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  • Cannabidiol (CBD)
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Molecular Targets of Cannabidiol in Experimental Models of Neurological Disease

Abstract Cannabidiol (CBD) is a non-psychoactive phytocannabinoid known for its beneficial effects including antioxidant and anti-inflammatory properties. Moreover, CBD is a compound with antidepressant, anxiolytic, anticonvulsant and antipsychotic effects. Thanks to all these properties, the interest of the scientific community for it has grown. Indeed, CBD is a great candidate for the management of neurological diseases. The purpose of our review is to summarize the in vitro and in vivo studies published in the last 15 years that describe the biochemical and molecular mechanisms underlying the effects of CBD and its therapeutic application in neurological diseases. CBD exerts its neuroprotective effects through three G...
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Cannabidiol Promotes Endothelial Cell Survival by Heme Oxygenase-1-Mediated Autophagy

Abstract Cannabidiol (CBD), a non-psychoactive cannabinoid, has been reported to mediate antioxidant, anti-inflammatory, and anti-angiogenic effects in endothelial cells. This study investigated the influence of CBD on the expression of heme oxygenase-1 (HO-1) and its functional role in regulating metabolic, autophagic, and apoptotic processes of human umbilical vein endothelial cells (HUVEC). Concentrations up to 10 µM CBD showed a concentration-dependent increase of HO-1 mRNA and protein and an increase of the HO-1-regulating transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). CBD-induced HO-1 expression was not decreased by antagonists of cannabinoid-activated receptors (CB1, CB2, transient receptor potential vanilloid 1), but by the reactive oxygen...
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Development of cannabidiol as a treatment for severe childhood epilepsies

Abstract In recent years, there has been a growing appreciation by regulatory authorities that cannabis-based medicines can play a useful role in disease therapy. Although often conflagrated by proponents of recreational use, the legislative rescheduling of cannabis-derived compounds, such as cannabidiol (CBD), has been associated with the steady increase in the pursuit of use of medicinal cannabis. One key driver in this interest has been the scientific demonstration of efficacy and safety of CBD in randomised, placebo-controlled clinical trials in children and young adults with difficult-to-treat epilepsies, which has encouraged increasing numbers of human trials of CBD for other indications and in other populations....
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Cannabidiol disrupts conditioned fear expression and cannabidiolic acid reduces trauma-induced anxiety-related behaviour in mice

Please use this link to access this publication. Abstract The major phytocannabinoid cannabidiol (CBD) has anxiolytic properties and lacks tetrahydrocannabinol-like psychoactivity. Cannabidiolic acid (CBDA) is the acidic precursor to CBD, and this compound appears more potent than CBD in animal models of emesis, pain and epilepsy. In this short report, we aimed to examine whether CBDA is more potent than CBD in disrupting expression of conditioned fear and generalised anxiety-related behaviour induced by Pavlovian fear conditioning. Mice underwent fear conditioning and 24 h later were administered CBD and CBDA before testing for fear expression and generalized anxiety-like behaviour. We found that CBD and CBDA had...
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The effects of cannabidiol on male reproductive system: A literature review

Please use this link to access this publication. Abstract Cannabidiol (CBD) is one of the most abundant phytocannabinoids present in the plant Cannabis sativa (marijuana). There have been several studies of CBD in the last few decades, mainly focused on its neuroprotective properties, particularly after the identification of the endocannabinoid system and its participation in the central nervous system. On the other hand, the peripheral effects of CBD, particularly on reproductive physiology, were also evidenced. A narrative review was conducted using the PubMed database to identify studies that analyzed the pharmacological effects of CBD on the male reproductive system of vertebrates and invertebrates. Thirty-two citations (in...
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Cannabinoids in the Treatment of Epilepsy: Current Status and Future Prospects

Abstract Cannabidiol (CBD) is one of the prominent phytocannabinoids found in Cannabis sativa, differentiating from Δ9-tetrahydrocannabinol (THC) for its non-intoxicating profile and its antianxiety/antipsychotic effects. CBD is a multi-target drug whose anti-convulsant properties are supposed to be independent of endocannabinoid receptor CB1 and might be related to several underlying mechanisms, such as antagonism on the orphan GPR55 receptor, regulation of adenosine tone, activation of 5HT1A receptors and modulation of calcium intracellular levels. CBD is a lipophilic compound with low oral bioavailability (6%) due to poor intestinal absorption and high first-pass metabolism. Its exposure parameters are greatly influenced by feeding status (ie, high fat-containing meals). It is mainly...
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Cannabidiol increases the nociceptive threshold in a preclinical model of Parkinson’s disease

Please use this link to access this publication. Abstract Medications that improve pain threshold can be useful in the pharmacotherapy of Parkinson's disease (PD). Pain is a prevalent PD's non-motor symptom with a higher prevalence of analgesic drugs prescription for patients. However, specific therapy for PD-related pain are not available. Since the endocannabinoid system is expressed extensively in different levels of pain pathway, drugs designed to target this system have promising therapeutic potential in the modulation of pain. Thus, we examined the effects of the 6-hydroxydopamine- induced PD on nociceptive responses of mice and the influence of cannabidiol (CBD) on 6-hydroxydopamine-induced nociception. Further, we investigated the pathway involved in the analgesic effect of the...
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Cannabidiol exerts protective effects in an in vitro model of Parkinson’s disease activating AKT/mTOR pathway

Please use this link to access this publication. Abstract Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of the nigrostriatal dopaminergic pathway with loss of substantia nigra pars compacta neurons and dopamine depletion. Various natural compounds showed protective actions against PD. In this work, the protective effects of cannabidiol (CBD), obtained from Cannabis sativa, were evaluated in retinoic acid differentiated SH-SY5Y cells exposed to 1-methyl-4-phenylpyridinium (MPP+), an in vitro PD model. In order to evaluate which receptor is involved in CBD actions CB1, CB2 and TRPV1 receptor antagonists were used. CBD counteracted the loss of cell viability caused by MPP+, reducing apoptosis as demonstrated by the reduction of Bax and caspase 3. Moreover, CBD reduced the nuclear levels...
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Cannabidiol inhibits multiple cardiac ion channels and shortens ventricular action potential duration in vitro

Please use this link to access this publication. Abstract Cannabidiol (CBD) is a non-psychoactive component of Cannabis which has recently received regulatory consideration for the treatment of intractable forms of epilepsy such as the Dravet and the Lennox-Gastaut syndromes. The mechanisms of the antiepileptic effects of CBD are unclear, but several pre-clinical studies suggest the involvement of ion channels. Therefore, we have evaluated the effects of CBD on seven major cardiac currents shaping the human ventricular action potential and on Purkinje fibers isolated from rabbit hearts to assess the in vitro cardiac safety profile of CBD. We found that CBD inhibits with comparable micromolar potencies the peak and late...
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Use of cannabidiol in anxiety and anxiety-related disorders

Please use this link to access this publication. Abstract Objective Cannabidiol (CBD) has a proposed novel role in the management of anxiety owing to its actions on the endocannabinoid system. The purpose of this systematic review was to evaluate the current evidence on the safety and efficacy of CBD in anxiety and anxiety-related disorders. Data sources A literature search was conducted on PubMed, Google Scholar, and International Pharmaceutical Abstracts from database inception through June 2019. A bibliographic search of relevant articles was also conducted. Study selection Articles published from case reports, case series, or randomized controlled trials on human subjects were included in the...
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