Cannabidiol, a Cannabis sativa constituent, as an anxiolytic drug

Schier, Alexandre Rafael de Mello; Ribeiro, Natalia Pinho de Oliveira; Silva, Adriana Cardoso de Oliveira e; Hallak, Jaime Eduardo Cecílio; Crippa, José Alexandre S; Nardi, Antônio Egídio; Zuardi, Antônio Waldo

doi:10.1016/s1516-4446(12)70057-0

Cited by 70 publications

(8 citation statements)

References 32 publications

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“…The anxiolytic effects show an inverted U-shaped dose-response curve in several models of anxiety protocols (Campos and Guimarães, 2009;Campos et al, 2013;Schier et al, 2012). Here, for the first time, we show that zebrafish also display anxiolytic responses to CBD in an inverted U-shaped dose-response curve.…”

Section: Discussionsupporting

confidence: 53%

Caffeine protects against memory loss induced by high and non-anxiolytic dose of cannabidiol in adult zebrafish (Danio rerio)

Nazario

Antonioli

Capiotti

et al. 2015

Pharmacology Biochemistry and Behavior

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Section: Discussionsupporting

confidence: 53%

Caffeine protects against memory loss induced by high and non-anxiolytic dose of cannabidiol in adult zebrafish (Danio rerio)

Nazario

Antonioli

Capiotti

et al. 2015

Pharmacology Biochemistry and Behavior

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“…Recently, some preclinical and clinical reports suggested the usefulness of CBD as a new alternative for the treatment of PTSD (Schier et al, 2012;Jurkus et al, 2016;Shannon and Opila-Lehman, 2016;Bitencourt and Takahashi, 2018;Crippa et al, 2018;Bonaccorso et al, 2019;Elms et al, 2019;Lisboa et al, 2019). Despite the available, although scarce, reports in rodents regarding the effects of CBD on fear extinction or anxiety-like behavior in animal models of PTSD (Campos et al, 2012;Shallcross et al, 2019), no previous studies evaluated the effects of the repeated administration of CBD, alone or in combination with STR, on long-term behavioral and neurochemical alterations produced by a chronic animal model of PTSD.…”

Section: Discussionmentioning

confidence: 99%

Cannabidiol and Sertraline Regulate Behavioral and Brain Gene Expression Alterations in an Animal Model of PTSD

2021

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This study evaluated the effects of cannabidiol (CBD) and/or sertraline (STR) on behavioral and gene expression alterations induced by a new chronic animal model of post-traumatic stress disorder (PTSD). C57BL/6J male mice were repeatedly exposed to physical and psychogenic alternate stressful stimuli. Fear-related memory and anxiety-like behaviors were evaluated. The effects of the administration of CBD (20 mg/kg, i.p.) and/or STR (10 mg/kg, p.o.) were analyzed on behavioral and gene expression changes induced by the model of PTSD. Gene expression alterations of targets related with stress regulation, endocannabinoid and serotonergic systems were analyzed by real-time PCR. The results revealed an increased and long-lasting fear-related memory and anxiety-like behaviors in mice exposed to the animal model of PTSD. Treatment with CBD improved these behaviors in PTSD animals, effects that were significantly potentiated when combined with STR. Gene expression analyses revealed a long-term increase of corticotropin releasing factor (Crf) that was significantly normalized with the combination CBD plus STR. Cannabinoid receptors (Cnr1 and Cnr2) were up regulated in PTSD mice whereas the serotonin transporter (Slc6a4) was reduced. Interestingly, CBD and STR alone or combined induced a significant and marked increase of Slc6a4 gene expression. These results point out the cooperative action of the combination CBD plus STR to enhance fear extinction and reduce anxiety-like behaviors, normalizing gene expression alterations in this animal model of PTSD and suggesting that the combination of CBD with STR deserves to be further explored for the treatment of patients with PTSD.

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“…CBD decreases autonomic arousal and subjective anxiety [65]; these anxiolytic effects were found to be linked to the modulation of limbic and paralimbic structures [57,62]. It remains to be determined if these properties translate in the attenuation of symptoms for other anxiety disorders than social phobia (e.g., post-traumatic stress disorder, panic disorder) [66]. There are contradictory results as to CBD's effect on sleep (similar to results from animal studies) as it has been associated with both wake-inducing and hypnotic properties in humans [11,67,68].…”

Section: Cbd and Neurobiological Targets/effectsmentioning

confidence: 99%

Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage

et al. 2015

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Multiple cannabinoids derived from the marijuana plant have potential therapeutic benefits but most have not been well investigated, despite the widespread legalization of medical marijuana in the USA and other countries. Therapeutic indications will depend on determinations as to which of the multiple cannabinoids, and other biologically active chemicals that are present in the marijuana plant, can be developed to treat specific symptoms and/or diseases. Such insights are particularly critical for addiction disorders, where different phytocannabinoids appear to induce opposing actions that can confound the development of treatment interventions. Whereas Δ 9 -tetracannabinol has been well documented to be rewarding and to enhance sensitivity to other drugs, cannabidiol (CBD), in contrast, appears to have low reinforcing properties with limited abuse potential and to inhibit drug-seeking behavior. Other considerations such as CBD's anxiolytic properties and minimal adverse side effects also support its potential viability as a treatment option for a variety of symptoms associated with drug addiction. However, significant research is still needed as CBD investigations published to date primarily relate to its effects on opioid drugs, and CBD's efficacy at different phases of the abuse cycle for different classes of addictive substances remain largely understudied. Our paper provides an overview of preclinical animal and human clinical investigations, and presents preliminary clinical data that collectively sets a strong foundation in support of the further exploration of CBD as a therapeutic intervention against opioid relapse. As the legal landscape for medical marijuana unfolds, it is important to distinguish it from Bmedical CBD^and other specific cannabinoids, that can more appropriately be used to maximize the medicinal potential of the marijuana plant.

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Cannabidiol, a Cannabis sativa constituent, as an anxiolytic drug

Cited by 70 publications

References 32 publications

Caffeine protects against memory loss induced by high and non-anxiolytic dose of cannabidiol in adult zebrafish (Danio rerio)

Caffeine protects against memory loss induced by high and non-anxiolytic dose of cannabidiol in adult zebrafish (Danio rerio)

Cannabidiol and Sertraline Regulate Behavioral and Brain Gene Expression Alterations in an Animal Model of PTSD

Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage

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