Bioavailability refers to how much (quantity) and how quickly (rate) an active substance (drug) absorbs and becomes available at the target site in the body. [1] From another perspective, it is the percent of a substance that reaches systemic circulation. An intravenous injection (IV) has a bioavailability of 100%: the substance is injected into the bloodstream instantly and made completely available. So IVs get an A+ for bioavailability.
Non-hospital administration methods fall elsewhere on the curve. These include CBD/cannabis inhalation, nasal spray, transdermal applications, and oils/tinctures/edibles. These administration routes put obstacles in the way of absorption. In the case of oil-based orals, the hurdles are significant.
Oral administration takes CBD/cannabis on a long journey. First, cannabinoids must navigate through the intestinal wall. Then they enter portal circulation, where they are beaten into submission (metabolized) by the liver. First-pass metabolism characterizes this great sojourn; at each stage, cannabinoids are rendered inactive and effectively useless. These inactive metabolites are then excreted by the kidneys… or simply wholesale. [2,3] But it gets worse.
From the start, cannabinoids were ill-equipped for the trip. The body readily absorbs water-soluble compounds. The water we drink boasts near 100% bioavailability. Cannabinoids are not water soluble. On the contrary, they are highly lipophilic, meaning they attract and dissolve in lipids/fats. Oil and water don’t play well together. Of course, the body does absorb lipids, but the process requires bile secretion and micelle formation. The result is that most cannabinoids cannot muster a sufficient rate of absorption before clearance.
Terrible absorption rates do not bode well for bioavailability:
- Oral THC bioavailability has been estimated at 4-20%. [2,4]
- Oral CBD bioavailability has been estimated at 13-19%. [3]
To put this in perspective, the bioavailability of THC inhalation has been estimated as high as 56%. [4] Average bioavailability from CBD inhalation has been estimated at 31 %. [3] Robust research is limited regarding bioavailability, especially in humans. Still, oral ingestion gets a solid D for bioavailability.
Tinctures represent the lion’s share of CBD products. [5] Tinctures aim to boost bioavailability with a simple instruction: hold the oil under your tongue for 60 seconds or longer. In general, the highly-vascularized tissue under the tongue (sublingual) is purported to afford 3-10 times greater absorption compared to simply swallowing. [6]
The problem is that available research (which is limited) suggests that bioavailability for oral cannabinoids does not significantly improve (statistically) with sublingual or oro-mucosal administration. [2-4, 6-8] Enhanced absorption from the sublingual route remains a hypothesis for cannabinoids. Perhaps this administration method extends to the upper range of the estimated oral bioavailability (19-20%). That is also a hypothesis!
But not all is lost… and volume 2 will offer some possible solutions.
References
- Chow, Shein-Chung. “Bioavailability and Bioequivalence in Drug Development.” Wiley Interdisciplinary Reviews: Computational Statistics,6, no.4, 2014, pp. 304-312, doi:10.1002/wics.1310. Journal Impact Factor = 1.75, Times Cited = 11 (ResearchGate)
- Mcgilveray, Iain J. “Pharmacokinetics of Cannabinoids.” Pain Research and Management, vol. 10, suppl. a, 2005, doi:10.1155/2005/242516. Journal Impact Factor = 1.685, Times Cited = 72 (ResearchGate)
- Millar, Sophie A., et al. “A Systematic Review on the Pharmacokinetics of Cannabidiol in Humans.” Frontiers in Pharmacology, vol. 9, 2018, doi:10.3389/fphar.2018.01365. Journal Impact Factor = 3.831, Times Cited = 10 (ResearchGate)
- Huestis, Marilyn A. “Human Cannabinoid Pharmacokinetics.” Chemistry & Biodiversity, 4, no. 8, 2007, pp. 1770-804. doi:10.1002/cbdv.200790152. Journal Impact Factor = 1.449, Times Cited = 284 (ResearchGate)
- Corroon, Jamie, and Joy A. Phillips. “A Cross-Sectional Study of Cannabidiol Users.” Cannabis and Cannabinoid Research, vol. 3, no. 1, 2018, pp. 152–161, doi:10.1089/can.2018.0006. Journal Impact Factor = NA, Times Cited = 12 (ResearchGate)
- Narang, N. & Jyoti Sharma. “Sublingual Mucosa as a Route for Systemic Drug Delivery.” International Journal of Pharmacy and Pharmaceutical Sciences, 3, no.2, 2011, pp. 18-22. Journal Impact Factor = 4.773, Times Cited = 65
- Schoedel, Kerri A., and Sarah Jane Harrison. “Subjective and Physiological Effects of Oromucosal Sprays Containing Cannabinoids (Nabiximols): Potentials and Limitations for Psychosis Research.” Current Pharmaceutical Design, vol. 18, no. 32, Dec. 2012, pp. 5008–5014., doi:10.2174/138161212802884708. Journal Impact Factor = 2.412, Times Cited = 6 (ResearchGate)
- Karschner, Erin L et al. “Plasma Cannabinoid Pharmacokinetics Following Controlled Oral Delta9-Tetrahydrocannabinol and Oromucosal Cannabis Extract Administration.” Clinical Chemistry, 57, no.1, 2011, pp. 66-75, doi:10.1373/clinchem.2010.152439. Journal Impact Factor = 8.008, Times Cited = 94 (ResearchGate)
