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Cannabinoids Protect Cells from Oxidative Cell Death: A Receptor-Independent Mechanism

Please use this link to access this publication. Abstract Serum is required for the survival and growth of most animal cells. In serum-free medium, B lymphoblastoid cells and fibroblasts die after 2 days. We report that submicromolar concentrations of Δ9-tetrahydrocannabinol (THC), Δ8-THC, cannabinol, or cannabidiol, but not WIN 55,212-2, prevented serum-deprived cell death. Δ9-THC also synergized with platelet-derived growth factor in activating resting NIH 3T3 fibroblasts. The cannabinoids' growth supportive effect did not correlate with their ability to bind to known cannabinoid receptors and showed no stereoselectivity, suggesting a nonreceptor-mediated pathway. Direct measurement of oxidative stress revealed that cannabinoids prevented serum-deprived cell death by...
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Serum-dependent effects of tamoxifen and cannabinoids upon C6 glioma cell viability

Please use this link to access this publication. Abstract In the present study, the effects of the combination of tamoxifen ((Z)-2[p-(1,2-diphenyl-1-butenyl)phenoxy]-N,N-dimethylamine citrate) and three cannabinoids (Δ9-tetrahydrocannabinol [Δ9-THC], cannabidiol, and anandamide [AEA]) upon the viability of C6 rat glioma cells was assessed at different incubation times and using different culturing concentrations of foetal bovine serum (FBS). Consistent with previous data for human glioblastoma cells, the tamoxifen sensitivity of the cells was increased as the FBS content of the culture medium was reduced from 10 to 0.4 and 0%. The cells expressed protein kinase C α and calmodulin (the concentration of which did not change significantly as the FBS concentration was reduced), but did not express estrogen receptors. Δ9-THC and...
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Cannabinoid CB1 Receptor Expression and Localization in the Dorsal Horn of Male and Female Rat and Human Spinal Cord

Abstract Cannabidiol (CBD), a non-psychotomimetic phytocannabinoid found in the Cannabis plant, has emerged as a potential therapeutic agent for psychostimulant use disorders. In recent work, we demonstrated that CBD is able to attenuate the expression of locomotor sensitization and the enhanced metabolic activity in the nucleus accumbens (NAc) generated by the combination of cocaine and caffeine. CDB interacts directly or indirectly with several molecular targets, so the underlying mechanisms of its beneficial effects are hard to determine. Here we used high-throughput RNA-sequencing in mice’s NAc after a sensitization protocol with combined cocaine plus caffeine and a CBD pre-treatment, to identify the major pathways and genes involved...
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Evaluating Sex Differences in Efficacy, Safety and Pharmacokinetics in Patients Treated with Cannabis by a Metered-Dose Inhaler

Abstract Background: Clinical studies on medical cannabis (MC) treatment have shown sex-related differences, including higher susceptibility to adverse events among women and greater analgesia among men. Here, we used the Syqe metered-dose inhaler (MDI) and a single chemovar to analyze sex differences. Methods: A total of 1249 Israeli chronic pain patients were assessed for pain intensity, sleep and adverse events (AEs) over 240 days. Results: Following the first two weeks, no significant sex differences were found in the effectiveness or safety of MC treatment (p > 0.05). Inhaled Δ9-THC doses did not vary significantly between sexes (p > 0.05) except in the first month of treatment....
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Effects of Chronic, Low-Dose Cannabinoids, Cannabidiol, Delta-9-Tetrahydrocannabinol and a Combination of Both, on Amyloid Pathology in the 5xFAD Mouse Model of Alzheimer’s Disease

Abstract Background: There is an urgent need for novel therapies to treat Alzheimer's disease. Among others, the use of cannabinoids such as delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) has been proposed as a putative approach based on their anti-inflammatory effects. Methods: The present work was designed to explore the effects of chronic (28 days) treatment with low doses of cannabinoids: CBD (0.273 mg/kg), THC (0.205 mg/kg) or a combination of both (CBD:THC; 0.273 mg/kg:0.205 mg/kg) in the 5xFAD mouse model of AD. Results: Our data revealed that THC-treated 5xFAD mice (but not other treatment groups) exhibited anxiogenic and depressant-like behavior. A significant improvement in spatial memory was observed only in the CBD:THC-treated...
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Prenatal Cannabinoid Exposure Elicits Memory Deficits Associated with Reduced PSA-NCAM Expression, Altered Glutamatergic Signaling, and Adaptations in Hippocampal Synaptic Plasticity

Abstract Cannabis is now one of the most commonly used illicit substances among pregnant women. This is particularly concerning since developmental exposure to cannabinoids can elicit enduring neurofunctional and cognitive alterations. This study investigates the mechanisms of learning and memory deficits resulting from prenatal cannabinoid exposure (PCE) in adolescent offspring. The synthetic cannabinoid agonist WIN55,212-2 was administered to pregnant rats, and a series of behavioral, electrophysiological, and immunochemical studies were performed to identify potential mechanisms of memory deficits in the adolescent offspring. Hippocampal-dependent memory deficits in adolescent PCE animals were associated with decreased long-term potentiation (LTP) and enhanced long-term depression (LTD) at hippocampal Schaffer...
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Cannabinoid treatments in epilepsy and seizure disorders

Please use this link to access this publication: https://journals.physiology.org/doi/epdf/10.1152/physrev.00049.2021 Abstract Cannabis was used to treat convulsions and other disorders since ancient times. In the last few decades, preclinical animal studies and clinical investigations have established the role of cannabidiol (CBD) in treating epilepsy and seizures and support potential therapeutic benefits for cannabinoids in other neurological and psychiatric disorders. Here, we comprehensively review the role of cannabinoids in epilepsy. We briefly review the diverse physiological processes mediating the central nervous system response to cannabinoids, including D9-THC, cannabidiol, and terpenes. Next, we characterize the anti- and proconvulsive effects of cannabinoids from animal studies of acute seizures and...
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Non-Intoxicating Cannabinoids in Visceral Pain

Please use this link to access this publication: https://www.liebertpub.com/doi/abs/10.1089/can.2023.0113 Abstract Cannabis and cannabis products are becoming increasingly popular options for symptom management of inflammatory bowel diseases, particularly abdominal pain. While anecdotal and patient reports suggest efficacy of these compounds for these conditions, clinical research has shown mixed results. To date, clinical research has focused primarily on delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is a ligand of classical cannabinoid receptors (CBRs). CBD is one of a large group of nonintoxicating cannabinoids (niCBs) that mediate their effects on both CBRs and through non-CBR mechanisms of action. Because they are not psychotropic, there is increasing interest and availability...
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Evaluation of different phytochemicals from Cannabis sativa against Myelin oligodendrocyte glycoprotein receptor

Abstract There is a rapid spread of multiple sclerosis (MS) disorder across the globe. There are around 2.8 million cases of Multiple Sclerosis in the world; among them, 1 million are just present in the US. Many drugs have been tested on MS patients but there is no effective treatment for MS till now. Many agonists, such as dronabinol, and nabilone, have been used to treat MS. So, in this study, different compounds from Cannabis sativa to inhibit the symptoms caused by MS had been evaluated. This study targeted the Myelin oligodendrocyte glycoprotein receptor as it has shown some good results in experimental labs. In this study, binding...
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Unlocking the Healing Potential Cannabinoids in Spine Surgery for Pain Relief and Recovery

Please use this link to access this publication: https://journals.lww.com/jbjsreviews/abstract/2023/11000/unlocking_the_healing_potential__cannabinoids_in.4.aspx Abstract » Cannabinoids, such as D9-tetrahydrocannabinol and cannabidiol, interact with endocannabinoid receptors in the central nervous system and immune system, potentially offering pain relief. The entourage effect, resulting from the interaction of multiple cannabis components, may enhance therapeutic impact and efficacy, making them promising candidates for exploring pain relief in spine operations, known to be among the most painful operative procedures. » The use of cannabinoids in pain management requires careful consideration of safety, including their cognitive and psychomotor effects, potential cardiovascular risks, risk of dependence, mental health implications, and drug interactions. » Few studies have...
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