A pilot safety, tolerability and pharmacokinetic study of an oro-buccal administered cannabidiol-dominant anti-inflammatory formulation in healthy individuals: a randomized placebo-controlled single-blinded study

Background: The cannabis plant presents a complex biochemical unit of over 500 constituents of which 70 or more molecules have been classified as cannabinoids binding to cannabinoid receptors. The study aimed to investigate the safety, tolerability, and preliminary pharmacokinetics of a nanoparticle CBD formulation.

Methods: The cannabis-based medicine was elaborated with a micellular technology, to produce a water-soluble nanoparticle CBD-dominant anti-inflammatory cannabis medicine (MDCNB-02). On day one, 12 participants administered 2 sprays and on day 2 administered 6 sprays to alternating right and left cheeks [18 mg of CBD and 0.72 mg of THC]. Four other participants administered 2 and 6 sprays on days 1 and 2, respectively of a nanoparticle placebo.

Results: The study met the primary outcomes of safety, tolerability, and preliminary pharmacokinetics of a standardized CBD-dominant anti-inflammatory extract for oro-buccal administration. Bioavailability of a 6 mg and 18 mg dose of CBD (median IQR) was 0.87 and 8.9 ng h mL^-1, respectively. The maximum concentration of CBD for the low and high doses administered once per day occurred at 60 min for both concentrations. The median half-life of the 6 mg and 18 mg CBD dose was 1.23 and 5.45 h, respectively. The apparent clearance of CBD was 115 and 34 L min^-1 for a 6 mg and 18 mg dose, respectively.

Conclusion: The oro-buccal nanoparticle formulation achieved plasma concentrations that were largely comparable to other commercial and investigated formulations relative to the concentrations administered. Moreover, there were no reports of adverse effects associated with unfavorable inflammatory sequalae.