Nagaraj, AnushreeSeyfoddin, Ali2026-04-012026-04-012026-03-06AAPS PharmSciTech, ISSN: 0163-5158 (Print); 1530-9932 (Online), Springer Science and Business Media LLC, 27(3), 132-. doi: 10.1208/s12249-026-03380-z0163-51581530-9932http://hdl.handle.net/10292/20859Cannabinoids such as cannabidiol (CBD) and tetrahydrocannabinol (THC) have garnered significant interest for their broad-spectrum pharmacological activity in managing chronic pain, neurological disorders, and cancer-associated symptoms. Despite their therapeutic promise, clinical translation remains hindered by poor aqueous solubility, extensive first-pass metabolism, and inconsistent systemic exposure following oral administration. Oral mucosal drug delivery systems offer a viable alternative by enabling transmucosal absorption, bypassing hepatic metabolism, and facilitating both rapid and sustained drug release. This review examines the evolution and design of oral mucosal dosage forms, including fast-dissolving films, mucoadhesive matrices, in situ gels, and particulate systems and highlights the critical role of formulation strategies in enhancing cannabinoid bioavailability. Fabrication techniques such as solvent casting, hot melt extrusion, and emerging 3D printing methods are also discussed, with a focus on their potential to enable personalized dosage forms. Furthermore, the integration of permeation enhancers like terpenes, and novel systems such as inclusion complexes and lipid-based carriers, presents new opportunities for improving the solubility and stability of lipophilic cannabinoids. Together, these innovations provide a framework for the development of stable, effective, and patient-centric oral mucosal cannabinoid delivery platforms with improved pharmacokinetic and therapeutic profiles.Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.cannabidiol (CBD)formulation strategiesoral mucosal deliverysustained releasetetrahydrocannabinol (THC)3214 Pharmacology and Pharmaceutical Sciences3206 Medical Biotechnology32 Biomedical and Clinical SciencesDental/Oral and Craniofacial DiseaseNatural ProductsBiotechnologyTherapeutic Cannabinoid ResearchComplementary and Integrative HealthCannabidiol Research5.1 Pharmaceuticals3 Good Health and Well Being1115 Pharmacology and Pharmaceutical SciencesPharmacology & PharmacyHumansCannabinoidsMouth MucosaAdministration, OralDrug Delivery SystemsChemistry, PharmaceuticalSolubilityAnimalsPermeabilityDrug CarriersBiological AvailabilityHumansCannabinoidsMouth MucosaAdministration, OralDrug Delivery SystemsChemistry, PharmaceuticalSolubilityAnimalsPermeabilityDrug CarriersBiological AvailabilityJournal ArticleOpenAccess10.1208/s12249-026-03380-z