Many so called “experts” insist that holding CBD-rich hemp oil via the oro-mucosal route (holding it under the tongue or in the mouth) causes higher blood levels and increases bioavailability of CBD as compared to taking it orally (swallowing it). The theory is that when taken orally, CBD was being metabolized by the liver before it could get distributed to the rest of the body and this didn’t happen when it was taken via the oro-mucosal routes. This occurred because of the unique circulation of the gut. Blood comes from the heart and goes to the stomach and intestines where it absorbs nutrients and material. After leaving the intestines, the blood then passes through the liver which takes up certain nutrients and materials and metabolizes them prior to returning them to the blood stream for circulation to the rest of the body. CBD is metabolized in the liver and its metabolites are not as active as the original CBD. This makes sense and older studies showed that the oral route was not as good as the oro-mucosal routes. However, this is where research can actually provide wrong answers
The older studies on which this “truth was based used the two armed study concept. One arm consisted of group of individuals taking hemp oil orally and another arm consisted of a different group of individuals taking it sublingually. Because there is tremendous variation in the absorption and metabolism of cannabinoids from one individual to another1, this is a terribly inaccurate method for comparing PK values and yielded results that we now know are untrue. Two newer studies using the same individuals in each arm of the study found that there are no differences in maximum blood levels or bioavailability between oral and sublingual administration of regular CBD hemp oil.2,3
Several years ago, nano-emulsification technology was first introduced into hemp products by CBD American Shaman. Hemp oil naturally forms into large droplets when mixed with water and water is abundant in the mouth and stomach. Nano-emulsification technology breaks the oil up into small droplets that are less than 100 nanometers in diameter with the droplets being coated with an emulsifier that keeps the droplets small when exposed to water (rather than coalescing into a large droplet). Two different studies have found that the maximum blood levels of oral “nano-emulsified” CBD was 1.7 to 4 times that of sublingual and the bioavailability was similarly increased 134% to 220%.4-6 This increase in oral absorption over sublingual absorption may be due to one or more of the following:

  1. Increased CBD absorption into the blood stream because of increased surface area of droplets contacting the gut surface.7
  2. Immediate protein binding of the CBD (because of its small size) after absorption into the blood stream (this inhibits the liver cells from taking up the CBD as it passes through the liver).1
  3. Absorption of so much CBD so fast directly from the stomach that it overcomes the ability of the liver cells to remove it all and a large amount of CBD passes stays in the blood stream as it passes through the liver.
  4. Direct absorption of the CBD into the cells of the gut and transportation to the rest of the body via the lymphatics which allows the CBD to bypass the liver and be distributed throughout the body.8
  5. Phagocytosis of the nano-CBD particles by macrophages which shield the CBD from being taken up by the liver.9
  6. Continued absorption as the CBD passes throughout the gut.7

Whatever, the reason, “nano-emulsification” of CBD hemp oil improves both the maximum blood levels and the bioavailability of CBD when taken orally over “untreated” CBD hemp oil taken sublingually.
Clinically in my and other physician practices, we have found that patients taking CBD American Shaman oral “nano-emusified” products require much less (about 4 times less) CBD than “non-nano” sublingual products. No “nano-emulsified” products for oromucosal use have not yet every been tested, although I expect this will occur soon. What the absorption characteristics of such a product might be is unknown at this time, theoretically they could be better in some aspects and worse in others. Only appropriate experimentation will be able to answer these questions.

Bottom Line:

Oral “nano-emulsified” CBD hemp oil is absorbed more completely and has better bioavailability than sublingual administration of “non-nano” treated CBD hemp oil.


  1. Huestis, M. Human Cannabinoid Pharmacokinetics. Chem Biodivers 4(8):1770-1804.
  2. Guy GW, Robson P. 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 difference areas of the buccal mucosa and to investigate the pharmacokinetics of CBME per oral in healthy male and female volunteers. J Cannabis Ther. 2003; 3:79–120.
  3. Karschner EL, etal. Plasma cannabinoid pharmacokinetics following controlled oral delta9-tetrahydrocannabinoil and oromucosal cannabis extract administration. Clin Chem 2011;57(1):66-75
  4. Atsmon J, etal. PTL401, a New Formulation Based on Pro-Nano Dispersion Technology, Improves Oral Cannabinoids Bioavailability in Healthy Volunteers. J Pharm Sci. 2018 May;107(5):1423-1429.
  5. Atsmon J, etal. Single-Dose Pharmacokinetics of Oral Cannabidiol Following Administration of PTL101: A New Formulation Based on Gelatin Matrix Pellets Technology. Clin Pharmacol Drug Dev. 2018
  6. Cherniakov I, etal. Piperine-pro-nanolipospheres as a novel oral delivery system of cannabinoids: Pharmacokinetic evaluation in healthy volunteers in comparison to buccal spray administration. J Control Release. 2017 Nov 28;266:1-7.
  7. Xie X, etal. PLGA nanoparticles improve the oral bioavailability of curcumin in rats: characterizations and mechanisms. J Agric Food Chem. 2011 Sep 14;59(17):9280-9.
  8. Zgair A, etal. Oral administration of cannabis with lipids leads to high levels of cannabinoids in the intestinal lymphatic system and prominent immunomodulation. Sci Rep 7(1):14542.
  9. Oh N, Park J. Endocytosis and exocytosis of nanoparticles in mammalian cells. Int J Nonomed 9 Suppl 1:51-63.

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