In the existing CBD supplement and cannabis market, there is a wide variety of products available which can be administered in a multitude of ways. The method of administration of any compound is extremely important as it can alter the uptake, distribution and duration (of effectivity) of the compound. Consequently this can dictate how effective the compound may be.
Cannabinoids can be delivered in many ways based on the requirements and preferences of the user. In practice, the preference of the user (how comfortable they are with the administration) can be a very important factor and it often plays a large role in the end chosen method. However, comfort should not be prioritized over bioavailability requirements, as the method of administration can tailor the treatment to a particular site of action.
The absorption of a cannabinoid supplement is its transfer from the site of administration to the bloodstream. This is commonly known as the bioavailability. Simply put it is, “the degree and rate at which a substance is absorbed into a living system or is made available at the site of physiological activity”. A substance delivered intravenously is assumed to have 100% bioavailability, and other methods of administration are compared to the intravenous route as a ratio for the percentage bioavailability.
The major forms of administration of cannabidiol (CBD), as well as any relevant bioavailability data, are discussed below.
The most common route of administration of supplemental CBD and CBDa products is orally. This is the easiest way in which consumers can take the product, cannabinoids can be added to food products or can be ingested easily with the use of capsules or oils.
However, oral administration has a relatively low bioavailability compared with other methods.
First pass metabolism is the main reason for the relatively low bioavailability of CBD when taken orally. First pass metabolism is caused by the actions of enzymes of the digestive system, gut wall enzymes, other bacterial enzymes, and hepatic enzymes-before CBD reaches the bloodstream. CBD is acted on by enzymes in the liver called CYP450 mixed function oxidases, to yield more than 100 different metabolites, which contributes to the beneficial entourage effect.
There are a few ways the oral bioavailability can be enhanced. Once such way is by co-administration of CBD with long-chain triglycerides (fatty acids). A recent study suggested that co-administration of CBD with long-chain triglycerides can bypass hepatic first pass metabolism.
More often associated with recreational users of cannabis, this route of administration does have benefits in terms of attaining higher bioavailability. Therefore users feel the psychoactive effects of THC faster when inhaled as compared to taking it orally, and this was observed in a clinical study. In this study, bioavailability of THC after inhalation was estimated to be 18% whereas oral THC in a chocolate cookie provided systemic availability of 6%. Given the similarity in the absorbability of THC and CBD, bioavailability data correlates between the two.
A key observation from this study was that the effects had a slower onset but lasted for a longer period of time. Henceforth the slower absorption of the oral route allows for less rapid elimination as compared to the inhaled route, and can therefore remain in the bloodstream longer.
This observation can be highly relevant for CBD type applications, especially due to the dramatic increase in the bioavailability seen through the inhaled route. CBD bioavailability after inhalation was found to have mean value of 31%, which is significantly higher than the oral method of administration.
The high bioavailability seen with this method of administration is due to the fact that the lungs have high permeability, a large surface area and a good blood supply for CBD to enter the systemic circulation. Hence why it is another means for bypassing first pass metabolism.
The sublingual method of administration is probably on par with the oral route with regards to comfort. The most common methods of sublingual administration include sublingual oil drops, sublingual tablets, lozenges and sprays.
A study performed with rabbits compared the bioavailability of oral and sublingual CBD solutions. The results of this study showed that the CBD delivered sublingually showed significantly higher bioavailability than the CBD delivered orally.
The sublingual route of administration also bypasses first-pass metabolism, as the high abundance of capillaries below the tongue allow CBD to enter the bloodstream through this route.
The suppository method of administration is generally favoured in situations where the oral method is not possible, such as in scenarios where users have trouble swallowing or suffer from nausea and vomiting for example.
Currently, there is a lack of data specifically calculating the bioavailability of CBD when administered as a suppository. Bioavailability data from numerous studies assessing THC showed that the suppository method of administration had approximately double the bioavailability as compared to the oral method. Another study found the bioavailability of THC from a suppository formulation to be 13.5%. Out of the three veins in the rectum, only one of them (the superior rectal vein) flows into the liver. Consequently there is only a partial first pass metabolic effect from this method of administration, and higher bioavailability is reported (as more CBD ends up in the blood circulation). As a result, suppositories have a faster onset of availability of CBD as compared to oral means of administration (oils, capsules).
One highly relevant study compared the effects of CBD delivered orally and rectally in mice. The results from this study showed that CBD delivered rectally was significantly faster than CBD delivered orally.
INHALATION VS ORAL: WHICH IS MORE EFFECTIVE?
In a study comparing three methods of administration of cannabinoids (oral, inhaled and intravenous), it was found that the oral route provided the longest period of “availability". This is contrary to the fact that the oral route produced the lowest plasma concentration out of the three.
Although the inhaled method can provide a more rapid onset, it also has a shorter availability (approximately 1-3 hours) as it is cleared rapidly. This is because the plasma concentrations peak extremely fast and CBD is eliminated from the bloodstream following first order elimination kinetics (rate of elimination is proportional to the amount of CBD in the body).
On the other hand, the oral route of administration is slowly released into the bloodstream. It maintains low concentrations in the blood over a longer period of time, and is therefore eliminated at a slower rate (slower elimination). Therefore it has a longer lasting availability (approximately 7 hours).
WHAT IS THE BEST ROUTE OF ADMINISTRATION?
In terms of bioavailability, the sublingual and inhalation routes are the most efficient in delivering CBD to the bloodstream. This can be important for some users that require fast amelioration, and high levels of CBD in the bloodstream.
However there isn’t a ‘one size fits all’ solution where one form trumps the others. (However advances in water soluble CBD technology may soon change this.)
Oral administration may be effective in terms of comfort and ease, and to satisfy the needs of users who only require a small concentration of CBD in the systemic circulation for a longer period of time. However the rectal method of administration can provide more well rounded availability, which could be pivotal for some users, as well as increased bioavailability to provide a higher concentration of CBD to the certain areas in the body.
PROS: Long lasting, simple to administer, other metabolites active.
PROS: Long lasting, slightly higher levels in bloodstream than swallowing, simple to administer.
CONS: Taste, relatively slow to become active.
PROS: High bioavailability, long lasting
CONS: No bad taste, not always practical.
PROS: Quick to become available, taste can be tailored/varied, simple to administer.
CONS: Not long lasting, not always practical.