracts

Just like with any other therapeutic compound, the bioavailability of a medical cannabis or hemp CBD product will largely depend on how it is taken and how bioavailable the product formulation is.  

 

 

Bioavailability of Methods of Administration

The way in which your body absorbs CBD is very much dependent on the way in which it is taken, with different ways of consuming CBD having different levels of bioavailability.  The reason for this is the pathway the CBD needs to take to enter into the bloodstream. 

 

Administration Method: Oral

Product Types:

  • CBD capsules
  • CBD gummies
  • CBD edibles (e.g. chocolates or baked goods)
  • CBD concentrates or powders (added to food or drinks)
  • CBD beverages (e.g. teas, coffee, juices, smoothies or drinks)

 

Time of Onset:

30 to 120 minutes

 

Elimination half-life (how long a therapeutic compound remains active in the body):

Between 1 to 2.5 hours after single dose administration. 2 to 5 days after chronic oral administration.

 

Bioavailability:

Oral administration is when cannabinoids like CBD is taken by mouth and swallowed. 

 

The bioavailability of oral ingestion is one of the lowest, falling at a level of anywhere between 10% to 20% while some studies even show it to be as low as 4% to 6%

 

The reason for this is because of something called the first-pass effect which refers to the low systemic availability of a therapeutic compound due to significant metabolism in the intestines and liver.  When a CBD product is ingested by mouth, it is broken down by the intestinal tract, from where the CBD immediately travels to the liver via the hepatic portal vein in what is called hepatic first pass.  Once the CBD reaches the liver, it is metabolised by enzymes in the liver called cytochrome P450 (CYP450) to such an extent, that most of it does not exit the liver

 

The end result is the vast majority of the CBD does not reach and enter the bloodstream and the rest of the body for systemic circulation, making oral administration one of the least efficient methods of consumption with one of the longest onset times.

 

 

Administration Method: Sublingual

Product Types:

  • CBD oils
  • CBD tinctures
  • CBD sprays

 

Time of Onset:

20 to 40 minutes

 

Elimination half-life:

Between 18 to 32 hours.

 

Bioavailability:

Sublingual administration is when a CBD oil, spray or tincture is placed under the tongue (sublingual) and held there for 1 to 2 minutes before the rest is swallowed. 

 

The bioavailability of sublingual administration is higher than oral administration with one study estimating it to be about 13% to 19%.  However, another study puts the bioavailability of sublingual delivery of cannabis oil as high as 35%

 

The reason for this increase in bioavailability with sublingual administration is due to the more direct path with which the CBD enters the bloodstream.  Unlike oral ingestion where the CBD is metabolised by the liver, placing the CBD oil under the tongue allows it to be directly absorbed by both the sublingual gland and mucous membranes.  Because of the close proximity of the blood vessels to the surface of the membranes, the CBD has a fast and efficient way to enter into the bloodstream for circulation and distribution throughout the body. 

 

The longer the CBD oil is kept under the tongue, the more CBD can be absorbed and the higher the level of absorption.  In addition, because the CBD enters the bloodstream in a more direct manner, the time of onset of action is shorter, and the effects last longer than oral administration.

 

 

Administration Method: Transcutaneous (Topical)

Product Types:

  • CBD transdermal patches
  • CBD salves and balms
  • CBD creams and lotions
  • CBD serums
  • CBD beauty products

 

Time of Onset:

20 to 90 minutes (from anecdotal evidence). 

 

Elimination half-life:

Unknown

 

Bioavailability:

Transcutaneous administration of CBD is when a cream, balm, serum or transdermal patch is applied directly to the skin.

 

Several studies have been done on the efficacy of CBD and other cannabinoid topicals and transcutaneous patches for a variety of symptoms, most notably for inflammation and pain relief.  However, despite these studies showing that transcutaneous administration of CBD is effective, its bioavailability have not been investigated.

 

The theory is that the application of these types of products enable the CBD to be absorbed through the surface of the skin from where it can be absorbed into the sub-dermal blood vessels while also interact with localized cannabinoid receptors. 

 

Although this hypothesis is sound, to date, no specific studies have actually assessed the bioavailability or onset time of CBD via the skin.

 

 

Administration Method: Transdermal via Mucosa

Product Types:

  • Intranasal CBD sprays (e.g. Sativex / Nabiximols)
  • CBD vaginal suppositories (e.g. CBD tampons)
  • CBD rectal suppositories
  • Oromucosal controlled-release chewing gum

 

Time of Onset:

10 minutes for intranasal administration. Other methods are unknown.

 

Elimination half-life:

1.5 and 11 hours for oromucosal spray administration.  Other methods unknown

 

Bioavailability:

Similar to topical administration, transdermal administration also involves the application of CBD to the body via the skin.  However, the preference in transdermal administration is for application to areas like the inside of the nose, vagina and rectum that consist of mucous membranes.

 

The bioavailability of intranasal transdermal delivery is quite high, with studies estimating it to be between 34% and 46%.  In a similar vein, one study found that rectal application of cannabinoids can be up to 25% to 50% more effective than oral administration, providing an average bioavailability of 13.5%.

 

Similar to the difference in bioavailability between oral and sublingual administration, the reason for an increase in bioavailability of mucosal transdermal compared to transcutaneous administration is because of the proximity of blood vessels to the surface in the application area. 

 

Administration Method: Inhalation

Product Types:

  • CBD inhalers
  • CBD vape liquids
  • CBD vape pens
  • CBD cigarettes & pre-rolls
  • Herbal vaporisers
  • CBD concentrates

 

Time of Onset:

2 to 10 minutes with maximum plasma levels after 3 minutes.

 

Elimination half-life:

31 hours

 

Bioavailability:

Inhalation is when cannabinoids like CBD is vaporised or burned, drawn into the mouth and inhaled into the lungs. 

 

A comprehensive large scale study found that bioavailability can range from as little as 2% to as much as 56%.  This variability in bioavailability of cannabinoids when inhaled is dependent factors such as how experienced the user is, as well as how controlled and how deeply the oil, concentrate, or plant material is inhaled. 

 

Inhalation is probably one of the most effective and bioavailable method of administration.  The reason for this is due to the large surface area and permeability of lung tissue.  When CBD is inhaled, it is almost immediately absorbed into the bloodstream via a thin tissue layer called the pleura, from where it can be distributed to the rest of the body.  More CBD is inhaled with each subsequent breath, providing a continuous dose of CBD that is quickly and efficiently absorbed.

 

Inhalation allows for a rapid onset of action as well as longer duration of effects and ease of dose titration making it ideal for acute conditions where quick symptom relief is needed.  However, inhalation can irritate lungs and is therefore not suitable for everyone.

 

 

Bioavailability in CBD Products & Formulations

As scientists begin to understand how cannabinoids like CBD enter the body in different concentrations depending on the method of administration, they are also starting to develop and understanding of the role of product formulations.  More specifically, how decreasing molecule size and increasing water solubility through nanotechnology can increase bioavailability.

 

Water Soluble CBD

Because the human body consists mostly of water, fat-soluble molecules like cannabinoids and terpenes, have by their very nature poor bioavailability.  It is a fundamental fact that oil and water do not mix, so when cannabinoids like CBD enter the bloodstream, they do not dissolve very well.  This makes it more difficult for the CBD, and more of it is needed, to reach high enough concentrations in the blood to reach therapeutic levels.

 

The trick then is to formulate and design products that work with the lipophilic (lipo = fat, philic = loving) nature of cannabinoids, creating a CBD product that achieves a fine dispersion of oil into water.  In order to this, the water must be kept in a continuous phase while the oil is in a dispersed phase, requiring the use of an emulsifier or surfactant to assist in the dispersal.

 

The three most common ways to do this is through:

 

  1. Liposomic transfer refers to either natural or man-made spherical structures that have a water attractive (hydrophilic) outer layer and in inner cavity capable of encapsulating the CBD molecules and literally pass them “inside” themselves.

 

  1. CBD Macroemulsions that mixes large (> 1µ) droplets with a carrier oil and surfactants. Macro emulsions are similar to mixing a regular cannabis or CBD oil with a lipid and then blending it into a drink. This method is rather unstable and works only marginally better than a good sublingual dosage.

 

  1. CBD Microemulsions that are basically macro emulsions but done on a smaller scale, with droplet sizes 1/10 of the size of a macro emulsion. However, micro emulsions require more surfactants that allow them to be more stable than macro emulsions but can also overwhelm the taste buds or exceed allowable limits for consumption.

 

  1. CBD Nanoemulsions discussed in detail below.

 

 

CBD Nanoemulsions & Nano Particles

CBD particles measure in the region of 2,000 nanometers while human cells only absorb molecules smaller than 80 nanometers.  This means that as much as 90% of CBD that is ingested is lost because the molecules are simple to large to permeate the cell. 

 

Transforming CBD molecules into that of nano particles and nanoemulsions to one that is more easily absorbed is one popular and cutting edge method of enhancing solubility, absorption and bioavailability. 

 

CBD nano particles generally refer to an active ingredient (in this case CBD) and carrier particles that are dispersed or disrupted with the use of sonic frequencies (sound waves).  The intended goal of these sonic frequencies is to “break” these particles into smaller and smaller sizes in a process known as ultrasonication.  This creates nano-sized particles that are composed of the active ingredient and carrier, but much smaller than their non-disrupted counterparts.  Because of their small size, these nano particles are capable of passing through the walls of cell membranes more readily and easily, resulting in a higher level of absorption, bioavailability and efficacy.

 

CBD nanoemulsions are created by blending these CBD nano particles with a surfactant (a compound that lowers the surface tension of a liquid) that is also extremely small and designed to be absorbed more efficiently by the body.  This allows the CBD nano particles it to get to the appropriate delivery points more quickly and efficiently.  Theoretically, CBD nanoemulsions are the most bioavailable option currently available since this nano-encapsulation technology increases the intestinal absorption, bioavailability and stability of the CBD molecule,.

 

 

Full-Spectrum CBD Extracts

Scientists like Dr Aaron Russo theorise that full-spectrum or broad-spectrum CBD oils and extracts are more bioavailable than their CBD isolate counterparts.  This is due to cannabis being an inherently polypharmaceutical, and a synergy (entourage effect) arises from the interactions between its multiple components.\

 

For instance, certain terpenes have been found to enhance the bioavailability of cannabinoids.  The terpene myrcene for instance has the ability to effect the permeability of cell membranes, particularly the blood–brain barrier (BBB), speeding up and increasing the absorption rates of cannabinoids into the brain.

 

In another study, scientists  investigating the anticonvulsant effects of CBD compared the effects of five types of full spectrum extracts, each of which contained the same amount of CBD but with different cannabinoid and terpene profiles.  Their results showed significant differences in the dosage requirements, efficacy and ceiling effects between each preparation potentially indicating that certain combinations of cannabinoids and terpenes affect bioavailability.

 

 

Carrier Bases

Because cannabinoids like CBD are lipophilic, some scientists hypothesise that under certain circumstance, the bioavailability of orally administered CBD products can be improved by adding fats

 

When an orally or sublingually administered CBD product is formulated with a lipid carrier base - especially a type of saturated fat called medium-chain triglycerides (MCTs) - studies have found that bioavailability can increase by as much as three times that of normal.

 

The reason for this is that the body is highly efficient in absorbing and breaking down MCTs. Therefore, when CBD is used together with an MCT carrier oil, the CBD is instantaneously and directly absorbed by the gastrointestinal tract, bypassing hepatic first pass, and enter directly into the bloodstream.

 

 

Understanding the bioavailability of CBD, consumers are able to make informed choices about the type of products that are right for their individual circumstances and lifestyles while at the same time increase its effectiveness.  The economic implications can also not be ignored.  However, from the above it is clear that the bioavailability of cannabinoids like CBD is a complicated and multi-facetted subject with more research being needed to truly understand the various factors involved.

 

Kanaco has curated a selection of highly bioavailable CBD products, we use nanoemuslions in our soft gel capsules to increase the absorption into the bloodstream and maximise the benefits of CBD.

 

Bioavailability & CBD

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