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Cannabidiol (CBD) and related phytocannabinoids have been proposed to modulate these channels, offering potential non-opioid analgesic strategies. This systematic review evaluated their in vitro effects on pain-related sodium channels, focusing on electrophysiological and biophysical mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Following PRISMA guidelines, Embase\n                      <jats:sup>\u00ae<\/jats:sup>\n                      , LILACS\n                      <jats:sup>\u00ae<\/jats:sup>\n                      , PubMed\n                      <jats:sup>\u00ae<\/jats:sup>\n                      \/MEDLINE\n                      <jats:sup>\u00ae<\/jats:sup>\n                      , and Scopus\n                      <jats:sup>\u00ae<\/jats:sup>\n                      were searched using the SPIDER strategy. Eligible studies evaluated CBD or its derivatives on voltage-gated sodium channels Na\n                      <jats:sub>v<\/jats:sub>\n                      1.3, Na\n                      <jats:sub>v<\/jats:sub>\n                      1.6, Na\n                      <jats:sub>v<\/jats:sub>\n                      1.7, Na\n                      <jats:sub>v<\/jats:sub>\n                      1.8, and Na\n                      <jats:sub>v<\/jats:sub>\n                      1.9 through electrophysiological assays. Data extraction and analysis were conducted independently by two reviewers, with inter-rater agreement assessed by Cohen\u2019s kappa. Seven studies met the inclusion criteria.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CBD consistently inhibited sodium currents with IC\u2085\u2080 values in the low micromolar range (2\u20133.3 \u00b5M), reduced action potential firing, induced hyperpolarizing shifts in steady-state inactivation, and delayed recovery from inactivation. Other phytocannabinoids, such as cannabigerol, cannabinol, cannabigerolic acid, and cannabidivarinic acid, also inhibited sodium channels, though with variable potency and distinct effects on channel gating.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Cannabinoids, particularly CBD, act as non-selective inhibitors of voltage-gated sodium channels implicated in pain signaling. Their ability to stabilize inactivated channel states and reduce neuronal excitability supports their therapeutic potential in neuropathic pain. These findings highlight the relevance of phytocannabinoids as promising candidates for the development of non-opioid analgesics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s42238-026-00436-6","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T09:57:30Z","timestamp":1776247050000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Electrophysiological modulation of pain\u2011related sodium channels by cannabinoids: a systematic review"],"prefix":"10.1186","volume":"8","author":[{"given":"Samuel Gon\u00e7alves","family":"Castro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah Eduarda","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio Cesar Moreira","family":"Brito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Matavel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"436_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/9195","author":"AN Akopian","year":"1999","unstructured":"Akopian AN, Souslova V, England S, Okuse K, Ogata N, Ure J, et al. 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