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Cited by 91Cannabis and Cannabinoid ResearchSleep and Wakefulness ResearchSleep and related disorders

Effect of cannabidiol on sleep disruption induced by the repeated combination tests consisting of open field and elevated plus-maze in rats

Hsiao, Yi-Tse, Yi, Pei-Lu, Li, Chia-Ling, Chang, Fang-Chia·2012·Neuropharmacology
DOI 10.1016/j.neuropharm.2011.08.013
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Abstract

Patients with post-traumatic stress disorder (PTSD) frequently complain of having sleep disturbances, such as insomnia and rapid eye movement (REM) sleep abnormality. Cannabidiol (CBD), a psycho-inactive constituent of marijuana, reduces physiological non-REM (NREM) sleep and REM sleep in normal rats, in addition to generating its anxiolytic effect. However, the effects of CBD on anxiety-induced sleep disturbances remain unclear. Because anxiety progression is caused by persistent stress for a period of time, we employed the repeated combination tests (RCT) consisting of a 50-min open field (OF) and a subsequent 10-min elevated plus-maze (EPM) for four consecutive days to simulate the development of anxiety. Time spent in the centre arena of OF and during open arms of the EPM was substantially decreased in latter days of RCT, suggesting the habituation, which potentially lessens anxiety-mediated behavioural responses, was not observed in current tests. CBD microinjected into the central nucleus of amygdala (CeA) significantly enhanced time spent in centre arena of OF, increased time during the open arms and decreased frequency of entry to the enclosed arms of EPM, further confirming its anxiolytic effect. The decrease of NREM sleep during the first hour and the suppression of REM sleep during hours 4-10 after the RCT represent the similar clinical observations (e.g. insomnia and REM sleep interruption) in PTSD patients. CBD efficiently blocked anxiety-induced REM sleep suppression, but had little effect on the alteration of NREM sleep. Conclusively, CBD may block anxiety-induced REM sleep alteration via its anxiolytic effect, rather than via sleep regulation per se. This article is part of a Special Issue entitled 'Anxiety and Depression'.

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  • Microinjections of CBD into the central nucleus of the amygdala produce anxiolytic-like effects.

    “Similar effects can be produced by microinjections of CBD into brain regions including the central nucleus of the amygdala (Hsiao et al., 2012)”

    From The endocannabinoid system as a target for novel anxiolytic drugs (2017) · cites this paper as Hsiao et al., 2012

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Authors
Hsiao, Y.-T., Yi, P.-L., Li, C.-L., & Chang, F.-C.
Affiliations
  • National Taiwan University (TW)
  • Aletheia University (TW)
Corresponding author
Chang, Fang-Chia
ORCID
Venue
Neuropharmacology
Publisher
Elsevier BV
Published
2012-01
Volume
62
Issue
1
Pages
373-384
ISSN
0028-3908 (ISSN-L)
DOI
10.1016/j.neuropharm.2011.08.013
OpenAlex
W2027206234
Cited by
91
References
54
Citations by year
2026: 7 · 2025: 7 · 2024: 5 · 2023: 4 · 2022: 11 · 2021: 14 · 2020: 8 · 2019: 5 · 2018: 5 · 2017: 8 · 2016: 5 · 2015: 3 · 2014: 3 · 2013: 3 · 2012: 3
FWCI
2.11
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuropharmacology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Science Council (NSC96-2628-B-002-029-MY3)
Topics
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
Keywords
cannabidiol, post-traumatic stress disorder, sleep disruption, REM sleep suppression, NREM sleep, anxiety, anxiolytic effects, central amygdala, microinjection, insomnia
MeSH terms
Acoustic Stimulation, Animals, Anxiety, Cannabidiol, Disease Models, Animal, Electroencephalography, Electromyography, Exploratory Behavior, Male, Sleep Wake Disorders, Time Factors, Rats, Wistar, Maze Learning, Rats

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