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CBN interacts with endocannabinoid (CB) receptors, but is also reported to interact with non-CB targets, including various ion channels. We assessed CBN effects on voltage-dependent sodium (Nav) channels expressed heterologously and in native dorsal root ganglion (DRG) neurons. Our results indicate that CBN is a functionally-selective, but structurally-non-selective Nav current inhibitor. CBN\u2019s main effect is on slow inactivation. CBN slows recovery from slow-inactivated states, and hyperpolarizes steady-state inactivation, as channels enter deeper and slower inactivated states. Multielectrode array recordings indicate that CBN attenuates DRG neuron excitability. Voltage- and current-clamp analysis of freshly isolated DRG neurons via our automated patch-clamp platform confirmed these findings. The inhibitory effects of CBN on Nav currents and on DRG neuron excitability add a new dimension to its actions and suggest that this cannabinoid may be useful for neuropathic pain.<\/jats:p>","DOI":"10.1038\/s42003-024-05781-x","type":"journal-article","created":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T18:02:43Z","timestamp":1706032963000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Functionally-selective inhibition of threshold sodium currents and excitability in dorsal root ganglion neurons by cannabinol"],"prefix":"10.1038","volume":"7","author":[{"given":"Mohammad-Reza","family":"Ghovanloo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip R.","family":"Effraim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6097-0541","authenticated-orcid":false,"given":"Sidharth","family":"Tyagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4137-1655","authenticated-orcid":false,"given":"Sulayman D.","family":"Dib-Hajj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5718-7177","authenticated-orcid":false,"given":"Stephen G.","family":"Waxman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,23]]},"reference":[{"key":"5781_CR1","doi-asserted-by":"publisher","unstructured":"Ghovanloo, M.-R. & Ruben, P. 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