Anxiogenic-like effects of chronic cannabidiol administration in rats

ElBatsh, Maha M.; Assareh, Neda; Marsden, C.A.; Kendall, David A.

doi:10.1007/s00213-011-2566-z

Cited by 73 publications

(51 citation statements)

References 58 publications

(69 reference statements)

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“…These findings agree with previous studies showing that acute CBD administration may produce anxiolytic-like effects according to an inverted U-shaped dose-response curve while higher doses or repeated CBD treatment may be ineffective in several anxiety paradigms (Campos et al, 2012). Anxiogenic-like effects were detected after 14 days of daily CBD administration (10 mg/kg), which is in clear opposition to the acute anxiolytic profile of the drug that was demonstrated in a conditioned emotional response paradigm in rats (ElBatsh et al, 2012). Long et al (2010) have shown that acute doses of CBD (1 and 50 mg/kg) that produced anxiolytic-like effects in the open field and light-dark tests after chronic administration had no effect in the EPM .…”

Section: Discussionsupporting

confidence: 86%

Influence of single and repeated cannabidiol administration on emotional behavior and markers of cell proliferation and neurogenesis in non-stressed mice

Schiavon

Bonato

Milani

et al. 2016

Progress in Neuro-Psychopharmacology and Biological Psychiatry

110

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Section: Discussionsupporting

confidence: 86%

Influence of single and repeated cannabidiol administration on emotional behavior and markers of cell proliferation and neurogenesis in non-stressed mice

Schiavon

Bonato

Milani

et al. 2016

Progress in Neuro-Psychopharmacology and Biological Psychiatry

110

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“…Later studies, also in male Wistar rats, reinforced the hypothesis that CBD (given in a single dose) is anxiolytic, using the Vogel conflict test [2], a model of contextual conditioned fear [3] and stress-induced behavior in the EPM [4]. Similar anxiolytic effects of CBD were demonstrated in mice subjected to chronic unpredictable stress, receiving CBD following each daily stressor [5]; however, when CBD was administered repeatedly (14 daily injections) to Lister-hooded rats [6] anxiogenic effects were found. Taken together, these data support testing the hypothesis that CBD may be used to treat anxiety in humans.…”

Section: Introductionmentioning

confidence: 92%

Prohedonic Effect of Cannabidiol in a Rat Model of Depression

Shoval

Shbiro²,

Hershkovitz³

et al. 2016

Neuropsychobiology

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Background: Accumulating evidence suggests that cannabidiol (CBD) may be an effective and safe anxiolytic agent and potentially also an antidepressant. Aim: The objective of this study was to further examine these properties of CBD using the ‘depressive-like' Wistar-Kyoto (WKY) rat, focusing on the drug's effect on anhedonia-like behaviors. Methods: Forty-eight WKY and 48 control Wistar adult male rats were pretreated orally with CBD (15, 30 and 45 mg/kg) or vehicle. The saccharin preference test (SPT), the elevated plus maze (EPM) test and the novel object exploration (NOE) test were used. Results: CBD showed a prohedonic effect on the WKY rats at 30 mg/kg in the SPT. In the NOE, CBD increased exploration of the novel object and locomotion at 45 mg/kg and increased locomotion at 15 mg/kg, indicating an improvement in the characteristically low motivation of WKY rats to explore. There was no similar effect at any dose in the EPM or in open-field behavior in the habituation to the NOE. Conclusions: These findings extend the limited knowledge on the antidepressant effect of CBD, now shown for the first time in a genetic animal model of depression. These results suggest that CBD may be beneficial for the treatment of clinical depression and other states with prominent anhedonia.

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“…This particular mechanism seems to be important during neuroinflammation and neurodegenerative process related to b-amyloid protein deposits in CNS [51]. Although the pro-neurogenic effect of CBD has not yet been studied in rats, it could help us to explain the recent report that repeated CBD treatment enhances contextual fear conditioning [22]. Immature newborn neurons are selectively activated by this task [74], and neurogenesis suppression impairs contextual fear memory [75].…”

Section: Cannabidiol and Anxietymentioning

confidence: 99%

Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders

Campos

Moreira

Gomes

et al. 2012

Phil. Trans. R. Soc. B

348

239

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Cannabidiol (CBD) is a major phytocannabinoid present in the Cannabis sativa plant. It lacks the psychotomimetic and other psychotropic effects that the main plant compound D 9 -tetrahydrocannabinol (THC) being able, on the contrary, to antagonize these effects. This property, together with its safety profile, was an initial stimulus for the investigation of CBD pharmacological properties. It is now clear that CBD has therapeutic potential over a wide range of non-psychiatric and psychiatric disorders such as anxiety, depression and psychosis. Although the pharmacological effects of CBD in different biological systems have been extensively investigated by in vitro studies, the mechanisms responsible for its therapeutic potential are still not clear. Here, we review recent in vivo studies indicating that these mechanisms are not unitary but rather depend on the behavioural response being measured. Acute anxiolytic and antidepressant-like effects seem to rely mainly on facilitation of 5-HT1A-mediated neurotransmission in key brain areas related to defensive responses, including the dorsal periaqueductal grey, bed nucleus of the stria terminalis and medial prefrontal cortex. Other effects, such as anti-compulsive, increased extinction and impaired reconsolidation of aversive memories, and facilitation of adult hippocampal neurogenesis could depend on potentiation of anandamidemediated neurotransmission. Finally, activation of TRPV1 channels may help us to explain the antipsychotic effect and the bell-shaped dose-response curves commonly observed with CBD. Considering its safety profile and wide range of therapeutic potential, however, further studies are needed to investigate the involvement of other possible mechanisms (e.g. inhibition of adenosine uptake, inverse agonism at CB2 receptor, CB1 receptor antagonism, GPR55 antagonism, PPARg receptors agonism, intracellular (Ca 2þ ) increase, etc.), on CBD behavioural effects.

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Anxiogenic-like effects of chronic cannabidiol administration in rats

Abstract: Chronic administration of CBD produced an anxiogenic-like effect in clear opposition to the acute anxiolytic profile previously reported. In addition, CBD decreased the expression of proteins that have been shown to be enhanced by chronic treatment with antidepressant/anxiolytic drugs.

Cited by 73 publications

References 58 publications

Influence of single and repeated cannabidiol administration on emotional behavior and markers of cell proliferation and neurogenesis in non-stressed mice

Influence of single and repeated cannabidiol administration on emotional behavior and markers of cell proliferation and neurogenesis in non-stressed mice

Prohedonic Effect of Cannabidiol in a Rat Model of Depression

Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders

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