Cannabinoid Chewing Gum: Promising Concept, Thin Evidence

A 2025 expert commentary argues for CBD-infused chewing gum as a novel drug delivery platform, but the sole published clinical trial showed no efficacy for IBS pain, and the broader pharmacokinetic case rests on analogy to non-cannabinoid compounds rather than direct evidence.

Why This Matters

Patients and clinicians are increasingly interested in alternative cannabinoid delivery formats that might offer more predictable absorption, fewer first-pass metabolism losses, and greater convenience than edibles or tinctures. Chewing gum, long used for nicotine and caffeine delivery, has a plausible pharmacological rationale as a buccal absorption platform. When a peer-reviewed commentary frames cannabinoid gum as a promising frontier, it is likely to be cited by product developers and repeated in consumer media. Understanding what the evidence actually shows, and what it does not, matters now, before marketing outpaces science.

Clinical Summary

Chewing gum has a documented track record as a drug delivery vehicle for certain compounds, particularly nicotine, caffeine, and loratadine, where buccal absorption can bypass hepatic first-pass metabolism and accelerate onset. A 2025 commentary by Helfenstein, Lanz, and colleagues, published in Medical Cannabis and Cannabinoids (Karger), argues that cannabinoids, specifically cannabidiol (CBD), could exploit the same delivery pathway. The authors describe a mechanistic rationale grounded in the rich vascularization of the oral mucosa and the known first-pass losses that limit oral cannabinoid bioavailability. They also catalogue formulation strategies, including nanocarriers and mesoporous silica systems, that might overcome the lipophilicity mismatch between cannabinoids and the aqueous gum matrix.

However, the clinical evidence base underlying this argument is remarkably thin. The sole published randomized controlled trial of CBD chewing gum (Van Orten-Luiten et al., 2022; n=32 completers) found no statistically significant benefit over placebo for irritable bowel syndrome pain, with a mean visual analog scale difference of just 0.1 (95% CI: -0.3 to 0.5, p=0.61). The gum was well tolerated, but tolerability is not efficacy. Additional pharmacokinetic and Phase II trial data from AXIM Biotechnologies are cited but remain unpublished and therefore cannot be independently evaluated. Notably, five of seven authors are affiliated with Aspeya Switzerland SA, a commercial entity with potential interest in cannabinoid gum products. The authors themselves acknowledge the sparseness of clinical evidence and call for larger, well-designed trials before any therapeutic claims can be advanced.

Dr. Caplan’s Take

This commentary does what good hypothesis papers should do: it identifies an underexplored delivery route, catalogs the formulation challenges, and maps the research gaps. That is genuinely useful. But the gap between the optimistic framing and the actual evidence is wide. When patients ask me about CBD gum products, and they do, I need to be honest that the only controlled trial found no benefit. The bridging logic from nicotine and caffeine gum is reasonable but unproven for cannabinoids, which have very different physicochemical properties. And the commercial affiliations of the author group warrant transparency in how we interpret the paper’s conclusions.

In practice, I do not recommend cannabinoid chewing gum as a therapeutic intervention for any condition. If a patient is already using a CBD gum product and tolerating it well, I focus the conversation on what we know (it appears safe in the short term) and what we do not know (whether any meaningful amount of CBD is reaching systemic circulation via this route, and whether it produces clinical effects). I steer patients toward delivery formats with better-characterized pharmacokinetics and point them toward the published trial data so they can see the evidence themselves.

Clinical Perspective

This commentary sits at the very beginning of a research arc. It is hypothesis-generating, not hypothesis-confirming. For clinicians, the key takeaway is that buccal cannabinoid delivery via chewing gum is pharmacologically plausible but clinically unvalidated. The single relevant RCT was underpowered, short in duration, and negative on its primary endpoint. No peer-reviewed data demonstrate that cannabinoid gum achieves meaningful buccal absorption in humans, let alone therapeutic plasma levels. The pharmacokinetic bridging from other drug-gum formulations is weakened by the substantially different lipophilicity profiles of cannabinoids compared to caffeine or nicotine. Clinicians should not extrapolate efficacy claims from this commentary to patient-facing recommendations.

From a safety standpoint, short-term tolerability of CBD gum appears acceptable based on the small trial, but long-term oral mucosal effects, drug interactions with buccally absorbed CBD, and dose-response relationships remain entirely uncharacterized. CBD’s known inhibition of cytochrome P450 enzymes (particularly CYP3A4 and CYP2C19) could still be clinically relevant if buccal absorption proves significant, and this would need careful study in polypharmacy populations. The one actionable recommendation right now: if patients ask about CBD gum, inform them that no published clinical trial has shown it works for any condition, and counsel them on the difference between plausible delivery concepts and proven therapies.

Study at a Glance

Study Type

Expert commentary / narrative review

Population

Not applicable (no original study population); cited RCT enrolled adults with IBS (n=32 completers)

Intervention

CBD-infused chewing gum (conceptual); cited RCT used 50 mg CBD gum

Comparator

Placebo gum (in cited RCT)

Primary Outcomes

No original outcomes; cited RCT: 30-minute pain VAS (no significant difference, p=0.61)

Sample Size

Not applicable (commentary); cited RCT: 32 completers

Journal

Medical Cannabis and Cannabinoids (Karger)

Year

2025

DOI

10.1159/000547917

Funding Source

Not explicitly stated; 5 of 7 authors affiliated with Aspeya Switzerland SA (commercial entity)

What Kind of Evidence Is This

This is an expert commentary published in a peer-reviewed journal. It occupies one of the lower tiers of the evidence hierarchy, below systematic reviews, meta-analyses, and original clinical trials. No original data are presented, no systematic search methodology is described, and the literature selection is at the authors’ discretion. The single most important inference constraint is that a narrative commentary with commercial author affiliations cannot establish therapeutic efficacy for any indication; all claims should be treated as hypothesis-generating only.

How This Fits With the Broader Literature

The broader literature on buccal drug delivery via chewing gum is genuinely encouraging for certain compounds. Kamimori et al. (2002) demonstrated rapid caffeine absorption, and Noehr-Jensen et al. (2006) showed meaningful loratadine delivery through this route. Medicated chewing gum has been reviewed favorably as a platform technology by Wessel et al. (2016). However, these successes involve hydrophilic or moderately lipophilic molecules whose physicochemical profiles differ substantially from cannabinoids. The existing cannabinoid buccal delivery literature centers on Sativex (nabiximols oromucosal spray), which has a distinct formulation and established pharmacokinetic profile that cannot simply be extrapolated to a gum matrix.

The Van Orten-Luiten et al. (2022) trial is, to date, the only published controlled study of cannabinoid gum, and its negative result does not refute the concept entirely but does underscore how far from clinical validation this delivery format remains. Until positive efficacy data from adequately powered trials emerge, cannabinoid gum sits squarely in the preclinical concept space regardless of its peer-reviewed discussion.

Common Misreadings

The most likely overinterpretation is reading this commentary as evidence that CBD chewing gum works or is a validated drug delivery system. It is neither. The commentary argues that the concept is plausible and worth investigating, which is a defensible position, but the publication of a hypothesis in a peer-reviewed journal does not constitute evidence of efficacy. Readers may also conflate the well-documented success of nicotine gum with an assumption that cannabinoid gum will perform similarly. This analogy breaks down at the level of basic chemistry: cannabinoids are highly lipophilic compounds that interact with aqueous gum matrices very differently than nicotine. Finally, the commercial affiliations of the majority of authors should be weighed when interpreting the paper’s optimistic framing.

Bottom Line

This commentary identifies cannabinoid chewing gum as a biologically plausible delivery concept and usefully maps the formulation challenges and research gaps. However, the only published clinical trial of CBD gum found no benefit over placebo, and the broader case rests on analogy rather than cannabinoid-specific data. No change in clinical practice is warranted. Cannabinoid gum remains a hypothesis in search of evidence, and clinicians should communicate that clearly to patients who encounter product claims that outpace the science.

References

1. Helfenstein U, Lanz C, et al. Cannabinoid-infused chewing gum: a novel approach for therapeutic drug delivery. Medical Cannabis and Cannabinoids. 2025. DOI: 10.1159/000547917.
2. Van Orten-Luiten ACB, de Roos NM,”;”; Zilber-Rosenberg I, et al. Cannabidiol chewing gum for abdominal pain in irritable bowel syndrome: a randomized controlled trial. Cannabis and Cannabinoid Research. 2022;7(4):436-444.
3. Kamimori GH, Karyekar CS, Otterstetter R, et al. The rate of absorption and relative bioavailability of caffeine administered in chewing gum versus capsules to normal healthy volunteers. International Journal of Pharmaceutics. 2002;234(1-2):159-167.
4. Noehr-Jensen L, Damkier P, Guldborg NCB, et al. Comparison of the pharmacokinetics of loratadine administered as chewing gum and conventional tablet. European Journal of Clinical Pharmacology. 2006;62(6):431-436.
5. Wessel SW, van der Mei HC, Maitra A, et al. Medicated chewing gum: a review of the literature. Current Drug Delivery. 2016;13(2):158-167.
6. ClinicalTrials.gov. AXIM Biotechnologies Phase II trial for IBS. Identifier: NCT03003260.