{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T11:07:27Z","timestamp":1794049647389,"version":"4.8.0"},"reference-count":38,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cannabis &amp; Cannabinoid Research"],"published-print":{"date-parts":[[2022,2,1]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction:<\/jats:title>\n                    <jats:p>\n                      The cannabinoid \u0394\n                      <jats:sup>9<\/jats:sup>\n                      -tetrahydrocannabinolic acid (\u0394\n                      <jats:sup>9<\/jats:sup>\n                      -THCA) has long been suggested in review articles and anecdotal reports to be anticonvulsant; yet, there is scant evidence supporting this notion. The objective of this study was to interrogate the anticonvulsant potential of \u0394\n                      <jats:sup>9<\/jats:sup>\n                      -THCA in various seizure models\u2014the\n                      <jats:italic toggle=\"yes\">Scn1a<\/jats:italic>\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                      mouse model of Dravet syndrome, the 6-Hz model of psychomotor seizures and the maximal electroshock (MES) model of generalized tonic-clonic seizures.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods:<\/jats:title>\n                    <jats:p>\n                      We examined the effect of acute \u0394\n                      <jats:sup>9<\/jats:sup>\n                      -THCA treatment against hyperthermia-induced seizures, and subchronic treatment on spontaneous seizures and survival in the\n                      <jats:italic toggle=\"yes\">Scn1a<\/jats:italic>\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                      mice. We also studied the effect of acute \u0394\n                      <jats:sup>9<\/jats:sup>\n                      -THCA treatment on the critical current thresholds in the 6-Hz and MES tests using outbred Swiss mice. Highly purified \u0394\n                      <jats:sup>9<\/jats:sup>\n                      -THCA was used in the studies or a mixture of \u0394\n                      <jats:sup>9<\/jats:sup>\n                      -THCA and \u0394\n                      <jats:sup>9<\/jats:sup>\n                      -THC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      We observed mixed anticonvulsant and proconvulsant effects of \u0394\n                      <jats:sup>9<\/jats:sup>\n                      -THCA across the seizure models. Highly pure \u0394\n                      <jats:sup>9<\/jats:sup>\n                      -THCA did not affect hyperthermia-induced seizures in\n                      <jats:italic toggle=\"yes\">Scn1a<\/jats:italic>\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                      mice. A \u0394\n                      <jats:sup>9<\/jats:sup>\n                      -THCA\/\u0394\n                      <jats:sup>9<\/jats:sup>\n                      -THC mixture was anticonvulsant in the 6-Hz threshold test, but purified \u0394\n                      <jats:sup>9<\/jats:sup>\n                      -THCA and \u0394\n                      <jats:sup>9<\/jats:sup>\n                      -THC had no effect. Conversely, both \u0394\n                      <jats:sup>9<\/jats:sup>\n                      -THCA and \u0394\n                      <jats:sup>9<\/jats:sup>\n                      -THC administered individually were proconvulsant in the MES threshold test but had no effect when administered as a \u0394\n                      <jats:sup>9<\/jats:sup>\n                      -THCA\/\u0394\n                      <jats:sup>9<\/jats:sup>\n                      -THC mixture. The \u0394\n                      <jats:sup>9<\/jats:sup>\n                      -THCA\/\u0394\n                      <jats:sup>9<\/jats:sup>\n                      -THC mixture, however, increased spontaneous seizure severity and increased mortality of\n                      <jats:italic toggle=\"yes\">Scn1a<\/jats:italic>\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                      mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion:<\/jats:title>\n                    <jats:p>\n                      The anticonvulsant profile of \u0394\n                      <jats:sup>9<\/jats:sup>\n                      -THCA was variable depending on the seizure model used and presence of \u0394\n                      <jats:sup>9<\/jats:sup>\n                      -THC. Because of the unstable nature of \u0394\n                      <jats:sup>9<\/jats:sup>\n                      -THCA, further exploration of \u0394\n                      <jats:sup>9<\/jats:sup>\n                      -THCA through formal anticonvulsant drug development is problematic without stabilization. Future studies may better focus on determining the mechanisms by which combined \u0394\n                      <jats:sup>9<\/jats:sup>\n                      -THCA and \u0394\n                      <jats:sup>9<\/jats:sup>\n                      -THC alters seizure thresholds, as this may uncover novel targets for the control of refractory partial seizures.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/can.2020.0073","type":"journal-article","created":{"date-parts":[[2020,9,9]],"date-time":"2020-09-09T23:05:42Z","timestamp":1599692742000},"page":"46-57","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":24,"title":["Evaluation of the Possible Anticonvulsant Effect of \u0394\n                    <sup>9<\/sup>\n                    -Tetrahydrocannabinolic Acid in Murine Seizure Models"],"prefix":"10.1177","volume":"7","author":[{"given":"Melissa J.","family":"Benson","sequence":"first","affiliation":[{"name":"Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia."},{"name":"Lambert Initiative for Cannabinoid Therapeutics, The University of Sydney, Sydney, New South Wales, Australia."},{"name":"Faculty of Science, School of Psychology, The University of Sydney, Sydney, New South Wales, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyndsey L.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia."},{"name":"Lambert Initiative for Cannabinoid Therapeutics, The University of Sydney, Sydney, New South Wales, Australia."},{"name":"Discipline of Pharmacology, Faculty of Medicine and Health, School of Medical Sciences, The University of Sydney, Sydney, New South Wales, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan K.","family":"Low","sequence":"additional","affiliation":[{"name":"Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia."},{"name":"Lambert Initiative for Cannabinoid Therapeutics, The University of Sydney, Sydney, New South Wales, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia Lin","family":"Luo","sequence":"additional","affiliation":[{"name":"Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia."},{"name":"Lambert Initiative for Cannabinoid Therapeutics, The University of Sydney, Sydney, New South Wales, Australia."},{"name":"Faculty of Science, School of Psychology, The University of Sydney, Sydney, New South Wales, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard C.","family":"Kevin","sequence":"additional","affiliation":[{"name":"Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia."},{"name":"Lambert Initiative for 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