Cannabinoids bioavailability – sublingual intake (3/6)

Cannabinoids bioavailability – sublingual intake (3/6)

Sublingual intake of cannabiboids can be compared to inhalation in terms of bioavailability because, as in the case of absorption in the lungs, absorption from the mucous membrane under the tongue allows for the cannabinoids to enter the bloodstream relatively fast and in their unaltered form [1]. Of course, the absorpton is also possible in the whole <oral – jama ustna> (eg, in between the cheeks and the gums, in the inside of the cheeks or in the throat already), but the sublingual application not only makes it possible to place a large amount of the substance at once, but also limits the intensive taste experience – a factor to be taken into consideration while intaking cannabinoids.

Studies conducted by GW Pharmaceuticals [2] on cannabis extracts in various solvents containing standardized THC and CBD levels showed that concentrations of these cannabinoids in blood plasma following the sublingual intake of one drop reached levels similar to those occuring after the use of oral spray and even lower ones in comparison to inhalations with the aid of nebulizer. It is also worth noting that the study participants considered the sublingual intake to be more convenient due to the lack of unpleasant effects such as scratching and coughing that frequetly follow the inhalation. Unfortunately, there is no data available on the relative bioavailability of sublingual intake (the relative bioavailability is defined as the relation between the concentration of substance in blood plasma following the intake method being examined compared to the IV intake referred to as the 100%). Note that as the clinical studies conducted for Sativex have always tended to show high individual variability in THC and CBD levels in the blood of patients in the study population, the recommended dosing regimen is titration [3].

Sublingual administration can be thought of as a kind of a compromise between inhalation and oral administration as it combines the advantages of both methods [4,5]. Compared with oral, the sublingual intake (or to the other oral membranes), allows for a significant portion of the cannabinoids to be delivered directly into the bloodstream in unmetabolised form, as in the case of inhalation. The remaining unabsorbed part after being swallowed is passed through the digestive tract, and this, in turn, results in a prolonged effect. Additionally, the pass through the digestive tract results in  various cannabinoids’ metabolites to enter or system, and those are likely to be attributable to at least some of the beneficial effects of cannabis, as the recent studies show [6,7]. Furthermore, sublingual administration allows for relatively rapid delivery of cannabinoids to the body, which facilitates efficient adjustment of optimal dosage by titration [8]. For all those reasons, this is the administration route we recommend.

PhD, Eng. Beata Plutowska

References:

[1] Whittle B.A., Guy G.W., Robson P. Prospects for new Cannabis-based prescription medicines. Journal of Cannabis Therapeutics 1 (2001) 183-205.
[2] Guy G.W., Flint M.E. A single centre, placebo-controlled, four period, crossover, tolerability study assesing, pharmacodynamic effects, pharmacokinetic characteristics and cognitive profiles of a single dose of three formulations of Cannabis Based Medicine Extracts (CBMEs) (GWPD9901), plus a two period tolerability study comparing pharmacodynamic effects and pharmacokinetic characteristics of a single dose of Cannabis Based Medicine Extract given via two administration routes (GWPD9901 EXT). The Haworth Press, Inc. 2003
[3] Guy G.W., Robson P.J. 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). The Haworth Press, Inc. 2003
[4] Hazekamp A., Ware M.A., Muller-Vahl K.R., Abrams D., Grotenhermen F. The medicinal use of Cannabis and cannabinoids—An international cross-sectional survey on administration forms. Journal of Psychoactive Drugs 45 (2013) 199–210.
[5] Grotenhermen F. Harm reduction associated with inhalation and oral administration of Cannabis and THC. Journal of Cannabis Therapeutics 1 (2001) 133-152.
[6] http://medycznyolej.org/arno-hazekamp- cz-2- olej-rso- cbd/
[7] Ujvary I., Hanus L. Human metabolites of cannabidiol: a rewiev on their formation, biological activity, and relevance in therapy. Cannabis and Cannabinoid Research 1.1 (2016) 90-101.
[8] Amar M.B. Cannabinoids in medicine: A review of their therapeutic potential. Journal of Ethnopharmacology 105 (2006) 1–25.