Cannabidiol mitigates cognitive impairment from LPS-induced neuroinflammation in mice

Year 2026, Volume: 30 Issue: 2, 529 - 534, 15.03.2026

Sultan Mente , Elif Beyzanur Polat , Hümeysa Kiyak-kırmacı , Büşra Ertaş

https://doi.org/10.12991/jrespharm.1711372

https://izlik.org/JA63CH98XZ

Abstract

Cannabidiol (CBD) is a non-psychoactive substance derived from the Cannabis sativa plant, with anti-inflammatory and antioxidant effects. Neuroinflammation is a pathological process triggered by multiple mechanisms in the brain and progresses in a spiral manner, commonly encountered in the pathology of many neurodegenerative diseases. The effects of neuroinflammation on memory problems that begin in the early stages of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease are discussed. In recent years, the search for effective drugs for these paradoxical pathologies has continued. Thus, our study aimed to evaluate the effect of CBD on learning and memory performance in a mouse model of lipopolysaccharide (LPS)-induced neuroinflammation. An in vivo neuroinflammation model was performed by administering LPS (2mg/kg; ip) to C57BL/6J mice on days 1 and 3. Mice that were given CBD treatment for 21 days were subjected to neurobehavioral tests on the last 4 days. In the open field test, no difference was observed between the groups in terms of spontaneous movements and anxiety. In the novel object recognition test, the movement time to recognise the new object was longer in the CBD treatment group than in the LPS group. Finally, in the passive avoidance test, the delay in moving to the dark compartment was longer in the CBD-treated group than in the LPS group. As a result, the cognitive functions impaired by LPS administration can be improved with CBD treatment, and the study will be carried forward by supporting these behavioural results with neurobiochemical results.

Keywords

Cannabidiol , Neuroinflammation , lipopolysaccharide , cognitive decline , neurobehavioral test

Ethical Statement

All protocols in this study were approved by the Animal Ethics Committee of the Medeniyet University (Protocol No:70)

Project Number

M.U. BAPKO-TYL-2024-11416

References

• [1] Ali MR, Abo-Youssef AM, Messiha BA, and Khattab MM. Tempol and perindopril protect against lipopolysaccharide-induced cognition impairment and amyloidogenesis by modulating brain-derived neurotropic factor, neuroinflammation and oxido-nitrosative stress. Naunyn Schmiedebergs Arch Pharmacol. 2016; 389(6): 637-56. https://doi.org/10.1007/s00210-016-1234-6
• [2] Dos-Santos-Pereira M, Guimarães FS, Del-Bel E, Raisman-Vozari R, and Michel PP. Cannabidiol prevents LPS-induced microglial inflammation by inhibiting ROS/NF-κB-dependent signaling and glucose consumption. Glia. 2020; 68(3): 561-573 https://doi.org/10.1002/glia.23738
• [3] Hickey JP, Collins AE, Nelson ML, Chen H, and Kalisch BE. Modulation of Oxidative Stress and Neuroinflammation by Cannabidiol (CBD): Promising Targets for the Treatment of Alzheimer's Disease. Curr Issues Mol Biol. 2024; 46(5): 4379-4402. https://doi.org/10.3390/cimb46050266
• [4] Yndart Arias A, Kolishetti N, Vashist A, Madepalli L, Llaguno L, and Nair M. Anti-inflammatory effects of CBD in human microglial cell line infected with HIV-1. Scientific Reports. 2023; 13(1): 7376. https://doi.org/10.1038/s41598-023-32927-4
• [5] Wang Z, Zheng P, Xie Y, Chen X, Solowij N, Green K, Chew YL, and Huang XF. Cannabidiol regulates CB1-pSTAT3 signaling for neurite outgrowth, prolongs lifespan, and improves health span in Caenorhabditis elegans of Aβ pathology models. Faseb j. 2021; 35(5): e21537. https://doi.org/10.1096/fj.202002724R
• [6] Yang Y, García-Cruzado M, Zeng H, Camprubí-Ferrer L, Bahatyrevich-Kharitonik B, Bachiller S, and Deierborg T. LPS priming before plaque deposition impedes microglial activation and restrains Aβ pathology in the 5xFAD mouse model of Alzheimer's disease. Brain Behav Immun. 2023; 113: 228-247 https://doi.org/10.1016/j.bbi.2023.07.006
• [7] Jaehne EJ, Corrigan F, Toben C, Jawahar MC, and Baune BT. The effect of the antipsychotic drug quetiapine and its metabolite norquetiapine on acute inflammation, memory and anhedonia. Pharmacol Biochem Behav. 2015; 135: 136-44. https://doi.org/10.1016/j.pbb.2015.05.021
• [8] Martin M, Pusceddu MM, Teichenné J, Negra T, Connolly A, Escoté X, Torrell Galceran H, Cereto Massagué A, Samarra Mestre I, Del Pino Rius A, Romero-Gimenez J, Egea C, Alcaide-Hidalgo JM, and Del Bas JM. Preventive Treatment with Astaxanthin Microencapsulated with Spirulina Powder, Administered in a Dose Range Equivalent to Human Consumption, Prevents LPS-Induced Cognitive Impairment in Rats. Nutrients. 2023; 15(13). https://doi.org/10.3390/nu15132854
• [9] Morici JF, Bekinschtein P, and Weisstaub NV. Medial prefrontal cortex role in recognition memory in rodents. Behav Brain Res. 2015; 292: 241-51. https://doi.org/10.1016/j.bbr.2015.06.030
• [10] Kraeuter AK, Guest PC, and Sarnyai Z. The Y-Maze for Assessment of Spatial Working and Reference Memory in Mice. Methods Mol Biol. 2019; 1916: 105-111. https://doi.org/10.1007/978-1-4939-8994-2_10
• [11] Zhao J, Bi W, Xiao S, Lan X, Cheng X, Zhang J, Lu D, Wei W, Wang Y, Li H, Fu Y, and Zhu L. Neuroinflammation induced by lipopolysaccharide causes cognitive impairment in mice. Sci Rep. 2019; 9(1): 5790. https://doi.org/10.1038/s41598-019-42286-8
• [12] Georgieva-Kotetarova M, Kandilarov I, Vilmosh N, Zlatanova-Tenisheva H, Yanchev N, Delev D, Dermendzhiev T, Murdjeva M, Kostadinova I, and Kostadinov I. Cannabidiol improves memory and decreases IL-1β serum levels in rats with lipopolysaccharide-induced inflammation. Folia Medica. 2023; 65: 940-949. https://doi.org/10.3897/folmed.65.e107259
• [13] Ertas B, Hazar-Yavuz AN, Topal F, Keles-Kaya R, Karakus Ö, Ozcan GS, Taskin T, and Cam ME. Rosa canina L. improves learning and memory-associated cognitive impairment by regulating glucose levels and reducing hippocampal insulin resistance in high-fat diet/streptozotocin-induced diabetic rats. J Ethnopharmacol. 2023; 313: 116541. https://doi.org/10.1016/j.jep.2023.116541