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Cannabidiol as a potential novel treatment for endometriosis by its anti-inflammatory, antioxidative and antiangiogenic effects in an experimental rat model

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Endometrial implants were surgically induced in 36 female Wistar albino rats. After confirmation of endometriotic foci, the rats were randomized into four groups. In the leuprolide acetate group, rats were given a single 1 mg/kg s.c. leuprolide acetate injection. The other groups were 5 mg/kg CBD (CBD5), saline solution and 20 mg/kg CBD (CBD20); daily i.p. injections were administered for 7 days. After 21 days, the rats were euthanised, and total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) measurements in blood and peritoneal fluid samples, and immunohistochemical staining for TNF-α, IL-6 and vascular endothelial growth factor (VEGF) of endometriotic tissues were evaluated.

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Is it the Ideal Time to Start Prescribing Cannabis Derivatives to Treat Endometriosis-associated Pain?

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Endometriosis affects 5%-10% of women of reproductive age and is often associated with painful symptoms like dysmenorrhea, dyschezia, dyspareunia, and even non cyclical pain. The disease is diagnosed in at least 20% of women with dysmenorrhea and/or non-menstrual pelvic pain, reaching a prevalence of 50% pain among adolescents. There is an alignment among international societies3,4 that the pre- sumed diagnosis of this disease is enough to start clinical treatment. Moreover, there seems to be a consensus that first-line treatment should be hormonal contraceptives since the efficacy is similar to that of surgery but with lower complication rates and costs. However, these drugs are
effective in only approximately two-thirds of patients, have limited long-term efficacy and may occasionally lead to undesirable side effects. Additionally, there are serious limitations in the interpretation of clinical trials.

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Anticancer properties of cannabidiol and Δ9-tetrahydrocannabinol and synergistic effects with gemcitabine and cisplatin in bladder cancer cell lines

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With the legalization of cannabis in multiple jurisdictions throughout the world, a larger proportion of the population consumes cannabis. Several studies have demonstrated anti-tumor effects of components present in cannabis in different models. Unfortunately, little is known about the potential anti-tumoral effects of cannabinoids in bladder cancer, and how cannabinoids could potentially synergize with chemotherapeutic agents. Our study aims to identify whether a combination of cannabinoids, like cannabidiol and Δ9-tetrahydrocannabinol with agents commonly used to treat bladder cancer, such as gemcitabine and cisplatin, is able to produce desirable synergistic effects. We also evaluated whether co-treatment of different cannabinoids also generated synergistic effects.

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Cannabidiol for the Treatment of Brain Disorders: Therapeutic Potential and Routes of Administration

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The use of cannabidiol (CBD) for treating brain disorders has gained increasing interest. While the mechanism of action of CBD in these conditions is still under investigation, CBD has been shown to affect numerous different drug targets in the brain that are involved in brain disorders. Here we review the preclinical and clinical evidence on the potential therapeutic use of CBD in treating various brain disorders. Moreover, we also examine various drug delivery approaches that have been applied to CBD. Due to the slow absorption and low bioavailability with the current oral CBD therapy, more efficient routes of administration to bypass hepatic metabolism, particularly pulmonary delivery, should be considered. Comparison of pharmacokinetic studies of different delivery routes highlight the advantages of intranasal and inhalation drug delivery over other routes of administration (oral, injection, sublingual, buccal, and transdermal) for treating brain disorders. These two routes of delivery, being non-invasive and able to achieve fast absorption and increase bioavailability, are attracting increasing interest for CBD applications, with more research and development expected in the near future.

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Cannabidiol as a potential novel treatment for endometriosis by its anti-inflammatory, antioxidative and anti-angiogenic effects in an experimental rat model

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Can cannabidiol (CBD) be used in the treatment of endometriosis by its anti-inflammatory, antioxidative, and anti-angiogenic effects? Endometrial implants were surgically induced in 36 female Wistar-Albino rats. After confirmation of endometriotic foci, the rats were randomized into four groups. In leuprolide acetate (LA) group, rats were given a single 1mg/kg subcutaneous LA injection. Other groups were 5 mg/kg CBD (CBD5), saline solution (SS), and 20 mg/kg CBD (CBD20) and daily intra-peritoneal injections were applied for seven days. After 21 days, the rats were sacrificed, and total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) measurements in blood and peritoneal fluid samples, and immunohistochemical staining for TNF-α, IL-6 and vascular endothelial growth factor (VEGF) of endometriotic tissues were evaluated.

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The synergistic anticancer effect of CBD and DOX in osteosarcoma

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Osteosarcoma is a malignant tumor that can present with pain in the bones, joints, and local masses. The incidence is highest in adolescents, and the most common sites are the distal femur, proximal tibia and proximal humerus metaphyseal. Doxorubicin is the first-line chemotherapeutic agent for the treatment of osteosarcoma, but it has many side effects. Cannabidiol is a non-psychoactive plant cannabinoid cannabinol (CBD) that has been shown to be effective against osteosarcoma; however, the molecular targets and mechanisms of CBD action in osteosarcoma remain unclear.

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Topical Cannabidiol in the Treatment of Digital Ulcers in Patients with Scleroderma: Comparative Analysis and Literature Review

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To explore the effect of topical cannabidiol (CBD) in treating digital ulcers in patients with systemic sclerosis (SSc). In total, 45 patients with SSc who had digital ulcers were consecutively enrolled between January 2019 and December 2019. Of the participants, 25 were treated with CBD during surgical debridement and 20 were treated with standard local therapy. A numeric rating scale for pain and Health Assessment Questionnaire Disability Index were administered at the baseline and at the end of treatment.

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Cannabidiol and Cannabigerol Exert Antimicrobial Activity without Compromising Skin Microbiota

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Cannabidiol (CBD) and cannabigerol (CBG) are two pharmacologically active phytocannabinoids of Cannabis sativa L. Their antimicrobial activity needs further elucidation, particularly for CBG, as reports on this cannabinoid are scarce. We investigated CBD and CBG’s antimicrobial potential, including their ability to inhibit the formation and cause the removal of biofilms. Our results demonstrate that both molecules present activity against planktonic bacteria and biofilms, with both cannabinoids removing mature biofilms at concentrations below the determined minimum inhibitory concentrations. We report for the first time minimum inhibitory and lethal concentrations for Pseudomonas aeruginosa and Escherichia coli (ranging from 400 to 3180 µM), as well as the ability of cannabinoids to inhibit Staphylococci adhesion to keratinocytes, with CBG demonstrating higher activity than CBD.

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The Effectiveness and Safety of Pharmaceutical-Grade Cannabidiol in the Treatment of Mastocytosis-Associated Pain: A Pilot Study

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Mastocytosis patients often experience a number of symptoms, including mastocytosis-associated pain that is difficult to manage due to resistance to usual antalgic treatments and/or the patient’s poor tolerance. Mastocytosis patients display significantly higher levels of indoleamine-2,3-dioxygenase-1 (IDO1) activity, leading to hyperactivation of the N-methyl-D-aspartate receptor. As cannabidiol (CBD) is known to inhibit IDO1′s enzymatic activity, we hypothesized that pharmaceutical-grade CBD is an effective treatment for mastocytosis-associated pain. Patients with non-advanced mastocytosis and refractory pain were eligible for inclusion in this observational pilot study.

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Cannabidiol: Bridge between Antioxidant Effect, Cellular Protection, and Cognitive and Physical Performance

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The literature provides scientific evidence for the beneficial effects of cannabidiol (CBD), and these effects extend beyond epilepsy treatment (e.g., Lennox–Gastaut and Dravet syndromes), notably the influence on oxidative status, neurodegeneration, cellular protection, cognitive function, and physical performance. However, products containing CBD are not allowed to be marketed everywhere in the world, which may ultimately have a negative effect on health as a result of the uncontrolled CBD market. After the isolation of CBD follows the discovery of CB1 and CB2 receptors and the main enzymatic components (diacylglycerol lipase (DAG lipase), monoacyl glycerol lipase (MAGL), fatty acid amino hydrolase (FAAH)).

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Beyond Pain Relief: A Review on Cannabidiol Potential in Medical Therapies

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The phytocannabinoid cannabidiol (CBD) is receiving increasing attention due to its pharmacological properties. Although CBD is extracted from Cannabis sativa, it lacks the psychoactive effects of Δ9-tetrahydrocannabinol (THC) and has become an attractive compound for pharmacological uses due to its anti-inflammatory, antioxidant, anticonvulsant, and anxiolytic potential. The molecular mechanisms involved in CBD’s biological effects are not limited to its interaction with classical cannabinoid receptors, exerting anti-inflammatory or pain-relief effects. Several pieces of evidence demonstrate that CBD interacts with other receptors and cellular signaling cascades, which further support CBD’s therapeutic potential beyond pain management. In this review, we take a closer look at the molecular mechanisms of CBD and its potential therapeutic application in the context of cancer, neurodegeneration, and autoimmune diseases.

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Effects of Cannabidiol on Innate Immunity Experimental Evidence and Clinical Evidence

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Cannabidiol (CBD) is the main non-psychotropic cannabinoid derived from cannabis (Cannabis sativa L., fam. Cannabaceae). CBD has received approval by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the treatment of seizures associated with Lennox–Gastaut syndrome or Dravet syndrome. However, CBD also has prominent anti-inflammatory and immunomodulatory effects; evidence exists that it could be beneficial in chronic inflammation, and even in acute inflammatory conditions, such as those due to SARS-CoV-2 infection. In this work, we review available evidence concerning CBD’s effects on the modulation of innate immunity. Despite the lack so far of clinical studies, extensive preclinical evidence in different models, including mice, rats, guinea pigs, and even ex vivo experiments on cells from human healthy subjects, shows that CBD exerts a wide range of inhibitory effects by decreasing cytokine production and tissue infiltration, and acting on a variety of other inflammation-related functions in several innate immune cells. Clinical studies are now warranted to establish the therapeutic role of CBD in diseases with a strong inflammatory component, such as multiple sclerosis and other autoimmune diseases, cancer, asthma, and cardiovascular diseases

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