A new narrative review examines whether mouth-dissolving films, adhesive gels, and other oral mucosal formulations can solve the notoriously low bioavailability of THC and CBD taken by mouth. While the pharmacokinetic rationale is sound, most evidence for these next-generation systems remains preclinical, and no head-to-head clinical trials yet confirm their superiority over conventional oral delivery.

Cannabinoid medicines are prescribed and recommended in growing numbers globally, yet the pharmacology behind their delivery remains frustratingly unreliable. When patients swallow a THC or CBD capsule, only about 6 to 19 percent of the active compound reaches the bloodstream, a problem rooted in first-pass liver metabolism and gastrointestinal degradation. This means that two patients taking the same dose can have vastly different clinical responses, undermining dosing precision and eroding confidence in cannabinoid therapeutics. Identifying delivery routes that could close this reliability gap is not merely an academic exercise; it is a prerequisite for cannabinoid medicine to mature into an evidence-based clinical discipline.

The oral mucosa, particularly the buccal and sublingual surfaces, has long been exploited in drug delivery for nitroglycerin, fentanyl, and certain antiemetics because of its rich vascular supply and its ability to send absorbed drug directly into the systemic circulation while bypassing the liver. The authors of this 2026 narrative review apply the same pharmacokinetic logic to cannabinoids, arguing that placing THC or CBD formulations against the cheek or under the tongue should yield higher and more predictable blood levels than swallowing or even inhaling them. They draw an important distinction between the thicker, less permeable buccal mucosa, which is better suited to sustained-release mucoadhesive systems, and the thinner, more permeable sublingual tissue, which favors rapid-dissolving dosage forms. The review catalogues formulation types including fast-dissolving films, mucoadhesive matrices, in situ gels, and lipid-based particulate carriers, and discusses fabrication techniques such as solvent casting, hot melt extrusion, and 3D printing.

The review’s most clinically grounded observation concerns Sativex, the only approved oromucosal cannabinoid spray, which the authors note frequently fails to achieve true mucosal absorption because much of the sprayed dose is inadvertently swallowed, effectively converting it into an oral formulation subject to the same first-pass losses. Permeation enhancers, including naturally occurring terpenes and lipid-based carrier systems, are presented as strategies to improve transmucosal flux. However, most of the cited evidence for these novel systems comes from in vitro dissolution studies or preclinical animal models, not from controlled clinical trials in human subjects. The authors themselves acknowledge the need for comparative human bioavailability data before these technologies can be recommended for clinical cannabinoid delivery.

This review is useful because it lays bare a problem that every clinician working with cannabinoid medicines sees daily: the gap between the dose on the label and the dose in the bloodstream. The pharmacokinetic rationale for buccal and sublingual delivery is solid, and the point about Sativex often being swallowed rather than absorbed through the mucosa resonates with what patients report. Where the review stretches beyond its evidence is in the enthusiasm for emerging fabrication technologies like 3D-printed dosage forms. These are fascinating from an engineering perspective, but they remain years away from anything a prescriber could actually use.

In my practice, I already counsel patients to hold sublingual tinctures under the tongue for 60 to 90 seconds before swallowing, precisely to take advantage of the transmucosal route this review describes. For patients who need rapid onset, I often recommend sublingual products over capsules. But I am honest with patients that even with good technique, sublingual absorption is incomplete and variable. I look forward to the day when a well-designed clinical trial compares a next-generation mucoadhesive film head-to-head against an oral capsule. Until that trial exists, this review is a promissory note, not a prescription change.

For clinicians who prescribe cannabinoid medicines, this review occupies an important but intermediate position in the research arc. It does not generate new data, but it successfully organizes the pharmaceutical rationale for why oral mucosal delivery should outperform oral ingestion, and it highlights the specific pharmacokinetic mechanisms, chiefly avoidance of first-pass hepatic metabolism, that underpin that expectation. The distinction between buccal and sublingual formulation requirements is a detail that matters for future product development and is too often ignored in the consumer cannabis space, where “sublingual” is applied loosely to products that may never contact sublingual tissue in meaningful concentrations.

Clinicians should be aware of several practical considerations. Permeation enhancers like terpenes and surfactants may alter local mucosal tolerance, and the review’s mention of ethanol-related mucosal

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