Article

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

Department of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan.
Neuropharmacology (Impact Factor: 4.82). 08/2011; 62(1):373-84. DOI: 10.1016/j.neuropharm.2011.08.013
Source: PubMed

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'.

0 Followers
 · 
115 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The present study is the first to explore links between PTSD and cannabis use characteristics immediately prior to a cannabis quit attempt, including motives, use problems, withdrawal, and craving. Measures of PTSD diagnosis, symptom severity, and cannabis use characteristics were administered to a sample of cannabis dependent military veterans (n = 94). Hypotheses were tested with a series of analyses of variance and covariance and hierarchical multiple regressions with Bonferroni corrections. Analyses were conducted with and without adjusting for variance shared with substance use (cannabis, alcohol, tobacco) in the previous 90 days, and co-occurring mood, anxiety, and substance use diagnoses. Compared to participants without PTSD, participants with PTSD reported significantly increased: (a) use of cannabis to cope, (b) severity of cannabis withdrawal, and (c) experiences of craving related to compulsivity, emotionality, and anticipation, with findings regarding coping and craving remaining significant after adjusting for covariates. Among the total sample, PTSD symptom severity was positively associated with (a) use of cannabis to cope, (b) cannabis use problems, (c) severity of cannabis withdrawal, and (d) experiences of craving related to compulsivity and emotionality, with findings regarding withdrawal and emotion-related craving remaining significant after adjusting for covariates. Thus, links between PTSD and using cannabis to cope, severity of cannabis withdrawal, and especially craving appear robust across measures of PTSD and analytical method. The results of this study provide support for models that posit a pernicious feedback loop between PTSD symptomatology and cannabis use. (Am J Addict 2013; 22:277-284).
    American Journal on Addictions 05/2013; 22(3):277-84. DOI:10.1111/j.1521-0391.2012.12018.x · 1.74 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Abnormal adaptation of the stress-response system following traumatic stress can lead to alterations in the hypothalamic-pituitary-adrenal (HPA) axis that may contribute to the development of post-traumatic stress disorder (PTSD). The present study used several behavioral tests to investigate the anxiolytic-like and antidepressant activity of L-tetrahydropalmatine (L-THP) in an experimental rat model of anxiety and depression induced by single prolonged stress (SPS), an animal model of PTSD. Male rats were treated intraperitoneally (i.p.) with vehicle or varied doses of THP 30 min prior to SPS for 8 consecutive days. Daily THP (50 mg/kg) administration significantly increased the number and duration of open arm visits in the elevated plus maze (EPM) test, reduced the anxiety index, increased the risk assessment, and increased the number of head dips over the borders of the open arms after SPS. THP was also associated with increased time spent at the center of the open field, reduced grooming behaviors in the EPM test, and reduced time spent immobile in the forced swimming test (FST). It also blocked the decrease in neuropeptide Y (NPY) and the increase in corticotrophin-releasing factor (CRF) expression in the hypothalamus. This is the first study to determine that THP exerts pronounced anxiolytic-like and antidepressant effects on the development of the behavioral and biochemical symptoms associated with PTSD, indicating its prophylactic potential. Thus, THP reversed several behavioral impairments triggered by the traumatic stress of SPS and is a potential non-invasive therapeutic intervention for PTSD.
    Biomolecules and Therapeutics 05/2014; 22(3):213-22. DOI:10.4062/biomolther.2014.032 · 0.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cannabidiol (CBD) is a constituent of Cannabis sativa that promotes wakefulness as well as enhances endogenous levels of wake-related neurotransmitters, including dopamine. However, at this date, the effects of CBD on the sleep-inducing molecules, such as adenosine (AD), are unknown. Here, we report that intrahypothalamic injection of CBD (10μg/1μL) increases the extracellular levels of AD collected from nucleus accumbens. Furthermore, the pharmacodynamic of this drug shows that effects on the contents of AD last 2h post-injection. These preliminary findings suggest that CBD promotes the endogenous accumulation of AD.
    Neuroscience Research 05/2014; 84. DOI:10.1016/j.neures.2014.04.006 · 2.15 Impact Factor

Full-text (2 Sources)

Download
11 Downloads
Available from
May 16, 2014