{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:16:38Z","timestamp":1789139798809,"version":"build-2803163510"},"reference-count":101,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T00:00:00Z","timestamp":1767484800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Naserdean Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Autophagy is a well-preserved biological mechanism that is essential for sustaining homeostasis by degradation and recycling damaged organelles, misfolded proteins, and other cytoplasmic detritus. Cannabinoid signaling has emerged as a prospective regulator of diverse cellular functions, including immunological modulation, oxidative stress response, apoptosis, and autophagy. Dysregulation of autophagy contributes to pathogenesis and treatment resistance of several oral diseases, including oral squamous cell carcinoma (OSCC), periodontitis, and gingival inflammation. This review delineates the molecular crosstalk between cannabinoid receptor type I (CB1) and type II (CB2) activation and autophagic pathways across oral tissues. Cannabinoids, including cannabidiol (CBD) and tetrahydrocannabinol (THC), modulate key regulators like mTOR, AMPK, and Beclin-1, thereby influencing autophagic flux, inflammation, and apoptosis. Experimental studies indicate that cannabinoids inhibit the PI3K\/AKT\/mTOR pathway, promote reactive oxygen species (ROS)-induced autophagy, and modulate cytokine secretion, mechanisms that underline their dual anti-inflammatory and anti-cancer capabilities. In addition, cannabinoid-induced autophagy has been shown to enhance stem cell survival and differentiation, offering promise for dental pulp regeneration. Despite these promising prospects, several challenges remain, including receptor selectivity, dose-dependent variability, limited oral bioavailability, and ongoing regulatory constraints. A deeper understanding of the context-dependent regulation of autophagy by cannabinoid signaling could pave the way for innovative therapeutic interventions in dentistry. Tailored cannabinoid-based formulations, engineered for receptor specificity, tissue selectivity, and optimized delivery, hold significant potential to revolutionize oral healthcare by modulating autophagy-related molecular pathways involved in disease resolution and tissue regeneration.<\/jats:p>","DOI":"10.3390\/ijms27010525","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T13:35:47Z","timestamp":1767620147000},"page":"525","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cannabinoid Signaling and Autophagy in Oral Disease: Molecular Mechanisms and Therapeutic Implications"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7241-9172","authenticated-orcid":false,"given":"Undral","family":"Munkhsaikhan","sequence":"first","affiliation":[{"name":"College of Dental Medicine, Lincoln Memorial University, 1705 St. Mary Street, Knoxville, TN 37917, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6649-3694","authenticated-orcid":false,"given":"Md Ataur","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alivia","family":"Shasteen","sequence":"additional","affiliation":[{"name":"College of Dental Medicine, Lincoln Memorial University, 1705 St. Mary Street, Knoxville, TN 37917, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7133-4767","authenticated-orcid":false,"given":"Karima","family":"Ait-Aissa","sequence":"additional","affiliation":[{"name":"College of Dental Medicine, Lincoln Memorial University, 1705 St. Mary Street, Knoxville, TN 37917, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal M.","family":"Sahyoun","sequence":"additional","affiliation":[{"name":"College of Dental Medicine, Lincoln Memorial University, 1705 St. Mary Street, Knoxville, TN 37917, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7680-676X","authenticated-orcid":false,"given":"Rajat Das","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA"},{"name":"Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9728-063X","authenticated-orcid":false,"given":"Modar","family":"Kassan","sequence":"additional","affiliation":[{"name":"College of Dental Medicine, Lincoln Memorial University, 1705 St. Mary Street, Knoxville, TN 37917, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6840-3787","authenticated-orcid":false,"given":"Ehsanul","family":"Hoque Apu","sequence":"additional","affiliation":[{"name":"College of Dental Medicine, Lincoln Memorial University, 1705 St. Mary Street, Knoxville, TN 37917, USA"},{"name":"Department of Specialty Dentistry, Bitonte College of Dentistry, Northeast Ohio Medical University, Rootstown, OH 44272, USA"},{"name":"Department of Biomedical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1826-9377","authenticated-orcid":false,"given":"Ammaar H.","family":"Abidi","sequence":"additional","affiliation":[{"name":"College of Dental Medicine, Lincoln Memorial University, 1705 St. Mary Street, Knoxville, TN 37917, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/s41580-018-0003-4","article-title":"Mechanism and medical implications of mammalian autophagy","volume":"19","author":"Dikic","year":"2018","journal-title":"Nat. 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