Sublingual, Buccal, Oromucosal, Oral: Which is Which?
Sublingual, Buccal, Oromucosal, Oral:
Which is Which?
by Dr Linda Klumpers
When browsing through cannabidiol (CBD) products, you will come across sublingual drops, oromucosal and buccal sprays, oral tablets, and many more. All of these products will go into your mouth, so you may wonder: Is there any difference between these administration methods? After reading this blog post, you will know all the differences without a doubt. Let us start by defining what these terms mean. They all originate from Latin: (Merriam-Webster, 2020)
- Sublingual comes from sub-, meaning under, and lingua, meaning tongue. It refers to anything administered under the tongue.
- Buccal comes from bucca, which means cheek.
- Oromucosal comes from os, meaning mouth, and mucosus, which is the mouth lining with mucous glands.
- Oral comes from os, meaning mouth.
Knowing the origin of these terms has already brought us one step closer to understanding what these administration methods entail. With a sublingual administration, the product goes under the tongue, see Figure 1. A buccal spray is directed to the inside of the cheeks, see Figure 2. Oromucosal products, which include sprays or gels, are applied anywhere on the oral mucosa. Although they are typically applied buccally, they can also be applied to the gums or on other mucosal surfaces in the mouth. Sublingual, buccal, and oromucosal administration forms are all part of transmucosal compound delivery, which describes absorption via mucous membranes. Oral administration is the odd one in the list, and the only administration form that does not stay long in the oral cavity: the products are always swallowed. Oral administrations are traditionally tablets, capsules, or liquids, but with many non-medical applications, almost any edible that you can imagine could have a CBD-infused version.
Transmucosal or Oral Route: When to use which
Does it even matter which administration method you use? Yes, it does, for various reasons. We will list the most important ones here.
Some people are not able to easily swallow tablets or capsules. Examples include smaller children, patients in a lying position, or patients who have trouble swallowing for other reasons. For these people, transmucosal administration forms can be a better solution.
When the mucosal lining of the mouth breaks, for example, because of ulcers, transmucosal administration forms should be avoided. On the other hand, transmucosal administration can also irritate the mouth, especially after prolonged dosing with solvents such as ethanol or other compounds. This can be avoided by, for example, alternating transmucosal administration forms with different routes.
Effect onset and duration
Transmucosal administration typically leads to a different effect onset than oral administration. The cause is the shorter route that a transmucosal administration takes to the bloodstream. The mucosal lining of the mouth is well vascularized. Compounds can travel from the oral cavity directly to the bloodstream via the mucosal lining and reach effect sites from there. When it comes to oral administration, the compounds first go through a part of the digestive system, and after that, they get absorbed into the bloodstream in the intestines. This route takes a while, so the transmucosal method has a preference when an effect needs to happen quickly by fast absorption. However, when a prolonged effect is a goal, the oral route is preferred. Extended-release products do not come as sublingual, buccal, or oromucosal formulations. They need to slowly release compounds from the gastrointestinal tract for an extended effect duration. Extended-release tablets always require oral administration.
First-pass metabolism effects
Not only does transmucosal administration lead to faster effects, but they can also be stronger or different from oral administration. By direct absorption into the bloodstream from the oral mucous, transmucosally absorbed compounds bypass the liver. The liver is the ‘cleaning machine’ of the body, breaking down products to prepare them for excretion.
When products get absorbed into the bloodstream from the gastrointestinal tract, they first undergo liver metabolism. CBD will dissolve into various break-down products (metabolites). Metabolites are most often pharmacologically inactive, which means that they will not induce effects. Whether CBD metabolites are pharmacologically active or inactive is mostly unknown.
Sublingual, buccal, oromucosal, and oral CBD products: what do we know?
Although there are thousands of sublingual, buccal, and oromucosal CBD products on the market, much of their workings are still a mystery - oral CBD products have been studied more thoroughly. For now, there is only one transmucosal CBD product that has been studied extensively, and that is an oromucosal spray in which CBD is combined with THC. We say “extensively” because this product was studied in various ways:
Sublingually vs. Buccally vs. Oro-pharyngeally vs. Orally.
Researchers Guy and Robson conducted this study in 2004 and published it in peer-reviewed literature. Oro-pharyngeally in this case means ‘generally in the mouth’. The three transmucosal administrations consisted of four sprays to the respective locations, while the oral administration were four capsules. There were some differences found between the four different forms, but the differences were not as large as some might think. The publication reported that “The sublingual and oro-pharyngeal routes of administration appear to have the same pharmacokinetic results.” With pharmacokinetics, the researchers mainly talk about properties with regards to plasma concentration curve: how long did CBD stay in the blood? When was the peak concentration, and how high was this concentration? They also stated that “The buccal pharmacokinetic parameters are lower when compared to the sublingual and oro-pharyngeal routes.” With regards to oral, it was stated that “The oral capsule has good bioavailability [...].” (Guy & Robson, 2004) How do these four compare? In Table 1, you can find a summary of the data with further explanation. When we try to interpret the results of this study, we can speculate two possible reasons for the small differences between the outcomes of transmucosal and oral routes of the product. First, it could be that CBD is either not well absorbed transmucosally, but is swallowed instead, or that CBD takes a while to travel from the oral cavity to the bloodstream through the mucosa. More research on a broader range of products is needed.
Knowing the outcomes of this study, it does not mean that the results can apply to other products, such as Green Earth Medicinals’ sublingual drops or buccal spray. Every product is developed differently and has different ingredients, meaning that each product can have different properties. We have learned from this blog post that the sublingual drops go under the tongue and that the buccal spray goes on to the cheeks. Although these products will not behave the same as the THC+CBD product in the research published by Guy & Robson in 2004, you do not have to expect any extreme differences if you decide to use the sublingual drops on your cheeks or the buccal spray under your tongue instead.
- Sublingual, buccal and oromucosal are three variations of transmucosal administration forms.
- Oral transmucosal administration forms lead to absorption from the oral mucosa directly to the bloodstream.
- When deciding between transmucosal and oral administration, various aspects play a role, including swallowing differences, risks of mucosal irritation, differences in effect onset and duration, and influence of the first-pass effect.
- One study found that there are plasma concentration differences between sublingual, buccal, oromucosal, and oral CBD, but the differences were not large.
A sublingual administration form goes under the tongue. This can be a tincture, a spray, a tablet (see illustration), etc.
A buccal spray is applied on the inner side of the cheeks.
A comparison of plasma concentration parameters of CBD for sublingual, buccal, oro-pharyngeal, and oral administration forms of a THC+CBD spray and capsules, respectively. The time to maximum concentration, often related to the relative peak effect, was shortest for oral administration, and longest for buccal administration. The maximum concentration was lowest for oral administration and the highest for buccal. The estimated area under the curve, which relates to total exposure, or bioavailability, was lowest for oral and highest for oro-pharyngeal administration. This table is a modification of Guy & Robson, 2004.
We are now working with our friends at Cannify to bring you more information on important topics. Cannify researches and educates about cannabis. It is the first company to match patients and products with science. Cannify's founder Dr. Linda Klumpers earned a Ph.D. in Clinical Pharmacology of cannabis and has been studying cannabis for over a decade. Cannify educates an audience that includes patients, healthcare providers, and university students, and is actively involved in various cannabis-related research projects.
Guy, G. W., & Robson, P. J. (2004). A Phase I, open label, four-way crossover study to compare the pharmacokinetic profiles of a single dose of 20 mg of a cannabis based medicine extract (CBME) administered on 3 different areas of the buccal mucosa and to investigate the pharmacokinetics of CBME per oral in healthy male and female volunteers (GWPK0112). Journal of Cannabis Therapeutics, 3(4), 79-120.
Merriam-Webster, accessed September 2020, https://www.merriam-webster.com/