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Under the umbrella of depression and Alzheimer’s disease physiopathology: can cannabinoids be a dual-pleiotropic therapy?

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Depression and Alzheimer´s disease (AD) are two disorders highly prevalent worldwide. Depression affects more than 300 million people worldwide while AD affects 60% to 80% of the 55 million cases of dementia. Both diseases are affected by aging with high prevalence in elderly and share not only the main brain affected areas but also several physiopathological mechanisms. Depression disease is already ascribed as a risk factor to the development of AD. Despite the wide diversity of pharmacological treatments currently available in clinical practice for depression management, they remain associated to a slow recovery process and to treatment-resistant depression. On the other hand, AD treatment is essentially based in symptomatology relieve. Thus, the need for new multi-target treatments arises.

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Long-term safety of medical cannabis in Parkinson’s disease: A retrospective case-control study

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Whole-plant medical cannabis (MC) products are widely used for controlling symptoms associated with Parkinson’s disease (PD). Despite its widespread use, few studies have investigated the long-term impact of MC on the progression of PD or its safety profile. This study examined the effects of MC on PD in a real-life setting. A retrospective case-control study of 152 idiopathic PD patients (mean age 69.1 ± 9.0 years), followed at the Sheba Medical Center Movement Disorders Institute (SMDI) from 2008 to 2022 was conducted. Seventy-six patients who used licensed whole-plant medical cannabis (MC) for at least a year were compared to a matched group who did not receive MC in terms of their Levodopa Equivalent Daily Dose (LEDD), Hoehn and Yahr (H&Y) stage, and cognitive, depressive, and psychotic symptoms.

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The Effect of Cannabidiol 3% on Neuropsychiatric Symptoms in Dementia – Six-Month Follow-Up

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To investigate the beneficial outcomes of giving cannabidiol (CBD) 3% over a six-month period in the BPSD, the management of which is a crucial issue for everyday clinical praxis and to compare the progress in BPSD of patients who receive Cannabidiol 3% with those who follow usual medical treatment (UMT) in everyday clinical praxis. A total of 20 PwD with severe BPSD were recruited from the database of Alzheimer Hellas with NPI score >30. Ten of them were assigned to UMT, while ten were assigned to a six-month treatment with CBD drops. The follow-up assessment was performed with NPI, both clinically and by structured telephone interview.

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Disorders of cancer metabolism: The therapeutic potential of cannabinoids

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Abnormal energy metabolism, as one of the important hallmarks of cancer, was induced by multiple carcinogenic factors and tumor-specific microenvironments. It comprises aerobic glycolysis, de novo lipid biosynthesis, and glutamine-dependent anaplerosis. Considering that metabolic reprogramming provides various nutrients for tumor survival and development, it has been considered a potential target for cancer therapy. Cannabinoids have been shown to exhibit a variety of anticancer activities by unclear mechanisms. This paper first reviews the recent progress of related signaling pathways (reactive oxygen species (ROS), AMP-activated protein kinase (AMPK), mitogen-activated protein kinases (MAPK), phosphoinositide 3-kinase (PI3K), hypoxia-inducible factor-1alpha (HIF-1α), and p53) mediating the reprogramming of cancer metabolism (including glucose metabolism, lipid metabolism, and amino acid metabolism). Then we comprehensively explore the latest discoveries and possible mechanisms of the anticancer effects of cannabinoids through the regulation of the above-mentioned related signaling pathways, to provide new targets and insights for cancer prevention and treatment.

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Antitumor Effects of Cannabis sativa Bioactive Compounds on Colorectal Carcinogenesis

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Cannabis sativa is a multipurpose plant that has been used in medicine for centuries. Recently, considerable research has focused on the bioactive compounds of this plant, particularly cannabinoids and terpenes. Among other properties, these compounds exhibit antitumor effects in several cancer types, including colorectal cancer (CRC). Cannabinoids show positive effects in the treatment of CRC by inducing apoptosis, proliferation, metastasis, inflammation, angiogenesis, oxidative stress, and autophagy. Terpenes, such as β-caryophyllene, limonene, and myrcene, have also been reported to have potential antitumor effects on CRC through the induction of apoptosis, the inhibition of cell proliferation, and angiogenesis. In addition, synergy effects between cannabinoids and terpenes are believed to be important factors in the treatment of CRC. This review focuses on the current knowledge about the potential of cannabinoids and terpenoids from C. sativa to serve as bioactive agents for the treatment of CRC while evidencing the need for further research to fully elucidate the mechanisms of action and the safety of these compounds.

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Phytocannabinoids in Triple Negative Breast Cancer Treatment: Current Knowledge and Future Insights

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Triple negative breast cancer (TNBC) represents an aggressive subtype of breast cancer, which is deficient in estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. Thus, TNBC cells are unable to respond to the conventional hormonal therapies, making chemotherapy the only therapeutic choice. Patients with TNBC develop metastasis and recurrence over time and have reduced survival compared to patients with other subtypes of breast cancer. Therefore, there is a need for innovative therapies. Data emerged from pre-clinical studies, highlighted various antitumor activities of plant-derived Cannabis sativa and synthetic cannabinoids (CBs), including delta-9-tetrahydrocannabinol (THC) and non-psychoactive cannabidiol (CBD). On the contrary, some studies indicated that CBs might also promote tumor progression. At present, clinical studies on the effects of CBs from Cannabis sativa in cancer patients are few. In the present study, we reviewed known and possible interactions between cannabinoids and TNBC therapies.

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Efficacy of cannabinoids in neurodevelopmental and neuropsychiatric disorders among children and adolescents: a systematic review

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A better understanding of the endocannabinoid system and a relaxation in regulatory control of cannabis globally has increased interest in the medicinal use of cannabinoid-based products (CBP). We provide a systematic review of the rationale and current clinical trial evidence for CBP in the treatment of neuropsychiatric and neurodevelopmental disorders in children and adolescents. A systematic search of MEDLINE, Embase, PsycINFO, and the Cochrane Central Register of Trials was performed to identify articles published after 1980 about CBP for medical purposes in individuals aged 18 years or younger with selected neuropsychiatric or neurodevelopmental conditions. Risk of bias and quality of evidence was assessed for each article. Of 4466 articles screened, 18 were eligible for inclusion, addressing eight conditions (anxiety disorders (n = 1); autism spectrum disorder (n = 5); foetal alcohol spectrum disorder (n = 1); fragile X syndrome (n = 2); intellectual disability (n = 1); mood disorders (n = 2); post-traumatic stress disorder (n = 3); and Tourette syndrome (n = 3)). Only one randomised controlled trial (RCT) was identified. The remaining seventeen articles included one open-label trial, three uncontrolled before-and-after trials, two case series and 11 case reports, thus the risk of bias was high. Despite growing community and scientific interest, our systematic review identified limited and generally poor-quality evidence for the efficacy of CBP in neuropsychiatric and neurodevelopmental disorders in children and adolescents. Large rigorous RCTs are required to inform clinical care. In the meantime, clinicians must balance patient expectations with the limited evidence available.

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Antiviral activities of hemp cannabinoids

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Hemp is an understudied source of pharmacologically active compounds and many unique plant secondary metabolites including more than 100 cannabinoids. After years of legal restriction, research on hemp has recently demonstrated antiviral activities in silico, in vitro, and in vivo for cannabidiol (CBD), Δ9-tetrahydrocannabinol (Δ9-THC), cannabidiolic acid (CBDA), cannabigerolic acid (CBGA), and several other cannabinoids against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), human immunodeficiency virus (HIV), and γ-herpes viruses. Mechanisms of action include inhibition of viral cell entry, inhibition of viral proteases, and stimulation of cellular innate immune responses. The anti-inflammatory properties of cannabinoids are also under investigation for mitigating the cytokine storm of COVID-19 and controlling chronic inflammation in people living with HIV. Retrospective clinical studies support antiviral activities of CBD, Δ9-THC, and cannabinoid mixtures as do some prospective clinical trials, but appropriately designed clinical trials of safety and efficacy of antiviral cannabinoids are urgently needed.

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Efficacy of cannabinoids in neurodevelopmental and neuropsychiatric disorders among children and adolescents: a systematic review

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A better understanding of the endocannabinoid system and a relaxation in regulatory control of cannabis globally has increased interest in the medicinal use of cannabinoid-based products (CBP). We provide a systematic review of the rationale and current clinical trial evidence for CBP in the treatment of neuropsychiatric and neurodevelopmental disorders in children and adolescents. A systematic search of MEDLINE, Embase, PsycINFO, and the Cochrane Central Register of Trials was performed to identify articles published after 1980 about CBP for medical purposes in individuals aged 18 years or younger with selected neuropsychiatric or neurodevelopmental conditions. Risk of bias and quality of evidence was assessed for each article. Of 4466 articles screened, 18 were eligible for inclusion, addressing eight conditions

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Potential, Limitations and Risks of Cannabis-Derived Products in Cancer Treatment

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It is easy to find success stories on the internet of patients with cancer who seem to benefit from using cannabis products. However, scientific substantiation is usually lacking. Therefore, there are critical questions among clinicians and other healthcare providers about the potential of cannabis products in cancer care. In this article, we aim to give direction for making choices about the responsible use of cannabis products in oncology by addressing the following questions: How does cannabis work? What is medicinal cannabis? What kind of cannabis products are in use? What is their legal status? Is there evidence for therapeutic effects in patients with cancer? What is the risk–benefit balance in terms of adverse effects, (potential) drug interactions, symptom management and antitumour activity? May cannabis products provide added value in the treatment of patients with cancer? We end up with an outlook and perspective determining the place of cannabis products in oncology.

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Clinical Practice Guidelines for Cannabis and Cannabinoid-Based Medicines in the Management of Chronic Pain and Co-Occurring Conditions

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The interest in the pharmacological applications of cannabinoids is largely increasing in a wide range of medical areas. Recently, research on its potential role in eye conditions, many of which are chronic and/or disabling and in need of new alternative treatments, has intensified. However, due to cannabinoids’ unfavorable physicochemical properties and adverse systemic effects, along with ocular biological barriers to local drug administration, drug delivery systems are needed. Hence, this review focused on the following: (i) identifying eye disease conditions potentially subject to treatment with cannabinoids and their pharmacological role, with emphasis on glaucoma, uveitis, diabetic retinopathy, keratitis and the prevention of Pseudomonas aeruginosa infections; (ii) reviewing the physicochemical properties of formulations that must be controlled and/or optimized for successful ocular administration; (iii) analyzing works evaluating cannabinoid-based formulations for ocular administration, with emphasis on results and limitations; and (iv) identifying alternative cannabinoid- based formulations that could potentially be useful for ocular administration strategies. Finally, an overview of the current advances and limitations in the field, the technological challenges to overcome and the prospective further developments, is provided.

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Cannabinoid-Based Ocular Therapies and Formulations

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The interest in the pharmacological applications of cannabinoids is largely increasing in a wide range of medical areas. Recently, research on its potential role in eye conditions, many of which are chronic and/or disabling and in need of new alternative treatments, has intensified. However, due to cannabinoids’ unfavorable physicochemical properties and adverse systemic effects, along with ocular biological barriers to local drug administration, drug delivery systems are needed. Hence, this review focused on the following: (i) identifying eye disease conditions potentially subject to treatment with cannabinoids and their pharmacological role, with emphasis on glaucoma, uveitis, diabetic retinopathy, keratitis and the prevention of Pseudomonas aeruginosa infections; (ii) reviewing the physicochemical properties of formulations that must be controlled and/or optimized for successful ocular administration; (iii) analyzing works evaluating cannabinoid-based formulations for ocular administration, with emphasis on results and limitations; and (iv) identifying alternative cannabinoid- based formulations that could potentially be useful for ocular administration strategies. Finally, an overview of the current advances and limitations in the field, the technological challenges to overcome and the prospective further developments, is provided.

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