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  • Cannabidiol (CBD)
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Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: role of 5-HT1A receptors

Please use this link to access this publication: https://www.sciencedirect.com/science/article/abs/pii/S0028390815302136?via%3Dihub Abstract Cannabidiol (CBD), the main non-psychotomimetic component of marihuana, exhibits anxiolytic-like properties in many behavioural tests, although its potential for treating major depression has been poorly explored. Moreover, the mechanism of action of CBD remains unclear. Herein, we have evaluated the effects of CBD following acute and chronic administration in the olfactory bulbectomy mouse model of depression (OBX), and investigated the underlying mechanism. For this purpose, we conducted behavioural (open field and sucrose preference tests) and neurochemical (microdialysis and autoradiography of 5-HT1A receptor functionality) studies following treatment with CBD. We also assayed the pharmacological antagonism of...
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Antidepressant-like effects of cannabidiol in mice: possible involvement of 5-HT1A receptors

Abstract Background and purpose: Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that induces anxiolytic- and antipsychotic-like effects in animal models. Effects of CBD may be mediated by the activation of 5-HT(1A) receptors. As 5-HT(1A) receptor activation may induce antidepressant-like effects, the aim of this work was to test the hypothesis that CBD would have antidepressant-like activity in mice as assessed by the forced swimming test. We also investigated if these responses depended on the activation of 5-HT(1A) receptors and on hippocampal expression of brain-derived neurotrophic factor (BDNF). Experimental approach: Male Swiss mice were given (i.p.) CBD (3, 10, 30, 100 mg*kg(-1)), imipramine (30 mg*kg(-1))...
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Abrupt withdrawal of cannabidiol (CBD): A randomized trial

Please use this link to access this publication. Abstract Rationale: The rationale of this study was to assess occurrence of withdrawal symptoms induced by abrupt cessation of cannabidiol (CBD) after prolonged administration in healthy volunteers. Methods: Thirty volunteers were randomized to receive 750 mg of a plant-derived pharmaceutical formulation of highly purified CBD in oral solution (100 mg/mL; Epidiolex® in the United States and Epidyolex® in Europe) twice daily (b.i.d.) for 4 weeks (Part 1) followed by 2 weeks of 750 mg b.i.d. CBD (Part 2, Arm 1) or matched placebo (Part 2, Arm 2). All volunteers completed the Cannabis Withdrawal Scale (CWS) and the 20-item...
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Involvement of serotonin-mediated neurotransmission in the dorsal periaqueductal gray matter on cannabidiol chronic effects in panic-like responses in rats

Please use this link to access this publication: https://link.springer.com/article/10.1007/s00213-012-2878-7 Abstract Rationale: Cannabidiol (CBD) is a non-psychotomimetic constituent of Cannabis sativa plant that promotes antianxiety and anti-panic effects in animal models after acute systemic or intra-dorsal periaqueductal gray (DPAG) administration. However, the effects of CBD repeated administration, and the possible mechanisms involved, in animal models of anxiety- and panic-related responses remain poorly understood. Objective: The present study evaluates the role of the serotonergic neurotransmission within the DPAG in the modulation of escape responses of rats chronically treated with CBD. Methods: Male Wistar rats received acute or repeated (5 mg/Kg/daily/21 days) administration of CBD and were submitted to the elevated...
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The anxiolytic-like effects of cannabidiol injected into the bed nucleus of the stria terminalis are mediated by 5-HT1A receptors

Please use this link to access this publication: https://link.springer.com/article/10.1007/s00213-010-2036-z Abstract Rationale: Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that induces anxiolytic-like effects in rodents and humans after systemic administration. Previous results from our group showed that CBD injection into the bed nucleus of the stria terminalis (BNST) attenuates conditioned aversive responses. The aim of this study was to further investigate the role of this region on the anxiolytic effects of the CBD. Moreover, considering that CBD can activate 5-HT1A receptors, we also verified a possible involvement of these receptors in those effects. Methods: Male Wistar rats received injections of CBD (15, 30, or 60 nmol)...
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Effects of intra-prelimbic prefrontal cortex injection of cannabidiol on anxiety-like behavior: involvement of 5HT1A receptors and previous stressful experience

Please use this link to access this publication: https://www.sciencedirect.com/science/article/abs/pii/S0924977X1300309X?via%3Dihub Abstract The prelimbic medial prefrontal cortex (PL) is an important encephalic structure involved in the expression of emotional states. In a previous study, intra-PL injection of cannabidiol (CBD), a major non-psychotomimetic cannabinoid present in the Cannabis sativa plant, reduced the expression of fear conditioning response. Although its mechanism remains unclear, CBD can facilitate 5HT1A receptor-mediated neurotransmission when injected into several brain structures. This study was aimed at verifying if intra-PL CBD could also induce anxiolytic-like effect in a conceptually distinct animal model, the elevated plus maze (EPM). We also verified if CBD effects in the EPM...
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Cannabidiol attenuates behavioral changes in a rodent model of schizophrenia through 5-HT1A, but not CB1 and CB2 receptors

Abstract Preclinical and clinical data indicate that cannabidiol (CBD), a non-psychotomimetic compound from the Cannabis sativa plant, can induce antipsychotic-like effects. In an animal model of schizophrenia based on the antagonism of NMDA receptors, the behavioral and molecular changes induced by repeated treatment with the NMDA receptor antagonist MK-801 were prevented when CBD was co-administered with MK-801. It is unknown, however, if CBD would reverse these changes once they have been established. Thus, in the present study we used male C57BL/6J mice, 6 weeks old, to evaluate whether daily CBD injection for seven days, starting after the end of the repeated treatment with MK-801...
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Anxiolytic Effects of Repeated Cannabidiol Treatment in Teenagers With Social Anxiety Disorders

Abstract Accumulated evidence indicates that cannabidiol (CBD), a nonpsychotomimetic and nonaddictive main component of the Cannabis sativa plant, reverses anxiety-like behavior. The purpose of the present study was to assess the efficacy of CBD treatment for Japanese late teenagers with social anxiety disorder (SAD). Thirty-seven 18–19-year-old Japanese teenagers with SAD and avoidant personality disorder received, in a double-blind study, cannabis oil (n = 17) containing 300 mg CBD or placebo (n = 20) daily for 4 weeks. SAD symptoms were measured at the beginning and end of the treatment period using the Fear of Negative Evaluation Questionnaire and the Liebowitz Social Anxiety Scale. CBD significantly decreased anxiety measured...
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Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients

Abstract Generalized Social Anxiety Disorder (SAD) is one of the most common anxiety conditions with impairment in social life. Cannabidiol (CBD), one major non-psychotomimetic compound of the cannabis sativa plant, has shown anxiolytic effects both in humans and in animals. This preliminary study aimed to compare the effects of a simulation public speaking test (SPST) on healthy control (HC) patients and treatment-naïve SAD patients who received a single dose of CBD or placebo. A total of 24 never-treated patients with SAD were allocated to receive either CBD (600 mg; n=12) or placebo (placebo; n=12) in a double-blind randomized design 1 h and a half...
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Oral cannabidiol does not produce a signal for abuse liability in frequent marijuana smokers

Abstract Background Cannabidiol (CBD) is a naturally occurring constituent of the marijuana plant. In the past few years, there has been great interest in the therapeutic effects of isolated CBD and it is currently being explored for numerous disease conditions (e.g., pain, epilepsy, cancer, various drug dependencies). However, CBD remains a Schedule I drug on the U.S. Controlled Substances Act (CSA). Despite its status, there are no well-controlled data available regarding its abuse liability. Methods Healthy, frequent marijuana users (n=31) were enrolled in this within subject, randomized, placebo-controlled, double-blind, multisite study that administered oral cannabidiol (0, 200, 400, 800 mg) alone and in combination...
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