A meta-opinion: cannabinoids delivered to oral mucosa by a spray for systemic absorption are rather ingested into gastro-intestinal tract: the influences of fed / fasting states

ABSTRACT

Introduction: Sativex® spray is clinically utilized to deliver delta9-tetrahydrocannabinol and cannabidiol to oral mucosa for systemic absorption. We challenge the consensus that the mechanism of absorption following the oro-mucosal application occurs via the buccal tissue.

Areas covered: Correctness of the consensus of this absorption pathway arose when reviewing publications regarding the influence fed versus fasting states have on pharmacokinetics of these cannabinoids administered to the oral mucosa. This finding is more suitable for peroral administration, where stomach content affects the absorption profile. We hypothesize that these cannabinoids are ingested and absorbed in the gastrointestinal tract.

Expert opinion: Although clinical importance of Sativex® is not disputed, the wide acceptance of its being a successful example of drug delivery through oral mucosa is questionable. Sativex® acts as an example for other drugs delivered to oral mucosa for systemic absorption and unintentionally washed by the saliva flow into the gastrointestinal tract. Delivery of each medicine through oral mucosa should be validated in-vivo to ensure this route to be the predominant one. Revealing the underlying absorption mechanisms would enable predicting the impact of different physiological parameters such as saliva flow and fed/fasting states on the pharmacokinetics of the delivered medication.

KEYWORDS:

• Sativex
• tetrahydrocannabinol
• cannabidiol
• cannabinoid
• oral mucosa
• buccal
• pharmacokinetics
• fed vs fasting
• drug delivery

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they have been involved in clinical trials of Sativex and other cannabinoids and have received funding for research and consultancy from GW Pharmaceuticals. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.