Cannabidiol regulates circadian rhythm to improve sleep disorders following general anesthesia in rats

doi:10.12122/j.issn.1673-4254.2025.04.09

Abstract

Abstract:

Objective To assess the regulatory effect of cannabidiol (CBD) on circadian rhythm sleep disorders following general anesthesia and explore its potential mechanism in a rat model of propofol-induced rhythm sleep disorder. Methods An electrode was embedded in the skull for cortical EEG recording in 24 male SD rats, which were randomized into control, propofol, CBD treatment, and diazepam treatment groups (n=6). Eight days later, a single dose of propofol (10 mg/kg) was injected via the tail vein with anesthesia maintenance for 3 h in the latter 3 groups, and daily treatment with saline, CBD or diazepam was administered via gavage; the control rats received only saline injection. A wireless system was used for collecting EEG, EMG, and body temperature data within 72 h after propofol injection. After data collection, blood samples and hypothalamic tissue samples were collected for determining serum levels of oxidative stress markers and hypothalamic expressions of the key clock proteins. Results Compared with the control rats, the rats with CBD treatment showed significantly increased sleep time at night (20:00-6:00), especially during the time period of 4:00-6:00 am. Compared with the rats in propofol group, which had prolonged SWS time and increased sleep episodes during 18:00-24:00 and sleep-wake transitions, the CBD-treated rats exhibited a significant reduction of SWS time and fewer SWS-to-active-awake transitions with increased SWS aspects and sleep-wake transitions at night (24:00-08:00). Diazepam treatment produced similar effect to CBD but with a weaker effect on sleep-wake transitions. Propofol caused significant changes in protein expressions and redox state, which were effectively reversed by CBD treatment. Conclusion CBD can improve sleep structure and circadian rhythm in rats with propofol-induced sleep disorder possibly by regulating hypothalamic expressions of the key circadian clock proteins, suggesting a new treatment option for perioperative sleep disorders.

Key words: postoperative sleep disturbance, propofol, cannabidiol, circadian clock proteins

Xinshun WU, Jingcao LI, Ying LIU, Renhong QIU, Henglin WANG, Rui XYE, Yang ZHANG, Shuo LI, Qiongyin FAN, Huajin DONG, Youzhi ZHANG, Jiangbei CAO. Cannabidiol regulates circadian rhythm to improve sleep disorders following general anesthesia in rats[J]. Journal of Southern Medical University, 2025, 45(4): 744-750.

Figures/Tables 5

Fig.1 Regulatory effects of CBD on sleep in normal rats. A: Timeline of experiments. B: Sleep duration of the rats in the day time (8:00-18:00) and the night time (20:00-6:00). C: Sleep duration at different time points. D: Average body temperature per hour. CBD: Cannabidiol; IG: Intragastric administration. *P<0.05, **P<0.01 vs baseline.

Fig.2 Regulatory effects of CBD on sleep architecture from 18:00 to 24:00 in rats following propofol anesthesia. A: Experimental flowchart. B: Duration of states in different pre-treatment groups. C: Mean duration of each state. D: State occurrence count. E: Number of entries into each state. Pro: Propofol; DZP: Diazepam; CBD: Cannabidiol; W: Wake; AW: Active wake; PS: Paradoxical sleep; SWS: Slow wave sleep. *P<0.05, **P<0.01.

Fig.3 Regulatory effects of CBD on sleep architecture from 24:00 to 08:00 in rats following propofol anesthesia. A: Experimental flowchart. B: Duration of states in different pre-treatment groups. C: Mean duration of each state. D: State occurrence count. E: Number of entries into each state. *P<0.05, **P<0.01.

Fig.4 Effects of CBD on expression levels of circadian clock proteins in rats following propofol anesthesia. A-F: Protein expressions of BMAL1, CLOCK, PER2, CRY2, GSK3β and SIRT1 in rat hypothalamus. The expression level of protein was quantified and presented as a ratio relative to GAPDH. *P<0.05, **P<0.01, ***P<0.001.

Fig.5 Regulatory effects of CBD on protein expression of CB1 (A) and serum levels of MDA (B) and SOD (C) of the rats. The expression level of protein was quantified and presented as a ratio relative to GAPDH. *P<0.05.

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