Differences between different forms of CBD

Not all CBD is the same. Discover the differences between different forms of CBD administration and their advantages and disadvantages. Learn how to choose the best form of CBD for you.

But for CBD to be effective, it needs to get into your endocannabinoid system. This means it must first be absorbed into your bloodstream, a concept known as bioavailability.

Once there, it must stay in circulation long enough to reach the organs and tissues where it is needed.

So how much CBD is actually absorbed and used? 

This depends on a process known as pharmacokinetics (the way compounds are processed by the body).

Pharmacokinetics, in short, refers to the totality of your body's absorption and excretion mechanisms, the properties of CBD itself, and the many external factors that can either help or hinder the way CBD is absorbed and used.

In addition, the route of entry, or route of administration, has a large impact on how much and how quickly CBD enters the bloodstream.

In this article, we'll look at the different routes of CBD administration, including oral, inhalation, mucosal, transdermal, and intravenous administration. We will discuss what current scientific knowledge tells us about each method and what their relative advantages and disadvantages are for practical use.

We will also examine some of the important factors that influence the absorption and metabolism of CBD. And you'll learn how to best manage these factors so that you can choose the ideal form of administration and dosage depending on what you want to get out of taking CBD.

Oral CBD: Capsules, oils and ingestibles

Oral CBD preparations such as drops, capsules, tinctures, foods, and beverages are among the most popular ways to consume CBD. However, oral administration of CBD has the lowest bioavailability of all forms of administration.

The average bioavailability of ingested CBD ranges from 6-19% [2, 3, 4].

One reason for this is that CBD is poorly absorbed after ingestion and therefore most of it is excreted without any effects.

This is due to the fact that CBD is fat soluble (as opposed to water soluble), which poses an absorption problem for the body.

In addition, digestive acids and enzymes destroy a large percentage of CBD before it can be absorbed. And the small amount that passes through the intestinal wall is metabolized in the liver before it reaches the rest of the body.

The half-life of oral CBD, the time it takes for half of the CBD to leave the bloodstream, can be faster than other routes of administration. At high doses between 750 mg and 1500 mg, half-lives of 10 to 17 hours have been reported [1].

Peak levels of oral CBD tend to be lower than with other forms of administration.

In one experiment, biscuits with 40 mg of CBD were found to have maximum blood levels of CBD between 1.5 and 3 hours after ingestion [5].

However, the low absorption of oral CBD may be offset by certain benefits - such as longer duration. A study in laboratory animals showed that the average time that an orally consumed CBD molecule is retained in the body, the so-called median residence time, is 4.2 hours.

In contrast, the mean residence time of CBD administered was 3.3 hours in the same study [3].

In animal studies, oral CBD administration has also been found to lead to higher levels in the brain compared to inhaled methods [6].

CBD inhalation: vaping and smoking

Inhalation is an effective way to consume CBD because it bypasses the digestive tract and liver, so CBD is easily absorbed through the thin membranes that line the air sacs of the lungs (alveoli), from where it enters the bloodstream directly. There are several ways to inhale CBD. 

1. Smoking

The most basic form of inhalation is smoking. In this case, a hemp cigarette contains unprocessed CBD-rich hemp buds (as opposed to THC-rich hemp). Smoking has a 31% biological potency, and a single CBD cigarette containing approximately 19 mg of CBD can induce peak blood levels within 3 minutes [5].

The half-life of smoked CBD is on average 31 hours.

The disadvantage of smoking is that it produces combustion by-products that can irritate and, in some cases, damage the lungs. These include fluorene, pyrene, acrylonitrile and acrylamide [7].

2. Vaping

A more sophisticated and less irritating form of inhalation, similar to smoking, is vaping, which is performed using a vaporizer.

In this method, you suck liquid CBD oil in a cartridge around a heating element, which atomizes the CBD and creates a vapor that you inhale.

Vaping causes similar concentrations and pharmacokinetics of CBD in the blood as smoking [8]. There is some risk of lung irritation with vaping, although less than with smoking.

3. Nebulization

A nebulizer is a device that administers CBD in the form of a mist that is inhaled into the lungs. Nebulizers are typically used in hospitals to administer medication to damaged or sensitive lungs.

Nebulizers produce peak blood levels in approximately 36 minutes [4].

Sublingual CBD: drops and sprays

This method takes advantage of CBD's ability to be absorbed directly through the lining of the mouth and nose - it bypasses the digestive process and enters the bloodstream directly.

1. Sublingual drops

Peak blood levels of CBD in this method, which involves administering liquid drops of CBD under the tongue, have been measured within approximately 2 hours [5]. 

A simple way to improve absorption of sublingual CBD is to hold the drops under the tongue for 20-30 seconds before swallowing. This gives the mucous membranes more time to absorb the CBD before it enters the digestive tract.

2. Oral spray

In one study, an oral spray consisting of a 50-50 combination of THC and CBD reached peak blood levels of CBD in 3.6 hours for a 5 mg dose of CBD and in 4.5 hours for a 15 mg dose of CBD, i.e. the triple dose took only 20% longer to reach peak blood levels.

This illustrates the benefit of higher doses on absorption efficiency.

Again, holding the spray in the mouth for approximately 30 seconds before swallowing optimises the efficacy of this route of administration.

3. Nasal spray

Absorption through the thin mucosa lining the nasal passages is relatively rapid and reaches maximum blood concentrations in 10 minutes or less [2].

Transdermal CBD: Transdermal patches and topical CBD

CBD can enter the bloodstream through a patch placed on the skin, a method known as transdermal administration. However, since cannabinoids are highly fat-soluble, they are repelled by the water-soluble layer of the skin - this acts as a barrier to absorption.

An effective solution is to combine CBD with approximately one-third ethanol, which makes CBD more water soluble and has been found to increase absorption by almost fourfold [2, 9].

Transdermal CBD is useful for maintaining steady levels that do not fluctuate [10]. Although it enters the bloodstream relatively slowly compared to other methods, this may be an advantage as it avoids the potential side effects associated with rapidly reaching peak levels.

Transdermal administration is particularly useful for chronic inflammatory conditions and for pain control in patients with chronic pain who have not responded well to conventional treatment options.

It is also more convenient to administer than other methods, so patients with these types of conditions use it more frequently.

Intravenous CBD: Injectable CBD (for hospital use only)

Intravenous injection directly into the bloodstream provides 100% bioavailability. However, when administered intravenously, the level of CBD in the blood decreases rapidly, so this may not be the most effective way to take CBD.

A study on marijuana smokers found that 20 mg doses of intravenous CBD had four times the bioavailability of 19 mg doses of vaped CBD, but within the first hour, it was reduced by about 93% [11]. As a result, intravenous CBD had a shorter half-life of 24 hours, while smoked CBD had a half-life of 31 hours.

Factors that affect the absorption and elimination of CBD

The pharmacokinetics of CBD is subject to many intrinsic and extrinsic factors. You can influence some of these factors and use them to your advantage. For those that you have no control over, you can maximize the effectiveness of CBD by choosing the best form of administration for your needs.

Here are a few of the many "moving parts" of CBD pharmacokinetics:

1. Health status

Your medical condition may affect the absorption of CBD, and you may need to adjust the dosage or route of administration.

Liver function

As the liver is very important in removing CBD from circulation and preparing it for export from the body, impaired liver function has a significant impact on the effectiveness of CBD and how long it remains in the body.

In one study, participants with moderate to severe hepatic impairment had higher blood CBD concentrations and longer clearance times after the same 200 mg doses compared to healthy controls [12].

This means that more CBD enters the bloodstream and stays in the bloodstream longer. As a result, these individuals experience greater effects than what a person without a liver disorder would get from the same dose. 

Other health problems

Neurological or other medical conditions can also affect the bioavailability of CBD.

In one study, patients with Huntington's disease receiving oral dietary supplements containing 700 mg of CBD daily for 6 weeks showed low maximum absorption levels and no beneficial effects [5].

In contrast, healthy volunteers who took a single 600 mg oral dose of CBD demonstrated better absorption and higher blood levels of CBD. [5].

2. Dosage

The equation can be shifted in favour of higher absorption by taking higher doses. Increasing the oral spray dose from 5 mg to 10 mg can double absorption, and increasing the dose from 10 mg to 20 mg can triple absorption [4].

However, when you get to higher doses between 400 mg and 800 mg, there seems to be a ceiling effect where higher doses do not lead to higher absorption rates [4].

This may occur in part because the tissues become saturated and are unable to absorb more CBD.

3. Post-fasting and post-feeding states

CBD absorption is significantly better - 3 to 5 times better - when taken with a meal compared to taking it fasted [4].

Since CBD is fat-soluble, including a healthy source of fat in meals, such as avocados, fish high in omega-3s, or nuts and seeds, will help even more [13]. This will dissolve the CBD in the fat envelope and disperse it into smaller particles that are more easily absorbed.

Food also slows the rate of CBD removal from the blood. It has been measured that clearance is up to almost 9 times faster in the fasted state (i.e. between meals) compared to the fed state [4].

The presence or absence of a meal may have a greater effect on the clearance rate than the amount of the dose. When single doses of oral spray were measured at 5 mg and 20 mg, the higher dose was found to be cleared only 14% faster [4].

4. Heat treatment

Heating cannabis extracts (which occurs with some inferior processing methods) converts the cannabinoids into forms that are also active but less readily absorbed. One study found that maximum CBD levels were four times higher in non-heat-treated extracts compared to heat-treated ones [5].

5. Dietary supplements with piperine

The compound piperine, found in black pepper, acts on multiple levels and provides potent effects to enhance absorption.

Piperine stimulates transport molecules in the intestinal lining that are responsible for transporting CBD across the intestinal membrane into the bloodstream. Once CBD is absorbed, piperine inhibits the enzymes that break down CBD, giving it more time to reach target tissues where it can be absorbed and utilized.

An oral CBD supplement whose formulation contained piperine showed a sixfold increase in peak blood concentration compared to the same CBD supplement without piperine [14]. Impressive enough!

A summary of all

CBD is widely available, but scientific knowledge of how CBD is processed in the body is still in its infancy. In addition, there are large differences in the absorption and assimilation of CBD in different species - including humans. Therefore, testing in animals such as mice may not always translate to humans.

Nevertheless, some conclusions can be drawn from this research:

- Oral use of CBD - has the lowest biological efficacy, but can be improved with supplements such as piperine, and by taking CBD along with fats.

- Inhaled CBD - offers a high rate of absorption, but can damage the lungs over time.

- Transdermal CBD - Provides slow and steady absorption and offers benefits to people who need to maintain a stable level of CBD in the blood.

- Sublingual CBD - For example, oral sprays and sublingual drops have similar absorption rates to CBD ingested in the body, while nasal inhalers have faster absorption comparable to inhaled CBD without negatively impacting lung tissue.

- Intravenous (IV) administration of CBD - this is the fastest method of administration, but also the fastest to leave the body. This method is reserved for physicians.

It is important to note that your medical condition will affect which forms of administration may or may not suit you. When in doubt, a competent health care professional will help you choose the best options for your specific health goals.

References:

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