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Cannabidiol Exerts Sedative and Hypnotic Effects in Normal and Insomnia Model Mice Through Activation of 5-HT1A Receptor

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Abstract

Cannabis sativa has been used for improving sleep for long history. Cannabidiol (CBD) has drown much attention as a non-addictive psychoactive component in Cannabis sativa extract. However, the effects of CBD on sleep architecture and it’s acting mechanism remains unclear. In the present study, we evaluated the sedative-hypnotic effect of cannabidiol (CBD), assessed the effects of CBD on sleep using a wireless physiological telemetry system. We further explored the therapeutic effects of CBD using 4-chloro-dl-phenylalanine (PCPA) induced insomnia model and changes in sleep latency, sleep duration and intestinal flora were evaluated. CBD shortened sleep latency and increases sleep duration in both normal and insomnia mice, and those effects were blocked by 5-HT1A receptor antagonist WAY100635. We determined that CBD increases 5-HT1A receptors expression and 5-HT content in the hypothalamus of PCPA-pretreated mice and affects tryptophan metabolism in the intestinal flora. These results showed that activation of 5-HT1A receptors is one of the potential mechanisms underlying the sedative-hypnotic effect of CBD. This study validated the effects of CBD on sleep and evaluated its potential therapeutic effects on insomnia.

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Data Availability

The data presented in this study are available on request from the corresponding author. The gut microbiota data can be download at: http://www.ncbi.nlm.nih.gov/bioproject/1029818.

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Funding

This work was supported by the National Key New Drug Creation Program (2017ZX09309020).

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  1. Yu-Meng Liu and **-Cao Li have equally contributed to this work.

Authors and Affiliations

  1. Shenyang Pharmaceutical University, Shenyang, 110016, China

    Yu-Meng Liu, Kuo Zhang & You-Zhi Zhang

  2. Bei**g Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures, Bei**g Key Laboratory of Neuropsychopharmacology, Bei**g, 100850, China

    Yu-Meng Liu, **-Cao Li, Yong-Fang Gu, Ren-Hong Qiu, Jia-Ying Huang, Rui Xue, Shuo Li, Yang Zhang & You-Zhi Zhang

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Contributions

Y-M. Liu, J-C. Li: Data curation, Methodology, Writing—original draft, Writing review and editing. Y-F Gu, R-H. Qiu; J-Y. Huang: Data curation. R. Xue, S. Li, Y. Zhang, K. Zhang: Writing—review and editing. Y-Z. Zhang: Funding acquisition, Project administration, Writing—review and editing.

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Correspondence to You-Zhi Zhang.

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All experimental procedures were approved by the Insti-tutional Animal Care and Use Committee (ethics approval number: IACUC-DWZX-2022-781), and all experiments followed the National Institutes of Health Guide for the Care and Use of La-boratory Animals. All efforts were made to minimize animal suffering.

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Liu, YM., Li, JC., Gu, YF. et al. Cannabidiol Exerts Sedative and Hypnotic Effects in Normal and Insomnia Model Mice Through Activation of 5-HT1A Receptor. Neurochem Res 49, 1150–1165 (2024). https://doi.org/10.1007/s11064-024-04102-2

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