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Studies have found that cannabidiol (CBD) can improve hyperactive and cognitive symptoms in children with ASD. However, little is known about the effect of CBD in combination with other medications, such as risperidone (RISP). This study aimed to evaluate the behavioral and biochemical effects of CBD in animals using a valproic acid (VPA)\u2010induced ASD animal model. VPA was administered in pregnant Wistar rats on Day 12.5 of gestation to induce the ASD model. From the 10th to the 16th postnatal day (PND), the neurodevelopment of the animals was assessed through eye\u2010opening, olfactory discrimination, and negative geotaxis behavioral tests. From PNDs 9 to 54, the animals were weighed. They were treated for 21 days with CBD alone (100\u00a0mg\/kg, by gavage, twice a day) or in combination with RISP (0.1\u00a0mg\/kg, by gavage, once a day). At PND 55, the animals were evaluated in social interaction and locomotor activity experiments. Finally, after behavioral assessment, the animals were euthanized, the brain was isolated, and oxidative stress parameters were evaluated in the hippocampus and cortex posterior. Animals exposed to VPA showed neurodevelopmental delays in opening their eyes, difficulties in turning around their axis, and took longer time to find the original nest when compared to control animals. They also exhibited impaired sociability and reduced exploratory activity, which indicates model impairments. Interestingly, animals exposed to VPA treated with CBD\u00a0+\u00a0RISP significantly improved sociability parameters, whereas isolated CBD did not affect this parameter. In the biochemical analysis, a significant decrease in the hippocampal sulfhydryl content was noted in the CT\u00a0+\u00a0CBD group and an increase in the VPA\u00a0+\u00a0CBD group. In conclusion, these results suggest that CBD, in combination with RISP, may be an interesting pharmacological approach to reducing ASD\u2010related symptoms.<\/jats:p><jats:p><jats:bold>Summary<\/jats:bold>: Besides the increased prevalence of ASD cases in recent years, there are no medications to improve the central symptoms of autism. Numerous studies discuss CBD as an important medication for improving ASD symptoms; however, it is not known how CBD interacts with commonly used drugs in ASD individuals, such as RISP. This study demonstrated that CBD therapy, only when combined with RISP, improved sociability in a VPA\u2010induced ASD animal model.<\/jats:p>","DOI":"10.1002\/dneu.22955","type":"journal-article","created":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T05:14:59Z","timestamp":1732770899000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Effects of Cannabidiol Isolated or in Association With Risperidone in an Animal Model of Autism"],"prefix":"10.1002","volume":"85","author":[{"given":"Maiara de Aguiar da","family":"Costa","sequence":"first","affiliation":[{"name":"Laboratory of Autism and Neurodevelopmental Research, Graduate Program in Health Sciences University of Southern Santa Catarina (UNESC)  Crici\u00fama Santa Catarina Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo Zanette","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Laboratory of Autism and 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