{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T03:06:43Z","timestamp":1768532803059,"version":"3.49.0"},"reference-count":204,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007045","name":"Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["CF-2023-I-812"],"award-info":[{"award-number":["CF-2023-I-812"]}],"id":[{"id":"10.13039\/501100007045","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathophysiology"],"abstract":"<jats:p>Hepatocellular carcinoma (HCC) is the main type of liver cancer and one of the malignancies with the highest mortality rates worldwide. HCC is associated with diverse etiological factors including alcohol use, viral infections, fatty liver disease, and liver cirrhosis (a major risk factor for HCC). Unfortunately, many patients are diagnosed at advanced stages of the disease and receive palliative treatment only. Therefore, early markers of HCC and novel therapeutic approaches are urgently needed. The endocannabinoid system is involved in various physiological processes such as motor coordination, emotional control, learning and memory, neuronal development, antinociception, and immunological processes. Interestingly, endocannabinoids modulate signaling pathways involved in cell survival, proliferation, apoptosis, autophagy, and immune response. Consistently, several cannabinoids have demonstrated potential antitumor properties in experimental models. The participation of metabotropic and ionotropic cannabinoid receptors in the biological effects of cannabinoids has been extensively described. In addition, cannabinoids interact with other targets, including several ion channels. Notably, several ion channels targeted by cannabinoids are involved in inflammation, proliferation, and apoptosis in liver diseases, including HCC. In this literature review, we describe and discuss both the endocannabinoid system and exogenous phytocannabinoids, such as cannabidiol and \u03949-tetrahydrocannabinol, along with their canonical receptors, as well as the cannabidiol-targeted ion channels and their role in liver cancer and its preceding liver diseases. The cannabidiol-ion channel association is an extraordinary opportunity in liver cancer prevention and therapy, with potential implications for several environments that are for the benefit of cancer patients, including sociocultural, public health, and economic systems.<\/jats:p>","DOI":"10.3390\/pathophysiology33010008","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T15:12:04Z","timestamp":1768403524000},"page":"8","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cannabidiol\u2013Ion Channel Interactions Represent a Promising Preventive and Therapeutic Strategy in Hepatocellular Carcinoma"],"prefix":"10.3390","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0325-8974","authenticated-orcid":false,"given":"Mar\u00eda de Guadalupe","family":"Ch\u00e1vez-L\u00f3pez","sequence":"first","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional, Av. IPN 2508, Ciudad de Mexico 07360, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3768-5314","authenticated-orcid":false,"given":"Arturo","family":"Avalos-Fuentes","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Biof\u00edsica y Neurociencias, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional, Av. IPN 2508, Ciudad de Mexico 07360, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2797-8359","authenticated-orcid":false,"given":"Estrella del C.","family":"Cruz-Manzo","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional, Av. IPN 2508, Ciudad de Mexico 07360, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5573-4599","authenticated-orcid":false,"given":"Pedro A.","family":"Aguirre-Arriaga","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional, Av. IPN 2508, Ciudad de Mexico 07360, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3430-9335","authenticated-orcid":false,"given":"Benjam\u00edn","family":"Flor\u00e1n","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Biof\u00edsica y Neurociencias, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional, Av. IPN 2508, Ciudad de Mexico 07360, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9284-7775","authenticated-orcid":false,"given":"Julio Isael","family":"P\u00e9rez-Carre\u00f3n","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Medicina Gen\u00f3mica (INMEGEN), Perif\u00e9rico Sur No. 4809, Col. Arenal Tepepan, Ciudad de Mexico 14610, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8168-4488","authenticated-orcid":false,"given":"Cecilia","family":"Ba\u00f1uelos","sequence":"additional","affiliation":[{"name":"Programa Transdisciplinario en Desarrollo Cient\u00edfico y Tecnol\u00f3gico para la Sociedad, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional, Av. 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