Cannabinoid Chewing Gum: Promising Concept, Weak Evidence

A 2025 commentary in Medical Cannabis and Cannabinoids argues that CBD-infused chewing gum could serve as an effective buccal drug delivery platform, but the clinical evidence base remains nearly empty, and the only published placebo-controlled trial of this approach found no meaningful benefit over placebo for irritable bowel syndrome pain.

Why This Matters

Cannabinoid bioavailability remains one of the most persistent barriers to translating promising preclinical findings into reliable clinical outcomes. Oral CBD is subject to extensive first-pass hepatic metabolism, with bioavailability estimates often falling below 10 percent, making alternative delivery routes a legitimate area of pharmaceutical interest. Chewing gum has proven effective for buccal delivery of other compounds, including nicotine and caffeine, and the concept of adapting this platform for cannabinoids is scientifically reasonable. Whether the concept actually works in practice, however, is a question this commentary raises but cannot answer.

Clinical Summary

Cannabinoids delivered orally face well-documented pharmacokinetic challenges, including poor aqueous solubility, high lipophilicity, and extensive first-pass metabolism that collectively limit systemic bioavailability. A 2025 narrative commentary published in Medical Cannabis and Cannabinoids by Soares and colleagues argues that medicated chewing gum could circumvent some of these obstacles by enabling buccal absorption through the highly vascularized oral mucosa. The authors draw on analogy from non-cannabinoid gum delivery studies, particularly caffeine and loratadine, and discuss formulation strategies such as lipid nanocarriers and mesoporous silica systems designed to overcome the hydrophobicity of cannabinoid compounds. The commentary consolidates existing pharmaceutical science around gum-based delivery and articulates a research agenda for this platform.

The critical problem is that the clinical evidence does not support the commentary’s optimistic framing. The sole published placebo-controlled trial of CBD chewing gum, conducted by Van Orten-Luiten and colleagues in 2022 with 32 participants experiencing IBS-related pain, found no statistically significant difference between CBD and placebo on primary outcomes, with a mean difference in 30-minute pain reduction of just 0.1 on a visual analog scale (95% CI: negative 0.3 to 0.5, p = 0.61). Additional pharmacokinetic data cited by the authors come from an unpublished industry study, and a Phase II randomized controlled trial referenced in trial registries appears to have gone unreported in the peer-reviewed literature. Four of the seven authors are affiliated with Aspeya Switzerland SA, a company with commercial interest in cannabinoid chewing gum products. The authors acknowledge the need for rigorous clinical trials before any therapeutic claims can be made.

Dr. Caplan’s Take

I regularly hear from patients interested in novel CBD delivery formats, and chewing gum comes up more often than you might expect. The mechanistic logic here is sound: buccal absorption is a real pharmacokinetic advantage for compounds that suffer heavy first-pass metabolism, and cannabinoids clearly fall into that category. But logic and evidence are not the same thing. When the only published clinical trial of this specific platform shows no difference from placebo, and the commentary promoting it is authored largely by employees of a company that would benefit from its adoption, we need to be honest about where we stand.

In practice, I do not recommend CBD chewing gum products to patients as a therapeutic intervention. There is simply no clinical evidence that they deliver meaningful benefit. When patients bring in these products, I use the conversation as an opportunity to discuss bioavailability broadly and to guide them toward delivery formats with better-characterized pharmacokinetics. If future trials with adequate sample sizes and independent funding demonstrate efficacy, that would change my approach. Until then, the concept remains a hypothesis, not a treatment.

Clinical Perspective

This commentary sits at the very beginning of a research arc. It is hypothesis-generating rather than hypothesis-confirming, and clinicians should recognize it as such. The pharmacokinetic rationale for buccal cannabinoid delivery is plausible and grounded in established drug delivery science, but plausibility has not translated into demonstrated efficacy. The bridging evidence from caffeine and loratadine gum studies shows that chewing gum can deliver some compounds effectively through the oral mucosa, yet cannabinoids present distinct formulation challenges, including extreme hydrophobicity and dose precision difficulties, that make direct analogy unreliable. The null result from the Van Orten-Luiten trial does not definitively disprove the concept, given its small sample size, but it certainly does not support recommending these products to patients.

From a safety standpoint, chewing gum as a delivery format does not raise unique pharmacological concerns beyond those associated with the cannabinoid itself, and the available tolerance data suggest acceptable short-term safety. However, clinicians should be aware that CBD’s well-documented interactions with cytochrome P450 enzymes, particularly CYP3A4 and CYP2C19, remain relevant regardless of delivery route, and buccal absorption could theoretically produce different peak plasma concentration profiles than oral ingestion, potentially altering drug interaction dynamics in unpredictable ways. The one concrete step clinicians can take now is to counsel patients that no CBD chewing gum product has demonstrated therapeutic efficacy in a published clinical trial, and that marketing claims for these products currently outpace the science.

Study at a Glance

Study Type

Expert commentary / narrative review (no original data)

Population

Not applicable (commentary); referenced trial studied adults with IBS pain

Intervention

Cannabinoid-infused medicated chewing gum (conceptual platform)

Comparator

Placebo gum in the referenced Van Orten-Luiten 2022 trial

Primary Outcomes

No primary outcomes (commentary); referenced trial measured pain reduction on VAS

Sample Size

Not applicable (commentary); referenced trial: n=32

Journal

Medical Cannabis and Cannabinoids (Karger)

Year

2025

DOI

10.1159/000547917

Funding Source

Not explicitly stated; 4 of 7 authors affiliated with Aspeya Switzerland SA

What Kind of Evidence Is This

This is a narrative commentary published in a peer-reviewed journal. It occupies one of the lowest tiers in the evidence hierarchy, below systematic reviews, meta-analyses, randomized controlled trials, and even observational studies. Narrative commentaries do not follow systematic search methodology and are inherently susceptible to selective citation and advocacy framing. The single most important inference constraint this imposes is that no conclusion drawn from this document, however well-reasoned, can substitute for direct clinical evidence, and readers should weigh its claims accordingly.

How This Fits With the Broader Literature

The broader literature on buccal drug delivery via chewing gum is well established for certain compounds. Nicotine gum is the paradigmatic example, with decades of clinical evidence supporting its efficacy for smoking cessation. Caffeine gum has demonstrated faster absorption kinetics than capsule delivery in military and sports performance research. These precedents make the concept of cannabinoid chewing gum scientifically reasonable but not self-evident, because cannabinoids present fundamentally different formulation challenges.

Within the cannabinoid-specific literature, this commentary does not meaningfully extend what is known. The Van Orten-Luiten 2022 trial remains the only published clinical data point, and it was negative. The unpublished pharmacokinetic study by AXIM Biotechnologies and an apparently unreported Phase II trial leave critical gaps that this commentary identifies but cannot fill. Until independent, adequately powered clinical trials are completed and published, cannabinoid chewing gum remains a formulation concept rather than an evidence-based intervention.

Common Misreadings

The most likely overinterpretation is concluding that this commentary constitutes evidence that CBD chewing gum works. It does not. The commentary presents a plausible pharmacokinetic rationale and a reasonable research agenda, but plausibility is not proof, and the only direct clinical test of this specific platform produced a null result. Readers may also mistakenly treat the bridging data from caffeine and loratadine gum studies as transferable evidence for cannabinoids, which it is not, given the distinct physicochemical properties of cannabinoid compounds. The material conflict of interest among the majority of authors should further temper any inclination to accept the commentary’s optimistic framing at face value.

Bottom Line

This commentary makes a scientifically plausible case that cannabinoid chewing gum deserves further investigation as a buccal delivery platform. It does not, however, provide or cite clinical evidence of efficacy. The sole published trial was negative, key pharmacokinetic data remain unpublished, and the authorship group carries significant commercial conflicts of interest. Clinicians should not recommend CBD chewing gum products on the basis of this publication, and patients should understand that the concept remains unproven.

References

1. Soares S, et al. Cannabinoid-infused medicated chewing gum as an innovative drug delivery system. Medical Cannabis and Cannabinoids. 2025. DOI: 10.1159/000547917.
2. Van Orten-Luiten ACB, et al.”; cannabidiol chewing gum for abdominal pain in irritable bowel syndrome: a randomized, double-blind, placebo-controlled crossover trial. Cannabis and Cannabinoid Research. 2022;7(6):845-852. DOI: 10.1089/can.2021.0154.
3. Millar SA, Stone NL, Yates AS, O’Sullivan SE. A systematic review on the pharmacokinetics of cannabidiol in humans. Frontiers in Pharmacology. 2018;9:1365. DOI: 10.3389/fphar.2018.01365.