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No effective treatment for ALS is currently available. Elevated neuroinflammation, oxidative stress and alterations to the endocannabinoid system are evident in ALS. The phytocannabinoid cannabidiol (CBD) has anti-inflammatory and anti-oxidant properties. Thus, we evaluated the remedial effects of chronic oral cannabidiol (CBD) treatment on ALS-relevant behavioural domains in the <jats:italic>copper-zinc superoxide dismutase 1<\/jats:italic> (<jats:italic>SOD1<\/jats:italic>) mouse model of ALS that carries a <jats:italic>G93A<\/jats:italic> mutation (<jats:italic>SOD1<\/jats:italic>\n              <jats:sup>\n                <jats:italic>G93A<\/jats:italic>\n              <\/jats:sup>).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Male and female <jats:italic>SOD1<\/jats:italic>\n              <jats:sup>\n                <jats:italic>G93A<\/jats:italic>\n              <\/jats:sup> and wild\u00a0type-like (WT) littermates were fed either a control (CHOW) or CBD-enriched chow diet (equivalent to a dose of 36 mg\/kg per day) beginning from 10 weeks of age. Bodyweight and motor performance were recorded weekly from 11 to 19 weeks and open field behaviours at 12 and 18 weeks. Mice were also tested for prepulse inhibition (PPI), social behaviours, as well as fear-associated memory.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>CBD treatment ameliorated the bodyweight loss in female <jats:italic>SOD1<\/jats:italic>\n              <jats:sup>\n                <jats:italic>G93A<\/jats:italic>\n              <\/jats:sup> mice, tended to reinstate sociability in <jats:italic>SOD1<\/jats:italic>\n              <jats:sup>\n                <jats:italic>G93A<\/jats:italic>\n              <\/jats:sup> males, strengthened social recognition memory in <jats:italic>SOD1<\/jats:italic>\n              <jats:sup>\n                <jats:italic>G93A<\/jats:italic>\n              <\/jats:sup> females, and improved the PPI response in younger <jats:italic>SOD1<\/jats:italic>\n              <jats:sup>\n                <jats:italic>G93A<\/jats:italic>\n              <\/jats:sup> females at higher prepulse intensities. CBD had no effect on motor impairments but instead reversed the anxiolytic-like phenotype of 12-week-old male <jats:italic>SOD1<\/jats:italic>\n              <jats:sup>\n                <jats:italic>G93A<\/jats:italic>\n              <\/jats:sup> mice and decreased the acoustic startle response and strengthened cue <jats:italic>freezing<\/jats:italic> in male mice.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Thus, the current remedial oral dose of CBD delayed disease progression (inferred by bodyweight) in both male and female mice and improve specific cognitive deficits of <jats:italic>SOD1<\/jats:italic>\n              <jats:sup>\n                <jats:italic>G93A<\/jats:italic>\n              <\/jats:sup> mice in a sex specific manner without altering the motor phenotype.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00213-025-06785-z","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T13:08:21Z","timestamp":1744636101000},"page":"2077-2095","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Behavioural effects of oral cannabidiol (CBD) treatment in the superoxide dismutase 1 G93 A (SOD1G93 A) mouse model of amyotrophic lateral sclerosis"],"prefix":"10.1007","volume":"242","author":[{"given":"Sandip","family":"Ghimire","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Kreilaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossana","family":"Rosa Porto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyndsey L.","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin J.","family":"Yerbury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathon C.","family":"Arnold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9904-8482","authenticated-orcid":false,"given":"Tim","family":"Karl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,14]]},"reference":[{"key":"6785_CR1","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1177\/026988119701100110","volume":"11","author":"KA Abduljawad","year":"1997","unstructured":"Abduljawad KA, Langley RW, Bradshaw CM, Szabadi E (1997) Effects of clonidine and diazepam on the acoustic startle response and on its inhibition by \u201cprepulses\u201d in man. 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